Alcohol and the liver

Since ethanol metabolism predominantly takes place in the liver it is not surprising that hepatic intermediary metabolism is strikingly influenced. Alcohol is metabolized via three enzyme systems: alcohol dehydrogenase (ADH), microsome ethanol oxidizing system (MEOS) and catalase. The ADH reaction produces reducing equivalents as NADH which results in various metabolic disorders such as hyperproteinemia IV and V, hypoglycaemia, lactacidosis, hyperuricaemia, and certain forms of porphyria. The metabolism of hormones is also disturbed. Alcohol fatty liver is a direct consequence of NADH production. Alcoholic liver disease comprises of fatty liver, alcoholic hepatitis and cirrhosis. Risk factors of alcoholic liver disease are the amount of alcohol consumed, drinking pattern, female gender and certain genetic predispositions. Alcoholic hepatitis is characterized by a typical clinical and laboratory feature, and specific heaptic morphology. Poor prognostic factors are continuous alcohol consumption, cholestatis and perivenular fibrosis. Alcoholic cirrhosis has similar complications as cirrhosis of other etiology. Therapy includes abstinence, antioxidative drugs, steroids, and S-adenosylmethionine. Liver transplantation is of long-term benefit.     

Alcoholic Liver Disease

Alcoholic liver disease consists of well defined entities. Fatty liver is the commonest hepatic abnormality in alcoholics and in most cases it is reversible. Possibly a sustained fatty liver occasionally may induce fibrosis. Alcoholic hepatitis or subclinical necrosis may also proceed to hepatic fibrosis. The latter can regress if no further injury occurs or it may develop into frank cirrhosis in case of continuing liver injury. A general model of alcoholic liver disease is presented.     

Recent developments in the treatment of alcoholic hepatitis

Alcoholic hepatitis is a form of acute injury to liver tissue that is also a precursor of cirrhosis, and carries significant morbidity and mortality. Severe alcoholic hepatitis in particular carries a high short-term mortality, and also places an enormous burden on stretched healthcare resources. Treatment of alcoholic hepatitis has been limited to supportive management and nutritional supplementation without clear improvements in outcome, and the timing and patient selection for hepatic transplantation is problematic. The use of corticosteroids has remained controversial for many years, but probably has a role in selected patients. Various other therapeutic strategies have been tested over the decades and none has shown any consistent benefit. Recently there have been major developments in our understanding of the mechanisms of alcoholic liver injury, including the role of cytokines and hepatocyte apoptosis. For the first time, there are exciting possibilities for specific therapies for this challenging and serious condition.     

1-14C]Ethanol breath test in alcoholic liver disease

The activity of ethanol metabolising enzymes was assessed in 51 patients with alcoholic and non-alcoholic liver disease using tracer doses of [1-14C]ethanol and measuring 14CO2 excretion in the breath. Alcoholic patients with only fatty infiltration of the liver showed significantly increased activity compared with controls. Comparing alcoholic patients with cirrhosis and a serum albumin greater than 28 g/l, activity in those with a recent history of continued heavy drinking was significantly greater than in patients who had abstained from alcohol. In addition, both groups of alcoholic cirrhosis showed significantly more activity than patients with non-alcoholic cirrhosis. The activities of patients with acute alcoholic or viral hepatitis were normal when their prothrombin times were less than 7 sec prolonged, but were reduced when prolongation exceeded 7 sec. These results demonstrate that in chronic alcoholic liver disease, even with cirrhosis, alcohol can still increase the activity of ethanol oxidising enzymes provided hepatic function remains adequate. However, this response is lost in acute liver damage and in chronic alcoholic disease with severe hepatic dysfunction.     

Liver disease of the alcoholic.

Significant liver disease including fatty metamorphosis, alcoholic hepatitis, cirrhosis, and hepatoma occur in two thirds of subjects who consume alcoholic beverages in sufficient quantities to interfere with work and social responsibilities; this is of major importance in the rapidly escalating morbidity and mortality from alcoholism. Chronic alcoholics should be routinely evaluated for the presence of altered liver function and structure. Clearance of indocyanine green using dichromatic ear densitometry and computer and analysis provides a simple and sensitive method for mass screening of such patients. Clinical studies of lymphocyte reactivity to purified alcoholic hyaline may be valuable in recognizing alcoholic hepatitis, the precursor of cirrhosis. Ethanol toxicity, malnutrition and constitutional factors contribute to the development of hepatic fibrosis and cirrhosis in alcoholics. Ethanol and/or acetaldehyde and the supernatant from lymphocytes stimulated by alcoholic hyaline cause a significant increase in the incorporation of proline into collagen of the damaged liver. Abstinence and correction of nutrient deficits are the cornerstones of treatment for alcoholic liver disease; a daily meal and dietary supplements should be provided for those with liver injury who continue to imbibe. Alcoholics with progressive liver disease despite supportive therapy may be aided by pharmacologic agents which suppress immunologic response and reduce fibrogenesis.     

大庆地区994例肝硬化患者临床流行病学分析

目的通过分析2000—2005年大庆地区综合医院消化内科肝硬化病人的病例资料，找出肝硬化的常见病因、并发症和病死率，为进一步防治肝硬化提供依据。方法采用回顾性调查方法，对大庆地区三家医院消化科2000—2005年6年间住院确诊为肝硬化的994例病历资料进行分析。结果本组患者男：女为3．01：1；发病年龄24—83岁，41-70岁为高发年龄段；6年来大庆地区肝硬化的发病构成比无明显变化。病因以病毒性肝炎最多见，占74．45％，其中与乙型肝炎相关肝硬化占70．32％；洒精性肝炎为第二位，占21．93％；病毒性肝炎和／或酒精性肝炎发生的肝硬化占肝硬化发病率的96．38％。肝硬化患者就诊的主要原因是发生腹水（30．58％）和上消化道出血（39．03％）。肝硬化最常见的并发症是上消化道出血（42．96％）。最常见的死亡原因是上消化道出血（47．55％）。结论病毒性肝炎和酒精性肝炎是大庆地区肝硬化的主要病因，防治病毒性肝炎，减低饮酒量是预防肝硬化的重要手段。积极防治肝硬化并发症是提高患者生活质量，延长患者生命最重要的环节。     

Alcoholic liver disease

Alcoholic liver disease presents a wide spectrum of clinical manifestations ranging from mild asymptomatic fatty liver to alcoholic hepatitis and severe life-threatening liver failure with ascites, hemorrhaging esophageal varices, and encephalopathy. Although still poorly understood, the mechanism of this injury is probably the result of numerous direct toxic and metabolic effects of alcohol on the hepatocyte. Therapy consists primarily of abstinence and supportive care. However, several newer treatments are actively being studied. These include prednisolone, anabolic steroids, glucagon and insulin, propylthiouracil, and cyanidanol. Colchicine is promising as an agent to inhibit fibrosis. Complications of cirrhosis, including ascites and variceal hemorrhage, are the result of end stage disease. A return to old techniques of ascitic fluid management suggests that therapeutic large-volume paracentesis with albumin infusion is a safe and effective form of therapy. Variceal hemorrhage is best treated with sclerotherapy, vasoconstrictors, and balloon tamponade. Little has been done to alter the ultimately dismal prognosis and long-term survival of alcoholic liver disease.     

Natural History of Alcoholic Hepatitis. IV. GLYCOSAMINOGLYCURONANS AND COLLAGEN IN THE HEPATIC CONNECTIVE TISSUE

The extractable and nonextractable collagen and glycosaminoglycuronans (GAG) were estimated and characterized in 32 dried, defatted human livers obtained at necropsy. 10 had normal livers. 22 of the 32 livers were from patients who drank in excess: 5 had fatty livers, 7 had alcholic hepatitis, and 10 had cirrhosis. Livers with alcoholic hepatitis or cirrhosis had significantly increased total and 1 N NaCl-extractable collagen. Only alcoholic hepatitis livers had significantly increased Tris-buffer-extractable GAG, but the amino acid composition of these GAG (proteoglycans) was no different from that of normal livers. The major fraction of these GAG had isoelectric pH (pI) 相似文献   

Care of chronic liver disease

Regardless of etiology, chronic liver disease generally involves a process of progressive destruction and regeneration of the liver parenchyma, leading to fibrosis and cirrhosis. At an early stage, most patients are asymptomatic and can easily go undiagnosed and untreated. Primary care physicians can often make the diagnosis but may offer little treatment. Better understanding about treatment is the key for primary care providers to provide better care for this group of patients. This review focuses on the treatment of the most common causes of chronic liver disease, including hepatitis B, hepatitis C, alcoholic cirrhosis, nonalcoholic fatty liver disease, and hemochromatosis.     

Acute,Withdrawal, and Chronic Alcohol Effects in Man: Event-Related Potential and Quantitative EEG Techniques

The association of metabolic disorders with liver disease is receiving increasing attention in the gastroenterological community. Cohort studies have shown that advanced liver disease may stem from metabolic disorders, via fatty liver, non‐alcoholic steatohepatitis, cryptogenic cirrhosis, and eventually hepatocellular carcinoma. In both obesity and diabetes, deaths from cirrhosis are higher than expected, mainly in subjects with no or moderate alcohol consumption, but high rates of fatty liver disease have been associated with all features of the metabolic syndrome. Also the risk of hepatocellular carcinoma is higher than normal, being dependent on body mass index (BMI) in obesity, and independent of age, BMI, gender and race in diabetes. Finally, metabolic liver disease may interact with hepatitis C virus infection, increasing the risk of steatosis and liver disease progression, as well as reducing the chances of an effective antiviral treatment. There is evidence that treatments aimed at reducing insulin resistance are also effective in improving liver histology. Although cardiovascular disease remains the major cause of increased morbidity and excess mortality in metabolic disorders, the risk of progressive liver disease should no longer be underestimated, being a threat to millions of people at risk in the present epidemics of obesity and diabetes, and therapeutic strategies need to be tested.     

Autoantibodies, sheep cell agglutinins and anti-albumin antibodies in alcoholic liver disease

The frequency of serum autoantibodies including anti-albumin antibodies was investigated for patients with various categories of alcoholic liver disease (ALD). The 95 patients were grouped into 3 categories: fatty liver (25 cases), alcoholic hepatitis (29 cases), and alcoholic cirrhosis (41 cases), and each group was matched with healthy controls by age, sex, ethnic origin and socio-economic status. For all patients with ALD, there was a 5-fold greater frequency over the controls of positive tests for antinuclear antibody (ANA), but titres were low; the pattern of ANA reactions was speckled in 50% of the cases. For patients with alcoholic cirrhosis, there was an 8-fold increase in frequency over the controls in anti-smooth muscle antibody (ASMA), but titres were low, pointing to a possibility that autoimmunity might be one of several determinants of progression of alcoholic hepatitis to cirrhosis. For none of the groups was there an increase over the controls in the mean titre of sheep red cell agglutinins, nor were there increased haemagglutinin titres of antibody to bovine serum albumin or to human albumin, arguing against a general increase in antibody production in ALD. Greater knowledge of the frequency, significance and pathogenicity of reactive autoantibodies which occur in response to various types of tissue damage is required for interpretation of the increase in ANA and ASMA in alcoholic liver disease.     

Alcoholic hepatitis

Alcoholic liver disease is a major cause of illness and death in the United States. The primary care physician can actively participate not only in the recognition and treatment of the clinical symptoms but also in the rehabilitative program for the alcoholic.     

Optimal duration of therapy in HBV-related cirrhosis

It is estimated that one-third of the world's population has been exposed to hepatitis B virus and that 300-400 million people have chronic hepatitis B. In areas of the world where hepatitis B infection is endemic, this chronic viral infection is a major cause of premature morbidity and mortality related to hepatocellular carcinoma (HCC) and complications of end-stage liver disease. Recent data from population-based studies suggest that the level of viral replication in chronic hepatitis B is an independent predictor of the future complications of the disease; patients with hepatitis B viral DNA titres >10(4) copies/mL (especially those with titres >10(5) copies) have a significantly greater risk of developing HCC and cirrhosis. There is also recent evidence that treatment with antiviral therapy in patients with chronic hepatitis B who have advanced hepatic fibrosis is associated with a reduction in the risk of decompensation of liver disease and HCC. Several new antiviral medications have been recently approved for the treatment of chronic hepatitis B. Several recent position statements and practice guidelines have recommended treatment of patients with chronic hepatitis B with oral antiviral medications. However, there remains some disagreement as to the threshold of viral load before treatment should be initiated and the optimal duration of therapy in patients with cirrhosis due to hepatitis B. This article describes the current recommendations regarding therapy in this group of patients and suggests some criteria for treatment of patients with chronic hepatitis B-related cirrhosis or advanced hepatic fibrosis.     

高原藏族酒精性肝病的临床病理和电镜观察

探讨酒精性肝病（ＡＬＤ）的超微结构特点及其与肝功能损害程度的关系。方法对２０例高原藏族ＡＬＤ患者行肝穿活检组织病理学观察。结果性脂肪肝（ＡＦＬ）、酒精性肝炎（ＡＨ）、酒精性肝硬化（ＡＬＣ）常相继发生或同时存在,主要表现为肝细胞大泡性脂变,窦周纤维化,肝细胞滑面内质网增生,小叶内灶状坏死伴中性粒细胞浸润。     

Alcoholic liver disease

Aggressive management to prevent alcoholic cirrhosis should include the use of biopsy results to diagnose and to monitor alcoholic liver disease. Guidelines for the interpretation of the liver biopsy are highlighted. The diagnosis, course, and treatment of alcoholic hepatitis and cirrhosis are presented in detail.     

酒精性肝病患者健康相关生存质量研究

目的研究酒精性肝病患者健康相关生存质量及其与疾病严重程度的关系以及对比酒精性肝病与慢性乙型肝炎患者健康相关生存质量的差别。方法 2010年12月至2011年10月收治的70例男性酒精性肝病患者(非肝硬化组45例,肝硬化组25例),56例男性慢性乙型肝炎患者(非肝硬化组24例,肝硬化组32例)以及42例男性健康对照组受试者参与试验。所有受试者回答SF-36V2(中文版)量表,通过SF-36V2软件计算出:生理功能、生理职能、躯体疼痛、总体健康、活力、社会功能、情感职能、精神健康共8个维度,以及躯体健康总评和精神健康总评。使用协方差分析对比健康对照组,酒精性肝病非肝硬化组,以及酒精性肝病肝硬化组健康相关生存质量;对比酒精性肝病与慢性乙型肝炎患者健康相关生存质量。结果和健康对照组相比,酒精性肝病患者随着疾病的加重,SF-36V2各维度评分明显降低(P<0.05)。酒精性肝病非肝硬化组患者较慢性乙型肝炎非肝硬化组患者仅生理功能、生理职能、活力、躯体健康总评四项评分轻度受损(P<0.05)。酒精性肝病肝硬化组与慢性乙型肝炎肝硬化组患者SF-36V2各维度评分相似(P>0.05)。结论酒精性肝病患者健康相关生存质量降低,且病情越重,健康相关生存质量越差。酒精性肝病患者健康相关生存质量与慢性乙型肝炎患者相似。     

Alcoholic liver disease in Scotland and northeastern England: presenting features in 510 patients

A study of 510 patients in Scotland and northeastern England with histological evidence of alcohol-induced liver disease showed no difference in the age of presentation between males and females. Single men and widowed females were particularly susceptible to alcoholic liver disease. The social class distribution was similar to the population in general. Women were more reluctant to volunteer a history of alcoholism than men, they had a higher incidence of previous psychiatric illness (usually due to alcohol abuse) and they developed liver disease at lower consumption thresholds of alcohol than men. Patients under 40 years of age were more likely to have alcoholic fatty liver and less likely to have active cirrhosis than those over 40. Most often, the presenting symptoms were non-specific and tended to be related to the gastrointestinal system, particularly in women. Five per cent of patients were asymptomatic and 14% came to hospital for conditions other than alcoholic liver disease. Important clues to asymptomatic alcoholic liver disease included hepatomegaly, clubbing of the fingers and abnormal liver function tests. Gastro-oesophageal varices accounted for 40% of instances of haemorrhage and the mortality from upper gastrointestinal bleeding was 17%. Anaemia was the most common haematological abnormality. Alcoholic hepatitis was observed more frequently in the Glasgow area then elsewhere.     

gamma-Glutamyl transpeptidase activity in liver disease: serum elevation is independent of hepatic GGTP activity

gamma-Glutamyl transpeptidase activity was measured in liver and serum from 110 patients undergoing diagnostic liver biopsy, including patients with alcoholic liver disease, fatty liver not due to alcohol, primary biliary cirrhosis, persistent hepatic disease, chronic active hepatitis and normal livers. Serum gamma-glutamyl transpeptidase was markedly elevated in patients with alcoholic liver disease and primary biliary cirrhosis while mean hepatic gamma-glutamyl transpeptidase activity was significantly increased only in the alcoholic liver disease group. There was considerable overlap of individual enzyme values among the different disease groups. There was no inhibitors or activators of liver gamma-glutamyl transpeptidase in any of these disorders. The increased liver activity was not related to the degree of hepatic fibrosis or cirrhosis. There was no correlation between hepatic and serum gamma-glutamyl transpeptidase activity. Hepatic and serum gamma activities were equally increased in individuals with alcoholic liver disease whether or not they were drinking at the time of the study. The data suggest that increased hepatic gamma-glutamyl transpeptidase activity is neither specific for alcoholic liver disease nor essential for serum GGTP to be elevated.     

Failure of interferon to prevent recurrent hepatitis B infection in hepatic allograft

Chronic liver disease associated with hepatitis B virus infection is both common and serious; no satisfactory treatment currently exists. Orthotopic liver transplantation is an option for patients with end-stage liver disease associated with hepatitis B virus infection despite the risk of allograft reinfection. Passive immunoprophylaxis has been attempted perioperatively to prevent graft infection but has not been beneficial. Some patients with chronic type B hepatitis have benefited clinically from antiviral therapy and, in particular, interferon, but its use has not previously been reported as an approach to prevent allograft infection. We administered recombinant leukocyte A interferon perioperatively to a patient who underwent liver transplantation for type B chronic active hepatitis and cirrhosis. Circulating hepatitis B virus DNA was found postoperatively while the patient was receiving interferon, and stainable viral antigen subsequently reappeared in the transplanted liver. Thus, the drug failed to prevent viral replication and allograft infection. Thus far, no evidence of progression of the chronic hepatitis has been noted.     

慢性肝病患者乙型 丙型 丁型肝炎病毒感染情况分析

目的为探讨慢性肝病患者乙型肝炎病毒(HBV)、丙型肝炎病毒(HCV)、丁型肝炎病毒(HDV)感染情况及其相互间的关系。方法采用酶联免疫吸附法对236例慢性肝病患者进行HBV、抗-HCV、抗-HDV的检测。并对慢性肝炎、重症肝炎、肝硬化、肝癌的感染率作一分析。结果单纯HBV的感染率为61.8%,远大于单纯HCV(8.5%)和HDV(0.4%)感染率。单纯HDV感染率很低,HBV和HDV重叠感染率较高为(12.3%),并且HBV和HDV重叠感染率按慢性肝炎、重症肝炎、肝硬化、肝癌呈顺序递增现象。肝癌组的HBV、HCV重叠感染率12.5%,与慢性肝炎组(4.9%)差异有统计学意义。结论 慢性肝病患者仍以感染HBV为主,HBV易与HCV、HDV发生重叠感染。重叠感染易使肝病加重。支持HDV要在感染HBV的基础上感染。