Review article: Non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease is a clinicopathological condition that comprises a wide spectrum of liver damage, ranging from simple steatosis to steatohepatitis, advanced fibrosis and cirrhosis. Non-alcoholic steatohepatitis represents only a stage within the spectrum of non-alcoholic fatty liver disease and is defined pathologically by the presence of steatosis together with necro-inflammatory activity. The true prevalence of non-alcoholic fatty liver disease is unknown, but it is estimated that it affects 10-24% of the general population in different countries. The diagnosis of non-alcoholic fatty liver disease is based upon convincing evidence of absent or minimal alcohol consumption, compatible histological changes in liver biopsy and the exclusion of other liver diseases. The natural history of non-alcoholic fatty liver disease remains to be defined. Patients with pure steatosis on liver biopsy follow a relatively benign course, whereas patients with histological necro-inflammatory changes and/or fibrosis may progress to end-stage liver disease. An initial step in the treatment of non-alcoholic fatty liver disease is the management of associated conditions, such as obesity, diabetes mellitus and hyperlipidaemia. Non-alcoholic fatty liver disease patients with steatohepatitis and/or fibrosis on liver biopsy may benefit from investigational pharmacological therapy. Patients with decompensated cirrhosis from non-alcoholic fatty liver disease may be candidates for liver transplantation.     

Review article: Drug therapy for non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease represents a spectrum of liver diseases, characterized mainly by macrovesicular steatosis in the absence of significant alcohol ingestion. Non-alcoholic fatty liver disease includes both non-alcoholic fatty liver and non-alcoholic steatohepatitis. Non-alcoholic steatohepatitis once considered a benign process is now known to lead to progressive fibrosis and cirrhosis. Histologically indistinguishable from alcoholic liver disease, the exact aetiology of non-alcoholic fatty liver disease remains unknown, but the fundamental pathophysiological process appears to be insulin resistance and oxidative stress related to the metabolic syndrome. Therapy has focused on risk factors, weight reduction and pharmacological intervention. Promising pharmacological treatments have been demonstrated with antioxidants, insulin sensitizers, hepatoprotectants and lipid-lowering agents. However, without larger randomized studies, no pharmacological treatments can be recommended at this time.     

Review article: diagnosis and treatment of non-alcoholic fatty liver disease

Background  Non-alcoholic fatty liver disease (NAFLD) is an increasingly prevalent condition affecting adults and children, leading to significant morbidity. It is often associated with the metabolic syndrome, although multiple pathogenetic mechanisms have been suggested. In the coming decades, it promises to be the leading cause of liver disease in industrial countries.
Aim  To provide a comprehensive, updated review of diagnosis and management of NAFLD and to appraise the evolution of new modalities in these areas.
Methods  An Ovid MEDLINE search was performed to identify pertinent original research and review articles. Selected references in these articles were also evaluated.
Results  The diagnosis of hepatic steatosis and steatohepatitis or non-alcoholic steatohepatitis (NASH) is not yet possible without liver biopsy. This is impractical given the large numbers affected by the condition. Current therapy has focused on improving insulin resistance and mediators of inflammation, factors probably associated with disease progression.
Conclusions  There are no proven non-invasive diagnostic modalities to distinguish NAFLD and NASH, but new biomarker panels are approximating the liver biopsy in accuracy. Therapeutic targets of drug development are in early stages, but a multifaceted approach will probably yield several treatment options in the years to come.     

Review article: hepatitis vaccination in patients with chronic liver disease

Evidence regarding the outcomes of viral super-infection in patients with chronic liver disease and practical strategies for hepatitis A and B vaccination of these individuals are reviewed. Patients with acute hepatitis A and chronic hepatitis B have a more severe clinical course and a higher death rate compared with otherwise healthy individuals with hepatitis A, and these differences are most pronounced in older patients and those with histological evidence of chronic hepatitis or cirrhosis, rather than in asymptomatic hepatitis B carriers. Patients with acute hepatitis A super-infection and chronic hepatitis C have an increased risk of fulminant hepatitis and death. In addition, patients with other chronic liver diseases also appear to be at increased risk for more severe disease with superimposed hepatitis A. Patients with chronic hepatitis B and hepatitis C virus co-infection have more severe laboratory abnormalities, more severe histological disease, a greater frequency of cirrhosis and complications of cirrhosis, and a higher incidence of hepatocellular carcinoma. Vaccines for both hepatitis A and B are safe and effective if used early in the course of chronic liver disease. Hepatitis A and B vaccination should be part of the routine management of patients with chronic liver disease, preferably as early as possible in the natural course of their disease.     

GI epidemiology: nonalcoholic fatty liver disease

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a common diagnosis in clinical practice. Insulin resistance and oxidative stress play an important role in NAFLD development and progression. AIM: To review the data available on the epidemiology and natural history of NAFLD as well as the risk factors for its development and the areas where future research is necessary. RESULTS /CONCLUSIONS: NAFLD may affect individuals of any age range and race/ethnicity. NAFLD affects one in three adults and one in ten children/adolescents in the United States. Mortality in patients with NAFLD is significantly higher than in the general population of same age and gender with liver-related complications being a common cause of death. Liver-related morbidity and mortality in NAFLD occurs when the disease has progressed to advanced fibrosis and cirrhosis. Further studies are necessary to determine the impact of NAFLD on health-related quality of life and resources utilization, and to the extent to which preventing the development of the metabolic syndrome would prevent NAFLD development and reduce liver-related morbidity and mortality. Lifestyle intervention may improve NAFLD, but medications that increase insulin sensitivity and the antioxidant defenses in the liver deserve evaluation in carefully controlled trials.     

脂肪细胞因子与非酒精性脂肪肝病

非酒精性脂肪肝病是发病率仅次于病毒性肝炎的常见肝病,是隐原性肝硬化的主要危险因素之一。多种脂肪细胞因子参与了脂肪肝的病理过程。本文就脂联素、瘦素、抵抗素、内脏脂肪素、Apelin、肠凝集素、网膜素等7种脂肪细胞因子与非酒精性脂肪肝的关系研究进展作一综述。     

Review article: hepatitis B and liver transplantation

Liver transplantation is an excellent treatment for hepatitis B virus infected patients who have acute or chronic liver failure and/or primary liver cancer. Advances in antiviral prophylaxis prevent clinically significant graft re-infection for the majority of patients. Graft and patient survival has improved significantly during the past decade, and results of transplantation for hepatitis B virus are now superior to those achieved for most other indications. In particular, the availability of lamivudine and adefovir have transformed outcome. The addition of lamivudine to passive immunoprophylaxis with hepatitis B virus immunoglobulin prevents re-infection in most cases. Adefovir should be added to this combination when the patient develops lamivudine resistance before transplantation. The significance of serum hepatitis B virus DNA positivity in the absence of circulating hepatitis B surface antigen is uncertain. Hepatitis B virus infection of the graft can be observed when prophylaxis is inadequate, when the donor liver contains latent hepatitis B virus infection (so-called de novo infection from the hepatitis B virus core antibody positive donor), and when the donor is exposed to third party infection (sexual or nosocomial transmission). Established hepatitis B virus graft infection is a good indication for combination nucleoside analogue therapy. Combination therapy can achieve sustained suppression of viral replication, and hepatitis B e antigen and hepatitis B surface antigen clearance can also be observed.     

Review article: current management of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis

Background  Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome.
Aim  To assess the epidemiological impact and the current management of patients with NAFLD.
Methods  Published peer-reviewed literature and abstracts concerning NAFLD and non-alcoholic steatohepatitis (NASH) were reviewed. Articles specifically related to epidemiology, diagnosis and current treatment strategies for NAFLD and NASH are summarized.
Results  NAFLD is strongly associated with the epidemic of obesity and type-2 diabetes mellitus, and is estimated to affect about 20–30% of the population in the US. From the spectrum of NAFLD, only patients with biopsy-proven NASH (estimated prevalence in the US population is about 3–5%) have been convincingly shown to progress to cirrhosis, liver failure and hepatocellular carcinoma. The clinical manifestation of NAFLD is usually absent or subtle, with abnormal aminotransferases or incidental radiographic findings of fatty liver. The pathogenesis of NAFLD is attributed to a multi-hit process involving insulin resistance, oxidative stress, apoptotic pathways, and adipocytokines. In 2008, there is no established treatment for NAFLD. Weight loss and treatment for each component of metabolic syndrome. Nevertheless, a large number of agents are being considered in clinical trials of patients with NASH.
Conclusions  Awareness of the tremendous impact of NAFLD as an important cause of chronic liver disease is increasing along with a great deal of information about its pathogenesis. Future, well-designed clinical trials that target specific pathways involved in the pathogenesis of NASH are urgently needed.     

非酒精性脂肪性肝病的药物治疗

<正>由于缺少有组织学终点以及远期并发症和死亡转归的随机对照研究,药物对非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)的治疗效     

天然免疫与非酒精性脂肪肝病

肝脏中大量的巨噬细胞、自然杀伤细胞(natural killer,NK)、自然杀伤T细胞(natural killer T cell,NKT)等构成了天然免疫系统.这一系统细胞功能紊乱,发生Th-1极化,使促炎症因子产生增多,促进了非酒精性脂肪性肝炎(nonalcoholic steatohepatitis,NASH)的形成;肝脏持续的暴露于这些炎症因子,可以促进多种促纤维化因子产生,但Th-2细胞因子分泌的不足, 使NASH进一步发展为肝硬化的现象却相对比较少见.本文就肝脏天然免疫系统在非酒精性脂肪肝病(nonalcoholic fatty liver disease, NAFLD)中的调节机制作一综述.     

Review article: the treatment of hepatitis C virus recurrence after liver transplantation

BACKGROUND: Recurrent hepatitis C represents a major challenge for the liver transplant community. Given the potentially significant impact that hepatitis C recurrence has on graft and patient survival, several treatment strategies have been utilized to prevent/slow the progression to hepatitis C-related graft failure. AIM: To review the efficacy and applicability of treatment strategies for managing recurrent hepatitis C. METHODS: Search of MEDLINE (1990 to December 2006) and national meeting abstracts. Search terms included hepatitis C, liver transplantation, treatment, sustained virological response (SVR), and end of treatment virological response. An emphasis was placed on randomized trials. RESULTS: The largest study of treatment prior to liver transplantation (n = 124) achieved SVR in 24%. Eight randomized trials (n = 383) examined the efficacy of preemptive therapy with SVR ranging from 0-33%. Eligibility for treatment was low and dose reduction common. Four randomized trials (n = 245; all abstracts) have reported SVR from 33-42% for treating those with histological evidence of recurrent disease. CONCLUSIONS: Therapies for treating hepatitis C recurrence have limited applicability and tolerability, and they have a low SVR. Based on available results, preemptive therapy is not recommended. Pegylated interferon and ribavirin is currently the preferred choice for treating established recurrence. There is an urgent need for safer and more effective anti-viral therapy in this situation.