是什么推动了NASH？

StephenW

What’s Driving NASH?

         

Abdelmalek_Manal_100x100_Circle
       

Manal F. Abdelmalek, MD, MPH

Nonalcoholic fatty liver disease (NAFLD) can progress in a minority of patients to advanced liver disease and has quickly become the most common chronic liver disease in the United States and in many developed countries worldwide. The most recent worldwide prevalence estimates for NAFLD among adults is approximately 25%. The worldwide prevalence estimates of nonalcoholic steatohepatitis (NASH), the progressive form of NAFLD, is 3% to 5%. These prevalence estimates nearly double in patients with diabetes, as NAFLD is closely linked with metabolic syndrome, obesity, and diabetes. With an estimated prevalence of 1% to 2% of adults with advanced hepatic fibrosis due to NASH, the potential burden on public health is enormous.

Early Identification
Despite the high prevalence of NAFLD, awareness for this otherwise asymptomatic condition is low. Whereas gastroenterologists and hepatologists diagnose and stage NAFLD with intention, other healthcare professionals typically discover NAFLD incidentally. The asymptomatic nature of the disease, low awareness, and lack of intentional diagnosis/staging results in patients being diagnosed and referred when symptoms related to advanced liver disease become clinically evident—a time at which there is increased risk for adverse outcomes and when treatment options have little benefit. Identifying NAFLD in the primary care setting can help with early intervention and prevention strategies that can decrease risk of disease progression.

Advanced Hepatic Fibrosis
Hepatic fibrosis is the strongest predictor for adverse clinical outcomes. Although the transition from mild-stage to intermediate-stage fibrosis may span many years and although disease activity may even wax and wane, the transition from bridging fibrosis (stage 3) to cirrhosis (stage 4) can occur in approximately 20% of patients in as quickly as 2-3 years. Likewise, approximately 20% of those with cirrhosis may have an adverse liver-related clinical event within 2-3 years.

Need for Routine Screening?
NAFLD is the outcome of a physiologic problem of altered metabolism. The metabolic syndrome is strongly associated with NAFLD as well as cancer, cardiovascular disease, diabetes, obesity, and chronic kidney disease. Although guidance for screening for other complications of metabolic syndrome exist, routine screening patients for NAFLD—even those at high risk—is not currently recommended by the AASLD owing to uncertainties around diagnostic tests and treatments options, along with knowledge gaps related to long-term benefits and cost-effectiveness of screening. However, guidance from the AASLD, the EASL-EASO-EASD, and ADA do recommend healthcare professionals have a “high index of suspicion for NAFLD/NASH, particularly in patients with type 2 diabetes,” the cohort of patients at highest risk for significant (stage ≥ 2) hepatic fibrosis. They all call out patients with type 2 diabetes as warranting workup.

Risk Stratification
Risk-stratifying patients with NASH boils down to recognizing risk factors for advanced hepatic fibrosis. The strongest risk factors for NAFLD/NASH are the presence of type 2 diabetes, aged older than 50 years, and a first-degree family member with NASH or NASH-related cirrhosis. Other clinical predictors of NASH with hepatic fibrosis include the presence of ≥ 3 features of metabolic syndrome, elevated liver aminotransferases, dyslipidemia, polycystic ovary syndrome, or obstructive sleep apnea.

FIB-4 Index
One simple and cost-effective tool to assist with risk-stratification of NAFLD/NASH is the Fibrosis-4 (FIB-4) Index for Liver Fibrosis. The FIB-4 score is calculated using liver biochemistries, age, and platelet count, which are readily available from routine bloodwork.

FIB-4 has an excellent negative predictive value, allowing for confident exclusion of patients with a low likelihood of advanced hepatic fibrosis. Patients with a low FIB-4 score (< 1.3) can be followed in a primary care setting with repeat annual FIB-4 measures to assess change over time.

Coupling the FIB-4 score with transient elastography or magnetic resonance elastography, or performing these tests sequentially, can optimize performance of a noninvasive approach to risk stratification. A liver biopsy may be required if there is concern for competing diagnoses or discordant or indeterminate results from noninvasive biomarkers, but biopsy should be performed selectively owing to its increased cost and risk.

The broader utilization of noninvasive biomarkers, when coupled with ascertainment of clinical risk factors, will facilitate identifying those patients who require referral to a specialist for consideration of liver biopsy and tailored therapeutic approaches.

Your Thoughts?
Do you screen for NAFLD or NASH in your patients? Click on the button below to join the conversation and to claim credit.

StephenW

是什么推动了NASH？

  

Abdelmalek_Manal_100x100_Circle


Manal F.Abdelmalek，MD，MPH

非酒精性脂肪肝疾病（NAFLD）可以在少数患者中发展为晚期肝病，并已迅速成为美国和全球许多发达国家中最常见的慢性肝病。成年人中NAFLD的最新全球患病率估计约为25％。非酒精性脂肪性肝炎（NASH）（NAFLD的发展形式）的全球患病率估计为3％至5％。由于NAFLD与代谢综合征，肥胖症和糖尿病密切相关，因此这些患病率估计为糖尿病患者的近两倍。据估计，由于NASH导致的晚期肝纤维化成人患病率为1％至2％，这给公共健康带来了巨大的潜在负担。

早期识别
尽管NAFLD的患病率很高，但对这种无症状疾病的认识仍然很低。胃肠病学家和肝病学家故意诊断和分期NAFLD，而其他医疗保健专业人员通常会偶然发现NAFLD。当与晚期肝病相关的症状在临床上变得明显时（即增加不良结局风险的时间和治疗选择的时间），该疾病的无症状性，低意识和缺乏故意的诊断/分期结果导致被诊断和转诊的患者没有什么好处。在基层医疗机构中确定NAFLD有助于早期干预和预防策略，从而降低疾病进展的风险。

晚期肝纤维化
肝纤维化是不良临床预后的最强预测因子。尽管从轻度纤维化到中期纤维化的过渡可能需要很多年，并且疾病活动甚至可能起伏不定，但是在大约20％的患者中，从桥接纤维化（第3期）到肝硬化（第4期）的过渡可能会发生。最快2-3年。同样，约有20％的肝硬化患者可能在2-3年内发生与肝脏相关的不良临床事件。

需要常规检查吗？
NAFLD是代谢改变的生理问题的结果。代谢综合症与NAFLD以及癌症，心血管疾病，糖尿病，肥胖症和慢性肾脏疾病密切相关。尽管存在筛查代谢综合征其他并发症的指南，但由于诊断测试和治疗方案的不确定性以及与长期相关的知识鸿沟，AASLD目前不建议常规筛查NAFLD患者（即使是高危患者）筛查的好处和成本效益。但是，AASLD，EASL-EASO-EASD和ADA的指南确实建议医疗保健专业人员“对NAFLD / NASH高度怀疑，特别是在2型糖尿病患者中，” （≥2期）肝纤维化。他们都将2型糖尿病患者列为值得接受的检查。

风险分层
NASH的风险分层患者归结为认识到晚期肝纤维化的危险因素。 NAFLD / NASH的最强风险因素是年龄大于50岁的2型糖尿病的存在，以及NASH或NASH相关肝硬化的一级家庭成员。 NASH肝纤维化的其他临床预测指标包括代谢综合征，肝氨基转移酶升高，血脂异常，多囊卵巢综合征或阻塞性睡眠呼吸暂停≥3个特征。

FIB-4指数
协助NAFLD / NASH风险分层的一种简单且经济高效的工具是肝纤维化的Fibrosis-4（FIB-4）指数。 FIB-4分数是使用肝脏的生物化学，年龄和血小板计数计算得出的，这些数据可以从常规血液检查中轻易获得。

FIB-4具有极好的阴性预测值，可以可靠地排除晚期肝纤维化可能性低的患者。 FIB-4分数低（<1.3）的患者可以在基层医疗机构中进行随访，每年重复FIB-4措施以评估随时间的变化。

将FIB-4评分与瞬态弹性成像或磁共振弹性成像相结合，或者依次执行这些测试，可以优化无创方法对风险分层的性能。如果担心竞争性诊断或非侵入性生物标志物的结果不一致或不确定，则可能需要进行肝活检，但由于其成本和风险增加，因此应有选择地进行活检。

无创生物标志物的广泛使用，加上对临床危险因素的确定，将有助于确定那些需要转介专科医生以考虑肝活检和定制治疗方法的患者。

你的意见？
您是否在患者中筛查NAFLD或NASH？单击下面的按钮以加入对话并获得积分。