世界胃肠病学会全球指南:非酒精性脂肪性肝病及非酒精性脂肪性肝炎

<正>1介绍过去数十年中,非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)及非酒精性脂肪性肝炎(nonalcoholic steatohepatitis,NASH)是西方国家肝病的首要原因。在过去20年其他慢性肝病发病率保持稳定甚至下降的情况下,NAFLD的发病率却呈现翻番。最近的数据证明,NAFLD及NASH在中东、远东、非洲、加勒     

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非酒精性脂肪性肝病(NAFLD)是临床实践中肝功能异常最为常见的原因,肥胖症、2型糖尿病和代谢综合征是其常见原因。临床医生在处理NAFLD这一日益增多的"新的疾病"及其代谢并发症中的作用至关重要。文章主要谈谈中华肝病学会新版NAFLD的诊疗指南的重要性及相关问题。     

Long‐term prognosis of nonalcoholic fatty liver disease: Is pharmacological therapy actually necessary?

Background and Aim: Nonalcoholic fatty liver disease (NAFLD) comprises a wide spectrum of liver injury, ranging from steatosis and steatohepatitis to cirrhosis. Reasons for the different natural course in individuals with NAFLD are still unclear. The aim of this study was to describe the natural course of disease in individuals with NAFLD who did not receive pharmacological therapy. Methods: A total of 27 individuals with NAFLD (male/female ratio: 10/17, mean age 49.7 years) were prospectively enrolled. Management after diagnosis consisted of establishment of an appropriate diet and exercise (walking and jogging) program, treatment of associated metabolic conditions such as diabetes and dyslipidemia, and discontinuation of potentially hepatotoxic drugs if the patient was taking these. Liver tests were performed at diagnosis and at 3‐month intervals during the follow‐up period. Mean follow‐up period was 43.3 months (range 36–49 months). Results: From baseline to the end of the follow‐up period, although there was no significant difference observed in terms of the mean body mass index, serum aminotransferase levels significantly improved (48.8 ± 29.9 U/L to 31.6 ± 16.0 U/L for aspartate aminotransferase [AST] and 66.3 ± 38.3 U/L to 39.6 ± 22.9 U/L for alanine aminotransferase [ALT]; P < 0.05). No significant differences in platelet counts, serum albumin level or prothrombin time were observed (P > 0.05). No patient developed signs of advanced liver disease during the follow‐up period. Conclusion: A treatment strategy comprising diet, exercise and management of associated metabolic conditions is associated with improvement in aminotransferases among patients with NAFLD. Further investigation is needed to examine the long‐term efficacy of this approach on liver histology and clinical outcomes.     

Sampling variability of liver biopsy in nonalcoholic fatty liver disease

BACKGROUND & AIMS: In nonalcoholic fatty liver disease (NAFLD), the distinction between steatosis and steatohepatitis (NASH) and the assessment of the severity of the disease rely on liver histology alone. The aim of this study was to assess the sampling error of liver biopsy and its impact on the diagnosis and staging of NASH. METHODS: Fifty-one patients with NAFLD underwent percutaneous liver biopsy with 2 samples collected. The agreement between paired biopsy specimens was assessed by the percentage of discordant results and by the kappa reliability test. RESULTS: No features displayed high agreement; substantial agreement was only seen for steatosis grade; moderate agreement for hepatocyte ballooning and perisinusoidal fibrosis; fair agreement for Mallory bodies; acidophilic bodies and lobular inflammation displayed only slight agreement. Overall, the discordance rate for the presence of hepatocyte ballooning was 18%, and ballooning would have been missed in 24% of patients had only 1 biopsy been performed. The negative predictive value of a single biopsy for the diagnosis of NASH was at best 0.74. Discordance of 1 stage or more was 41%. Six of 17 patients with bridging fibrosis (35%) on 1 sample had only mild or no fibrosis on the other and therefore could have been under staged with only 1 biopsy. Intraobserver variability was systematically lower than sampling variability and therefore could not account for most of the sampling error. CONCLUSIONS: Histologic lesions of NASH are unevenly distributed throughout the liver parenchyma; therefore, sampling error of liver biopsy can result in substantial misdiagnosis and staging inaccuracies.     

Progression from Nonalcoholic Fatty Liver to Nonalcoholic Steatohepatitis Cirrhosis Confirmed by Liver Histology after 14 Years

A 44-year-old patient progressed from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) cirrhosis. She was diagnosed with NAFL via a liver biopsy. At 56 years old, she was diagnosed with NASH stage 3 via a second liver biopsy. One year later, she was diagnosed with NASH cirrhosis via a third liver biopsy. This is the first study to report the gradual deterioration of liver histology shown via three liver biopsies and fibrosis markers in a patient who progressed from NAFL to NASH cirrhosis. Following menopause, it is necessary to be aware of the rapid development of liver fibrosis.     

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近年来肥胖症的发病率显著增加。肥胖症与多种肝病相关,尤其是非酒精性脂肪性肝病(NAFLD),后者已成为中国和西方发达国家最常见的肝病。肥胖及其相关疾病成为公共健康的一个严重威胁。内脏脂肪组织(VAT)促使单纯性脂肪变性进展到非酒精性脂肪性肝炎(NASH)。此外,肥胖是肝硬化患者失代偿的一个独立危险因素,亦似乎是肝细胞肝癌的危险因素之一。甚至在急性肝衰竭时,高体重指数(BMI)意味着更差的预后,近来的研究提示肥胖在慢性乙型和丙型肝炎的进展中亦有一定作用,肥胖是慢性丙型肝炎抗病毒治疗应答不佳的预测因素之一。     

Nonalcoholic Fatty Liver Disease: A Clinical Review

Nonalcoholic fatty liver disease may be the most common liver disease in the United States, with a high prevalence in the obese, type 2 diabetic population, and it is probably underestimated as a cause for cirrhosis. Clinicopathologically, it represents a wide spectrum of histologic abnormalities and clinical outcomes, ranging from benign hepatic steatosis to cirrhosis. Pathophysiologically, insulin resistance is thought to be pivotal in the development of steatosis, after which a second oxidative stressor produces lipid peroxidation and nonalcoholic steatohepatitis (NASH). Liver biopsy is the gold standard for diagnosis and prognosis. The need for an effective treatment is both clear and urgent, yet in the absence of proven therapies, treatment is directed toward weight loss and comorbidity management. For patients with NAFLD at risk of disease progression, there is a lack of large, randomized, placebo-controlled trials of adequate treatment duration, with baseline stratification according to histologic severity.     

Non-invasive diagnosis of nonalcoholic fatty liver and nonalcoholic steatohepatitis

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the USA and many other parts of the world. Its prevalence continues to rise; currently affecting about one in four adults and 10% of children in the USA. NAFLD represents a wide spectrum of conditions ranging from fatty liver, which in general follows a benign, no-progressive clinical course, to nonalcoholic steatohepatitis (NASH), a more serious form of NAFLD that may progress to cirrhosis and end-stage liver disease. Currently, the diagnosis of NASH requires an invasive liver biopsy with drawbacks of sampling and interpretation error. Clinical risk factors for NASH include diabetes and the metabolic syndrome; however, these are not sufficiently predictive of the condition by themselves. Routine liver enzyme levels are not reliable; however, novel plasma hepatocyte cell death markers either alone or in combination with clinical risk factors are potential non-invasive diagnostic tools for the future. This review provides a concise overview of the role non-invasive diagnostic tools for the differentiation of fatty liver from NASH as well as for the determination of presence and extent of fibrosis.     

Leptin in the treatment of lipodystrophy-associated nonalcoholic fatty liver disease: are we there already?

Evaluation of: In general, nonalcoholic fatty liver disease (NAFLD) consists of ectopic fat accumulation in the liver, when the ability to store fat in inert reservoirs is overcome. That occurs either when we have an excess of energy/fat such as in obesity, or when adipose tissue is defective, not being able to store even regular amounts of energy, such as in lipodystrophies (LDs). LD associates with metabolic deregulation: insulin resistance/diabetes mellitus and dyslipidemia. Several small studies have shown a beneficial effect of leptin replacement, an adipocyte-derived hormone, in the metabolic profile of patients with LD. The paper under evaluation studied 50 patients with LD-associated NAFLD treated with leptin, suggesting a beneficial effect in liver histology and in decreasing not only steatosis, but also nonalcoholic steatohepatitis, although with no effect on fibrosis after 2 years of treatment.     

Symptoms of Obstructive Sleep Apnea in Patients with Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is a term often used to describe two related conditions: a relatively benign, nonalcoholic fatty liver (NAFL) and potentially aggressive, nonalcoholic steatohepatitis (NASH). Both conditions (NAFL and NASH) occur in the setting of peripheral insulin resistance. Recently, obstructive sleep apnea (OSA) has been proposed as an independent risk factor for insulin resistance. To date, few studies have documented the prevalence of OSA or symptoms of OSA (SOSA) in NAFLD patients. The objectives of this study were (1) to document the prevalence of SOSA in patients with NAFLD and (2) to determine whether prevalence rates for SOSA differ in NAFL versus NASH patients. One hundred ninety biochemically defined NAFLD patients (116 NAFL and 74 NASH), of whom 50 (18 NAFL and 32 NASH) had undergone liver biopsy, completed a Modified Berlin Sleep Apnea Questionnaire for SOSA. Risk factors for NAFLD were also documented in NAFL and NASH patients. Eighty-seven of the 190 (46%) NAFLD patients met questionnaire criteria for SOSA. The prevalence of SOSA was similar in both biochemically (45% versus 49%, respectively; P= 0.66) and histologically (39% versus 63%, respectively; P= 0.11) defined NAFL and NASH patients. Other risk factors for NAFLD such as body mass index, plasma cholesterol and triglyceride levels, and prevalence of diabetes were also similar in the two groups. Approximately one-half of NAFLD patients, whether NAFL or NASH, have SOSA. Further studies are required to determine whether a causal link exists between NAFLD and OSA.     

护肝宁片治疗非酒精性脂肪肝疗效观察

[目的]观察护肝宁片治疗非酒精性脂肪肝(NASH)的疗效.[方法]将165例NASH患者随机分为治疗组(110例)和对照组(55例),分别应用护肝宁片和硫普罗宁片治疗.观察两组患者治疗前及治疗6、12周时,肝功能及血脂指标的变化.[结果]两组患者治疗后的肝功能及血脂指标与治疗前比较均得到明显改善(P＜0.05);在治疗后6周及12周时,治疗组与对照组肝功能指标的比较差异无统计学意义(P＞0.05);治疗组治疗后12周时,三酰甘油(TG)降低,与对照组比较差异有统计学意义(P＜0.05).[结论]护肝宁片治疗NASH疗效明显,显著改善患者肝功能;且降低TG的疗效及安全性优于硫普罗宁片,值得临床上推广应用.     

Nonalcoholic fatty liver disease and steatohepatitis in people living with HIV

ABSTRACT

Introduction: The burden of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) is increasing worldwide. This phenomenon poses a potentially dangerous risk of rise in mortalities caused by cirrhosis and liver cancer. Owing to a complex combination of factors, NAFLD and NASH arise in a majority of people living with HIV (PLWH), but accurate estimates of prevalence differ, depending on sample selection, type of analysis, and data interpretation. The wide range of diagnostic tools used to assess liver steatosis and lack of control groups in many studies further contributes to current difficulties in properly assessing prevalence of these conditions.

Areas covered: Thoroughly scrutinizing the current literature, we compared the prevalence of NAFLD and NASH in PLWH to rates found in the general population. We highlighted strengths and limitations of the studies, in order to determine the effective impact of these medical conditions in PLWH.

Expert opinion: The prevalence and progression of NAFLD in human immunodeficiency virus (HIV) infection are reported to be widely variable. HIV infection itself and antiretroviral treatment have been demonstrated to play a role in the development of NAFLD. Larger and more effective studies are needed to evaluate the effects of NASH in PLWH and its progression.     

Liver steatosis,but not fibrosis,is associated with insulin resistance in nonalcoholic fatty liver disease

Background To address the hypothesis that liver steatosis causes systemic insulin resistance, we sought to determine the liver histological feature that most strongly contributes to insulin resistance in patients with nonalcoholic fatty liver disease (NAFLD). Methods Liver biopsy specimens were obtained from 131 patients with clinically suspected NAFLD. The stage, grade of nonalcoholic steatohepatitis (NASH), and level of steatosis were scored and analyzed in relation to the homeostasis model assessment of insulin resistance (HOMA-IR) and the metabolic clearance rate (MCR), measured using the glucose clamp method. Results In the univariate analysis, the degree of hepatic steatosis (r = 0.458, P < 0.001), stage (r = 0.360, P < 0.001), and grade (r = 0.349, P < 0.01) of NASH were significantly correlated with the HOMA-IR. Multiple regression analysis adjusting for age, sex, body mass index, and each histological score showed that steatosis was significantly and independently associated with HOMA-IR (coefficient = 1.42, P < 0.001), but not with the stage (coefficient = 0.33, P = 0.307) or grade (coefficient = 0.67, P = 0.134) of NASH. Similar independent relationships were observed between steatosis and MCR, but the relationship was weaker (coefficient = −0.98, P = 0.076). Conclusions Steatosis of the liver, but not the stage or the grade of NASH, is associated with insulin resistance in patients with NAFLD.