National Survey of Hepatocellular Carcinoma in Heavy Drinkers in Japan

Background: The major cause of hepatocellular carcinoma (HCC) in the general Japanese population is an infection related to hepatotropic viruses, especially hepatitis virus C (HCV). Even in heavy drinkers, the major cause of HCC is HCV infection. However, HCC without viral infection has been reported in heavy drinkers. Alcohol has been also reported to be associated with an increased risk of cancer. In this study, we investigated aspects of HCC pathogenesis in heavy drinkers in Japan.
Methods: Questionnaires were sent to 1350 hospitals authorized by the Japanese Society of Gastroenterology. The questionnaires asked about the number of inpatients with the different types of alcoholic liver diseases, admitted to each hospital between 1998 and 2001.
Results: The percentage of heavy drinkers among all admitted patients with liver diseases or liver cirrhosis was approximately 15%. Of the patients with alcoholic liver cirrhosis, the cirrhosis was derived from alcohol alone in 61% and from alcohol plus a virus in 39% of patients. Furthermore, the percentage of patients with alcoholic liver cirrhosis caused by alcohol alone and who did not have HCC was 80%. However, the percentage of HCC patients who tested negative for viral hepatitis serum markers was 27% of the total number of heavy drinkers admitted for HCC. A study mainly on liver cirrhosis performed in the early 1990s demonstrated that the alcohol-alone group accounted for 44% of admitted patients with alcoholic liver cirrhosis and 18% of heavy drinkers admitted for HCC.
Conclusions: Because the consumption of alcohol is increasing in Japan, the frequency and number of cases of alcoholic liver cirrhosis are increasing. Viral hepatitis infection, however, still plays an important role in hepatocarcinogenesis in heavy drinkers. Radiographical examination is recommended even in patients with alcoholic liver cirrhosis who test negative for serum markers of viral hepatitis.     

National survey of alcoholic liver disease in Japan (1968–91)

National surveys of alcoholic liver disease (ALD) in Japan were performed in 1978 and 1985 by a previous Japanese study group for ALD (the Takeuchi group). In the present study, a subsequent nationwide survey of ALD in Japan was conducted from 1986 to 1991 and the results compared with the previous studies. In order to clarify the aetiological relationship between hepatitis C virus (HCV) infection and ALD, results were also analysed according to new diagnostic criteria for ALD proposed by the current ALD study group (the Takada group). According to the diagnostic criteria of the Takeuchi group, the incidence of ALD did not differ significantly from 1986 to 1991. However, the incidence of hepatocellular carcinoma (HCC) in alcoholic cirrhosis (AL-LC) clearly increased during this period. The analysis, which included analysis of results from the previous studies, indicated that the incidence of ALD reached a plateau in 1980 and then stablized. However, HCC in AL-LC continued to show a linear increase from 1976 to 1991. The new diagnostic criteria of the Takada group were used to analyse cases from 1990 and 1991. Approximately two out of every three cases of ALD were caused by alcohol alone, and the remainder were caused by a combination of alcohol and HCV. Cases caused only by HCV were very rare. The main aetiology in patients with alcoholic hepatitis and fibrosis was alcohol alone, and in the case of chronic hepatitis, in heavy drinkers, it was a combination of alcohol and HCV. In half the patients with AL-LC the aetiology was alcohol alone, and in the other half it was a combination of both alcohol and HCV. In the majority of patients with HCC, the aetiology was a combination of alcohol and HCV, indicating that HCV infection may be important in the development of HCC in alcoholics.     

Outcomes after liver transplantation for combined alcohol and hepatitis C virus infection

Alcohol abuse and chronic hepatitis C virus(HCV)infection are two major causes of chronic liver disease in the United States.About 10%-15%of liver transplants performed in the United States are for patients with cirrhosis due to combined alcohol and HCV infection.Data on outcomes on graft and patient survival,HCV recurrence,and relapse of alcohol use comparing transplants in hepatitis C positive drinkers compared to alcohol abuse or hepatitis C alone are conflicting in the literature.Some studies report a slightly better overall outcome in patients who were transplanted for alcoholic cirrhosis vs those transplanted for HCV alone or for combined HCV and alcohol related cirrhosis.However,some other studies do not support these observations.However,most studies are limited to a retrospective design or small sample size.Larger prospective multicenter studies are needed to better define the outcomes in hepatitis C drinkers.     

Liver disease in heavy drinkers with and without alcohol withdrawal syndrome

BACKGROUND: Withdrawal syndrome is a hallmark of alcohol dependence. The characteristics of alcohol consumption, closely related to dependence, could influence the development of alcoholic liver disease. The study aimed to investigate if patients with severe alcohol withdrawal syndrome have a peculiar profile of liver disease. METHODS: The study included 256 heavy drinkers (aged 19-75 years, 70.3% males) admitted to an Internal Medicine Department. Patients admitted for complications of liver disease were not included. Severe alcohol withdrawal syndrome (seizures, disordered perceptions, or delirium) developed in 150 patients (58.6%). Alcohol consumption (daily quantity, duration, and pattern [regular or irregular]) was assessed by questionnaire. Liver biopsy was performed in all cases. RESULTS: Patients with alcohol withdrawal syndrome showed a lower prevalence of liver cirrhosis and a higher prevalence of alcoholic hepatitis than patients without it. The negative association of alcohol withdrawal syndrome with liver cirrhosis persisted after we adjusted for sex, daily intake, duration, and pattern of alcohol consumption. Alcoholic hepatitis was independently associated with the irregular pattern of alcohol consumption, which was closely associated with severe alcohol withdrawal syndrome. CONCLUSIONS: The profile of liver injury is different in heavy drinkers who develop and who do not develop a severe alcohol withdrawal syndrome when admitted to the hospital.     

Roles of Alcohol, Hepatitis Virus Infection, and Gender in the Development of Hepatocellular Carcinoma in Patients with Liver Cirrhosis

To assess the interaction of alcohol, hepatitis C virus (HCV), and hepatitis B virus (HBV) infection in hepatocarcinogenesis, we prospectively observed 449 patients with liver cirrhosis (LC) who presented to our outpatient clinics in 1 month; 164 patients with habitual drinking [alcoholic liver-liver cirrhosis (AL-LC)] who had taken ≥72 g alcohol/day (HCV-positive 81 cases: HCV + AL; HCV-negative 83 cases: AL); 176 patients with HCV infection, but without alcohol intake; 34 patients with HBV infection; 6 patients with HCV and HBV coinfection; and 82 patients with liver diseases from other etiologies, such as primary biliary cirrhosis. In the HCV group, the cumulative occurrence rate of hepatocellular carcinoma (HCC) was 9%, 18%, and 23% in the first, second, and third years, respectively. In the HCV + AL group, that was 13%, 17%, and 28%, respectively. There was no difference in the HCC occurrence rate between the two groups. In the AL group, the cumulative HCC occurrence rate was only 1% during the observation period of 3 years. The occurrence rate was significantly lower in the AL group, compared with the HCV and the HCV + AL groups. In the HBV group, the cumulative occurrence rate of HCC during the observation period of 3 years was 17%, which was similar to that of the HBV + AL group, 14%. We also examined some other variables that might be related to the development of HCC. The cumulative occurrence rate of HCC in male patients was 31%, whereas that was 18% in female patients. In the HCV group, there was a significant increase of HCC occurrence rate in male patients. In contrast, no difference was observed in the HCC occurrence rate between male and female patients in the HBV group. The present study suggests that alcohol alone may not be an independent risk factor for HCC, nor does it accelerate HCC development in LC patients with HCV and HBV infection during the prospective observation of 3 years.     

High prevalence of antibody to hepatitis C virus in heavy drinkers with chronic liver diseases in Japan

To investigate the prevalence of antibody to hepatitis C virus (anti-HCV) in heavy drinkers with liver disease in Japan, we tested serum samples from 113 heavy drinkers with liver disease and 121 without liver disease. All were negative for HBsAg with no history of blood transfusion. These subjects had consumed more than 80 g of ethanol daily for 5 years or more. Findings for anti-HCV determined by recombinant immunoblot assay testing were positive in 14 (35.9%) of the 39 patients with liver cirrhosis, 14 (58.3%) of the 24 patients with hepatocellular carcinoma and in 8 (53.3%) of the 15 patients with chronic hepatitis. The anti-HCV positive rate in the drinkers with these liver diseases was significantly higher than in those with such disorders as fatty liver (0/10), hepatic fibrosis (0/22), and alcoholic hepatitis (0/3), as well as in the alcoholics without liver disease (5/121, 4.2%). Considering histologic findings in the anti-HCV positive cirrhotics, the occurrence of lymph follicle formation (71.4%), piecemeal necrosis (78.6%) and loose fibrosis (64.3%) were observed to a significantly higher extent than in cirrhotics who were negative for anti-HCV. These findings suggest that advanced chronic liver disease among heavy drinkers in Japan, especially of hepatocellular carcinoma, is closely associated with HCV infection. In the livers of heavy drinkers who were positive for anti-HCV, histologic findings indicated the possibility of viral infection.     

Histological features after liver transplantation in alcoholic cirrhotics.

BACKGROUND/AIMS: Though alcoholic cirrhosis is a common indication for liver transplantation, it carries the risk of alcohol recidivism and consequent graft failure. This study aims to evaluate the effect of alcohol recidivism on survival rates and histological parameters in patients transplanted for alcoholic cirrhosis, with and without hepatitis C virus (HCV) infection. METHODS: Fifty-one out of 189 consecutive transplanted patients underwent psychosocial evaluation and liver biopsy at 6 and 12 months, then yearly after transplantation. RESULTS: The cumulative 84 month survival rate was identical in patients transplanted for alcoholic (51%) and non-alcoholic cirrhosis (52%). No difference emerged between anti-HCV negative vs. positive alcoholic cirrhosis patients. Psycho-social evaluation revealed alcohol recidivism in 11/34 long-term survivors, but this did not affect overall survival rate in patients with or without HCV. In anti-HCV negative cases, fatty changes and pericellular fibrosis were significantly more common in heavy drinkers than in occasional drinkers and abstainers. When HCV status was considered regardless of alcohol intake, fibrosis was significantly more frequent in patients with HCV. CONCLUSION: Alcohol recidivism after transplantation in alcoholic cirrhosis patients does not affect survival, irrespective of HCV status. Fatty changes and pericellular fibrosis are the most relevant histological signs of heavy alcohol intake.     

Effect of drinking on the outcome of cirrhosis in patients with hepatitis B or C

Survival rates were calculated for 251 patients with cirrhosis of the liver but without hepatocellular carcinoma, primary biliary cirrhosis, or autoimmune cirrhosis who underwent laparoscopy during the past 21 years at the authors' hospital. The survival rates were calculated by the Kaplan-Meier method. Stored serum was assayed for hepatitis B surface antigen (HBsAg) and antibodies to the hepatitis C virus (HCV). Patients with alcoholic cirrhosis had significantly better survival rates than patients with HBsAg, HCV, or both. Differences in survival rates between patients with hepatitis B and C were insignificant. In both groups, habitual drinkers had a significantly lower survival rate. The results suggested that alcohol accelerates liver damage in subjects with viral hepatitis.     

Contribution of Hepatitis C Virus to the Progression of Alcoholic Liver Disease

Background: We determined hepatitis C virus (HCV) antibody, HCV RNA, and genotype in patients with alcoholic liver disease and studied the involvement of HCV in alcoholic liver disease. Additionally, we used the histological activity index (HAI) to study the influence of HCV on the severity of inflammation. Methods: The subjects were 143 patients with alcoholic liver disease: 7 with fatty liver (FL), 18 with hepatic fibrosis (HF), 24 with alcoholic hepatitis (ALH), 39 with chronic hepatitis (CH), 42 with liver cirrhosis (LC), and 13 with hepatocellular carcinoma (HCC). The HCV RNA positivity rate in each type of disease was 0/7 (0%), 1/18 (6%), 2/24 (8%), 27/39 (69%), 24/42 (57%), and 7/13 (54%), respectively. It was high in the advanced hepatic lesions. Results: Clinically, the serum hepatic function tests after abstinence from drinking improved significantly in the HCV RNA negative patients compared with the positive patients. The proportion of genotype II in each type of disease was 0/0, 0/1 (0%), 1/2 (50%), 18/27 (67%), 18/24 (75%), and 7/7 (100%), respectively. It became high with the advance of pathophysiology. The HCV RNA amount stood at 7.5 ± 0.4 [log (copies/ml)] in CH, 7.9 ± 0.4 in LC, and 8.4 ± 0.8 in HCC, with a statistically significant difference between CH and HCC. However, we found no changes in the HCV RNA amount due to abstinence from drinking. The HAI score was high in the HCV RNA positive patients, but several cases in the HCV RNA negative group showed severe inflammatory changes. Therefore, judging the presence or absence of HCV RNA with the HAI score alone was considered difficult. Conclusions:: These results suggest that HCV, particularly genotype II, plays an important role in the advance of disease to LC and HCC in heavy drinkers.     

Hepatocellular Carcinoma Associated with AlcoholicLiver Disease: A Clinicopathological Study and Genetic Polymorphism of Aldehyde Dehydrogenase 2

In this paper, we describe a clinicopathological study of primary hepatocellular carcinoma (HCC) associated with alcoholic liver disease without hepatitis virus infection. In 180 HCC patients who were admitted to Asahikawa Medical College Hospital from 1987 to 1995, 10 patients (6%) had HCC associated with pure alcoholic liver disease (AI-HCC), whereas the HCC in 165 patients was associated with chronic viral liver diseases, in 2 with primary biliary cirrhosis, in 1 each with coexistence of the hepatitis C virus infection and hemochromatosis, and in 2 with cirrhosis of unknown origin. In the AI-HCC group, all patients were male. The diagnosis of HCC was obtained at the age of 54 to 67 years old, and the duration of ethanol intake was 33 to 40 years. Four cases had a history of temperance. As an underlying liver disease, liver fibrosis was found in three cases and liver cirrhosis in seven cases. HCC was diagnosed histologically in all cases. Serum α-fetoprotein and PIVKA-II were positive in patients with advanced HCC. In cases with small HCC, the tumor was resected surgically in three cases and percutaneous ethanol injection was performed in two cases. In four cases with small HCC, the patients were alive without tumor recurrence during the observation period. In advanced HCC, transcatheter arterial chemolipiodolization was performed. In the analysis of genetic polymorphism of ALDH 2, all AI-HCC had ALDH 2¹/2¹.     

Analysis of Risk Factors for Hepatocellular Carcinoma in Patients With HBs Antigen- and Anti-HCV Antibody-Negative Alcoholic Cirrhosis: Clinical Significance of Prior Hepatitis B Virus Infection

Background: The hepatitis B virus (HBV) or hepatitis C virus (HCV) markers frequently are detected in alcoholic patients with hepatocellular carcinoma (HCC). However, risk factors for the development of HCC in patients with HBs antigen (Ag)- and anti-HCV antibody (anti-HCV)-negative alcoholic cirrhosis have not been clearly documented. The present study was conducted to elucidate the occurrence rates of HCC in HBs Ag- and anti-HCV-negative male alcoholic cirrhosis and to assess the risk factors for hepatocellular carcinogenesis.
Method: We prospectively studied 91 consecutive patients with HBs Ag- and anti-HCV-negative alcoholic cirrhosis for 0.5 to 12.5 years (median 5.9 years). Potential risk factors assessed for liver carcinogenesis included the following six variables: age, total alcohol intake, association of continuing alcohol intake after diagnosis, indocyanine green retention rate at 15 min, anti-HB core antibodies (anti-HBc), and association of diabetes mellitus.
Results: Cumulative occurrence rates of HCC were 6.4%, 18.9%, and 28.7% at the end of the 5th, 7th and 10th years, respectively. When classified by anti-HBc, the occurrence rates of HCC in 31 patients with anti-HBc and 60 patients without anti-HBc were 15.6% and 2.9% at the 5th year, 28.4% and 13.5% at the 7th year, and 40.4% and 22.1% at the 10th year, respectively. The occurrence rates of HCC were also significantly related to the cumulative alcohol intake. Cox proportional hazard model identified that cumulative alcohol intake ( p = 0.0047) and positive anti-HBc antibodies ( p = 0.0598) were independently associated with the occurrence rates of HCC.
Conclusion: These epidemiologic results suggest that heavy cumulative alcohol intake and prior exposure to HBV infection are risk factors for the development of HCC in patients with HBs Ag- and anti-HCV-negative alcoholic cirrhosis.     

Hepatocellular carcinoma in Austria: aetiological and clinical characteristics at presentation

BACKGROUND AND AIMS: The aetiology of chronic liver disease leading to hepatocellular carcinoma (HCC) and the clinical characteristics at the time of presentation vary considerably among different parts of the world and over time. The number of patients seen at our institution has increased as compared to a period 20 years earlier. We investigated baseline characteristics of patients with hepatocellular carcinoma such as cirrhosis, hepatitis virus markers, age at presentation and stage of the tumour in an area with low prevalence of viral hepatitis. METHODS: All 245 patients seen at the Department of Gastroenterology and Hepatology at the University of Vienna, Austria, from July 1991 to March 1998 were included in this retrospective study, and 19 different clinical characteristics were studied. RESULTS: The median age at detection of HCC was 63.3 years, and alcoholic liver disease (35.1%) and hepatitis C virus (HCV) infection (36.7%) were the most frequent underlying diseases. Both chronic alcoholism and HCV infection as risk factors were present in 6.9% of the patients. Liver cirrhosis was present in 86.5%. At the time of diagnosis, 43.5% had multi-nodular tumours. Of the remaining patients with a single nodule, only 10% had HCC < or =2 cm. Most of our patients presented at a late stage of the disease (TNM stage 3 29.4%, TNM stage 4 69.7%; Okuda stage 2 65.7%, Okuda stage 3 18.0%). Due to the late stage of the disease at the time of presentation, 145 patients (59.2%) received palliative care only, 24 (9.8%) underwent liver resection, 38 (15.5%) liver transplantation and 38 (15.5%) chemotherapy. CONCLUSIONS: In this large single-centre series of HCC, the dominant contribution of HCV infection and chronic alcohol abuse as the underlying aetiology is documented. Diagnosis is usually made very late as reflected in the high proportion of patients in TNM stages 3 and 4 or Okuda stages 2 and 3. This resulted in a high percentage of patients who received palliative care only and very few who were eligible for treatment modalities with curative potential such as resection and liver transplantation.     

Hepatitis C and alcohol

A close relationship and possible interaction has been noted between alcohol intake and hepatitis C virus infection, since the discovery of HCV markers. It is not understood whether these are additive or synergistic effects in causing liver injury. Interactions between alcohol and HCV may be studied at several levels, including epidemiology, virology (including viral load), histology (effect on the severity of liver lesions), carcinogenesis (the role of alcohol in the occurrence of hepatocellular carcinoma), and the effect on the extrahepatic manifestations or severity of HCV infection. At the epidemiological level, a high prevalence of HCV infection was noted in patients with alcoholic liver diseases (14-37%), also characterized by a high rate of viral replication as detected by PCR, which was present in over 90% of patients tested. Moreover, the prevalence of anti-HCV antibodies increased proportionally with the severity of liver lesions. Virological analysis based on the determination of HCV RNA levels in the serum showed variations of HCV RNA levels with diet, and a clear relationship between self reported alcohol consumption and the levels of serum HCV RNA (r = .26, p = .001). At the histologic level the role of alcohol may be evaluated either through the development of fibrosis or by determination of the incidence of cirrhosis. A study on the effect of alcohol intake below or over 40 g per day on the histologic progression of liver lesions has confirmed a more rapid increase in fibrosis and a doubling in the incidence of cirrhosis in patients admitting to alcohol consumption >40 g per day. The role of alcohol in the occurrence of hepatocellular carcinoma in patients with cirrhosis due to HCV infection has been extensively studied with controversial results. A recent case control study performed in Italy showed that the relative risk of HCC in patients with HCV infection and heavy alcohol consumption doubled. Finally, alcohol consumption potentially worsens the evolution of dermatological diseases associated with HCV infection such as porphyria cutanea tarda. All of the above are strong arguments which should be used to advise HCV patients against alcohol consumption, regardless of the degree of liver injury. However, the deleterious effect of the occasional intake of small amounts of alcohol has not been demonstrated and therefore an occasional drink may be allowed in some cases.     

The relationship of acute transfusion-associated hepatitis to the development of cirrhosis in the presence of alcohol abuse

BACKGROUND: Although concomitant alcoholism is widely believed to enhance liver disease progression in persons with hepatitis C virus (HCV) infection, this relationship has not been well quantified. OBJECTIVE: To quantify the relationship of transfusion-associated HCV infection and history of heavy alcohol abuse to development of cirrhosis. DESIGN: Retrospective cohort study. SETTING: Liver clinics in university and government hospitals. PATIENTS: Extended follow-up of 1030 patients in prospective investigations of transfusion-associated viral hepatitis conducted in the United States between 1968 and 1980. MEASUREMENTS: Development of cirrhosis and history of heavy alcohol abuse were determined from review of interviews with patients or their proxies, medical records, death certificates, and autopsy and biopsy reports. Logistic regression was used to estimate the risk for cirrhosis associated with transfusion-associated HCV infection and history of heavy alcohol abuse. RESULTS: The absolute risk for cirrhosis was 17% among patients with transfusion-associated HCV; 3.2% among patients with transfusion-associated non-A, non-B, non-C hepatitis; and 2.8% among controls. Patients with transfusion-associated HCV were more likely than controls to develop cirrhosis (odds ratio, 7.8 [95% CI, 4.0 to 15.1]). A history of heavy alcohol abuse was associated with a fourfold increased risk for cirrhosis. Hepatitis C virus infection plus a history of heavy alcohol abuse led to a substantial increase in risk for cirrhosis (odds ratio, 31.1 [CI, 11.4 to 84.5]) compared with controls without such a history. CONCLUSIONS: Heavy alcohol abuse greatly exacerbates the risk for cirrhosis among patients with HCV infection. This finding emphasizes the need to counsel such patients about their drinking habits.     

Relative Risk for the Development of Hepatocellular Carcinoma in Alcoholic Patients with Cirrhosis: A Multiple Logistic-Regression Coefficient Analysis

The hepatitis B virus (HBV) or hepatitis C virus (HVC) markers are frequently positive in alcoholic patients with hepatocellular carcinoma (HCC). However, the role of the relationship between HBV or HCV infection and alcohol drinking in the development of HCC has not been clearly documented. In the present study, the relative risk in 1200 cirrhotic patients with different etiologies who were admitted to five different hospitals in Japan was calculated using the multiple logistic-regression coefficient analysis. In the HCV+ alcohol group, HCC patients tended to be younger, and the odds ratio for the development of HCC was significantly higher compared with the HCV-alone group. Furthermore, the interaction coefficient of alcohol and HCV for the development of HCC was significant statistically. However, the interaction between HBV and alcohol was not significant. Because the proportion of male patients with HCC was significantly higher in the alcohol-alone and HBV-related groups than in the HCV-related group, the multiple logistic-regression analysis was also performed in male patients only. The results were nearly the same as those in male and female patients combined. These results suggest strongly that alcohol and HCV together accelerate the development of HCC. However, a similar relationship was not found between alcohol and HBV.     

Profile of hepatocellular carcinoma in India: An insight into the possible etiologic associations

BACKGROUND: Several etiologic factors including hepatitis viruses, alcohol and aflatoxin have been implicated in the pathogenesis of hepatocellular carcinoma (HCC). There is, however, limited information from the Indian subcontinent. METHODS: Seventy-four consecutive cases of HCC were studied. A detailed history, tests for hepatitis B virus (HBV; HBsAg, HBeAg, anti-HBe, IgG anti-HBc, anti-HBs and HBV-DNA), hepatitis C virus (HCV; anti-HCV and HCV-RNA) infection, liver histopathology and HBV-DNA integration by using Southern blot hybridization were studied. A p53 gene mutation was also studied by using PCR and single-strand conformation polymorphism. RESULTS: Hepatocellular carcinoma patients were predominantly males (mean age 49.5 +/- 14.0 years). Portal hypertension and cirrhosis were seen in 56 (76%) patients, more often (P < 0.05) in viral marker positive cases. Forty-five percent of patients had features of hepatic decompensation at presentation. Evidence of HBV infection was present in 53 (71%) patients. Twenty-six (49%) of these patients had either HBeAg + ve, HBV-DNA + ve (n = 12), or HBsAg - ve, HBV-DNA + ve (n = 14) forms of HBV infection. Hepatitis B virus DNA integration in the liver tissue was seen in 10 of 17 (59%) patients. Infection with HCV alone was detected in three (4%) and dual HBV and HCV infection in six (8%) patients. A majority (78.5%) of the chronic alcoholics had associated viral infection. The etiology of HCC remained undetermined in 15 (20%) patients. The p53 gene mutations were detected only in three of 21 (14%) liver tissues. Aflatoxin toxicity, oral contraceptive use or metabolic disorder were not seen. CONCLUSIONS: In India: (i) HBV infection is the predominant factor for the development of HCC, often related to mutant forms of HBV; (ii) a majority of the HCC patients have overt cirrhosis of the liver; and (iii) HCV and alcohol per se are uncommonly associated.     

2002至2011年中国“北方”地区住院肝硬化患者病因构成及变化趋势分析

目的：分析2002年至2011年10年间中国“北方”地区住院肝硬化患者病因构成及变化趋势。方法对我院过去10年出院第一诊断为肝硬化的53092例患者的病因构成及变化趋势进行分析。结果乙型肝炎、丙型肝炎、酒精和自身免疫性肝病为前4位的病因,分别占74.2%、10.8%、5.8%和3.9%;乙型肝炎肝硬化的构成比从2002年的81.5%下降至2011年的66.8%,而酒精性肝硬化从2002年的3.3%上升至2011年的7.7%,10年间上升了2.3倍;自身免疫性肝病肝硬化患者多为女性（84.3%）,而乙型肝炎肝硬化和酒精性肝硬化患者男性占绝大多数,分别占80.1%和98.0%,差异有统计学意义（P〈0.01）;酒精性肝硬化患者与乙型肝炎肝硬化患者的平均年龄均不足50岁,而丙型肝炎肝硬化、自身免疫性肝病肝硬化患者的平均年龄均在50岁以上,差异有统计学意义（P〈0.01）;患者的籍贯以华北地区最多;4种常见病因所致的肝硬化患者的好转率均在70%以上,酒精性肝硬化和自身免疫性肝病肝硬化患者好转率接近80%,差异有统计学意义（P〈0.01）。结论乙型肝炎、丙型肝炎、酒精和自身免疫性肝病是肝硬化前4位的病因,乙型肝炎肝硬化的构成比在逐年下降,而酒精性肝硬化的构成比在不断上升。     

Is Heavy Alcohol Consumption an Attributable Factor for Cancer‐Related Deaths Among Japanese Men?

BACKGROUND: Over the past four decades, per capita alcohol consumption in Japan has increased 4-fold. Age-adjusted cirrhosis mortality rates for men have also increased, whereas the rates for women have declined gradually. This widening difference in mortality could be due to a decreasing prevalence of viral hepatitis infection for both sexes and to differences in alcohol consumption between the sexes. Difficulties in estimating the impact of increased alcohol consumption on mortality rates in Japan also arise from changes in the prevalence of non-alcohol-related risk factors. METHODS: To measure the relative contribution of alcohol to death from cirrhosis, liver cancer, esophageal cancer, and head and neck cancer among Japanese men, we used the mortality rate for Japanese women as the standard because alcohol consumption for women has been low. We used published vital statistics data from 1992 to 1996 to calculate the attributable risk percent (ARP) in 5-year cohorts of Japanese men age 20 and older. RESULTS: Among Japanese men, heavy alcohol consumption accounted for 70.7% of deaths due to cirrhosis, 76.8% of liver cancer deaths, 88.5% of esophageal cancer deaths, and 87.4% of head and neck cancer deaths. When we examined ARPs by age group, ARPs for these four diseases were approximately 80% in the middle age groups. However, for older groups, the ARPs for cirrhosis and liver cancer were much lower than those for esophageal cancer and head and neck cancer. The prevalence of previous hepatitis C virus infection, considered to be the major cause of cirrhosis and liver cancer, increased with age. CONCLUSIONS: The results support previous epidemiologic studies conducted in Japan. Heavy alcohol consumption is a major public health problem among younger Japanese men, accounting for approximately 80% of the deaths for the four diseases examined.     

Hepatitis B virus infection and alcohol consumption

Hepatocellular carcinoma(HCC) is the most common type of primary liver cancer, and the second most common cause of cancer deaths worldwide. The top three causes of HCC are hepatitis B virus(HBV),hepatitis C virus(HCV), and alcoholic liver disease. Owing to recent advances in direct-acting antiviral agents, HCV can now be eradicated in almost all patients. HBV infection and alcoholic liver disease are expected, therefore, to become the leading causes of HCC in the future. However, the association between alcohol consumption and chronic hepatitis B in the progression of liver disease is less well understood than with chronic hepatitis C. The mechanisms underlying the complex interaction between HBV and alcohol are not fully understood, and enhanced viral replication, increased oxidative stress and a weakened immune response could each play an important role in the development of HCC. It remains controversial whether HBV and alcohol synergistically increase the incidence of HCC. Herein, we review the currently available literature regarding the interaction of HBV infection and alcohol consumption on disease progression.     

Alcohol has no effect on hepatitis C virus replication: a meta-analysis

BACKGROUND: Patients with chronic hepatitis C virus (HCV) infection who consume large quantities of alcohol have more severe liver disease compared with HCV patients without a history of alcohol consumption. The mechanism by which alcohol worsens HCV related liver disease is not properly understood. One possibility is that alcohol stimulates HCV replication, and the present meta-analysis was performed to examine this issue. METHODS: The effect of alcohol on viral titres was assessed in three ways: comparison of the heaviest drinkers with non-drinkers; effect of graded doses of alcohol; and effect of abstinence in the same individual. RESULTS: A total of 14 studies were identified. Comparison of patients with the highest alcohol use with the abstinent group showed a significant association with viral load in three studies, five studies had a positive direction, while the remaining four studies found a negative relationship. Analysis of the combined results showed no association between alcohol consumption and virus levels (p = 0.29). Assessment of graded doses of alcohol also showed no significant difference between non-drinkers and moderate drinkers (p = 0.50), between non-drinkers and heavy drinkers (p = 0.35), or between moderate drinkers and heavy drinkers (p = 0.32). Five studies examined the influence of abstinence on viral titres but none provided sufficient data for statistical analysis. CONCLUSIONS: The present study has failed to show an association between alcohol use and HCV viral titres. These observations raise the possibility that the hepatic damage caused by alcohol and HCV may be purely additive, involving different mechanisms and pathways.