Tezacaftor

- Data on ALYFTREK in children ages 2 to 5 years demonstrate recovery of pancreatic function in some children – - Additional abstracts on clinical and real-world evidence on CFTR modulators also presented - BOSTON--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced new interim data from the ALYFTREK ® (vanzacaftor/tezacaftor/deutivacaftor) 2 to 5 years old open-label extension study, highlighting recovery of exocrine pancreatic function in some children in that age group, allowing those children to discontinue pancreatic enzyme replacement therapy (PERT). Pancreatic exocrine insufficiency in children with cystic fibrosis (CF) was previously believed to be irreversible. These data were presented at the North American Cystic Fibrosis Conference (NACFC). “The data presented at NACFC underscore the safety and efficacy of our CF medicines in the real world and in clinical trials in younger age groups. The data from the Phase 3 open-label study in 2 to 5 year olds evaluating exocrine pancreatic function represent a profound shift in how we understand the benefits of treating cystic fibrosis in its earliest stages,” said Carmen Bozic, M.D., Executive Vice President, Global Medicines Development and Medical Affairs, and Chief Medical Officer at Vertex. “For decades, pancreatic organ failure and resulting exocrine pancreatic insufficiency has been accepted as an irreversible consequence of CF, but these remarkable data in younger children treated with ALYFTREK show that, in fact, pancreatic failure can be reversed.” ALYFTREK interim data on exocrine pancreatic function Presented as a late breaker poster at NACFC, the new interim data from 48 children who enrolled in a PERT discontinuation substudy VX22-121-106 (Study 106) Cohort 2, an ongoing open-label extension study of vanzacaftor/tezacaftor/deutivacaftor in children 2 to 5 years of age, demonstrate that early intervention with vanzacaftor/tezacaftor/deutivacaftor has a positive impact on exocrine pancreatic insufficiency (EPI) and can help achieve PERT independence. EPI is one of the earliest and most severe manifestations of CF, occurring in ~90% of children during the first year of life, requiring lifelong treatment, and driving serious downstream comorbidities. Specifically, data from the interim analysis conducted after children received at least 48 weeks of vanzacaftor/tezacaftor/deutivacaftor treatment showed: Meaningful improvement in fecal elastase-1 (FE-1) levels demonstrates restored pancreatic function: Mean FE-1, a well-established endpoint of exocrine pancreatic function, was 239.7 μg/g, representing a mean increase of 110.2 µg/g from baseline, with nearly half (48.6%) of children reaching the pancreatic sufficiency threshold of ≥200 µg/g. Of the 48 children eligible for the PERT discontinuation substudy, 18 (37.5%) successfully discontinued PERT for a mean duration of 8.6 weeks (range: 1.9 to 17.6 weeks) at the time of the interim data analysis. Additionally, 7 participants had discontinued PERT prior to the substudy eligibility. Across the full enrolled cohort of 66 children, 50% were not on PERT at the time of the data cut. The ability to discontinue PERT suggests reversal of prior pancreatic exocrine organ failure for those participants. The use of ALYFTREK in children with CF 2 to 5 years old is investigational. Additional data presented at NACFC from October 7-10 in Atlanta, Georgia Vertex also presented the following abstracts on clinical and real-world evidence on CFTR modulators as listed below. These abstracts are published in the Journal of Cystic Fibrosis : “Long-term benefits of VNZ/TEZ/D-IVA in reducing IV antibiotic use in people with CF aged 12 years and older: Post-hoc analyses of 96-week open-label extension analysis” “Natural history study of exocrine pancreatic function in infants with cystic fibrosis less than 12 months of Age” “Lifetime treatment burden and cost of PERT among people with cystic fibrosis” U.S. IMPORTANT SAFETY INFORMATION AND INDICATIONS FOR ALYFTREK AND TRIKAFTA INDICATIONS AND USAGE ALYFTREK is indicated for the treatment of patients ≥6 years who have a clinical diagnosis of cystic fibrosis (CF) and ≥1 variant in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that is responsive based on clinical and/or in vitro data or results in CFTR protein production.* TRIKAFTA is indicated for the treatment of patients ≥2 years who have a clinical diagnosis of CF and ≥1 variant in the CFTR gene that is responsive based on clinical and/or in vitro data or results in CFTR protein production.* *If the patient’s genotype is unknown, an FDA-cleared CF genetic test should be used to confirm the presence of ≥1 indicated variant. IMPORTANT SAFETY INFORMATION BOXED WARNING: DRUG-INDUCED LIVER INJURY AND LIVER FAILURE Elevated transaminases have been observed in patients treated with ALYFTREK. TRIKAFTA can cause serious and potentially fatal drug-induced liver injury. Cases of liver failure leading to transplantation and death have been reported in both clinical trials and the postmarketing setting in patients with and without a history of liver disease taking TRIKAFTA, a fixed-dose combination drug containing elexacaftor (ELX), tezacaftor (TEZ), and ivacaftor (IVA), the same or similar active ingredients as ALYFTREK. Liver injury has been reported within the first month of therapy and up to 15 months following initiation of TRIKAFTA. Assess liver function tests (ALT, AST, alkaline phosphatase, and bilirubin) in all patients prior to initiating ALYFTREK or TRIKAFTA, then every month during the first 6 months of treatment, every 3 months for the next 12 months, and at least annually thereafter. Consider more frequent monitoring for patients with a history of liver disease or liver function test (LFT) elevations at baseline. Interrupt ALYFTREK or TRIKAFTA for significant elevations in LFTs or in the event of signs or symptoms of liver injury. Consider referral to a hepatologist. Follow patients closely with clinical and laboratory monitoring until abnormalities resolve. If resolved, resume treatment only if benefit is expected to outweigh risk. Closer monitoring is advised after resuming treatment. ALYFTREK or TRIKAFTA should not be used in patients with severe hepatic impairment (Child-Pugh Class C). ALYFTREK or TRIKAFTA is not recommended in patients with moderate hepatic impairment (Child-Pugh Class B). ALYFTREK or TRIKAFTA should only be considered when there is a clear medical need and benefit outweighs risk. If ALYFTREK is used, monitor patients closely. If TRIKAFTA is used, use with caution at a reduced dosage and monitor patients closely. WARNINGS AND PRECAUTIONS DRUG-INDUCED LIVER INJURY AND LIVER FAILURE Elevated transaminases have been observed in patients treated with ALYFTREK. TRIKAFTA can cause serious and potentially fatal drug-induced liver injury. Liver failure leading to transplantation and death has been reported in patients with and without a history of liver disease taking TRIKAFTA. Liver injury has been reported within the first month of therapy and up to 15 months following initiation of TRIKAFTA Assess LFTs in all patients prior to initiating ALYFTREK or TRIKAFTA, then every month during the first 6 months of treatment, every 3 months for the next 12 months, and at least annually thereafter. Consider more frequent monitoring for patients with a history of liver disease or LFT elevations at baseline, or a history of elevated LFTs with drugs containing ELX, TEZ, and/or IVA Interrupt ALYFTREK or TRIKAFTA in the event of signs or symptoms of liver injury, which may include: Significant elevations in LFTs (e.g., ALT or AST >5x the upper limit of normal (ULN) or ALT or AST >3x ULN with bilirubin >2x ULN) Clinical symptoms suggestive of liver injury (e.g., jaundice, right upper quadrant pain, nausea, vomiting, altered mental status, ascites) Consider referral to a hepatologist and follow patients closely with clinical and laboratory monitoring until abnormalities resolve. If resolved, and if benefit is expected to outweigh risk, resume treatment with close monitoring ALYFTREK and TRIKAFTA should not be used in patients with severe hepatic impairment, are not recommended in patients with moderate hepatic impairment, and should only be considered when there is a clear medical need and benefit outweighs risk. If ALYFTREK is used, monitor patients closely. If TRIKAFTA is used, use with caution at a reduced dosage and monitor patients closely HYPERSENSITIVITY REACTIONS, INCLUDING ANAPHYLAXIS Hypersensitivity reactions, including cases of angioedema and anaphylaxis, have been reported in the postmarketing setting for TRIKAFTA. If signs or symptoms of serious hypersensitivity reactions develop during treatment, discontinue ALYFTREK or TRIKAFTA and institute appropriate therapy. Consider benefits and risks to determine whether to resume treatment PATIENTS WHO DISCONTINUED OR INTERRUPTED ELX-, TEZ-, OR IVA-CONTAINING DRUGS DUE TO ADVERSE REACTIONS ALYFTREK There are no available safety data for ALYFTREK in patients who previously discontinued or interrupted treatment with drugs containing ELX, TEZ, or IVA due to adverse reactions. Consider benefits and risks before using ALYFTREK in these patients and if used, closely monitor for adverse reactions INTRACRANIAL HYPERTENSION (IH) IH has been reported in the postmarketing setting with TRIKAFTA, which contains the same or similar active ingredients as ALYFTREK. Clinical manifestations of IH include headache, blurred vision, diplopia, and potential vision loss; papilledema can be found on fundoscopy. If an unusual headache or visual disturbances occur during treatment, and IH is suspected, interrupt treatment and refer for prompt medical evaluation. Consider benefits and risks to determine whether to resume treatment. Patients should be monitored until IH resolution and for recurrence. Patients with elevated vitamin A levels may be at increased risk NEUROPSYCHIATRIC EVENTS, INCLUDING SUICIDAL THOUGHTS AND BEHAVIORS Serious neuropsychiatric events, including symptoms of anxiety, depression, suicidal ideation and behavior, and sleep disturbances, have been reported in the postmarketing setting in patients with and without a previous history of neuropsychiatric symptoms taking ALYFTREK or TRIKAFTA. Symptoms may occur within the first 3 months of treatment. Assess patients for baseline neuropsychiatric symptoms and monitor for new or worsening symptoms. Consider the benefits and risks to determine if treatment should be interrupted at symptom occurrence or resumed with symptom improvement DRUG INTERACTIONS Use With CYP3A Inducers Following concomitant use of strong or moderate CYP3A inducers with ALYFTREK, exposures of vanzacaftor, TEZ, and deutivacaftor were decreased, which may reduce ALYFTREK effectiveness. Concomitant use with strong or moderate CYP3A inducers is not recommended Exposure to IVA is significantly decreased and exposure to ELX and TEZ are expected to decrease with concomitant use of CYP3A inducers, which may reduce effectiveness of TRIKAFTA. Concomitant use with strong CYP3A inducers is not recommended Use With CYP3A Inhibitors Exposure to vanzacaftor, TEZ, and deutivacaftor or ELX, TEZ, and IVA are increased when used concomitantly with strong or moderate CYP3A inhibitors. The dose of ALYFTREK or TRIKAFTA should be reduced when used concomitantly with moderate or strong CYP3A inhibitors CATARACTS Non-congenital lens opacities have been reported in pediatric patients treated with TRIKAFTA, which contains IVA (similar to an active ingredient in ALYFTREK). Baseline and follow-up ophthalmological examinations are recommended in pediatric patients ADVERSE REACTIONS ALYFTREK Serious adverse reactions that occurred more frequently with ALYFTREK than with ELX/TEZ/IVA in 2 or more patients (≥0.4%) were influenza (1.5%), increased AST (0.4%), increased GGT (0.4%), depression (0.4%), and syncope (0.4%) The most common adverse reactions occurring in ≥5% of patients and at a frequency higher than ELX/TEZ/IVA by ≥1% were cough, nasopharyngitis, upper respiratory tract infection (URTI), headache, oropharyngeal pain, influenza, fatigue, increased ALT and AST, rash, and sinus congestion TRIKAFTA Serious adverse reactions that occurred more frequently in patients treated with TRIKAFTA compared to placebo included rash (1% vs <1%) and influenza (1% vs 0%) The most common adverse reactions occurring in ≥5% of patients treated with TRIKAFTA and at a rate higher than placebo by ≥1% were headache; URTI; abdominal pain; diarrhea; rash; increased ALT, blood creatine phosphokinase, AST, and blood bilirubin; nasal congestion; rhinorrhea; rhinitis; influenza; sinusitis; and constipation USE IN SPECIFIC POPULATIONS PEDIATRIC USE Safety and effectiveness have not been established for ALYFTREK in patients <6 years, nor for TRIKAFTA in patients <2 years. The use in children under these ages is not recommended Please see full Prescribing Information, including Boxed WARNING , for ALYFTREK and TRIKAFTA . About Cystic Fibrosis Cystic fibrosis (CF) is a rare, life-shortening genetic disease affecting more than 112,000 people, including approximately 97,000 people in the United States, Europe, Australia and Canada. CF is a progressive, multi-organ disease that affects the lungs, liver, pancreas, GI tract, sinuses, sweat glands and reproductive tract. CF is caused by a defective and/or missing CFTR protein resulting from certain variants in the CFTR gene. Children must inherit two defective CFTR genes — one from each parent — to have CF, and these mutations can be identified by a genetic test. While there are many different types of CFTR mutations that can cause the disease, the vast majority of people with CF have at least one F508del mutation. CFTR mutations lead to CF by causing CFTR protein to be defective or by leading to a shortage or absence of CFTR protein at the cell surface. The defective function and/or absence of CFTR protein results in poor flow of salt and water into and out of the cells in a number of organs. In the lungs, this leads to the buildup of abnormally thick, sticky mucus, chronic lung infections and progressive lung damage that eventually leads to death for many patients. The median age of death is in the 30s, but with treatment, projected survival is improving. Learn more about the importance of sweat chloride (SwCl) in cystic fibrosis. As of today, our CF medicines are available in more than 80 countries across six continents, treating more than 80,000 people with CF. This represents the vast majority of known patients diagnosed with CF, and we are committed to expanding access even further. About Vertex Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases and conditions. The company has approved therapies for cystic fibrosis, sickle cell disease, transfusion-dependent beta thalassemia, acute pain and acromegaly, and it continues to advance clinical and research programs in these areas. Vertex also has a robust clinical pipeline of investigational therapies across a range of modalities in other serious diseases where it has deep insight into causal human biology, including IgA nephropathy, neuropathic pain, APOL1-mediated kidney disease, primary membranous nephropathy, congenital adrenal hyperplasia, ACTH-dependent Cushing's syndrome, autosomal dominant polycystic kidney disease, type 1 diabetes, generalized myasthenia gravis, and myotonic dystrophy type 1. Vertex was founded in 1989 and has its global headquarters in Boston, with international headquarters in London. Additionally, the company has research and development sites and commercial offices in North America, Europe, Australia, Latin America and the Middle East. Vertex is consistently recognized as one of the industry's top places to work, including 16 consecutive years on Science magazine's Top Employers list and one of Fortune’s 100 Best Companies to Work For. For company updates and to learn more about Vertex's history of innovation, visit or follow us on LinkedIn , Facebook , Instagram , YouTube and X . Special Note Regarding Forward-Looking Statements This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, the statements made by Carmen Bozic, M.D., statements regarding expectations for the clinical benefits of ALYFTREK, statements about Vertex’s commitment to further expand access to its CF medicines, and expectations for the data presented at NACFC. While Vertex believes the forward-looking statements contained in this press release are accurate, these forward-looking statements represent the company's beliefs only as of the date of this press release and there are a number of risks and uncertainties that could cause actual events or results to differ materially from those expressed or implied by such forward-looking statements. Those risks and uncertainties include, among other things, that data from the company's research and development programs may not support registration or further development of its potential medicines in a timely manner, or at all, due to safety, efficacy, and other risks listed under the heading “Risk Factors” in Vertex's most recent annual report and subsequent quarterly reports filed with the Securities and Exchange Commission at and available through the company's website at . You should not place undue reliance on these statements, or the scientific data presented. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available. (VRTX-GEN) Contacts Vertex Pharmaceuticals Incorporated Investors: InvestorInfo@vrtx.com Media: mediainfo@vrtx.com or U.S.: 617-341-6992

来源：中华胰腺病杂志指南与共识胰腺炎患者基因胚系变异检测与临床应用专家共识（2026 版）Expert consensus on germline variant testing and clinical applications for patients with pancreatitis (2026 version)中国医师协会胰腺病学专业委员会　消化系统疾病国家临床医学研究中心（上海）　中关村胰腺疾病诊疗技术创新联盟通信作者：廖专，海军军医大学第一附属医院消化内科，上海 200433；李兆申，海军军医大学第一附属医院消化内科，上海 200433；李维勤，东部战区总医院重症医学科，南京 210000；孙备，哈尔滨医科大学附属第一医院胰胆外科，哈尔滨 150001；马端，复旦大学代谢分子医学教育部重点实验室，上海200032；邹文斌，海军军医大学第一附属医院消化内科　上海市胰腺疾病研究所，上海 200433。共识核心内容胰腺炎的全球疾病负担沉重，是消化系统疾病相关住院的第三大病因。我国胰腺炎患病人数居全球首位，属于消化系统难治性疾病。胰腺炎通常因胰液流出受阻、胰酶异常激活，导致胰腺自身消化和炎症损伤。传统观念认为，胆道疾病、酒精摄入、高脂血症等是胰腺炎的主要病因。然而临床实践中发现，部分胰腺炎患者缺乏明确的诱因，或呈现明显的家族聚集性，提示遗传因素在疾病发生中发挥重要作用。自1960年发现脂蛋白脂酶（lipoprotein lipase，LPL）基因与高脂血症相关、1996年首次发现阳离子胰蛋白酶原（cationic trypsinogen，PRSS1）基因变异与遗传性胰腺炎相关以来，陆续鉴定出多种胰腺炎相关基因和脂代谢相关基因。这些基因变异不仅与胰腺炎的发生密切相关，还可能影响疾病的临床表现、进展和预后。因此，基因检测在胰腺炎的病因诊断、风险评估、治疗决策和随访管理中具有重要临床价值。然而，目前尚缺乏针对中国人群基因变异谱的系统性临床应用规范，导致检测适应证、检测方法、报告解读等方面存在较大差异。为此，中国医师协会胰腺病学专业委员会、消化系统疾病国家临床医学研究中心（上海）、中关村胰腺疾病诊疗技术创新联盟联合组织相关专家制定本共识，旨在填补我国胰腺炎基因检测领域的规范化空白，为临床医师提供规范化指导。推荐意见一、胰腺炎基因检测目标人群输推荐意见1：慢性胰腺炎（chronic pancreatitis，CP）、复发性急性胰腺炎（recurrent acute pancreatitis，RAP）、高甘油三酯血症性急性胰腺炎（hypertriglyceridemia⁃induced acute pancreatitis，HTG⁃AP）与遗传因素密切相关。证据等级：3b；推荐强度：强胰腺炎主要包括急性胰腺炎（acute pancreatitis，AP）、RAP和CP三大类型，均为消化系统难治性疾病，三者为连续变化的疾病谱，并非完全独立。约20%的AP患者可进展为持续性器官功能衰竭，一旦发生多器官功能衰竭，病死率高达40%以上。约1/5的AP患者会反复发作，如AP发作次数≥2次且2次发作的间隔时间≥3个月，称为RAP；约36%的RAP最终发展为以胰腺慢性炎症和进行性纤维化为特征的CP。随着病程进展，患者出现胰腺内外分泌功能不全，胰腺癌发生风险显著升高，生活质量低下，社会负担沉重。在我国AP患者中，HTG⁃AP占23%~50%，且呈逐年上升趋势，其与胆结石共同构成我国AP的两大首要病因。RAP的病因构成同样以高甘油三酯血症（hypertriglyceridemia，HTG）为主，约占44.6%，胆源性和酒精性分别占28.6%和12.5%；荟萃分析显示，高脂血症是我国胰腺炎复发的重要危险因素（OR=2.16）。在HTG⁃AP患者中，脂代谢相关基因如载脂蛋白A5（apolipoprotein A⁃Ⅴ，APOA5）等的变异携带率达55.8%。CP的病因在西方以酒精性为主（40%~70%），而我国则以特发性慢性胰腺炎（idiopathic chronic pancreatitis，ICP）居首位（76%）。我国ICP患者中约有57.1%携带胰腺炎易感基因变异。儿童胰腺炎患者的病因与成人有较大差异，胆源性、药源性、特发性为儿童AP的主要病因；遗传因素是儿童RAP和CP最常见的病因。在30岁以下特发性胰腺炎患者中，高达32%的患者携带PRSS1、丝氨酸肽酶抑制因子Kazal 1型（serine protease inhibitor Kazal type 1， SPINK1）或囊性纤维化跨膜传导调节因子（cystic fibrosis transmembrane conductance regulator，CFTR）基因变异。输推荐意见2：建议对有家族史的胰腺炎家系成员、不明原因的RAP及CP患者、儿童或青少年时期发病的不明原因胰腺炎患者进行胰腺炎相关基因检测。证据等级：2b；推荐强度：强基因检测对胰腺炎诊疗具有重要临床价值，有助于明确病因，尤其对特发性、年轻或有家族史的患者，可识别潜在遗传因素，缩短诊断流程并指导个体化管理。美国胃肠病学会（American College of Gastroenterology，ACG）CP临床指南推荐对病因不明的CP进行基因检测；国际胰腺病学会AP修订指南也建议对病因不明的RAP可考虑基因检测。携带致病基因变异的患者，其一级亲属可能携带相同基因变异，高外显率者发病风险高，对家族成员进行基因检测和遗传咨询有助于早期预警与干预。除了儿童和青少年患者以外，≥35岁患者中亦可检出具有临床意义的基因变异 ，提示基因检测不应局限于年龄，而需结合病因、家族史、复发风险和临床表型综合评估。根据现有研究，推荐以下人群进行胰腺炎相关基因检测。1.有胰腺炎家族史的胰腺炎患者及家系成员：遗传性胰腺炎主要由PRSS1突变引起，其中p.Arg122His和p.Asn29Ile是常见的两种突变类型，外显率约为80%。家族中存在已知遗传性胰腺炎相关基因变异的亲属是基因检测的明确指征。对于符合家族性胰腺炎定义的患者，基因检测既可确认诊断，亦可明确家族致病基因变异，为其他家系成员提供检测依据。PRSS1、CFTR等基因变异与胰腺癌风险升高密切相关，对此类患者进行基因检测有助于识别胰腺癌高风险个体，从而制定个体化早期筛查方案（详见推荐意见10及21）。2.不明原因的RAP和CP患者：在排除酒精性、胆石性、创伤、感染、药物、高脂血症等常见病因的RAP和ICP患者中，应考虑遗传因素可能。在特发性RAP患者中，SPINK1、CFTR、PRSS1、胰凝乳蛋白酶C（chymotrypsin C，CTRC）等基因变异检出率高达56.0%。相较于酒精性CP患者，ICP患者中易感基因变异比例更高。3.儿童或青少年期发病的早发型胰腺炎患者：在儿童期或青少年时期（通常年龄≤20岁）发生不明原因AP、RAP或CP的患者，应高度怀疑遗传性胰腺炎。儿童期起病的特发性胰腺炎患者中，SPINK1、CFTR、PRSS1、CTRC等基因变异检出率>60%，且发病年龄越小基因检测阳性率越高。因此，对于儿童期或青少年时期发病者，建议进行积极基因检测。输推荐意见3：对于HTG⁃AP患者，若伴有家族性乳糜微粒血症综合征（familial chylomicronemia syndrome，FCS）家族史、极重度HTG、儿童期起病或AP复发病史，建议进行脂代谢相关基因检测。证据等级：3b；推荐强度：强LPL、APOA5等脂代谢相关基因变异是HTG⁃AP的重要遗传病因，根据现有研究证据推荐以下人群进行脂代谢相关基因检测。1.伴有FCS家族史的HTG⁃AP患者：FCS是一种常染色体隐性遗传病，主要由LPL双等位基因功能缺失型变异引起，少数与糖基化磷脂酰肌醇锚定高密度脂蛋白结合蛋白1（glycosylphosphatidylinositol⁃anchored high density lipoprotein binding protein 1，GPIHBP1）、APOA5、载脂蛋白CⅡ（apolipoprotein C⁃Ⅱ，APOC2）和脂肪酶成熟因子1（lipase maturation factor 1， LMF1）等基因变异有关。FCS患者临床表现为持续性重度或极重度HTG，具有高RAP发生风险。对于一级亲属确诊FCS或家系中检出脂代谢相关基因变异的HTG⁃AP患者，基因检测有助于明确病因并指导家系筛查。2.伴有极重度HTG的HTG⁃AP患者：极重度HTG患者常表现为空腹甘油三酯≥11.3 mmol/L（1 000 mg/dl）。我国研究显示，对极重度HTG人群进行脂代谢基因检测可使基因罕见变异检出率提高19.5%；其中有AP病史者LPL基因罕见变异检出率显著高于无AP病史者（27.8%比4.7%）。3.儿童HTG⁃AP患者：儿童HTG⁃AP相对少见，对于起病年龄小、极重度HTG、反复发生HTG⁃AP、有胰腺炎家族史，或缺乏肥胖、糖尿病、药物等明确继发因素的患儿，应考虑开展脂代谢相关基因检测。4.复发性HTG⁃AP患者：HTG⁃AP首次发作后的复发风险约为30.3%，携带LPL等脂代谢基因变异的FCS患者中复发性HTG⁃AP比例高达92%。二、胰腺炎基因胚系变异的分类输推荐意见4：胰腺炎相关基因胚系变异主要涉及SPINK1、PRSS1、CTRC、CFTR等基因，我国CP患者中最常见的变异是SPINK1 c.194+2T>C。证据等级：3b；推荐强度：强胰腺炎的发病机制核心在于胰蛋白酶原异常激活。生理状态下，胰蛋白酶原在胰腺腺泡细胞内合成，以无活性酶原形式经导管分泌至十二指肠，被肠激酶激活而发挥消化功能。目前已鉴定的胰腺炎相关基因大多参与胰蛋白酶原激活、抑制调控或导管转运过程，其变异可导致胰蛋白酶原在胰腺内过早激活，进而引发胰腺自身消化和炎症反应。1. SPINK1基因：SPINK1基因编码胰蛋白酶抑制因子，可防止胰蛋白酶原在胰腺内异常激活。其变异多为功能缺失性（loss⁃of⁃function，LoF），导致对胰蛋白酶的抑制功能减弱。SPINK1基因常见风险位点包括：（1）c.194+2T>C。该剪切位点变异是东亚人群CP最常见的遗传易感因素（OR=73.16）；该变异导致胰蛋白酶抑制功能下降90%，纯合外显率接近100%，杂合外显率在不同研究中可达10.53%；（2）c.101A>G（p.Asn34Ser）。该变异是西方人群中最常见的SPINK1变异（OR=13.92），其与启动子区c.-4141G>T存在连锁不平衡，导致SPINK1表达水平下降，胰蛋白酶抑制功能降低73%，纯合外显率为55%，杂合外显率为0.47%。2. PRSS1基因：PRSS1基因编码阳离子胰蛋白酶原。其常见风险位点根据致病机制可分为功能获得性（gain⁃of⁃function，GoF）与蛋白毒性获得性（gain⁃of⁃proteotoxicity，GoP）变异。GoF变异主要包括：（1）c.365G>A（p.Arg122His），是西方人群遗传性胰腺炎最常见的致病性变异，能使胰蛋白酶原自激活能力增强1.5倍，同时降解能力下降11倍；（2）c.86A>T（p.Asn29Ile），是西方人群遗传性胰腺炎第二常见的致病性变异，可使胰蛋白酶原自激活能力增强1.5倍，自切割能力下降1.2倍；（3）c.47C>T（p.Ala16Val），是第三常见的PRSS1变异，在遗传性胰腺炎、家族性CP以及ICP中均有报道。GoP变异主要包括：（1）c.623G>C（p.Gly208Arg），是我国CP患者最常见的PRSS1变异，该变异导致蛋白质错误折叠，使其分泌量减少40%~50%，携带者罹患胰腺炎的风险增高（OR=4.72）；（2）c.346C>T（p.Arg116Cys），该变异导致蛋白毒性，内质网应激指标较野生型升高1.8倍，其致病性已在至少2个独立家系研究中得到证实。3. CTRC基因：CTRC基因编码的蛋白参与胰蛋白酶原的正确激活及错误胰蛋白酶的降解，对维持胰腺组织结构和功能完整性具有重要作用。我国人群常见风险位点为c.180C>T（p.Gly60=），该同义变异通过影响mRNA剪接或稳定性而减少蛋白质表达，纯合变异和杂合变异个体患CP的风险均增高（OR=10、2.5）。4. CFTR基因：CFTR基因编码的CFTR蛋白介导氯离子（Cl-）和碳酸氢根离子（HCO3-）跨上皮转运，在气道、胰腺导管等分泌上皮细胞中高表达。其变异分为Ⅰ~Ⅵ六类，与胰腺炎相关的主要为Ⅳ、Ⅴ或Ⅵ类胰腺功能充足型变异，这些变异导致胰液中的水和Cl-分泌减少，造成胰液黏稠、导管阻塞，以及胰酶提前激活。CFTR单等位基因变异或杂合变异在CP患者中携带率高达15.3%，c.1521_1523delCTT（p.Phe508del）是西方人群最常见的致病性变异，我国人群则以c.3205G>A （p.Gly1069Arg）和c.4056G>C（p.Gln1352His）较为常见。上述易感基因的变异谱在中西方人群中存在显著差异。我国CP患者以SPINK1致病性变异为主（39.31%），其中c.194+2T>C位点占主导（94.21%）；其次为PRSS1（11.21%），以c.623G>C位点为主（65.99%）；CTRC和CFTR致病性变异携带率较低（分别为2.40%和5.35%），分别以c.180C>T位点（76.19%）和c.4056G>C位点（55.32%）为主。在西方遗传性胰腺炎人群中，PRSS1变异占比>90%，其中以c.365G>A位点（78%）和c.86A>T位点（12%）为主；西方CP患者CTRC c.180C>T位点变异占比高（30%），其次为SPINK1基因变异（约10%患者携带），以c.101A>G变异为主，各国报道的CFTR变异携带率为7%~23%不等，PRSS1变异在儿童患者中携带率达20%~30%。一项基于西方INSPPIRE队列的研究发现，儿童RAP患者中，4种胰腺炎易感基因的变异携带率由高至低依次为CFTR（40.3%）、SPINK1（18.0%）、PRSS1（14.1%）、CTRC（9.9%），其中约17.2%患儿存在至少2种易感基因变异。需要特别指出的是，与传统孟德尔遗传模式不同，胰腺炎存在多基因协同效应。多个低风险遗传变异组合与环境因素（如吸烟、饮酒）可共同致病，且不同致病通路的变异叠加程度随疾病慢性化进展而增高。与携带单个易感基因变异的AP患者相比，携带双易感基因变异者进展为CP的速度更快。不同变异组合对胰腺炎风险影响程度不同：相对于不携带基因变异者而言，CFTR与SPINK1联合变异可致CP风险升高84.4倍；其中CFTR p.Phe508del单独携带时CP风险为2.75倍，与SPINK1联合后风险升至131.5倍；CFTR p.Arg75Gln单独携带时CP风险为3.43倍，与SPINK1联合后风险升至62.5倍；PRSS1 p.Gly208Arg与SPINK1 c.194+2T>C联合变异可致CP风险较未携带者升高110.1倍。除上述4种核心基因外，部分其他基因变异也显示与胰腺炎易感性相关，但因证据强度、变异频率、人群异质性或种族差异等因素，目前暂不纳入常规检测推荐。如下2种单基因遗传病，因可表现为胰腺外分泌功能不全（pancreatic exocrine insufficiency，PEI），需要与胰腺炎进行鉴别。5. Shwachman⁃Bodian⁃Diamond（SBDS）基因：SBDS编码蛋白参与核糖体成熟过程，其变异可导致核糖体成熟缺陷，与常染色体隐性遗传病Shwachman⁃Diamond综合征（Shwachman⁃Diamond syndrome，SDS）相关。超90%的SDS患者存在SBDS双等位基因变异，主要表现为PEI（>90%）、中性粒细胞减少（>95%）和骨骼异常（约60%）等。胰腺外分泌功能障碍通常在婴儿期起病，表现为营养不良、脂肪泻和生长迟缓等。6.泛素蛋白连接酶E3组件N端识别子1 （ubiquitin protein ligase E3 component N⁃recognin 1，UBR1）基因：UBR1编码蛋白参与细胞内蛋白质降解过程。该基因是常染色体隐性遗传病Johanson⁃Blizzard综合征的唯一已知致病基因，该疾病特征性表现为严重的PEI，同时伴有多系统发育异常，包括鼻发育异常、甲状腺功能减退、头皮缺损和肛门闭锁等，症状可在妊娠期间、出生时和婴儿期出现。输推荐意见5：HTG⁃AP相关基因胚系变异主要涉及LPL、APOA5、GPIHBP1、APOC2、APOC3、LMF1等基因，我国以APOA5基因变异最为常见。证据等级：3b；推荐强度：强1. LPL基因：LPL负责水解乳糜微粒和极低密度脂蛋白中的甘油三酯。致病性LPL变异通常为LoF，通过催化功能丧失、分泌障碍、GPIHBP1结合障碍、mRNA剪接异常、蛋白质稳定性下降等机制，导致LPL活性下降或缺失，造成甘油三酯水解障碍。我国常见LoF变异位点包括：（1）c.292G>A（p.Ala98Thr）。杂合子LPL活性平均降低约32%。体外功能实验显示，纯合变异导致细胞培养上清液中LPL酶活性由对照组的63.6 nmol/min降至3.3 nmol/min，LPL酶分泌量由494 ng降至187 ng；该变异在我国HTG⁃AP患者中的频率高于健康人群（0.76%比0.16%，OR=4.8）；（2）c.835C>G（p.Leu279Val）。体外功能实验发现该变异导致酶活性显著降低，细胞上清液中未检出LPL活性；我国HTG⁃AP患者携带率高于健康人群（0.61%比0.11%，OR=5.5）。此外，LPL GoF变异具有保护作用，如c.1595C>G（p.Ser474X）可增强LPL蛋白稳定性，使受体结合能力更强、脂解效率更高，已被用于药物研发。2. APOA5基因：APOA5基因编码的载脂蛋白A⁃V主要在肝脏合成，分布于乳糜微粒、极低密度脂蛋白和高密度脂蛋白中，是血浆HTG代谢的重要调节因子，通过激活LPL、促进富含甘油三酯脂蛋白的清除而发挥作用。APOA5 LoF变异通常导致LPL活性下降，引发严重HTG。我国HTG⁃AP患者中最常见的风险变异位点为c.553G>T（p.Gly185Cys），变异频率为17.40%，高于健康人群的5.89%（OR=3.3）；纯合T等位基因者HTG风险增加11.73倍，该突变与妊娠期HTG⁃AP风险显著相关（杂合变异OR=4.25，纯合变异OR=192.35）。体外功能实验显示，突变导致APOA5对LPL的激活能力下降23%。3. GPIHBP1基因：GPIHBP1基因编码蛋白仅在毛细血管内皮细胞基底侧表达，负责将新合成的LPL转运到毛细血管腔，并在内皮细胞表面稳定LPL，对甘油三酯的分解代谢至关重要。GPIHBP1 LoF变异导致LPL无法转运至毛细血管内皮表面，造成乳糜微粒清除障碍，其常见风险位点包括c.194G>C（p.Cys65Ser）、c.194G>A（p.Cys65Tyr）、c.202T>G（p.Cys68Gly）、c.203G>A（p.Cys68Tyr）、c.202T>C（p.Cys68Arg）、c.247T>C（p.Cys83Arg）、c.266G>T（p.Cys89Phe）、c.329G>A（p.Cys110Val）、c.344G>A（p.Cys115Tyr）。4. APOC2基因：APOC2是极低密度脂蛋白和乳糜微粒的组分，可增强LPL水解甘油三酯的活性。APOC2功能缺失变异致使脂蛋白脂酶无法被有效激活，造成乳糜微粒和甘油三酯清除障碍。5.载脂蛋白C⁃Ⅲ（APOC3）基因：APOC3于肝脏表达，是极低密度脂蛋白和高密度脂蛋白的组分，可抑制LPL活性，并干扰肝脏对富含甘油三酯脂蛋白的清除功能。APOC3 GoF变异导致载脂蛋白C⁃Ⅲ表达升高，抑制LPL活性，使甘油三酯水平升高；LoF变异则与改善的脂代谢表型相关。6. LMF1基因：LMF1定位于内质网，作为分子伴侣参与LPL翻译后折叠与成熟过程。LMF1 LoF变异导致LPL无法正确折叠和形成活性二聚体，造成混合性脂酶缺陷症，从而引发严重HTG。基于我国现有最大样本（495例）单中心HTG‐AP队列研究分析脂代谢相关基因分布的初步研究发现，APOA5基因变异（含SNP，55.78%）与LMF1基因变异（含SNP，43.61%）较为常见，其次为LPL（14.81%）、GPIHBP1（1.62%）、APOC2（0.61%）基因变异。未来仍需进一步加强基因突变谱研究，明确每个基因变异的功能和临床意义。三、胰腺炎基因胚系变异检测的临床应用输推荐意见6：胰腺炎基因胚系变异检测首选外周血样本，无法获取血液样本时可选用唾液或口腔拭子；检测实验室应建立覆盖样本采集、运输、保存及检测全流程的标准化操作程序。证据等级：5；推荐强度：强1.检测样本选择：胰腺炎基因胚系变异检测可采用多种生物样本。外周血样本采集方便、DNA含量丰富，拥有标准化的操作流程和质量控制体系，确保了结果的稳定性和可重复性，是临床基因检测的首选样本类型。2~5 ml乙二胺四乙酸抗凝全血可提取足量高质量DNA，满足二代测序技术（next⁃generation sequencing，NGS）、Sanger测序和PCR等检测需求。唾液或口腔拭子样本采集方便、无创、可居家采集，依从性高，适用于大规模人群筛查、儿童和行动不便者。唾液收集采用被动流涎法，0.1~1.0 ml可满足检测需求；口咽拭子样本利用医用单头棉签收集。唾液或口腔中提取的DNA检测结果与外周血具有高度的一致性，但DNA主要来自口腔黏膜脱落细胞，含量较低，且可能含口腔微生物DNA和食物残渣酶，影响纯度与完整性，故采集前应避免进食、饮水、吸烟，采集后及时处理或保存。对于已故先证者或无法采血者，可选用存档组织标本，主要包括手术切除或内镜超声引导下细针穿刺（endoscopic ultrasound⁃guided fine⁃needle aspiration，EUS⁃FNA）获取的胰腺组织，多经石蜡包埋保存。需注意，甲醛固定可能导致DNA降解和片段化，影响检测灵敏度，尤其对NGS检测的文库构建构成挑战。建议在检测前对石蜡包埋样本进行DNA质量评估，必要时可选用针对石蜡包埋样本优化的检测方案。2.质量控制：本流程主要参考《遗传病基因变异全外显子组测序技术规范化应用专家共识》与《临床分子病理实验室二代基因测序检测专家共识》，具体如下。（1）样本质量控制：外周血样本采集后及时送检，避免溶血；唾液样本使用专用采集管，按说明书要求保存；组织样本规范固定包埋，避免反复冻融。样本运输过程中需低温保存，短期可置于4℃环境，长期保存则需-80℃。检测前对提取的DNA进行浓度、纯度及完整性评估。PCR检测前评估核酸总量、浓度和纯度；NGS检测需满足文库构建的最低DNA投入量和质量要求。（2）实验室内部质量控制：实验室应具备完整的样本处理、检测、分析、解读及报告出具的全流程体系，并制定标准化操作程序（standard operating procedure， SOP）。NGS检测应包含阳性对照、阴性对照和空白对照，监控文库构建、测序和数据分析各环节。检测平台应设置独立的功能分区，包括试剂储存及准备区、样本处理区、扩增区、产物分析区等，以避免气溶胶等污染对检测结果造成影响。检测仪器应定期校准和维护，试剂应按规定条件储存和使用，确保检测批次间的稳定性。数据分析人员和报告解读人员应具有临床医学、分子生物学或遗传学知识背景，并接受生物信息学培训。输推荐意见7：推荐首先使用胰腺炎或脂代谢相关基因靶向测序；有条件的单位可根据患者需求直接进行全外显子组测序（whole exome sequencing， WES）或全基因组测序（whole genome sequencing， WGS）。证据等级：5；推荐强度：强胰腺炎基因检测的常用方法包括NGS（包括靶向基因测序、WES、WGS）、Sanger测序及实时荧光定量聚合酶链反应（quantitative real‑time polymerase chain reaction， qPCR），不同方法各有优劣，应根据检测目的、样本条件和平台可及性合理选择。1. NGS：NGS具有高通量、高灵敏度、高准确性的特点，包括靶向基因测序、WES和WGS，已广泛应用于遗传病诊断。其中，靶向测序通过探针捕获或多重PCR富集几十至几百个目标基因区域进行高深度测序，兼顾诊断效率与成本效益，但无法检测panel外变异。WES捕获基因组中所有外显子区域，可包含>85%已知致病性变异，提供编码区最全面覆盖，是无偏倚的基因发现策略，但成本较高。WGS则对全基因组全覆盖测序，涵盖编码区、非编码区、内含子等，能可靠识别全基因组拷贝数变异（copy number variant，CNV）、染色体结构重排及复杂重复序列异常，但数据量巨大，对存储、计算和分析能力要求极高。NGS流程涵盖DNA提取、文库制备、测序及数据分析，其中文库制备和生物信息分析是关键环节，具体流程参照《临床分子病理实验室二代基因测序检测专家共识》。（1）qPCR：qPCR中的TaqMan探针等位基因分辨技术适用于胚系变异检测，通过加入不同荧光标记的等位基因特异性探针，实时监测荧光信号差异来判读基因型。qPCR通量较高、检测周期短、成本适中，主要用于已知固定位点变异的快速筛查（如SPINK1 c.194+2T>C、APOA5 c.553G>T）。（2）Sanger测序：Sanger测序是经典测序方法，被誉为基因检测的“金标准”。在胰腺炎基因检测中，主要用于已知致病性变异的确认、NGS结果验证和单基因检测。但其通量低、对低频变异检测灵敏度有限，限制了其作为一线筛查手段的应用。（3）多重连接探针扩增技术（multiplex ligation⁃ dependent probe amplification，MLPA）：MLPA适用于大片段基因组结构变异的检测，如外显子或整个基因的缺失或重复（即CNV），需要专门技术检测。MLPA技术成熟、结果稳定可靠、操作简便，是临床实验室检测目标区域CNV的“金标准”，可作为NGS的补充检测手段。考虑到我国不同层级医疗机构的设备条件及患者经济负担存在差异，建议采取分级管理的胰腺炎基因检测策略。（1）热点变异快速筛查：适用于所有疑诊遗传因素相关胰腺炎患者，可采用qPCR或Sanger测序检测胰腺炎胚系基因的已知热点变异，包括但不限于PRSS1 c.365G>A、SPINK1（c.101A>G、c.194+2T>C）、CTRC c.180C>T、CFTR（c.4056G>C、c.3205G>A），以及LPL（c.292G>A、c.835C>G）、APOA5 c.553G>T等。（2）核心基因靶向测序：目前临床应用条件较为成熟，对于早发型胰腺炎（诊断年龄≤20岁）、有明确家族史、不明原因RAP或CP、临床高度怀疑脂代谢异常相关胰腺炎者，推荐优先进行包含已知胰腺炎相关基因和脂代谢相关基因的靶向基因测序。若首诊单位不具备NGS条件，应将样本转送至具备资质的区域性中心实验室或第三方检测机构完成。（3）全面基因组测序：对于靶向panel检测为阴性，但临床强烈提示存在未发现的遗传因素的患者或其家属在充分知情后具有更高层次的检测意愿且经济条件允许时，可采用WES或WGS进行检测。本部分变异分类主要参考美国医学遗传学与基因组学学会（American College of Medical Genetics and Genomics，ACMG）联合美国分子病理学会（Association for Molecular Pathology，AMP）制定的相关标准和近期研究进展进行解读与报告。输推荐意见8：基因检测报告应明确标注变异位点、变异分类和临床意义解读，主要参考ACMG变异分类标准和相关功能实验结果，由具备临床分子生物学或遗传学知识背景的专业人员签署。证据等级：5；推荐强度：强1.胰腺炎基因胚系变异分类：根据ACMG和AMP联合制定的《遗传变异分类标准与指南》，列出了28条证据标准，将变异分为5个等级：致病性（pathogenic）、可能致病性（likely pathogenic）、意义未明（variants of unknown significance，VUS）、可能良性（likely benign）、良性（benign）。然而，胰腺炎基因胚系变异的遗传模式表现出非经典孟德尔遗传特征，属于剂量依赖性连续谱系基因病。根据TIGAR⁃O version 2分类，遗传性胰腺炎的PRSS1变异可呈现常染色体显性遗传模式，部分CFTR基因和SPINK1基因可呈现常染色体隐性遗传模式。ACMG和AMP联合制定的分类标准主要针对孟德尔遗传性疾病，难以充分反映胰腺炎复杂的遗传效应。本共识基于近期研究建议采用以下胰腺炎基因热点胚系变异的分类方法（表1）：（1）致病性（pathogenic）：此类变异参考ACMG和AMP联合制定的五级分类标准，主要适用于PRSS1 GoF变异，以及SPINK1和（或）LPL完全或近乎完全功能丧失变异（LoF>95%）等。（2）可能致病性（likely pathogenic）：此类变异参考ACMG和AMP联合制定的五级分类标准，适用于符合以下特征的变异：功能实验证据支持致病性，但尚未在独立家系中验证；在多例患者中检出但对照人群频率极低；新发变异且表型高度符合。（3）易感性（predisposing）：此类变异显著增加疾病风险（OR>10），但单独存在时不足以致病，需结合其他遗传或环境因素。此类变异在ACMG和AMP联合制定的五级分类中通常对应于“可能致病性”或“意义未明”，但因其复杂的遗传模式，建议在检测报告中明确标注为“易感性”。（4）风险（risk）：此类变异增加疾病风险，但效应较弱（OR<10）。此类变异在ACMG和AMP联合制定的五级分类中通常对应于“意义未明”或“可能良性”，但因其明确的统计学关联，建议在报告中明确标注为“风险”。（5）VUS：此类变异参考ACMG和AMP联合制定的五级分类标准，适用于①罕见变异（人群频率<0.001）但缺乏功能数据；②计算预测结果不一致；③仅在1例患者中报道，无家系数据支持；④功能实验结果显示部分功能丧失（功能丧失率为20%~70%），但缺乏流行病学验证。关于实验室报告的“意义未明”变异风险，临床决策的最终责任由临床医师承担。对于此类变异，临床上可通过以下方法协助调整其分类：①通过补充检测完善临床表型，进一步明确与疾病高度特异性的表型证据（ACMG证据等级PP4）；②检测先证者父母，确认该变异是否为新生变异（ACMG证据等级PS2/PM6）；③在有家族史的先证者大家系中开展共分离分析（ACMG证据等级PP1）；④进行功能性验证，持续跟踪文献更新，并定期对变异进行再评估。（6）可能良性（likely benign）：适用于人群变异频率为0.1%~1%，且功能实验证实无显著影响；计算预测结果为良性，且变异位于非保守区域；在健康对照中有少量检出，且患者表型不符合疾病特征。（7）良性（benign）：适用于无功能影响的变异，如SPINK1功能丧失<10%的变异、LPL功能获得（gain‑of‑function， GoF）变异c.1595C>G等。2.基因变异报告核心要素，包括以下4个方面：（1）基本信息。包括患者信息（姓名、性别、年龄、门诊和（或）住院号、送检科室及医师）、样本信息（样本类型、采样日期、接收日期、报告日期、检测机构信息）。（2）检测方法与技术参数。包括检测项目名称、检测基因范围、检测方法（如NGS、Sanger测序、qPCR等）、检测灵敏度、检测局限性、参考序列，明确标注转录本编号（如SPINK1：NM_001379610.1）和基因组版本（如GRCh38/hg38）。（3）变异解读。简述变异的功能影响如功能丧失百分比、对蛋白质结构的影响、与胰腺炎表型的关联强度（如OR值、外显率、种族特异性）；对于VUS应明确标注，并建议进行家系验证或功能研究。（4）医学建议：提供治疗建议、随访建议和遗传咨询建议（见本共识）。3.报告签署与质量控制，相关内容如下：（1）签署人员。报告应由具备临床医学、分子生物学或遗传学知识背景，并接受过生物信息学或遗传咨询培训的专业人员审核并签署。（2）报告更新。当变异分类依据发生重大变化（如新的人群频率数据、新发表的功能研究）时，实验室应主动更新报告，并及时通知临床医师。（3）质量控制。实验室应定期参加国家或省级临床检验中心组织的室间质评，确保检测结果的准确性。四、胰腺炎基因胚系变异与临床影响输推荐意见9：胰腺炎基因胚系变异状态显著影响患者的起病年龄、疾病进展、胰腺内外分泌功能状态，对个体化预后评估具有重要参考价值。证据等级：3b；推荐强度：强1.基因变异与患者起病年龄：携带PRSS1、SPINK1、CTRC、CFTR基因变异会显著提前患者的发病年龄。相较于未携带上述基因变异的CP患者，SPINK1 c.194+2T>C纯合变异患者首发年龄提前27年，杂合变异患者提前16.2年（P值均<0.001）；PRSS1 c.365G>A杂合变异患者提前27年（P<0.001）；在北美CP队列中，CFTR变异可使轻中度饮酒CP患者的发病年龄提前9年（P=0.03）。儿童队列研究进一步证实上述关联。一项包含342例儿童RAP或CP患者的研究显示，PRSS1变异（主要为c.365G>A）携带者CP发病年龄更早（P<0.01），CTRC变异显著增加6岁前CP发生风险（P=0.01）。2.基因变异与疾病重症化及慢性化转归：重症化层面，SPINK1变异在重症AP患者中的检出率（10.4%）显著高于轻症患者（4.2%）（P<0.05）。在AP⁃RAP⁃CP转归层面，INSPPIRE队列研究发现PRSS1变异加速儿童RAP进展为CP，病程缩短1.96年（P=0.003）。另一项纳入111例儿童期AP的队列随访研究发现，携带SPINK1（P=0.0006）、PRSS1（P=0.048）或CFTR（P=0.03）变异者进展为CP的速度更快。3.基因变异与胰腺内外分泌功能：在外分泌功能方面，携带SPINK1变异的CP患者发生PEI的时间较未携带者提前15.7年（P<0.001）。在内分泌功能方面，胰腺炎相关基因变异与首次AP发作后12个月内发生内分泌功能不全相关（P=0.01）；SPINK1变异导致CP患者糖尿病发病年龄提前约13.8年（P=0.018）。印度一项纳入180例纤维钙化性胰腺糖尿病患者和861例非糖尿病对照的研究显示，SPINK1 p.Asn34Ser变异显著增加纤维钙化性胰腺糖尿病发生风险（OR=10.8，P<0.0001）。此外，CEL基因可变数目串联重复序列区域的单碱基缺失可导致青少年时期起病的成人型糖尿病8型（MODY8或CEL⁃MODY），表现为胰腺外分泌和内分泌功能双重障碍。4.基因变异与胰腺病理改变：胰腺炎基因变异与特定胰腺病理改变密切相关。SPINK1 c.194+2T>C变异携带者胰管结石发生率显著高于非携带者（P=0.024），结石诊断年龄比非携带者提前24.7年（P<0.001）。欧洲研究表明，SPINK1变异携带者比非携带者更容易发生导管异常（P<0.001），且SPINK1 p.Asn34Ser变异携带者主胰管扩张更明显。CFTR变异与胰腺分裂等解剖学异常存在显著关联。组织病理学层面，SPINK1变异携带者表现为胰腺外分泌实质组织逐渐丧失，并被显著纤维化组织所取代；PRSS1变异携带者表现为胰腺进行性脂肪萎缩；CFTR变异携带者则以胰腺脂肪替代为组织学特点。输推荐意见10：PRSS1和CFTR基因变异可增加胰腺癌发生风险，SPINK1基因胚系变异与胰腺癌的关联尚存在争议。证据等级：3b；推荐强度：弱不同基因变异对胰腺癌风险的影响存在显著差异，且呈现种族异质性。1. PRSS1变异：PRSS1变异携带者终生胰腺癌风险为40%~53%，相对风险高达53~87倍，这种关联主要归因于c.365G>A（p.Arg122His）变异（OR=72.34，P<0.001）。此外，大型病例报道亦提示PRSS1⁃PRSS2⁃rs10273639变异携带者胰腺癌风险增加（OR=1.19，P=0.023）。2. CFTR变异：CFTR基因变异可增加胰腺癌的发生风险（OR=1.40），且在吸烟者和年轻患者中风险更高；我国人群研究显示，胰腺癌患者中CFTR有害变异的携带率显著高于健康对照组（3.9%比1.4%，P=0.001），其中p.Gly451Arg和p.Gly970Asp变异此前被报道与胰腺炎有关。另一项我国人群研究表明，CP进展为胰腺癌患者的CFTR变异携带率显著高于单纯CP患者（OR=24.64，P<0.001），二者p.Gly970Asp变异差异亦有统计学意义（P=0.031）。3. SPINK1变异：SPINK1变异对于胰腺癌发生风险的影响尚存在争议。欧洲队列研究显示，SPINK1变异（主要为p.Asn34Ser）携带者的胰腺癌发生风险显著增加（HR=12.0，P<0.001）。但我国CP队列中SPINK1 c.194+2T>C携带者胰腺癌风险并未升高（HR=0.39，P=0.059），亚组分析显示非吸烟组中SPINK1 c.194+2T>C携带者胰腺癌风险更低（HR=0.18，P=0.025）。五、胰腺炎基因胚系变异与临床精准管理输推荐意见11：对于携带易感基因变异的胰腺炎患者应终身严格戒酒、戒烟、低脂饮食，定期监测血糖，可延缓疾病进展，减少并发症。证据等级：3a；推荐强度：强生活方式干预是胰腺炎管理的基石，对于携带易感基因变异的患者尤为重要。1.戒酒：饮酒是胰腺炎发生的独立危险因素，酒精的损伤作用因胰腺炎相关遗传缺陷而进一步放大：相较于未饮酒CP患者，酒精性CP患者发生糖尿病（OR=1.31）、脂肪泻（OR=2.1）、胰管结石（OR=2.54）、假性囊肿（OR=1.34）的风险更高，且并发症出现年龄更早。一项系统综述提示，携带弱效应遗传变异的饮酒者CP发病风险会协同增加，携带强效应变异者若同时饮酒导致起病年龄显著提前，提示无论携带何种基因风险变异，饮酒均会以不同形式加速疾病进展。因此，对于任何有遗传风险的个体，严格戒酒是延缓疾病进展的关键措施。2.戒烟：吸烟是胰腺炎的独立危险因素，且促进胰腺炎的病程进展。在携带遗传致病性变异的背景下，吸烟等环境因素会显著加速CP患者胰腺功能不全的进程；对于遗传性胰腺炎患者，吸烟者发生胰腺癌的风险是非吸烟者的2倍以上（OR=2.1），并且吸烟者诊断胰腺癌的中位年龄提前了20年（P=0.02）。由此可见，终身戒烟可有效降低遗传性胰腺炎人群胰腺功能恶化和癌变风险。3.低脂饮食：高脂饮食可刺激胰腺分泌大量胰液，增加胰腺负担。研究表明，FCS患者体内甘油三酯水平随脂代谢相关基因变异负荷增加而升高，严格限制脂肪摄入的极低脂饮食是FCS治疗的基石。目前尚无研究报道低脂饮食对携带胰腺炎相关基因变异者的疾病控制作用，但动物实验表明高脂饮食显著加剧人源化PRSS1 p.Arg122His小鼠胰腺纤维化进程。低脂饮食推荐限制高脂肪、高胆固醇食物的摄入，减少动物油脂和油炸食品，增加富含不饱和脂肪酸的食物和膳食纤维的摄入。4.血糖控制：携带胰腺炎相关基因变异的患者发生胰源性糖尿病的风险远高于普通胰腺炎人群。首发AP患儿中，胰腺炎相关基因胚系变异是胰腺内分泌功能不全发生的独立预测因素（OR=4.89）。胰源性糖尿病以血糖波动大、低血糖风险高、控制难度大为临床特点，治疗通常首选二甲双胍，但由于胰岛β细胞功能进行性丧失，大多数患者最终仍需胰岛素治疗，且需配合胰酶替代治疗和严格的饮食管理，以稳定血糖并防范低血糖的发生。输推荐意见12：对于携带SPINK1等胰腺炎相关基因变异的患者，应早期检测胰腺外分泌功能，确诊PEI者应尽早进行胰酶替代治疗。证据等级：2b；推荐强度：强胰腺组织萎缩破坏后胰液分泌减少，影响食物的正常消化和吸收，临床上可表现为脂肪泻、营养不良和体重减轻等PEI相关症状，多项共识或专家建议推荐将口服胰酶替代治疗（pancreatic enzyme replacement therapy，PERT）作为PEI的核心治疗手段。与基线期和安慰剂治疗相比，PERT可减少粪便脂肪排泄量，改善粪脂吸收系数和氮吸收率，保护AP患者肠道功能，并改善CP患者的体重、营养状况和生活质量。在RAP和CP患儿中，PERT治疗后AP年发作率显著下降；其中携带PRSS1变异的患儿更倾向于接受PERT治疗（P=0.008），携带SPINK1变异的患儿在PERT治疗后复发及AP发作的风险更低（P=0.008）。输推荐意见13：携带SPINK1等基因变异可影响内镜微创治疗疗效。证据等级：4；推荐强度：弱基因变异状态可能影响胰腺炎患者部分治疗手段如内镜微创治疗的预后。一项观察性研究提示，SPINK1 c.194+2T>C变异与内镜治疗后疼痛缓解显著相关（HR=0.434，P=0.011），不携带该变异的患者疼痛缓解出现时间更早（P=0.003）；此外，携带SPINK1 c.194+2T>C的患者在内镜治疗后仍出现胰腺内分泌功能不全，发生率更高（41%比12%），且接受胰岛素治疗（34.5%比9.3%，P=0.003）和PERT治疗（39.7%比16.3%，P=0.011）的比例亦显著升高。未来需要进一步高质量临床研究验证。输推荐意见14：对于FCS、极重度HTG、复发性HTG⁃AP成年患者，可考虑使用APOC3靶向核酸类药物，以降低甘油三酯水平和长期胰腺炎复发风险。证据等级：1b；推荐强度：弱临床实践表明，将血甘油三酯水平降至5.7 mmol/L（500 mg/dl）以下是治疗HTG⁃AP的关键，也能预防AP复发风险。对于反复发作、常规降脂治疗反应不佳的HTG⁃AP患者，建议先行基因检测明确病因，之后可考虑基因靶向治疗，从根源上纠正脂质代谢缺陷。LPL为甘油三酯水解限速酶，其功能缺失是HTG常见遗传病因；APOC3是LPL强效抑制因子，故成为基因抑制的重要靶点。目前已有4款靶向APOC3的基因药物获批或曾获批临床应用，其中plozasiran已在我国获批上市，为面临复发风险的HTG⁃AP患者提供了全新治疗选择。1. volanesorsen：该药是一种靶向APOC3 mRNA的反义寡核苷酸药物，通过抑制APOC3的合成降低血甘油三酯水平。重度HTG和FCS全球Ⅲ期临床试验结果显示，每周1次皮下注射volanesorsen可使APOC3和甘油三酯水平下降约70%，治疗期间无胰腺炎发作。2019年该药获欧洲联盟批准用于降低基因确诊且有胰腺炎高风险的FCS患者的发病风险。但需关注血小板减少等不良反应，慢性或不明原因血小板减少症者禁用。2. olezarsen：该药同为靶向APOC3 mRNA的反义寡核苷酸药物。重度HTG全球Ⅲ期临床试验显示，每月1次皮下注射olezarsen可使甘油三酯水平下降约72%，AP事件减少85%，表现出良好的安全性和耐受性。FCS全球Ⅲ期临床试验显示，olezarsen治疗6个月后，甘油三酯降低43.5%，APOC3降低73.7%，AP风险降低约85%。该药先后于2024年获美国食品药品监督管理局批准、2025年获欧洲联盟批准，用于FCS饮食控制的辅助治疗以降低甘油三酯水平。使用该药时需警惕过敏反应，出现严重症状时应立即停药就医。3. plozasiran：该药是一种靶向APOC3 mRNA的小干扰RNA药物，每3个月给药1次，通过LPL依赖和非LPL依赖双重途径降低甘油三酯。FCS全球Ⅲ期临床试验显示，plozasiran治疗可使甘油三酯和APOC3水平分别下降80%和93%，AP复发率降低83%。重度HTG全球Ⅱ期2年开放标签扩展试验显示，在治疗第6、12、24个月时，甘油三酯分别降低76%、82%和83%，APOC3分别降低73%、79%和81%，2年期间无AP事件发生。该产品于2025年获美国食品药品监督管理局批准、2026年获我国国家药品监督管理局批准用于治疗FCS。目前试验阶段plozasiran报道的常见不良反应包括高血糖、头痛、恶心等。4. alipogene tiparvovec：该药通过腺相关病毒血清型1载体递送功能性LPL基因（LPLS447X），单次肌内注射后血甘油三酯下降40%~60%，胰腺炎事件减少59%。该药于2012年获欧洲联盟批准用于LPL缺陷所致AP的治疗，但已于2017年退出市场。目前国外已有多款APOC3相关靶向核酸类药物获批用于成年FCS患者，且获批适应证尚不包括HTG⁃AP；国内HTG⁃AP患者可经伦理委员会批准后，申请参加相关临床试验或者同情用药。上述药物均需关注注射部位反应，且对相关活性成分或辅料过敏者禁用。输推荐意见15：对于携带CFTR变异的囊性纤维化（cystic fibrosis，CF）患者，尤其是胰腺功能型CF，使用CFTR调节剂有助于降低AP发作风险，但CP患者能否获益仍未知。证据等级：4；推荐强度：弱CFTR调节剂对胰腺炎方面的获益程度与患者的基础胰腺功能状态有关。治疗后可使胰腺功能型CF患者胰腺外分泌功能改善，AP事件减少87%；但在胰腺功能不全型CF患者中，CFTR调节剂治疗与AP风险的关系尚不明确。根据作用机制，目前已上市的CFTR调节剂可分为5类。1.增强剂：增加CFTR在细胞表面开放的时间增强阴离子转运，以依伐卡托（ivacaftor/VX⁃770）为代表，适用于CFTR p.Gly551Asp等Ⅲ类、Ⅳ类变异。Ⅲ期临床试验（KIWI）结果显示依伐卡托可改善CF患儿的胰腺外分泌功能。2.校正剂：改善CFTR蛋白折叠与加工，促进其顺利转运至细胞膜并发挥作用，代表性药物包括鲁玛卡托（lumacaftor/VX809）、替扎卡托（tezacaftor/VX⁃661），常与增效剂联合使用，主要适用于CFTR p.Phe508del等Ⅱ类变异患者。最新病例报告显示，2例CFTR相关疾病患者在接受VX⁃809、VX⁃770复方制剂治疗后，随访第9、37个月内胰腺炎发作次数显著减少。3.通读剂：降低核糖体对终止密码子的识别精度，使其忽略终止密码子并继续沿着mRNA翻译，从而合成完整的CFTR蛋白。代表药物如阿他鲁仑（ataluren，PTC124），但由于未能改善CF患者肺功能，该药物的开发已终止。4.稳定剂：与CFTR蛋白的特定结构域结合，将其锚定在细胞膜上，干扰溶酶体降解途径，减慢CFTR蛋白的降解速率，延长其在细胞膜表面的停留时间，如cavosonstat（N91115）。目前尚无该药治疗胰腺炎的相关证据。5.放大剂：增加CFTR mRNA表达促进蛋白质合成，如PTI⁃428（nesolicaftor），目前尚无研究报道该类放大剂对胰腺功能的改善作用。目前临床CFTR调节剂治疗策略主要包括增强剂单药疗法、增强剂+校正剂二联疗法、校正剂+校正剂+增强剂三联疗法。具体方案的选择需结合患者基因测序结果，并密切关注肝功能损害等不良反应。六、胰腺炎基因胚系变异与遗传咨询输推荐意见16：PRSS1基因胚系变异遗传外显率高，对于携带该类基因变异的患者应在孕前进行遗传咨询，明确遗传模式及相应的子代遗传风险。证据等级：3b；推荐强度：弱遗传性胰腺炎最常见的致病基因为PRSS1，占所有遗传性胰腺炎家系的60%~80%。PRSS1功能获得性变异（如p.Arg122His和p.Asn29Ile）可呈现常染色体显性遗传模式，外显率高达80%。对于该基因携带者的最佳遗传风险评估及产前基因检测咨询时机为孕前阶段。1.先证者的父母：多数PRSS1相关遗传性胰腺炎的先证者可追溯至受影响的父母一方。若父母双方外周血DNA中均未检测到该致病性变异，提示该变异可能为先证者新发变异，或存在父母生殖细胞嵌合的可能。2.先证者的兄弟姐妹：先证者同胞的遗传风险取决于其父母的基因型。若父母一方为PRSS1致病性变异携带者或已确诊为遗传性胰腺炎，则同胞遗传该变异的概率为50%。若先证者携带的致病性变异在父母双方外周血中均未检出，则同胞的遗传风险理论上约为1%（主要源于父母生殖细胞嵌合的可能性）。若父母尚未进行基因检测但临床表型正常，先证者同胞罹患PRSS1相关遗传性胰腺炎的风险仍较普通人群升高。3.先证者的后代：PRSS1相关遗传性胰腺炎患者子代有50%的概率遗传致病性变异。4.其他家庭成员：其他家庭成员的遗传风险取决于先证者父母的基因状态。若父母一方携带致病性基因变异，则其亲属亦可能面临相应的遗传风险。值得注意的是，我国CP人群中最主要变异SPINK1 c.194+2T>C的纯合子外显率近100%，但杂合子外显率仅为10.53%，后者通常需与其他基因变异或环境因素共同作用导致CP发生。因此，若父母双方均存在致病性变异，则子代遗传风险显著升高；当患者同时携带多个不同通路的易感基因变异时，疾病发生风险及CP进展速度会呈非线性显著上升。在进行产前遗传咨询时，应重点向家庭充分告知该基因较低的外显率和临床表型的广泛变异性。对于有明确生育需求且携带上述致病性或易感性基因变异的家庭，可在充分遗传咨询后，评估辅助生殖技术阻断疾病遗传的可行性。输推荐意见17：对于具有胰腺炎病史的孕妇，可进行SPINK1和CFTR基因检测，以评估不良妊娠结局的风险。证据等级：2b；推荐强度：弱我国一项CP队列研究显示，在38例有不良妊娠结局和122例无不良妊娠结局的患者中，SPINK1变异显著增加早产、流产等不良妊娠结局的发生风险（OR=2.60，P=0.037）。此外，我国一项前瞻性队列研究发现，与无CFTR变异的胎儿相比，携带CFTR变异的胎儿早产发生率显著升高（43.1%比17.5%，P<0.001），早产风险增加了3.39倍（P=0.007）。上述证据提示，在妊娠期对母体和胎儿进行SPINK1和CFTR基因型筛查，对妊娠期保健具有一定的临床指导价值。输推荐意见18：对于妊娠期HTG女性，可考虑进行脂代谢相关基因检测，以评估HTG⁃AP发生风险。证据等级：4；推荐强度：弱妊娠期雌激素水平的改变可增加血液循环中甘油三酯的生成并减少其清除，导致甘油三酯水平生理性升高，健康妊娠女性血清总甘油三酯峰值>3.3 mmol/L的情况少见。然而，对于本身存在脂质代谢异常的女性，妊娠期发生严重HTG的风险显著增高，成为妊娠期AP的重要诱发因素。一项针对严重妊娠期AP患者的基因检测研究显示，60%的患者携带APOA5基因纯合变异c.553G>T（p.Gly185Cys），另有2例患者携带LPL基因杂合变异c.292G>A（p.Ala98Thr）。我国关于HTG⁃AP患者的研究证实，APOA5 c.553G>T与妊娠期HTG⁃AP存在强关联，该位点TT基因型频率（20%）显著高于对照组（男性和未妊娠女性均<6%）。因此，建议对妊娠期HTG女性进行脂代谢相关基因变异检测，以评估HTG⁃AP的发生风险，并加强临床管理将甘油三酯降至正常参考值范围内。输推荐意见19：胰腺炎基因检测应由具有遗传咨询资质的临床医师提供遗传咨询。检测前解释检测目的、潜在结果及对家属的影响，待受试者和（或）家属充分知情后自愿签署知情同意书；检测后根据结果提供个体化管理建议和家属风险评估。证据等级：5；推荐强度：强遗传咨询旨在帮助个体和家庭理解并适应遗传因素对胰腺炎带来的医学、心理影响。从事胰腺炎遗传咨询的临床医师应具备遗传学专业背景，并接受系统化遗传咨询培训，需全面了解基因检测的目的、方法和局限性，充分认知预期结果和可能风险，熟悉数据和样本处理规范。遗传咨询的方法和实践建立在道德伦理基础上，强调个人自主权和尊重原则。具体评估内容包括以下几方面。1.患者的需求和关注点：介绍胰腺炎基因检测的益处、风险和局限性，帮助患者决定是否检测。因个人检测结果可能对亲属产生重大影响，故事先需询问患者希望与谁分享检测结果，并告知其家庭成员可能的反应。2.家族史评估：获取至少三代详细家族信息，包括所有亲属的生存状况、当前或死亡年龄，已故亲属应记录死因。完整家族史是风险评估的基础，也可为理解家庭沟通模式提供线索。需关注亲属胰腺癌病史，询问是否患有其他癌症及是否进行过基因检测。对有癌症聚集倾向的家庭，应转诊至癌症遗传学专科。对于已知癌症易感家庭，胰腺癌风险评估权重应相应调整。3.胰腺疾病相关信息：记录胰腺炎病程、起病年龄和诊断年龄，尽可能获取脂肪酶和淀粉酶数据，询问糖尿病或PEI情况。4.相关系统疾病和暴露因素：询问与特定基因变异相关的临床表现，如男性不育、慢性鼻窦炎或鼻息肉（提示CFTR变异可能）、CF确诊史或CFTR基因检测史、HTG病史、亲属早发性心脏病死亡史（提示遗传性高脂血症）、吸烟和酗酒史（作为风险修正因素）。检测前进行遗传咨询有助于受检者充分理解基因检测的目的、意义及潜在影响，保障受检者知情权与自主选择权。检测前需获得受检者或法定监护人签署的书面知情同意书，内容如下：（1）送检的目的和意义；（2）检测指征；（3）检测方法和周期；（4）检测基因范围和结果告知方式；（5）预期结果和可能的风险，如果发现阳性结果，则告知受检者对诊断、治疗、预后和家系成员的影响，如果是阴性结果，则说明不能完全排除遗传因素，可能源于技术局限或未知致病基因；（6）受检者及其家属的信息和隐私保护。检测后建议由专业人员提供遗传咨询，解释检测结果和临床意义，告知对家系成员的潜在影响，建议有风险亲属进行遗传咨询。基因检测遵循自愿原则，受检者可随时撤回知情同意，检测结果仅用于医疗和科研目的，严格遵守隐私保护相关法律法规。七、胰腺炎基因胚系变异与随访管理输推荐意见20：携带PRSS1基因变异的遗传性胰腺炎患者从40岁起每年进行胰腺癌筛查，使用MRI、CT或超声内镜；其他基因变异携带者开展常规胰腺癌筛查。证据等级：3b；推荐强度：强虽然多数遗传性胰腺炎病例在18岁前发病，但部分患者可能延迟至30岁甚至更晚才出现临床表现。持续性炎症是CP进展为胰腺癌的重要危险因素，尤其是遗传性胰腺炎患者在70岁时患胰腺癌风险较普通人群增加53倍，累计风险高达40%，开展胰腺癌筛查具有重要临床意义。1.筛查对象和起始年龄：根据胰腺癌监测国际共识，PRSS1相关遗传性胰腺炎患者患胰腺癌的风险显著升高，需定期监测。一项基于欧洲胰腺癌研究联盟病例的研究显示，307例携带PRSS1相关变异的遗传性胰腺炎患者中，有20例被诊断为胰腺癌，主要携带p.Arg122His、p.Asn29Ile、p.Ala16Val变异。进一步研究表明，p.Arg122His与p.Asn29Ile变异携带者胰腺癌发生风险最高。美国胃肠病协会（American Gastroenterological Association，AGA）和美国消化内镜学会（American Society for Gastrointestinal Endoscopy，ASGE）均建议，携带PRSS1变异的遗传性胰腺炎患者应从40岁开始考虑胰腺癌筛查。CFTR基因变异携带者属胰腺癌高危人群，暂无专门筛查指南，但若已进展为CP且合并新发糖尿病、伴有吸烟史或胰腺癌家族史等附加风险因素时，可参照PRSS1相关筛查策略监测。对于SPINK1 p.Asn34Ser和SPINK1 c.194+2T>C携带者，国际共识表明其胰腺癌发生风险尚不足以支持对该类人群实施常规监测，若同时合并胰腺癌的一级亲属≥2人，则可参照家族性胰腺癌筛查建议。其他胚系变异（包括CTRC、CPA1和CEL变异）相关的CP患者患胰腺癌的风险尚不足以支持筛查或监测。2.筛查手段：AGA和ASGE推荐MRI和超声内镜作为胰腺癌筛查的优选检查手段，两者均具有高灵敏度和低风险的特点。《中国胰腺癌高危人群早期筛查和监测共识意见(2021年,南京)》建议在胰腺癌早期筛查中CT、MRI和超声内镜均可选择，在随访中发现可疑征象优先推荐使用MRI或超声内镜。超声内镜与MRI在胰腺病变的大小、数量和位置检测方面具有良好一致性，且可互为补充：MRI对囊性病变的检出更为敏感，而EUS对实性病变的检出更为敏感，并可进行EUS⁃FNA以实现精确的病变取样。输推荐意见21：对胰腺炎相关基因变异携带者从20岁起进行糖尿病筛查。证据等级：4；推荐强度：弱胰腺炎后糖尿病是特殊类型糖尿病的首要病因，在AP和CP患者中的发生率分别约为20%和80%。如前文所述，胰腺炎相关基因致病性或易感性变异（如SPINK1 c.194+2T>C）携带可显著加速糖尿病的发生，其中CFTR功能障碍或缺失引起的CF患者中有30%~50%伴有糖尿病。中华医学会糖尿病学分会建议一般人群应在35岁时进行糖尿病筛查，携带胰腺炎相关基因胚系变异的ICP患者较未携带患者糖尿病确诊时间提前15.9年，因此针对携带基因胚系变异的ICP患者，建议可从20岁起开展糖尿病筛查。建议采用空腹血糖联合75 g口服葡萄糖耐量试验2 h血糖评估，结果正常者建议每3年复查1次，结果为糖尿病前期者建议每年复查1次。输推荐意见22：建议胰腺炎相关基因胚系变异携带者在确诊胰腺炎后检测胰腺外分泌功能，首选粪胰弹性蛋白酶1检测。证据等级：2b；推荐强度：强胰腺炎后由于外分泌部损伤造成PEI，可导致骨质疏松、免疫力下降、生活质量降低和心血管事件风险增加等一系列严重并发症。CP确诊时PEI发病率为36%，5年后约为60%，晚期CP患者的PEI发生率可达100%；在重症胰腺炎恢复期，约1/3的患者可出现PEI。携带胰腺炎相关基因胚系变异的CP患者诊断脂肪泻的中位年龄较无变异患者早6年，并且其60岁的脂肪泻累积发病率显著高于无变异患者（57.7%比31.0%）。欧洲胰腺外分泌功能不全诊断与治疗指南建议所有胰腺炎发作后的患者都应接受PEI筛查，在确诊CP后每年需要进行PEI评估。目前针对PEI的诊断包括直接胰腺功能试验和间接胰腺功能试验。直接胰腺功能试验为收集胰液进行检测，成本高昂且属侵入性检查，不适合作为临床常规检查。间接胰腺功能试验中，粪脂肪吸收系数测定操作复杂，患者依从性差；13C⁃混合甘油三酯呼气试验操作复杂，人群使用受限；N⁃苯甲酰⁃L酪氨酸⁃对氨基苯甲酸（N⁃benzoyl⁃L⁃tyrosyl⁃p⁃aminobenzoic acid， BT⁃PABA）试验检测特异性不足。现阶段多国指南明确提出PEI诊断的首选方法为粪胰弹性蛋白酶1检测。胰弹性蛋白酶1由胰腺分泌，在肠道中不被分解，完全经粪便排出，检验结果不受外源性胰酶制剂干扰，且操作方便，试验成本相对低廉，适用于PEI的检测和PEI确诊病例的长期随访。输推荐意见23：对于携带脂代谢相关基因变异的胰腺炎患者，应密切监测血脂尤其是甘油三酯水平，并评估胰腺炎复发风险。证据等级：2b；推荐强度：强血甘油三酯水平与HTG⁃AP发生风险、严重程度、复发风险正相关。血甘油三酯每升高100 mg/dl （1.13 mmol/L），AP发病风险增加4%。脂代谢相关基因变异者可表现为不同程度的HTG。研究发现，LPL、APOA5、LMF1、GPIHBP1、APOC2变异在重度HTG患者中的检出率高于血甘油三酯正常者，其中LPL和APOA5的罕见变异与极重度HTG密切相关。LPL杂合变异者血清甘油三酯通常为200~750 mg/dL（2.26~8.47 mmol/L），而LPL纯合变异者血甘油三酯可高达10 000 mg/dl（113 mmol/L）。HTG⁃AP长期管理重点是降低血甘油三酯、预防AP发生，以控制血甘油三酯<200 mg/dl（2.26 mmol/L）为目标。中国血脂管理指南建议血脂筛查频率为年龄<40岁人群每2~5年检测1次血脂4项，年龄≥40岁人群每年至少进行1次检测。携带脂代谢相关基因变异者应当纳入重点对象，其血脂监测应较同年龄段一般人群更为密集，建议至少每半年检测1次。HTG-AP的临床表现与其他病因引起的AP类似，当出现急性发作的典型胰腺炎疼痛特征时，应及时就诊评估与治疗。本共识基于国内外最新循证医学证据，系统阐述了胰腺炎基因胚系变异检测的临床应用，首次提出了适合中国人群的检测基因变异谱、目标人群分层、变异分类细化方案和治疗管理策略（图1）。未来，随着NGS的普及和精准医学的发展，胰腺炎的基因检测有望纳入常规诊疗流程。本共识将根据循证医学证据的积累不断更新，以期为临床医师提供与时俱进的指导，最终改善胰腺炎患者的长期预后和生活质量。指导组成员（按姓氏汉语拼音排序）：边   云 海军军医大学第一附属医院邓朝晖 上海交通大学医学院附属上海儿童医学中心杜奕奇 海军军医大学第一附属医院黄涛生 复旦大学医学遗传研究院黄   伟 四川大学华西医院李   晶 海军军医大学第一附属医院李维勤 东部战区总医院李兆申 海军军医大学第一附属医院廖   专 海军军医大学第一附属医院刘改芳 河北省人民医院陆子鹏 江苏省人民医院/南京医科大学第一附属医院马   端 复旦大学代谢分子医学教育部重点实验室石   乔 武汉大学人民医院孙   备 哈尔滨医科大学附属第一医院涂建锋 浙江省人民医院王   刚 哈尔滨医科大学附属第一医院王   伟 上海市第一人民医院王晓艳 中南大学湘雅三医院文   礼 北京协和医院吴   捷 首都医科大学附属北京儿童医院肖   园 上海交通大学医学院附属瑞金医院谢   芳 南方医科大学第三附属医院徐桂芳 安徽医科大学第一附属医院许鸿志 厦门大学附属中山医院杨   琦 东部战区总医院殷   涛 华中科技大学同济医学院附属协和医院张   锋 复旦大学医学遗传研究院周智航 重庆医科大学附属第二医院祝   荫 南昌大学第一附属医院邹文斌 海军军医大学第一附属医院执笔组成员：王元辰 海军军医大学第一附属医院杨   琦 东部战区总医院郑奕洲 海军军医大学第一附属医院吴   笛 海军军医大学第一附属医院杜甑衎 海军军医大学第一附属医院特邀专家：陈建敏 法国国家医学与健康研究院胡煜明 John Wiley & Sons, Inc.沈亦平 哈佛医学院波士顿儿童医院首席方法学家：陈耀龙 兰州大学专家组成员（按姓氏汉语拼音排序）：白荣盘 浙江大学医学院附属邵逸夫医院边   云 海军军医大学第一附属医院曹   锋 首都医科大学宣武医院陈科全 广州医科大学附属第一医院陈炜炜 扬州大学医学部陈   鑫 天津医科大学总医院程   斌 华中科技大学同济医学院附属同济医院邓朝晖 上海交通大学医学院附属上海儿童医学中心丁   震 中山大学附属第一医院杜奕奇 海军军医大学第一附属医院冯云路 北京协和医院郭瑾陶 中国医科大学附属盛京医院郭世伟 海军军医大学第一附属医院胡良皞 海军军医大学第一附属医院黄涛生 复旦大学医学遗传研究院黄   伟 四川大学华西医院黄志寅 四川大学华西医院贾   林 广州市第一人民医院蒋   慧 海军军医大学第一附属医院江振宇 包头医学院第二附属医院赖人旭 中山大学附属第五医院李惠萍 温州医科大学附属第一医院李   晶 海军军医大学第一附属医院李   鹏 首都医科大学附属北京友谊医院李   拓 海军军医大学第二附属医院李维勤 东部战区总医院李晓宇 青岛大学附属医院李兆申 海军军医大学第一附属医院廖   专 海军军医大学第一附属医院刘改芳 河北省人民医院刘   丕 深圳市龙华区人民医院刘添文 广东省中医院刘一品 山东医药大学烟台附属医院刘志峰 南京医科大学附属儿童医院路国涛 扬州大学附属医院陆子鹏 江苏省人民医院/南京医科大学第一附属医院吕   梁 中南大学湘雅二医院马   端 复旦大学代谢分子医学教育部重点实验室彭   杰 中南大学湘雅医院彭铁立 广州医科大学附属清远医院乔伟光 南方医科大学南方医院覃山羽 广西医科大学第一附属医院屈伟明 中南大学湘雅医学院附属株洲医院石   乔 武汉大学人民医院孙   备 哈尔滨医科大学附属第一医院涂建锋 浙江省人民医院王   刚 哈尔滨医科大学附属第一医院汪胡根 安徽医科大学第一附属医院王   伟 上海市第一人民医院王晓艳 中南大学湘雅三医院王元辰 海军军医大学第一附属医院王   铮 西安交通大学第一附属医院文   礼 北京协和医院吴   东 北京协和医院吴   捷 首都医科大学附属北京儿童医院肖   园 上海交通大学医学院附属瑞金医院谢   芳 南方医科大学第三附属医院徐桂芳 安徽医科大学第一附属医院许鸿志 厦门大学附属中山医院薛   婧 上海交通大学医学院附属仁济医院，上海市肿瘤研究所颜宏利 海军军医大学第一附属医院杨建锋 西湖大学医学院附属杭州市第一人民医院杨   琦 东部战区总医院姚   君 深圳市人民医院殷   涛 华中科技大学同济医学院附属协和医院袁继行 海军军医大学基础医学院张   锋 复旦大学医学遗传研究院张荣春 厦门弘爱医院张筱凤 西湖大学医学院附属杭州市第一人民医院周春华 上海交通大学医学院附属瑞金医院周智航 重庆医科大学附属第二医院朱克祥 兰州大学第一医院祝   荫 南昌大学第一附属医院邹多武 上海交通大学医学院附属瑞金医院邹文斌 海军军医大学第一附属医院  参考文献[1] Petrov MS, Yadav D. Global epidemiology and holistic prevention of pancreatitis[J]. Nat Rev Gastroenterol Hepatol, 2019, 16(3):175-184. DOI: 10.1038/s41575-018-0087-5.[2] Schepers NJ, Bakker OJ, Besselink MG, et al. Impact of characteristics of organ failure and infected necrosis on mortality in necrotising pancreatitis[J]. Gut, 2019, 68(6):1044-1051. DOI: 10.1136/gutjnl-2017-314657.[3] Sternby H, Bolado F, Canaval-Zuleta HJ, et al. Determinants of severity in acute pancreatitis: a nation-wide multicenter prospective cohort study[J]. Ann Surg, 2019, 270(2):348-355. DOI: 10.1097/sla.0000000000002766.[4] Machicado JD, Gougol A, Tan X, et al. Mortality in acute pancreatitis with persistent organ failure is determined by the number, type, and sequence of organ systems affected[J]. United European Gastroenterol J, 2021, 9(2):139-149. DOI: 10.1002/ueg2.12057.[5] Jagannath S, Garg PK. Recurrent acute pancreatitis: current concepts in the diagnosis and management[J]. Curr Treat Options Gastroenterol, 2018, 16(4):449-465. DOI: 10.1007/s11938-018-0196-9.[6] Thierens N, Verdonk RC, Löhr JM, et al. Chronic pancreatitis[J]. Lancet, 2025, 404(10471):2605-2618. DOI: 10.1016/s0140-6736(24)02187-1.[7] Ke L, Zhou J, Mao W, et al. Immune enhancement in patients with predicted severe acute necrotising pancreatitis: a multicentre double-blind randomised controlled trial [J]. Intensive Care Med, 2022, 48(7):899-909. DOI: 10.1007/s00134-022-06745-7.[8] Huang L, Feng Z, Yang W, et al. Parecoxib sequential with imrecoxib for occurrence and remission of severe acute pancreatitis: a multicentre, double-blind, randomised, placebo-controlled trial[J]. Gut, 2025, 74(9):1467-1475. DOI: 10.1136/gutjnl-2024-334038.[9] Fan Z, Zhang Y, Li J, et al. Global burden and characterization of hypertriglyceridemia-induced acute pancreatitis: results from a systematic review and a multi-center cohort study[J]. Sci China Life Sci, 2025, 68(10):3010-3020. DOI: 10.1007/s11427-024-2900-6.[10] Yu B, Li J, Li N, et al. Progression to recurrent acute pancreatitis after a first attack of acute pancreatitis in adults[J]. Pancreatology, 2020, 20(7):1340-1346. DOI: 10.1016/j.pan.2020.09.006.[11] 郭英杰, 宋文, 李晓宇, 等. 中国近十年复发性急性胰腺炎病因及临床特征的Meta分析[J]. 中华胰腺病杂志, 2017, 17(4):231-237. DOI: 10.3760/cma.j.issn.1674-1935.2017.04.005.[12] 杨琦, 濮娜, 段逸尘,等. 高三酰甘油血症性急性胰腺炎患者的脂代谢基因突变及其致病性分析[J]. 中华胰腺病杂志, 2025, 25(1):44-49. DOI: 10.3760/cma.j.cn115667-20241103-00185.[13] Kleeff J, Whitcomb DC, Shimosegawa T, et al. Chronic pancreatitis[J/OL]. Nat Rev Dis Primers, 2017, 3:17060(2017-09-07)[2026-07-23]. http://doi.org/10.1038/nrdp.2017.60. DOI: 10.1038/nrdp.2017.60.[14] Hao L, Pan J, Wang D, et al. Risk factors and nomogram for pancreatic pseudocysts in chronic pancreatitis: a cohort of 1 998 patients[J]. J Gastroenterol Hepatol, 2017, 32(7):1403-1411. DOI: 10.1111/jgh.13748.[15] Zou WB, Tang XY, Zhou DZ, et al. SPINK1, PRSS1, CTRC, and CFTR genotypes influence disease onset and clinical outcomes in chronic pancreatitis[J/OL]. Clin Transl Gastroenterol, 2018, 9(11):204(2018-11-12)[2026-07-23]. http://doi.org/10.1038/s41424-018-0069-5. DOI: 10.1038/s41424-018-0069-5.[16] Uc A, Husain SZ. Pancreatitis in children[J]. Gastroenterology, 2019, 156(7):1969-1978. DOI: 10.1053/j.gastro.2018.12.043.[17] Joergensen M, Brusgaard K, Crüger DG, et al. Incidence, etiology and prognosis of first-time acute pancreatitis in young patients: a population-based cohort study[J]. Pancreatology, 2010, 10(4):453-461. DOI: 10.1159/000260666.[18] Gardner TB, Adler DG, Forsmark CE, et al. ACG clinical guideline: chronic pancreatitis[J]. Am J Gastroenterol, 2020, 115(3):322-339. DOI: 10.14309/ajg.0000000000000535.[19] IAP/APA/EPC/IPC/JPS Working Group. International Association of Pancreatology revised guidelines on acute pancreatitis 2025: supported and endorsed by the American Pancreatic Association, European Pancreatic Club, Indian Pancreas Club, and Japan Pancreas Society [J]. Pancreatology, 2025, 25(6):770-814. DOI: 10.1016/j.pan.2025.04.020.[20] Ellis I, Lerch MM, Whitcomb DC. Genetic testing for hereditary pancreatitis: guidelines for indications, counselling, consent and privacy issues[J]. Pancreatology, 2001, 1(5):405-415. DOI: 10.1159/000055840.[21] Müller R, Aghdassi AA, Kruse J, et al. Perceptions of genetic testing in patients with hereditary chronic pancreatitis and their families: a qualitative triangulation[J]. Eur J Hum Genet, 2021, 29(1):29-38. DOI: 10.1038/s41431-020-00705-9.[22] Ramsey ML, Heald B, Gokun Y, et al. Germline multigene panel testing in acute and chronic pancreatitis[J/OL]. PLoS One, 2024, 19(8):e0307076(2024-08-22)[2026-07-23]. http://doi.org/10.1371/journal.pone.0307076. DOI: 10.1371/journal.pone.0307076.[23] Rebours V, Boutron-Ruault MC, Schnee M, et al. Risk of pancreatic adenocarcinoma in patients with hereditary pancreatitis: a national exhaustive series[J]. Am J Gastroenterol, 2008, 103(1):111-119. DOI: 10.1111/j.1572-0241.2007.01597.x.[24] Fink EN, Kant JA, Whitcomb DC. Genetic counseling for nonsyndromic pancreatitis [J]. Gastroenterol Clin North Am, 2007, 36(2):325-333, ix. DOI: 10.1016/j.gtc.2007.03.007.[25] Wu H, Gao SZ, Yin LD, et al. Germline mutations and pancreatic cancer risk in chronic pancreatitis[J]. Gut, 2025, 74(7):1195-1196. DOI: 10.1136/gutjnl-2024-334277.[26] Yin X, Shen H, Wang H, et al. Pathogenic germline variants in Chinese pancreatic adenocarcinoma patients[J/OL]. Nat Commun, 2025, 16(1):2214(2025-03-05)[2026-07-23]. http://doi.org/10.1038/s41467-025-57520-3. DOI: 10.1038/s41467-025-57520-3.[27] Jalaly NY, Moran RA, Fargahi F, et al. An Evaluation of factors associated with pathogenic PRSS1, SPINK1, CTFR, and/or CTRC genetic variants in patients with idiopathic pancreatitis[J]. Am J Gastroenterol, 2017, 112(8):1320-1329. DOI: 10.1038/ajg.2017.106.[28] 中国医师协会胰腺病专业委员会慢性胰腺炎专委会. 慢性胰腺炎诊治指南(2018年，广州)[J]. 中华消化杂志,2018,38(11)：739-746. DOI:10.3760/cma.j.issn.0254-1432.2018.11.003.[29] Löhr JM, Dominguez-Munoz E, Rosendahl J, et al. United European Gastroenterology evidence-based guidelines for the diagnosis and therapy of chronic pancreatitis (HaPanEU)[J]. United European Gastroenterol J, 2017, 5(2):153-199. DOI: 10.1177/2050640616684695.[30] Palermo JJ, Lin TK, Hornung L, et al. Genophenotypic analysis of pediatric patients with acute recurrent and chronic pancreatitis [J]. Pancreas, 2016, 45(9):1347-1352. DOI: 10.1097/mpa.0000000000000655.[31] Abu-El-Haija M, Valencia CA, Hornung L, et al. Genetic variants in acute, acute recurrent and chronic pancreatitis affect the progression of disease in children[J]. Pancreatology, 2019, 19(4):535-540. DOI: 10.1016/j.pan.2019.05.001.[32] Giefer MJ, Lowe ME, Werlin SL, et al. Early-onset acute recurrent and chronic pancreatitis is associated with PRSS1 or CTRC gene mutations[J]. J Pediatr, 2017, 186:95-100. DOI: 10.1016/j.jpeds.2017.03.063.[33] Moulin P, Dufour R, Averna M, et al. Identification and diagnosis of patients with familial chylomicronaemia syndrome (FCS): expert panel recommendations and proposal of an "FCS score"[J]. Atherosclerosis, 2018, 275:265-272. DOI: 10.1016/j.atherosclerosis.2018.06.814.[34] Jin JL, Sun D, Cao YX, et al. Intensive genetic analysis for Chinese patients with very high triglyceride levels: relations of mutations to triglyceride levels and acute pancreatitis [J]. EBioMedicine, 2018, 38:171-177. DOI: 10.1016/j.ebiom.2018.11.001.[35] Khan SA, Khan A, Malik MI. Primary hypertriglyceridemia induced pancreatitis in a cohort of Pakistani children[J]. J Pediatr Endocrinol Metab, 2022, 35(5):669-672. DOI: 10.1515/jpem-2022-0007.[36] Hajibandeh S, Jurdon R, Heaton E, et al. The risk of recurrent pancreatitis after first episode of acute pancreatitis in relation to etiology and severity of disease: a systematic review, meta-analysis and meta-regression analysis[J]. J Gastroenterol Hepatol, 2023, 38(10):1718-1733. DOI: 10.1111/jgh.16264.[37] Bashir B, Downie P, Forrester N, et al. Ethnic diversity and distinctive features of familial versus multifactorial chylomicronemia syndrome: insights from the UK FCS National Registry[J]. Arterioscler Thromb Vasc Biol, 2024, 44(11):2334-2346. DOI: 10.1161/atvbaha.124.320955.[38] Chen JM, Mercier B, Audrezet MP, et al. Mutational analysis of the human pancreatic secretory trypsin inhibitor (PSTI) gene in hereditary and sporadic chronic pancreatitis[J]. J Med Genet, 2000, 37(1):67-69. DOI: 10.1136/jmg.37.1.67.[39] Witt H, Luck W, Hennies HC, et al. Mutations in the gene encoding the serine protease inhibitor, Kazal type 1 are associated with chronic pancreatitis[J]. Nat Genet, 2000, 25(2):213-216. DOI: 10.1038/76088.[40] Wang YC, Masson E, Wang QW, et al. SPINK1-related chronic pancreatitis: A model that encapsulates the spectrum of variant effects, genetic complexity, and classificatory challenges [J]. Am J Hum Genet, 2025, 112(9):2043-2066. DOI: 10.1016/j.ajhg.2025.07.013.[41] Tang XY, Zou WB, Yu FF, et al. Meta-analysis of the impact of the SPINK1 c.194 + 2T > C variant in chronic pancreatitis [J]. Dig Liver Dis, 2020, 52(2):143-148. DOI: 10.1016/j.dld.2019.07.004.[42] Whitcomb DC, Gorry MC, Preston RA, et al. Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene[J]. Nat Genet, 1996, 14(2):141-145. DOI: 10.1038/ng1096-141.[43] Masson E, Zou WB, Pu N, et al. Classification of PRSS1 variants responsible for chronic pancreatitis: an expert perspective from the Franco-Chinese GREPAN study group[J]. Pancreatology, 2023, 23(5):491-506. DOI: 10.1016/j.pan.2023.04.004.[44] Szabó A, Sahin-Tóth M. Increased activation of hereditary pancreatitis-associated human cationic trypsinogen mutants in presence of chymotrypsin C[J]. J Biol Chem, 2012, 287(24):20701-20710. DOI: 10.1074/jbc.M112.360065.[45] 王元辰, 邹文斌, 郑奕洲, 等. 我国1 758例散发慢性胰腺炎患者易感致病基因突变谱及地区分布[J]. 中华胰腺病杂志, 2024, 24(6):413-418. DOI: 10.3760/cma.j.cn115667-20240506-00090.[46] Chen JM, Herzig AF, Génin E, et al. Scale and scope of gene-alcohol interactions in chronic pancreatitis: a systematic review[J/OL]. Genes (Basel), 2021, 12(4):471(2021-03-25)[2026-07-23]. http://doi.org/10.3390/genes12040471. DOI: 10.3390/genes12040471.[47] Kereszturi E, Szmola R, Kukor Z, et al. Hereditary pancreatitis caused by mutation-induced misfolding of human cationic trypsinogen: a novel disease mechanism[J]. Hum Mutat, 2009, 30(4):575-582. DOI: 10.1002/humu.20853.[48] Rosendahl J, Witt H, Szmola R, et al. Chymotrypsin C (CTRC) variants that diminish activity or secretion are associated with chronic pancreatitis[J]. Nat Genet, 2008, 40(1):78-82. DOI: 10.1038/ng.2007.44.[49] Mayerle J, Sendler M, Hegyi E, et al. Genetics, cell biology, and pathophysiology of pancreatitis[J]. Gastroenterology, 2019, 156(7):1951-1968.e1. DOI: 10.1053/j.gastro.2018.11.081.[50] Cohn JA, Friedman KJ, Noone PG, et al. Relation between mutations of the cystic fibrosis gene and idiopathic pancreatitis[J]. N Engl J Med, 1998, 339(10):653-658. DOI: 10.1056/nejm199809033391002.[51] Sharer N, Schwarz M, Malone G, et al. Mutations of the cystic fibrosis gene in patients with chronic pancreatitis[J]. N Engl J Med, 1998, 339(10):645-652. DOI: 10.1056/nejm199809033391001.[52] Shteinberg M, Haq IJ, Polineni D, et al. Cystic fibrosis[J]. Lancet, 2021, 397(10290):2195-2211. DOI: 10.1016/s0140-6736(20)32542-3.[53] Jiang J, Waidyaratne G, Mussad S, et al. Prevalence of CFTR pathogenic variants in pancreatitis: a systematic review and meta-analysis[J/OL]. Clin Transl Gastroenterol, 2025, 16(7):e00846(2025-04-18)[2026-07-23]. http://doi.org/10.14309/ctg.0000000000000846. DOI: 10.14309/ctg.0000000000000846.[54] Rebours V, Boutron-Ruault MC, Schnee M, et al. The natural history of hereditary pancreatitis: a national series [J]. Gut, 2009, 58(1):97-103. DOI: 10.1136/gut.2008.149179.[55] Beyer G, Habtezion A, Werner J, et al. Chronic pancreatitis[J]. Lancet, 2020, 396(10249):499-512. DOI: 10.1016/s0140-6736(20)31318-0.[56] Gonska T. Genetic predisposition in pancreatitis[J]. Curr Opin Pediatr, 2018, 30(5):660-664. DOI: 10.1097/mop.0000000000000668.[57] Downs EM, Perito ER, Wang F, et al. Long-term disease progression in pediatric acute recurrent and chronic pancreatitis: a report from INSPPIRE[J]. Pancreatology, 2026, 26(4):525-531. DOI: 10.1016/j.pan.2026.01.076.[58] Ellison MA, Spagnolo DM, Shelton C, et al. Complex genetics in pancreatitis: insights gained from a new candidate locus panel[J]. Pancreas, 2020, 49(7):983-998. DOI: 10.1097/mpa.0000000000001612.[59] Schneider A, Larusch J, Sun X, et al. Combined bicarbonate conductance-impairing variants in CFTR and SPINK1 variants are associated with chronic pancreatitis in patients without cystic fibrosis[J]. Gastroenterology, 2011, 140(1):162-171. DOI: 10.1053/j.gastro.2010.10.045.[60] 王元辰，邹文斌，廖专. 精准医学模式下慢性胰腺炎基因检测及治疗的探索. 中华消化杂志，2024, 44(5):340-343.[61] Nelson AS, Myers KC. Diagnosis, treatment, and molecular pathology of shwachman-diamond syndrome[J]. Hematol Oncol Clin North Am, 2018, 32(4):687-700. DOI: 10.1016/j.hoc.2018.04.006.[62] Nelson A, Myers K. Shwachman-Diamond Syndrome[M/OL]//Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews. Seattle (WA): University of Washington, Seattle, 1993-2020.[63] Sukalo M, Fiedler A, Guzmán C, et al. Mutations in the human UBR1 gene and the associated phenotypic spectrum[J]. Hum Mutat, 2014, 35(5):521-531. DOI: 10.1002/humu.22538.[64] Perera SD, Wang J, McIntyre AD, et al. Lipoprotein lipase: structure, function, and genetic variation[J/OL]. Genes (Basel), 2025, 16(1):55(2025-01-05)[2026-07-23]. http://doi.org/10.3390/genes16010055. DOI: 10.3390/genes16010055.[65] Chan LY, Lam CW, Mak YT, et al. Genotype-phenotype studies of six novel LPL mutations in Chinese patients with hypertriglyceridemia[J]. Hum Mutat, 2002, 20(3):232-233. DOI: 10.1002/humu.9054.[66] Chan L, Mak Y, Tomlinson B, et al. Compound heterozygosity of Leu252Val and Leu252Arg causing lipoprotein lipase deficiency in a Chinese patient with hypertriglyceridemia[J]. Eur J Clin Invest, 2000, 30(1):33-40. DOI: 10.1046/j.1365-2362.2000.00587.x.[67] Scott LJ. Alipogene tiparvovec: a review of its use in adults with familial lipoprotein lipase deficiency [J]. Drugs. 2015;75(2):175-82. DOI: 10.1007/s40265-014-0339-9[68] Yang Y, Konrad RJ, Ploug M, et al. APOA5 deficiency causes hypertriglyceridemia by reducing amounts of lipoprotein lipase in capillaries[J]. J Lipid Res, 2024, 65(7):100578. DOI: 10.1016/j.jlr.2024.100578.[69] Kao JT, Wen HC, Chien KL, et al. A novel genetic variant in the apolipoprotein A5 gene is associated with hypertriglyceridemia[J]. Hum Mol Genet, 2003, 12(19):2533-2539. DOI: 10.1093/hmg/ddg255.[70] Dorfmeister B, Zeng WW, Dichlberger A, et al. Effects of six APOA5 variants, identified in patients with severe hypertriglyceridemia, on in vitro lipoprotein lipase activity and receptor binding[J]. Arterioscler Thromb Vasc Biol, 2008, 28(10):1866-1871. DOI: 10.1161/atvbaha.108.172866.[71] Beigneux AP, Fong LG, Bensadoun A, et al. GPIHBP1 missense mutations often cause multimerization of GPIHBP1 and thereby prevent lipoprotein lipase binding[J]. Circ Res, 2015, 116(4):624-632. DOI: 10.1161/circresaha.116.305085.[72] Alves M, Laranjeira F, Correia-da-Silva G. Understanding hypertriglyceridemia: integrating genetic insights[J/OL]. Genes (Basel), 2024, 15(2):190(2024-01-30)[2026-07-23]. http://doi.org/10.3390/genes15020190. DOI: 10.3390/genes15020190.[73] Wolska A, Dunbar RL, Freeman LA, et al. Apolipoprotein C-Ⅱ: new findings related to genetics, biochemistry, and role in triglyceride metabolism[J]. Atherosclerosis, 2017, 267:49-60. DOI: 10.1016/j.atherosclerosis.2017.10.025.[74] Jin JL, Guo YL, Li JJ. Apoprotein C-Ⅲ: a review of its clinical implications[J]. Clin Chim Acta, 2016, 460:50-54. DOI: 10.1016/j.cca.2016.06.016.[75] Dabravolski SA, Churov AV, Sukhorukov VN, et al. The role of lipase maturation factor 1 in hypertriglyceridaemia and atherosclerosis: an update[J]. SAGE Open Med, 2024, 12:20503121241289828(2024-10-16)[2026-07-23]. http://doi.org/10.1177/20503121241289828. DOI: 10.1177/20503121241289828.[76] Chen WW, Yang Q, Li XY, et al. Identification of a novel and heterozygous LMF1 nonsense mutation in an acute pancreatitis patient with severe hypertriglyceridemia, severe obesity and heavy smoking[J/OL]. Lipids Health Dis, 2019, 18(1):68(2019-03-18)[2026-07-23]. http://doi.org/10.1186/s12944-019-1012-9. DOI: 10.1186/s12944-019-1012-9.[77] 中国医师协会医学遗传医师分会, 中国妇幼保健协会出生缺陷与分子遗传分会, 上海市医师协会临床遗传专业委员会, 等. 遗传病基因变异全外显子组测序技术规范化应用专家共识 [J]. 中华医学遗传学杂志, 2025, 42(1):1-11. DOI: 10.3760/cma.j.cn511374-20240723-00404.[78] Nemoda Z, Horvat-Gordon M, Fortunato CK, et al. Assessing genetic polymorphisms using DNA extracted from cells present in saliva samples[J/OL]. BMC Med Res Methodol, 2011, 11:170(2011-12-19)[2026-07-23]. http://doi.org/10.1186/1471-2288-11-170. DOI: 10.1186/1471-2288-11-170.[79] Granger DA, Kivlighan KT, Fortunato C, et al. Integration of salivary biomarkers into developmental and behaviorally-oriented research: problems and solutions for collecting specimens[J]. Physiol Behav, 2007, 92(4):583-590. DOI: 10.1016/j.physbeh.2007.05.004.[80] Abraham JE, Maranian MJ, Spiteri I, et al. Saliva samples are a viable alternative to blood samples as a source of DNA for high throughput genotyping[J/OL]. BMC Med Genomics, 2012, 5:19(2012-05-30)[2026-07-23]. http://doi.org/10.1186/1755-8794-5-19. DOI: 10.1186/1755-8794-5-19.[81] Bennett S, Alexander E, Fraser H, et al. Germline FFPE inherited cancer panel testing in deceased family members: implications for clinical management of unaffected relatives[J]. Eur J Hum Genet, 2021, 29(5):861-871. DOI: 10.1038/s41431-021-00817-w.[82] 《临床分子病理实验室二代基因测序检测专家共识》编写组. 临床分子病理实验室二代基因测序检测专家共识[J]. 中华病理学杂志, 2017, 46(3):145-148. DOI: 10.3760/cma.j.issn.0529-5807.2017.03.001.[83] DePristo MA, Banks E, Poplin R, et al. A framework for variation discovery and genotyping using next-generation DNA sequencing data[J]. Nat Genet, 2011, 43(5):491-498. DOI: 10.1038/ng.806.[84] UK Biobank Whole-Genome Sequencing Consortium. Whole-genome sequencing of 490 640 UK Biobank participants[J]. Nature, 2025, 645(8081):692-701. DOI: 10.1038/s41586-025-09272-9.[85] Shen GQ, Abdullah KG, Wang QK. The TaqMan method for SNP genotyping[J]. Methods Mol Biol, 2009, 578:293-306. DOI: 10.1007/978-1-60327-411-1_19.[86] 卢宇蓝, 李国壮, 王雅琼, 等. 临床基因组测序解读与报告专家共识[J]. 遗传, 2025, 47(3):314-328. DOI: 10.16288/j.yczz.24-296.[87] 姚如恩, 余永国, 耿娟, 等. MLPA技术在3种遗传性疾病基因诊断中的应用[J]. 中华检验医学杂志, 2013, 36(2):136-141. DOI: 10.3760/cma.j.issn.1009-9158.2013.02.010.[88] Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology[J]. Genet Med, 2015, 17(5):405-424. DOI: 10.1038/gim.2015.30.[89] Whitcomb DC. Pancreatitis: TIGAR-O version 2 risk/etiology checklist with topic reviews, updates, and use primers[J/OL]. Clin Transl Gastroenterol, 2019, 10(6):e00027(2019-06-05)[2026-07-23]. http://doi.org/10.14309/ctg.0000000000000027. DOI: 10.14309/ctg.0000000000000027.[90] Masson E, Zou WB, Génin E, et al. Expanding ACMG variant classification guidelines into a general framework[J/OL]. Hum Genomics, 2022, 16(1):31(2022-08-16)[2026-07-23]. http://doi.org/10.1186/s40246-022-00407-x. DOI: 10.1186/s40246-022-00407-x.[91] Whitcomb DC. Adoption of a “pathogenic, predisposing, risk and benign” classification of DNA variants for precision medicine: a step forward[J]. SMART-MD Journal of Precision Medicine, 2025, 2(3):ei-ii. DOI: 10.69734/h7x6zm57.[92] Lewis MD, Talluri J, Wilcox CM, et al. Differences in age at onset of symptoms, and effects of genetic variants, in patients with early vs late-onset idiopathic chronic pancreatitis in a North American cohort[J]. Clin Gastroenterol Hepatol, 2021, 19(2):349-357. DOI: 10.1016/j.cgh.2020.03.047.[93] Koziel D, Gluszek S, Kowalik A, et al. Genetic mutations in SPINK1, CFTR, CTRC genes in acute pancreatitis[J]. BMC Gastroenterol, 2015, 15:70. DOI: 10.1186/s12876-015-0302-6.[94] Liu QY, Abu-El-Haija M, Husain SZ, et al. Risk factors for rapid progression from acute recurrent to chronic pancreatitis in children: report from INSPPIRE[J]. J Pediatr Gastroenterol Nutr, 2019, 69(2):206-211. DOI: 10.1097/mpg.0000000000002405.[95] Muller N, Sarantitis I, Rouanet M, et al. Natural history of SPINK1 germline mutation related-pancreatitis[J]. EBioMedicine, 2019, 48:581-591. DOI: 10.1016/j.ebiom.2019.09.032.[96] Abu-El-Haija M, Zhang W, Karns R, et al. The role of pancreatitis risk genes in endocrine insufficiency development after acute pancreatitis in children[J]. Clin Gastroenterol Hepatol, 2024, 22(10):2033-2043.e2. DOI: 10.1016/j.cgh.2024.05.039.[97] Hassan Z, Mohan V, Ali L, et al. SPINK1 is a susceptibility gene for fibrocalculous pancreatic diabetes in subjects from the Indian subcontinent[J]. Am J Hum Genet, 2002, 71(4):964-968. DOI: 10.1086/342731.[98] El Jellas K, Dušátková P, Haldorsen IS, et al. Two new mutations in the CEL gene causing diabetes and hereditary pancreatitis: how to correctly identify MODY8 cases[J]. J Clin Endocrinol Metab, 2022, 107(4):e1455-e1466. DOI: 10.1210/clinem/dgab864.[99] Cho SM, Shin S, Lee KA. PRSS1, SPINK1, CFTR, and CTRC pathogenic variants in Korean patients with idiopathic pancreatitis[J]. Ann Lab Med, 2016, 36(6):555-560. DOI: 10.3343/alm.2016.36.6.555.[100] Masamune A, Kume K, Shimosegawa T. Differential roles of the SPINK1 gene mutations in alcoholic and nonalcoholic chronic pancreatitis[J]. J Gastroenterol, 2007, 42 Suppl 17:S135-S140. DOI: 10.1007/s00535-006-1921-z.[101] Bertin C, Pelletier AL, Vullierme MP, et al. Pancreas divisum is not a cause of pancreatitis by itself but acts as a partner of genetic mutations[J]. Am J Gastroenterol, 2012, 107(2):311-317. DOI: 10.1038/ajg.2011.424.[102] Jones TE, Bellin MD, Yadav D, et al. The histopathology of SPINK1-associated chronic pancreatitis[J]. Pancreatology, 2020, 20(8):1648-1655. DOI: 10.1016/j.pan.2020.10.030.[103] Singhi AD, Pai RK, Kant JA, et al. The histopathology of PRSS1 hereditary pancreatitis[J]. Am J Surg Pathol, 2014, 38(3):346-353. DOI: 10.1097/pas.0000000000000164.[104] Soyer P, Spelle L, Pelage JP, et al. Cystic fibrosis in adolescents and adults: fatty replacement of the pancreas—CT evaluation and functional correlation[J]. Radiology, 1999, 210(3):611-615. DOI: 10.1148/radiology.210.3.r99mr08611.[105] Shelton CA, Umapathy C, Stello K, et al. Hereditary pancreatitis in the United States: survival and rates of pancreatic cancer[J]. Am J Gastroenterol, 2018, 113(9):1376. DOI: 10.1038/s41395-018-0194-5.[106] Greenhalf W, Lévy P, Gress T, et al. International consensus guidelines on surveillance for pancreatic cancer in chronic pancreatitis. Recommendations from the working group for the international consensus guidelines for chronic pancreatitis in collaboration with the International Association of Pancreatology, the American Pancreatic Association, the Japan Pancreas Society, and European Pancreatic Club[J]. Pancreatology, 2020, 20(5):910-918. DOI: 10.1016/j.pan.2020.05.011.[107] Antwi SO, Rabe KG, Carlson EE, et al. Germline Variants in chronic pancreatitis-associated genes and risk of pancreatic ductal adenocarcinoma[J]. Clin Gastroenterol Hepatol, 2026:S1542-3565(26)00284-3. DOI: 10.1016/j.cgh.2026.03.043.[108] Campa D, Pastore M, Capurso G, et al. Do pancreatic cancer and chronic pancreatitis share the same genetic risk factors A PANcreatic Disease ReseArch (PANDoRA) consortium investigation[J]. Int J Cancer, 2018, 142(2):290-296. DOI: 10.1002/ijc.31047.[109] McWilliams RR, Petersen GM, Rabe KG, et al. Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations and risk for pancreatic adenocarcinoma [J]. Cancer, 2010, 116(1):203-209. DOI: 10.1002/cncr.24697.[110] Ru N, Wu SY, Wang L, et al. SPINK1 mutations and risk of pancreatic cancer in a Chinese cohort[J]. Pancreatology, 2021, 21(5):848-853. DOI: 10.1016/j.pan.2021.05.304.[111] Kristiansen L, Grønbaek M, Becker U, et al. Risk of pancreatitis according to alcohol drinking habits: a population-based cohort study[J]. Am J Epidemiol, 2008, 168(8):932-937. DOI: 10.1093/aje/kwn222.[112] Wang YC, Zou WB, Tang DH, et al. High clinical and genetic similarity between chronic pancreatitis associated with light-to-moderate alcohol consumption and classical alcoholic chronic pancreatitis[J]. Gastro Hep Advances, 2023, 2(2):186-195. DOI: 10.1016/j.gastha.2022.09.009.[113] Sankaran SJ, Xiao AY, Wu LM, et al. Frequency of progression from acute to chronic pancreatitis and risk factors: a meta-analysis[J]. Gastroenterology, 2015, 149(6):1490-1500.e1. DOI: 10.1053/j.gastro.2015.07.066.[114] Ru N, Xu XN, Cao Y, et al. The impacts of genetic and environmental factors on the progression of chronic pancreatitis[J]. Clin Gastroenterol Hepatol, 2022, 20(6):e1378-e1387. DOI: 10.1016/j.cgh.2021.08.033.[115] 急性高甘油三酯血症胰腺炎康复期多学科管理专家共识组, 浙江省预防医学会急性病预防与控制专业委员会, 涂建锋, 等. 急性高甘油三酯血症胰腺炎康复期多学科管理专家共识[J]. 中华急诊医学杂志, 2025, 34(10):1331-1342. DOI: 10.3760/cma.j.cn114656-20250917-00664.[116] Huang H, Swidnicka-Siergiejko AK, Daniluk J, et al. Transgenic expression of PRSS1(R122H) sensitizes mice to pancreatitis[J]. Gastroenterology, 2020, 158(4):1072-1082.e7. DOI: 10.1053/j.gastro.2019.08.016.[117] Dominguez-Muñoz JE, Vujasinovic M, de la Iglesia D, et al. European guidelines for the diagnosis and treatment of pancreatic exocrine insufficiency: UEG, EPC, EDS, ESPEN, ESPGHAN, ESDO, and ESPCG evidence-based recommendations[J]. United European Gastroenterol J, 2025, 13(1):125-172. DOI: 10.1002/ueg2.12674.[118] Hart PA, Bellin MD, Andersen DK, et al. Type 3c (pancreatogenic) diabetes mellitus secondary to chronic pancreatitis and pancreatic cancer[J]. Lancet Gastroenterol Hepatol, 2016, 1(3):226-237. DOI: 10.1016/s2468-1253(16)30106-6.[119] Hart PA, Bradley D, Conwell DL, et al. Diabetes following acute pancreatitis[J]. Lancet Gastroenterol Hepatol, 2021, 6(8):668-675. DOI: 10.1016/s2468-1253(21)00019-4.[120] 中华医学会内分泌学分会, 李玲, 王卫庆, 等. 胰源性糖尿病诊断与治疗中国专家共识(2025版) [J]. 中华糖尿病杂志, 2025, 17(12):1569-1585. DOI: 10.3760/cma.j.cn115791-20250827-00436.[121] Phillips ME, Hopper AD, Leeds JS, et al. Consensus for the management of pancreatic exocrine insufficiency: UK practical guidelines[J]. BMJ Open Gastroenterol, 2021, 8(1):e000643. DOI: 10.1136/bmjgast-2021-000643.[122] Whitcomb DC, Buchner AM, Forsmark CE. AGA clinical practice update on the epidemiology, evaluation, and management of exocrine pancreatic insufficiency: expert review[J]. Gastroenterology, 2023, 165(5):1292-1301. DOI: 10.1053/j.gastro.2023.07.007.[123] de la Iglesia-García D, Huang W, Szatmary P, et al. Efficacy of pancreatic enzyme replacement therapy in chronic pancreatitis: systematic review and meta-analysis[J]. Gut, 2017, 66(8):1354-1355. DOI: 10.1136/gutjnl-2016-312529.[124] Niu D, Li N, He J, et al. Incidence of pancreatic exocrine insufficiency and efficacy of pancreatic enzyme replacement therapy in acute pancreatitis patients[J]. Am J Transl Res, 2025, 17(10):8281-8295. DOI: 10.62347/osbm8396.[125] Gubergrits N, Malecka-Panas E, Lehman GA, et al. A 6-month, open-label clinical trial of pancrelipase delayed-release capsules (Creon) in patients with exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatic surgery[J]. Aliment Pharmacol Ther, 2011, 33(10):1152-1161. DOI: 10.1111/j.1365-2036.2011.04631.x.[126] D'Haese JG, Ceyhan GO, Demir IE, et al. Pancreatic enzyme replacement therapy in patients with exocrine pancreatic insufficiency due to chronic pancreatitis: a 1-year disease management study on symptom control and quality of life[J]. Pancreas, 2014, 43(6):834-841. DOI: 10.1097/mpa.0000000000000131.[127] Freeman AJ, Ng K, Wang F, et al. Pancreatic enzyme use reduces pancreatitis frequency in children with acute recurrent or chronic pancreatitis: a report from INSPPIRE [J]. Am J Gastroenterol, 2024, 119(10):2094-2102. DOI: 10.14309/ajg.0000000000002772.[128] Sun C, Liu MY, Liu XG, et al. Serine protease inhibitor Kazal type 1 (SPINK1) c.194+2T > C mutation may predict long-term outcome of endoscopic treatments in idiopathic chronic pancreatitis[J]. Medicine (Baltimore), 2015, 94(47):e2046. DOI: 10.1097/md.0000000000002046.[129] 高甘油三酯血症性急性胰腺炎诊治急诊共识专家组. 高甘油三酯血症性急性胰腺炎诊治急诊专家共识[J]. 中华急诊医学杂志, 2021, 30(8):11.[130] Paik J, Duggan S. Volanesorsen: first global approval[J]. Drugs, 2019, 79(12):1349-1354. DOI: 10.1007/s40265-019-01168-z.[131] Marston NA, Bergmark BA, Alexander VJ, et al. Olezarsen for managing severe hypertriglyceridemia and pancreatitis risk[J]. N Engl J Med, 2026, 394(5):429-441. DOI: 10.1056/NEJMoa2512761.[132] Stroes ESG, Alexander VJ, Karwatowska-Prokopczuk E, et al. Olezarsen, acute pancreatitis, and familial chylomicronemia syndrome[J]. N Engl J Med, 2024, 390(19):1781-1792. DOI: 10.1056/NEJMoa2400201.[133] Watts GF, Rosenson RS, Hegele RA, et al. Plozasiran for managing persistent chylomicronemia and pancreatitis risk[J]. N Engl J Med, 2025, 392(2):127-137. DOI: 10.1056/NEJMoa2409368.[134] Ballantyne CM, Baass A, Rosenson RS, et al. Use of plozasiran across a spectrum of hypertriglyceridemia: long-term efficacy and safety data from the open-label extension period of SHASTA-2 and MUIR Trials[J]. Am J Prev Cardiol, 2026, 27101523. DOI: 10.1016/j.ajpc.2026.101523.[135] Scott LJ. Alipogene tiparvovec: a review of its use in adults with familial lipoprotein lipase deficiency[J]. Drugs, 2015, 75(2):175-182. DOI: 10.1007/s40265-014-0339-9.[136] Ramsey ML, Li SS, Lara LF, et al. Cystic fibrosis transmembrane conductance regulator modulators and the exocrine pancreas: a scoping review[J]. J Cyst Fibros, 2023, 22(2):193-200. DOI: 10.1016/j.jcf.2022.08.008.[137] Gould MJ, Smith H, Rayment JH, et al. CFTR modulators increase risk of acute pancreatitis in pancreatic insufficient patients with cystic fibrosis[J]. J Cyst Fibros, 2022, 21(4):600-602. DOI: 10.1016/j.jcf.2021.09.010.[138] Ramsey ML, Gokun Y, Sobotka LA, et al. Cystic fibrosis transmembrane conductance regulator modulator use is associated with reduced pancreatitis hospitalizations in patients with cystic fibrosis[J]. Am J Gastroenterol, 2021, 116(12):2446-2454. DOI: 10.14309/ajg.0000000000001527.[139] Van Goor F, Yu H, Burton B, et al. Effect of ivacaftor on CFTR forms with missense mutations associated with defects in protein processing or function[J]. J Cyst Fibros, 2014, 13(1):29-36. DOI: 10.1016/j.jcf.2013.06.008.[140] Davies JC, Cunningham S, Harris WT, et al. Safety, pharmacokinetics, and pharmacodynamics of ivacaftor in patients aged 2-5 years with cystic fibrosis and a CFTR gating mutation (KIWI): an open-label, single-arm study[J]. Lancet Respir Med, 2016, 4(2):107-115. DOI: 10.1016/s2213-2600(15)00545-7.[141] Wainwright CE, Elborn JS, Ramsey BW. Lumacaftor-Ivacaftor in patients with cystic fibrosis homozygous for phe508del CFTR[J]. N Engl J Med, 2015, 373(18):1783-1784. DOI: 10.1056/NEJMc1510466.[142] Rowe SM, Daines C, Ringshausen FC, et al. Tezacaftor-ivacaftor in residual-function heterozygotes with cystic fibrosis[J]. N Engl J Med, 2017, 377(21):2024-2035. DOI: 10.1056/NEJMoa1709847.[143] Gohy S, Le A, Sermet-Gaudelus I, et al. Therapeutic hopes for CFTR-related recurrent pancreatitis: a case-series[J]. J Cyst Fibros, 2026, 25(3):509-512. DOI: 10.1016/j.jcf.2026.02.008.[144] Kerem E, Konstan MW, De Boeck K, et al. Ataluren for the treatment of nonsense-mutation cystic fibrosis: a randomised, double-blind, placebo-controlled phase 3 trial [J]. Lancet Respir Med, 2014, 2(7):539-547. DOI: 10.1016/s2213-2600(14)70100-6.[145] Donaldson SH, Solomon GM, Zeitlin PL, et al. Pharmacokinetics and safety of cavosonstat (N91115) in healthy and cystic fibrosis adults homozygous for F508DEL-CFTR[J]. J Cyst Fibros, 2017, 16(3):371-379. DOI: 10.1016/j.jcf.2017.01.009.[146] 囊性纤维化诊断与治疗中国专家共识编写组, 中国罕见病联盟呼吸病学分会, 中国支气管扩张症临床诊治与研究联盟. 囊性纤维化诊断与治疗中国专家共识（2023版）[J]. 中华结核和呼吸杂志, 2023, 46(4):352-372. DOI: 10.3760/cma.j.cn112147-20221214-00971.[147] Patel MR, Eppolito AL, Willingham FF. Hereditary pancreatitis for the endoscopist[J]. Ther Adv Gastroenterol, 2013, 6(2):169-179. DOI: 10.1177/1756283x12467565.[148] Whitcomb DC. PRSS1-Related Hereditary Pancreatitis[M/OL]//Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews. Seattle (WA): University of Washington, Seattle, 1993-2020.[149] Wu D, Ru N, Wang YC, et al. Genetic factors associated with adverse pregnancy outcomes in chronic pancreatitis[J]. Clin Transl Gastroenterol, 2024, 15(4):e00691. DOI: 10.14309/ctg.0000000000000691.[150] Li J, Zhang L, Xi F, et al. The CFTR K464N variant in fetuses potential increases premature birth risk in Chinese families[J]. Hum Genomics, 2025, 19(1):25. DOI: 10.1186/s40246-025-00736-7.[151] Cruciat G, Nemeti G, Goidescu I, et al. Hypertriglyceridemia triggered acute pancreatitis in pregnancy: diagnostic approach, management and follow-up care[J]. Lipids in Health and Disease, 2020, 19(1):2. DOI: 10.1186/s12944-019-1180-7.[152] 吴迪, 代大华, 梁文美, 等. 妊娠期急性胰腺炎的临床特征及危险因素分析 [J]. 临床肝胆病杂志, 2024, 40(5):1009-1015. DOI: 10.12449/JCH240522.[153] Xie SL, Chen TZ, Huang XL, et al. Genetic variants associated with gestational hypertriglyceridemia and pancreatitis[J]. PloS one, 2015, 10(6):e0129488. DOI: 10.1371/journal.pone.0129488.[154] Pu N, Yang Q, Shi XL, et al. Gene-environment interaction between APOA5 c.553G>T and pregnancy in hypertriglyceridemia-induced acute pancreatitis[J]. Journal of clinical lipidology, 2020, 14(4):498-506. DOI: 10.1016/j.jacl.2020.05.003.[155] Solomon S, Whitcomb DC. Genetics of pancreatitis: an update for clinicians and genetic counselors[J]. Curr Gastroenterol Rep, 2012, 14(2):112-117. DOI: 10.1007/s11894-012-0240-1.[156] Ellis I. Genetic counseling for hereditary pancreatitis: the role of molecular genetics testing for the cationic trypsinogen gene, cystic fibrosis and serine protease inhibitor Kazal type 1[J]. Gastroenterol Clin North Am, 2004, 33(4):839-854. DOI: 10.1016/j.gtc.2004.07.010.[157] Rego S, Grove ME, Cho MK, et al. Informed consent in the genomics era[J]. Cold Spring Harb Perspect Med, 2020, 10(8):a036582. DOI: 10.1101/cshperspect.a036582.[158] Cormack M, Irving KB, Cunningham F, et al. Mainstreaming genomic testing: pre-test counselling and informed consent[J]. Med J Aust, 2024, 220(8):403-406. DOI: 10.5694/mja2.52254.[159] Charnley RM. Hereditary pancreatitis [J]. World J Gastroenterol, 2003, 9(1):1-4. DOI: 10.3748/wjg.v9.i1.1.[160] Howes N, Lerch MM, Greenhalf W, et al. Clinical and genetic characteristics of hereditary pancreatitis in Europe[J]. Clin Gastroenterol Hepatol, 2004, 2(3):252-261. DOI: 10.1016/s1542-3565(04)00013-8.[161] Aslanian HR, Lee JH, Canto MI. AGA clinical practice update on pancreas cancer screening in high-risk individuals: expert review[J]. Gastroenterology, 2020, 159(1):358-362. DOI: 10.1053/j.gastro.2020.03.088.[162] Sawhney MS, Calderwood AH, Thosani NC, et al. ASGE guideline on screening for pancreatic cancer in individuals with genetic susceptibility: summary and recommendations [J]. Gastrointest Endosc, 2022, 95(5):817-826. DOI: 10.1016/j.gie.2021.12.001.[163] 中华医学会消化内镜学分会胰腺疾病协作组. 中国胰腺癌高危人群早期筛查和监测共识意见(2021年,南京)[J]. 胃肠病学, 2022, 27(7):415-428. DOI: 10.3969/j.issn.1008-7125.2022.07.006.[164] Scheuing N, Holl RW, Dockter G, et al. Diabetes in cystic fibrosis: multicenter screening results based on current guidelines [J]. PLoS One, 2013, 8(12):e81545. DOI: 10.1371/journal.pone.0081545.[165] 中华医学会糖尿病学分会. 中国糖尿病防治指南（2024版）[J]. 中华糖尿病杂志, 2025, 17(01):16-139. DOI: 10.3760/cma.j.cn115791-20241203-00705.[166] Chung S, Azar KM, Baek M, et al. Reconsidering the age thresholds for type Ⅱ diabetes screening in the U.S[J]. Am J Prev Med, 2014, 47(4):375-381. DOI: 10.1016/j.amepre.2014.05.012.[167] Bhullar FA, Faghih M, Akshintala VS, et al. Prevalence of primary painless chronic pancreatitis: a systematic review and meta-analysis[J]. Pancreatology, 2022, 22(1):20-29. DOI: 10.1016/j.pan.2021.11.006.[168] Hollemans RA, Hallensleben NDL, Mager DJ, et al. Pancreatic exocrine insufficiency following acute pancreatitis: systematic review and study level meta-analysis[J]. Pancreatology, 2018, 18(3):253-262. DOI: 10.1016/j.pan.2018.02.009.[169] Singh VK, Yadav D, Garg PK. Diagnosis and management of chronic pancreatitis: a review[J]. JAMA, 2019, 322(24):2422-2434. DOI: 10.1001/jama.2019.19411.[170] Yang AL, McNabb-Baltar J. Hypertriglyceridemia and acute pancreatitis[J]. Pancreatology, 2020, 20(5):795-800. DOI: 10.1016/j.pan.2020.06.005.[171] Murphy MJ, Sheng X, MacDonald TM, et al. Hypertriglyceridemia and acute pancreatitis[J]. JAMA Intern Med, 2013, 173(2):162-164. DOI: 10.1001/2013.jamainternmed.477.[172] Balasubramanian S, Aggarwal P, Sharma S. Lipoprotein lipase deficiency[M/OL]//StatPearls. Treasure Island (FL): StatPearls Publishing, 2024.[173] Wu BU, Batech M, Dong EY, et al. Influence of ambulatory triglyceride levels on risk of recurrence in patients with hypertriglyceridemic pancreatitis[J]. Dig Dis Sci, 2019, 64(3):890-897. DOI: 10.1007/s10620-018-5226-x.[174] 高甘油三酯血症临床管理多学科专家共识工作组. 高甘油三酯血症临床管理多学科专家共识[J]. 中国循环杂志, 2023, 38(6):621-633. DOI: 10.3969/j.issn.1000-3614.2023.06.003医脉通是专业的在线医生平台，“感知世界医学脉搏，助力中国临床决策”是平台的使命。医脉通旗下拥有「临床指南」「用药参考」「医学文献王」「医知源」「e研通」「e脉播」等系列产品，全面满足医学工作者临床决策、获取新知及提升科研效率等方面的需求。本平台旨在为医疗卫生专业人士传递更多医学信息。本平台发布的内容，不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议。如该等信息被用于了解医学信息以外的目的，本平台不承担相关责任。本平台对发布的内容，并不代表同意其描述和观点。若涉及版权问题，烦请权利人与我们联系，我们将尽快处理。