The objective of this report is to provide clarification on the interaction among hepatitis B virus (HBV), hepatitis C virus (HCV) and alcohol in the development of hepatocellular carcinoma (HCC). A systematic search was performed in PubMed, Web of Science and Scopus databases up to July 18, 2023. The inclusion criteria involved observational studies that examined the relationship between HBV, HCV, alcohol use and the development of HCC. To assess between-study heterogeneity, the I2 statistics were employed. Publication bias was evaluated using the Begg and Egger tests. The effect sizes were estimated as odds ratios (ORs) with 95% confidence intervals (CIs) utilising a random-effects model. Among the initial pool of 31,021 studies identified, 28 studies involving 42,406 participants met the inclusion criteria. Through our meta-analysis, we found that the combined effect of HBV and alcohol was associated with an OR of 14.56 (95% CI: 9.80, 21.65). The combined impact of HCV and alcohol showed an OR of 42.44 (95% CI: 20.11, 89.56). Coinfection with both HBV and HCV was associated with an OR of 32.58 (95% CI: 20.57, 51.60). These results emphasising the importance of reducing alcohol consumption and implementing effective viral hepatitis prevention and treatment.

Hepatitis virus and alcohol are the main factors leading to liver damage. Synergy between hepatitis B virus (HBV) and alcohol in promoting liver cell damage and disease progression has been reported. However, the interaction of HBV and ethanol in hepatic steatosis development has not been fully elucidated.

Eight-week-old male C57BL/6 mice were treated with or without HBV, ethanol, or the combination of HBV and ethanol (HBV+EtOH), followed by a three-week high-fat diet (HFD) regimen. Liver histology, serum biomarkers, and liver triglyceride levels were analysed. Furthermore, a meta-analysis of the effects of alcohol and HBV on hepatic steatosis in populations was performed.

Hepatic steatosis was significantly more severe in the HBV+EtOH group than in the other groups. The serum alanine aminotransferase, aspartate aminotransferase and liver triglyceride levels in the HBV+EtOH group were also significantly higher than those in the other groups. The HBeAg and HBsAg levels in the HBV+EtOH group were significantly higher than those in the pair-fed HBV-infected mice. In addition, the meta-analysis showed that alcohol consumption increased the risk of hepatic steatosis by 43% in HBV-infected patients (pooled risk ratio (RR)=1.43, P<0.01).

Alcohol and HBV synergistically promote high-fat diet-induced hepatic steatosis in mice. In addition, alcohol consumption increases the risk of hepatic steatosis in HBV-infected patients.

Hepatitis B virus (HBV) is a major risk factor for liver diseases, in which HBV covalently closed circular DNA (cccDNA), as the genomic form that templates viral transcription, plays crucial roles in sustaining viral persistence. Clinically, the excessive ethanol intake accelerates the progression of liver diseases with HBV infection. Here, we supposed that ethanol might trigger HBV cccDNA in the liver. Interestingly, we observed that the ethanol remarkably elevated the levels of HBeAg, HBsAg, HBV DNA and cccDNA in HBV-expressing hepatoma cells. Mechanically, the ethanol increased the levels of HBx and MSL2 in vivo and in HBV-expressing HepG2 cells, but not in HBV-free HepG2 cells. Moreover, the down-regulation of MSL2 by small interference RNA could block the ethanol-promoted HBV cccDNA in HepG2.2.15 cells. As a commonly administered treatment for HBV, the effect of IFNα on ethanol-triggered HBV cccDNA remains poorly understood. Strikingly, we showed that the treatment with IFN-α2b inhibited the ethanol-promoted cccDNA through depressing MSL2 in the cells. Thus, we conclude that IFN-α2b inhibits the ethanol-enriched HBV cccDNA through blocking a positive feedback loop of HBx/MSL2/cccDNA/HBV/HBx. Our finding provides new insights into the mechanism by which IFN-α2b inhibits ethanol-enhanced HBV cccDNA. Therapeutically, IFNα may contribute to the cccDNA induced by ethanol in liver.

Excessive alcohol intake accelerates disease progression in chronic hepatitis B virus (HBV) infection, but the mechanisms by which ethanol worsens the prognosis of chronic hepatitis B (CHB) are not fully understood. The aim of this study was to investigate whether HBV replication is augmented by alcohol or alcohol-induced cytochrome p450 2E1 (CYP2E1), and if so, whether oxidative stress is involved in the process. Ethanol treatment promoted HBV replication in HepAD38 cells that permit the conditional viral replication. Luciferase reporter assays confirmed that HBV core, preS1 and preS2/S promoter activities were augmented by ethanol. Ethanol did not induce oxidative stress in HepAD38 cells with minimal expression of CYP2E1. However, over-expression of CYP2E1 induced oxidative stress and amplified transcriptional activation of HBV by ethanol. Antioxidant glutathione treatment attenuated CYP2E1-mediated augmentation of HBV replication in ethanol-treated cells. In conclusion, ethanol enhances transcriptional activity of HBV promoters in human hepatoma cells in an oxidative stress-independent manner; and CYP2E1-mediated oxidative stress potentiates the ethanol-induced transactivation of HBV.

Alcoholics have higher prevalence of hepatitis B virus (HBV) infection than non-alcoholics and such fact may influence in the development of liver cirrhosis and/or hepatocellular carcinoma.

To evaluate the response to hepatitis B vaccine in alcoholics without liver cirrhosis.

Twenty male alcoholics with mean age of 46.6 +/- 10.9 years were vaccinated; they ingested more than 80 g of ethanol/day for more than 10 years. As control group 40 male non-alcoholics with mean age of 37.8 +/- 9.7 years were also vaccinated. No serological evidence of contact with HBV, hepatitis C virus or human immunodeficiency virus was found among the subjects of both groups. The vaccine Euvax B (20 microg) was administered intramuscularly into the deltoid area at 0, 1 and 6 months. Serum anti-HBs were determined after one month of the last dose. Levels <10 mUI/mL were considered as non-response, between 10 and 99 mUI/mL as seroconversion, and > or = 100 mUI/mL as seroprotection.

No significant difference was found between alcoholics and controls, respectively, in the frequency of non-response (35.0% vs 32.5%), seroconversion (15.0% vs 15.0%) and seroprotection (50.0% vs 52.5%). Among responders, mean levels of anti-HBs in alcoholics (511 +/- 448 mUI/mL) were similar to the controls (696 +/- 410 mUI/mL). No negative interference on the response was associated with the body mass index, tabagism, being drinking or concurrent chronic pancreatitis without pancreatic insufficiency.

Male alcoholics without liver cirrhosis had similar frequency and serum levels of anti-HBs to the non-alcoholics in response to HBV vaccination.

Chronic hepatitis B is an international health concern that causes cirrhosis, hepatocellular carcinoma, liver failure, and death. Current treatment options are expensive and associated with side effects; however, indirect evidence suggests a relationship between relative thiamine deficiency and chronic hepatitis B infection.

The authors present three case studies wherein multiple crossovers of daily thiamine administration were used to evaluate a hypothesized association between thiamine treatment and aminotransferase levels.

In each case study, thiamine administration was associated with reduction in aminotransferase levels and the fall of HBV DNA to undetectable levels. Analyses by t test demonstrated a statistically significant reduction in aminotransferase levels in all three cases.

The relationship between thiamine administration and chronic hepatitis B infection warrants further study. If proven effective in reducing liver damage or inducing remission of the hepatitis B virus in larger trials, thiamine will offer obvious advantages over the current treatments for chronic viral hepatitis B infection.

To verify the prevalence of infection by human immunodeficiency virus (HIV) in alcoholics we studied 131 alcoholic patients (119 males and 12 females) with a mean age of 44.3 +/- 10.8 years. Serum samples were collected from this group and analysed, by ELISA, for antibodies against HIV as well as for serological markers for hepatitis B virus (HBV) and hepatitis C virus (HCV). As we have previously described, we found a high prevalence of HBV (26.4%) and HCV (4.2%) markers as compared to the prevalence of these markers in samples of normal blood donors from Uberlândia's Hemocentro Regional, which are 4% and 0.4%, respectively. Of the 131 patients, four (3%) had antibodies against HIV, three (75%) of which were injecting drug users (IDU). In the HIV-negative group, only one patient was an IDU. The prevalence of HIV in our population, according to data from the city's Health Secretary, varies from 3.1% to 6.2%. We conclude that, at least for the moment, alcoholism per se, did not constitute an important risk factor for HIV infection. However, acquired immunodeficiency syndrome is a rather recent disease as compared to hepatitis B and C and, as the transmission routes are similar for HIV and hepatitis viruses, an increase in the incidence of HIV infection in alcoholics may be just a question of time.

We assessed the frequency of serological markers of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in 365 alcoholics by determining, by ELISA, the presence of HBsAg, anti-HBc, anti-HBs and anti-HCV. Fifty patients were cirrhotics and 315 had no evidence of hepatic cirrhosis; of the latter HBsAg was assessed in all, anti-HBc and anti-HBs in 130, and anti-HCV in 210. Among the alcoholics the frequencies of HBsAg (1.9%), anti-HBc (28.3%) and anti-HCV (3.8%) were higher (p < 0.001) than among the controls (N = 17,059), 0.4%, 4.0% and 0.4% respectively. The frequency of positive HBsAg was higher (p < 0.001) in the cirrhotic patients (8.0%) than in alcoholics without cirrhosis (0.95%) and in controls (0.4%), and similar between the latter; of anti-HBc in alcoholics without cirrhosis (28.5%) was similar in cirrhotics patients (28.0%) and higher (p < 0.001) than in the controls (4.0%); of anti-HBs in alcoholics without cirrhosis (20.8%) was similar to that of the cirrhotic patients (10.0%), and the anti-HCV was similar between alcoholics with (6.0%) and without cirrhosis (3.3%) and higher (p < 0.001) than in controls (0.4%). We concluded that: a) alcoholics with or without cirrhosis have similar frequencies of infection with HBV and HCV between them, and higher than in nonalcoholics; b) alcoholics without cirrhosis had a frequency of HBV active infection (HBsAg+) which was similar to the controls, whereas among those who progressed to cirrhosis this frequency was significantly higher, what suggests that HBV may be implicated in the pathogenesis of cirrhosis in a few alcoholic individuals.

In chronic liver disease, alcoholism and hepatitis C virus (HCV) frequently coexist, and it is widely believed that they interact to result in more severe disease. However, the issue is far more complex and that view may be incorrect. Newer HCV assays cast doubt on the earlier results. Data acquired in one country are often at variance with those from other countries, suggesting that other factors may be involved in the variability of the disease. Further comparison of histologically different groups of individuals with excess alcohol intake is unlikely to shed further light on the issue unless information on the duration and quantity of alcohol consumption and the duration of HCV infection is available. The net evidence is that HCV and alcohol produce different histological appearances in the precirrhosis stage with the end result cirrhosis often being indistinguishable, regardless of aetiology. Nevertheless, even with both aetiologies, progression is slow and only a minority of people develop cirrhosis despite the combination of HCV and heavy alcoholism. As yet there is no definite evidence that cirrhosis develops more frequently or sooner if both HCV and alcohol are present . Although the majority of the evidence suggests that these insults are probably additive, there is a possibility that alcohol and HCV do interact in the pathogenesis of chronic liver disease. Further studies will be necessary, however, to clarify their relationship.

Among the reported interactions between ethanol and hepatitis B virus (HBV), studies of transgenic mice have suggested an effect of ethanol on the secretion of viral envelope proteins.

We further investigated these interactions in vitro by determining HBs antigen levels and performing northern blots of viral mRNA in human cell culture (HepG2 HBV positive cells) exposed for 3 to 12 days to various concentrations of ethanol.

In cultures exposed to 200 mM ethanol, HBs antigen concentrations increased in the medium (p < 0.05) after 3 days as Pre-S1 and Pre-S2 protein concentrations. This increase was not specific, as albumin and ferritin increased in the same proportions. Ethanol also increased the HBs antigen concentration in the cells (p < 0.05), whereas levels of viral mRNA encoding surface proteins were unaffected.

These findings show that short-term ethanol exposure in vitro can induce HBs antigen overexpression via a post-transcriptional mechanism.

Sixty-seven formalin-fixed and paraffin-embedded liver biopsies from HBsAg-negative alcoholics without previous blood transfusions or intravenous drug abuse were analyzed for the presence of low-level hepatitis B virus DNA by the polymerase chain reaction. To simplify and standardize the amplification procedure, aliquots of a complete polymerase chain reaction mix were prepared and frozen for storage; random samples were tested prior to analysis of clinical material. Freezing and storage of the aliquots did not affect the activity of Taq polymerase. One large batch of ready-to-use aliquots could thus be used as a standardized polymerase chain reaction kit for all experiments. The suitability of the extracted material for polymerase chain reaction analysis was tested in two ways. First, the absence of nonspecific polymerase chain reaction inhibitors was demonstrated in all samples by amplifying cloned hepatitis B virus DNA in the presence of extracted material. Second, the integrity of the extracted DNA was tested by amplifying a segment of the beta-globin gene. Twenty-three samples were beta-globin DNA positive and thus contained sufficient amounts of nondegraded DNA. These results emphasize the importance of testing both the absence of nonspecific inhibitors and DNA integrity in DNA samples extracted from fixed tissue. Among the 23 beta-globin positive samples, 12 had cirrhosis (52.1%). Two of these samples were hepatitis B virus DNA positive (8.7%); one of these cases had cirrhosis. Thus, even in the absence of common risk factors, the incidence of hepatitis B virus in this alcoholic population was increased compared to the general population.

The aim of our work was to study the prevalence of HBV markers in Alcoholic Liver Disease (ALD) by evaluating clinical and biochemical parameters that could further characterize the association. A prospective and sequential study of 107 patients with ALD was performed, including 83 cases of cirrhosis and 24 cases of alcoholic hepatitis. Daily ingestion of pure ethanol was of at least 70 gm for seven years or more and always associated with hepatocellular disfunction. According to the serological profile for HBV markers the patients were allocated to one of four groups: group I infected (positivity of HBsAg and anti-HBc); group II immunized (positivity of anti-HBs and anti-HBc); group III without HBV markers (negativity of HBsAg, anti-HBc and anti-HBs); group IV isolated anti-HBc. The prevalence of HBsAg positivity in ALD was high: 15.89% whereas immunity was low: 26.17% suggesting a great exposure to the virus and a deficient immunological response. No significant statistical differences were found among the three groups when clinical and biochemical parameters were individually considered. Nevertheless, when a Child/Campbell classification was applied, patients with ALD associated with HBV (group I) showed a significant difference, presenting a predominance of child C, with a bad prognosis.

In heavy drinkers with clinical evidence of liver disease, routine investigations should exclude the possibility of other chronic liver diseases of non-alcoholic aetiology requiring specific therapy--these include chronic viral hepatitis, autoimmune diseases of the liver, Wilson's disease and genetic haemochromatosis. If abnormalities in liver biochemistry persist despite abstinence, or if the diagnosis of alcoholic liver disease is in doubt, a liver biopsy should be carried out. Studies evaluating the role of liver biopsy in alcoholic liver disease suggest that without histological confirmation the diagnosis will be inaccurate in 10-20% of patients. Serum biochemistry and the currently available imaging modalities have severe limitations in determining the relative contributions of fatty liver, alcoholic hepatitis and cirrhosis to the overall picture in alcoholic liver disease. Histological examination is therefore of additional value in determining the prognosis, which is worst in patients with a combination of alcoholic hepatitis and cirrhosis. There are a number of indices available, based on clinical and laboratory information, for evaluating the short-term prognosis, but these can only be used with accuracy if the histological pattern of damage has initially been evaluated.

The efficacy of full vaccination against hepatitis B virus (i.e., including the 1-year booster injection) was evaluated in 28 alcoholic patients with minimal liver disease. Although such patients are reportedly poor responders, the proportion of those protected (anti-HBs titer > = 10 mlU/ml) rose from 42.8% after primary immunization to 82% after the booster. The mean anti-HBs titer, which remained low in the overall group, was significantly lower in the subjects who resumed drinking during the follow-up period than in those who did not. This suggests a direct influence of alcohol itself on the response, because none of our patients had cirrhosis and none were clearly malnourished. Among the 17 patients for whom the 2-year post-booster anti-HBs titer could be determined, all those with a 1-month postbooster titer above 1000 mlU/ml still had a high anti-HBs level (> 100), whereas 80% of those with a 1-month postbooster titer < 1000 had 2 years later only a low (< 100) or even an unprotective anti-HBs level; this means that only the latter should be considered for a new booster injection. Our data indicate that protection against hepatitis B virus can be achieved in a good proportion of alcoholics with a full vaccination protocol. We suggest that efficacy should be evaluated 1 month after the booster, and that patients with low postbooster anti-HBs titers should be tested at regular intervals, because they can also be protected provided an adapted schedule of further injections is conducted.

HCV-RNA detection was investigated in 66 chronic alcoholic patients divided into 3 groups according to the severity of liver injury: group 1 included 22 chronic alcoholics without cirrhosis, group 2, 20 patients with alcoholic cirrhosis and group 3, 24 patients with alcoholic cirrhosis and hepatocellular carcinoma. The 'nested' polymerase chain reaction (PCR) technique amplifying the 5' non-coding region was used to detect HCV-RNA. For comparison, ELISA1, ELISA2 and RIBA2 tests (Ortho Diagnostics System) were also used to detect anti-HCV antibodies. Finally HBV markers (HBsAg, anti-HBc and anti-HBs antibodies) were detected in all patients as well as HBV-DNA by PCR. In group 1, only 1 patient (4.5%) showed an HCV-RNA-positive PCR, while 3 patients (13.6%) were found to have anti-HCV antibodies detected by RIBA2. In group 2, 3 patients (15%) showed positive PCRs, whereas 4 patients (20%) had anti-HCV antibodies. Finally, in group 3, the PCR was positive in 3 patients (12.5%), while 9 (37.5%) had anti-HCV antibodies. All patients with positive PCRs showed positive anti-HCV antibodies detected by second-generation assays. On the other hand, these patients often had past HBV infection markers but rarely had HBV-DNA detected by PCR. These results suggest that in chronic alcoholic patients, regardless of the severity of liver injury, HCV replication is rarely observed by PCR. Indeed, replication is only observed when anti-HCV antibody detection is positive in second-generation assays, particularly with strong reactivity against C33-C and C22-3 antigens. The relatively high prevalence of anti-HCV antibodies in this population compared to the usual rates could be explained by the age, geographic and perhaps even socioeconomic origin of the patients.

The prevalence of HCV, HBV and HAV markers was investigated in unselected patients attending an outpatient alcoholic clinic. Anti-HCV were detected in 35 (24%) of 144 patients studied, and at least one marker of HBV infection was present in 72 (50%). These results are significantly higher than in a matched control population. The presence of anti-HCV was related to previous blood transfusions and familial history of alcoholism. We conclude that alcoholics should be considered a high risk group for both HCV and HBV infection.

Hepatitis B virus (HBV) infections with an unusual serological profile, viz. positivity of HBV-DNA in the absence of hepatitis B surface antigen (HBsAg), have been described in alcoholics. This atypical pattern could be due to a low circulating level of viral particles rendering HBsAg undetectable with commercial kits, whereas HBV-DNA remains positive using the highly sensitive hybridization technique. We hypothesize that the well-known alcohol-induced impairment of protein secretion could also concern HBsAg particles and leads to a decrease in serum levels of the HBs antigen. To verify this hypothesis, we used HBsAg-positive transgenic mice as an animal model. Twelve HBsAg+ mice were separated into two groups; one group (n = 6) was submitted to increasing alcoholisation over an 18-week period, while the other (n = 6) was water fed. Seven HBsAg- littermates acted as controls: three received the alcohol regimen and the remaining four water. Chronic excessive alcoholisation lead to a significant decrease in serum HBsAg concentrations, while there was no obvious change in liver S mRNA. Ultrastructural studies showed a significant decrease in the number of microtubules in the livers of alcohol-fed mice. Finally, immunohistochemical studies performed at the end of the experiment showed a greater accumulation of HBsAg in the livers of HBsAg+ alcohol-fed (mainly located in the centrilobular area) than in the HBsAg+ water-fed mice. Our results (i) validate our initial hypothesis that chronic alcohol abuse leads to a decrease in serum HBsAg concentrations. This could explain, in part at least, the serological dissociations which were observed. (ii) Confirm the utility of screening serum HBV-DNA in alcoholics.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Viral infection may play a role in alcoholic liver disease with histological features of chronic active hepatitis (CAH). Human leucocyte antigen (HLA) hepatocellular display is supposed to allow HLA-restricted T-lymphocyte cytotoxicity in chronic viral hepatitis. We studied the presence of serum anti-hepatitis C virus (HCV) antibodies, the hepatic HLA display and the composition of the mononuclear cell infiltrate in 16 patients with alcoholic liver disease and histological features of CAH and in 11 patients with alcohol-related degenerative changes. All patients were negative for hepatitis B virus (HBV) markers. Anti-HCV were tested by microplate ELISA. Class I HLA A, B, class II HLA DR, lymphocytes pan T, T helper/inducer, T suppressor/cytotoxic, B, and K NK cells were stained on liver cryostat sections by monoclonal antibodies and double indirect immunoperoxidase. Anti-HCV were present in all the patients with features of CAH and absent in those with only degenerative changes. In livers with features of CAH the mononuclear cell infiltrate consisted largely of T lymphocytes with marked prevalence of suppressor/cytotoxic cells in periportal and lobular areas. K NK cells were rare. Class I HLA, diffusely displayed on bile duct epithelium and on sinusoidal cells, also appeared on liver cells in the areas of periportal and lobular necrosis, namely on the hepatocytes in close contact with suppressor/cytotoxic T cells. In livers with only degenerative changes class I HLA were diffusely displayed on bile duct epithelium and on sinusoidal cells but absent on the hepatocytes. In all the specimens HLA DR antigens were expressed on sinusoidal and inflammatory cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Patients with overt alcoholic liver disease who had participated in a multicenter therapeutic trial and subgroups of controls (i.e., alcoholic patients without liver disease and patients with neither alcoholism nor liver disease) were tested for hepatitis B virus and hepatitis C virus antibodies to determine the prevalence of these antibodies to determine the prevalence of these antibodies and any clinical association in the progression and outcome of alcoholic liver disease. Antibodies to hepatitis B (anti-HBs and/or anti-HBc) were found in 29.2% of patients with alcoholic liver disease, in 26.1% of hospitalized alcoholic patients without liver disease and in 24.2% of hospitalized nonalcoholic patients without liver disease; frequencies were not significantly different from one another. HBsAg was not evaluated because HBsAg+ patients had been excluded from the original trial. The presence of these antibody markers correlated with ethnic origin of and immunoglobulin levels in the patients. In contrast, antibody to hepatitis C, as detected by enzyme immunoassay, was positive in 27.1%, 4.8% and 3.0% of the three groups, respectively, the first differing significantly from the other two. Antibody to hepatitis C virus positivity correlated significantly with clinical severity of the disease and with the presence of histological features that imply chronic viral infection (periportal inflammation, cirrhosis), despite the fact that the supplementary assay for antibody to hepatitis C virus, using recombinant immunoblot assay, reduced the positive rate by 79%.(ABSTRACT TRUNCATED AT 250 WORDS)

Liver biopsies were taken from 54 alcoholic HBV carriers with liver dysfunction to assess whether HBV infection or habitual drinking was the main cause of their illness. In 28 cases, ultrastructural studies were done. Results showed that 50% of the cases predominantly displayed virus-related histological changes, whereas 13% of them mainly had alcohol-related ones. Both pathological changes were evenly distributed in four cases. The remaining 15 cases showed nonspecific or other histological changes. Electron microscopy revealed that HBV core and Dane particles were seen with Mallory bodies in the same hepatocytes. Thus, we postulate that HBV-related changes are more often encountered than alcoholic ones in alcoholic HBV carriers and that HBV replication can occur even in hepatocytes bearing Mallory bodies.

Seventy-six chronic alcoholics in Japan were evaluated for histological changes of liver needle biopsies, Chiron C100 antibody (C-100) for hepatitis C virus, as well as clinical and laboratory data. In biopsies, the presence of necroinflammations within the parenchyma, lymphocytic reaction in the portal tracts, or both, might indicate non-A, non-B (NANB) chronic hepatitis. Using these histological criteria, the patients were previously classified into two groups: alcoholic liver disease (ALD) alone and ALD complicating NANB chronic hepatitis. The C100-positive ratio was found to be 12% in the former group and 69% in the latter. Further clinical and laboratory comparison revealed that there were significant differences in gamma-glutamyl transpeptidase, gamma-globulin, and adenosine deaminase levels in the sera between the ALD alone and the ALD complicating NANB chronic hepatitis groups. Since some chronic alcoholics are also affected by chronic type C hepatitis, detailed evaluations of the liver biopsy and C-100 assay are required for the differentiation of these hepatic disorders.

Alcoholic liver disease includes steatosis, alcoholic hepatitis and cirrhosis. Other liver diseases of genetic origin, but with a curious association with alcohol intake, are hemochromatosis and porphyria cutanea tarda. The attribution of chronic hepatitis to alcohol intake remains speculative, and the association may reflect hepatitis C infection. Hepatic injury attributed to alcohol includes the changes reported in the fetal alcohol syndrome. Steatosis, the characteristic consequence of excess alcohol intake, is usually macrovesicular and rarely microvesicular. Acute intrahepatic cholestasis, which in rare instances accompanies steatosis, must be distinguished from other causes of intrahepatic cholestasis (e.g., drug-induced) and from mechanical obstruction of the intrahepatic bile ducts (e.g., pancreatitis, choledocholithiasis) before being accepted. Alcoholic hepatitis (steatonecrosis) is characterized by a constellation of lesions: steatosis, Mallory bodies (with or without a neutrophilic inflammatory response), megamitochondria, occlusive lesions of terminal hepatic venules, and a lattice-like pattern of pericellular fibrosis. All these lesions mainly affect zone 3 of the hepatic acinus. Other changes, observed at the ultrastructural level, are of importance in progression of the disease. They include widespread cytoplasmic shedding, and capillarization and defenestration of sinusoids. Progressive fibrosis complicating alcoholic hepatitis eventually leads to cirrhosis that is typically micronodular but can evolve to a mixed or macronodular pattern. Hepatocellular carcinoma occurs in 5 to 15% of patients with alcoholic liver disease. The clinical syndrome of alcoholic liver disease is the result of three factors--parenchymal insufficiency, portal hypertension and the clinical consequences of extrahepatic damage produced by alcohol. At the several phases of the life history of alcoholic liver disease, the individual factors play a different role. The clinical manifestations of alcoholic steatosis are mainly extrahepatic in origin. Those of alcoholic hepatitis reflect mainly parenchymal insufficiency and those of cirrhosis are mainly those of portal hypertension. Alcoholic liver injury appears to be generated by the effects of ethanol metabolism and the toxic effects of acetaldehyde, perhaps the immune responses to alcohol- or acetaldehyde-altered proteins, and questionably enhanced by viral hepatitis. Alcoholic hepatitis may be mimicked histologically, and to a varying degree clinically, by a number of conditions (obesity, diabetes, several drug-induced injuries, jejunoileal bypass, and related "shortcircuiting" of the bowel). Perhaps the most important facet of the hepatotoxicity of alcohol is its enhancement of the effects of a number of other hepatotoxic agents, among which acetaminophen is the prime example.

We conducted a retrospective study in 229 patients to determine the prevalence of hepatitis C virus (HCV) according to the type of liver disease and also the serum hepatitis B virus (HBV) status. There were 55 cases of hepatocellular carcinoma (HCC), 78 cases of alcoholic cirrhosis (AC) and 96 cases of non-cirrhotic alcohol liver disease (NCA). Half the AC and NCA groups were constituted of patients with or without serum HBV markers. The prevalence of anti-HCV antibodies in HCC (58.2%) was significantly higher than in the other groups (AC, 35.9%; NCA, 17.7%). Combining the two AC and NCA groups gave a 25.8% anti-HCV prevalence in the alcoholics. Altogether anti-HCV antibodies were more frequently present in HBV-positive than in HBV-negative patients (42.2 vs. 26.1%, p less than 0.01), although the difference was not significant when the HCC group was separately analysed. The S/N ratio of anti-HCV-positive samples varied according to the type of the disease (tumorous vs. non-tumorous) and to the serum HBV status. Indeed, 65.6% of HCC had a S/N greater than 4 compared to only 32.2 and 23.5% in AC and NCA, respectively (p less than 0.01). On the other hand more than half of the AC and NCA had a S/N less than 2, indicating possible artefacts in certain cases. The 15 HBsAg and anti-HCV-positive patients had a significantly lower mean S/N than patients displaying only antibodies against HBV, even in the HCC group.(ABSTRACT TRUNCATED AT 250 WORDS)

The prevalence of hepatitis C virus antibody and its relationship to the severity of liver disease in chronic alcoholic patients has been assessed, using a recently developed enzyme immunoassay and confirmed by a recombinant immunoblot assay, in 144 patients (mean age +/- S.D. = 44.4 +/- 11.3 yr) who had consumed greater than 80 gm/day ethanol for greater than 5 yr. Hepatic disease was evaluated by clinical and biochemical studies and by liver biopsy when appropriate. In addition, 76 liver biopsy specimens from these patients were analyzed to determine whether liver lesions were similar in alcoholic patients with and without hepatitis C virus antibodies. According to clinical and histological features alcoholic patients were divided into five groups: normal liver (45 patients), fibrosteatosis (20 patients), alcoholic hepatitis (14 patients), cirrhosis (61 patients) and chronic hepatitis (4 patients). Hepatitis C virus antibodies were present in 35 alcoholic patients (24.3%). The prevalence of hepatitis C virus antibodies correlated with the severity of liver injury: 2.2% in patients without liver disease, 20% in those with fibrosteatosis, 41.4% in those with alcoholic hepatitis and 42.6% in those with cirrhosis. Hepatitis C virus antibodies were found in one of the four patients with chronic hepatitis (p less than 0.001). Furthermore, patients positive for hepatitis C virus antibodies with normal liver or fibrosteatosis showed higher serum bilirubin and gamma-globulin concentrations and lower aminopyrine breath test scores than did patients negative for hepatitis C virus antibodies with normal liver or fibrosteatosis. Similar differences between patients with and without hepatitis C virus antibodies were observed in patients with alcoholic hepatitis or cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)

A group of 70 chronic alcoholics--65 men and 6 women--has been studied. HBsAg was found in 11 (16%), and at least one marker of HBV infection was present in sera from 31 (44%) persons, these results being significantly higher than in a matched control population. The commonest single histological patterns were: steatosis (18 cases), and alcoholic hepatitis (18 cases), followed by normal liver (14 cases) and chronic active hepatitis (12 cases). Cirrhosis was diagnosed in only 4 cases. Five cases of chronic active hepatitis could be attributed to infection with HBV or HDV; in the remaining 7 cases the etiology was unclear. Infection with HBV seems to play an important role as the cause of liver disease among alcoholics in Poland, and chronic active hepatitis of various etiology may be an important form of liver pathology among them.

Alcoholic hepatitis is a necrotizing, often inflammatory, process that is an important precursor to the development of cirrhosis. Acetaldehyde, which is derived from alcohol by the action of alcohol dehydrogenase, is apparently the most important factor leading to alcohol-induced liver injury. Other factors of importance in determining the appearance and rate of progression of liver diseases in patients who are chronic alcoholics include sex, nutritional status, and various immunologic reactions. In addition, there is an incompletely understood genetic predisposition to the development of alcoholic hepatitis. Several histologic features found in patients with alcoholic hepatitis have been evaluated in efforts to determine which are of prognostic value. The predominance of the alcohol-induced injury in zone III of the hepatic lobule; deposition of collagen, IgA, and fibronectin in the space of Disse; defenestration of endothelial cells; and transformation of lipocytes and myofibroblasts to fibroblasts have been investigated. Prolongation of the prothrombin time and marked elevation of serum bilirubin levels are indicators of a subgroup of patients with alcoholic hepatitis who have a poor prognosis, especially if there is also evidence of hepatic encephalopathy. Supportive care and abstinence from alcohol are the foundations of therapy. Corticosteroid therapy appears to decrease the number of early deaths in patients with severe alcoholic hepatitis. Other experimental approaches to therapy include the use of propylthiouracil, anabolic-androgenic steroids, and insulin and glucagon.

One hundred and fifty-seven patients with alcoholic liver disease were studied. Hepatitis B surface antigen (HBsAg) was positive in 20.4% of the patients. Those who were positive for the HBsAg presented at an earlier age, had a lower albumin level, a higher globulin level, a more prolonged prothrombin time, were more likely to have features of cirrhosis in the liver biopsy, and were probably more likely to suffer from hepatic encephalopathy in the follow-up compared with those negative for HBsAg. The mortality of subjects was low both on admission and during follow-up. It is concluded that chronic alcoholism and hepatitis B virus infection act synergistically in producing more severe liver damage and causing cirrhosis at a younger age compared with chronic alcoholism alone. One possible reason for the low mortality of the patients might have been their relatively good nutritional status.

124 consecutive patients (mean age: 41.1 years; range: 20-63 years) attending an outpatient alcoholic clinic were tested for the presence of markers of HBV infection. HBsAg was found in 26 (21%), anti-HBs and/or anti-HBc in the absence of HBsAg in 35 (28%). Altogether, at least one marker was present in 61 (49%), these results being significantly higher than in a matched control population. In 70 cases HBV status was compared with epidemiological data. No relationship was found with past blood transfusions, hospitalization or jaundice. HBV infection was, however, more common when parents of the subjects were alcoholics, which points to a possible role of family spreading. Furthermore, chronic infection with HBV was related to high alcohol intake.

Alcoholics are at risk to develop hepatitis B infections, chronic active hepatitis, and even hepatoma. Hence, immunization with hepatitis B vaccine is recommended. However, immune abnormalities may coexist which alter their responsiveness to vaccination. This study compares the immune response to this vaccine in controls (group I), alcoholics without overt liver disease (group II), and alcoholics with clinical liver disease (group III). By the seventh month after the initial vaccination, 89% in group I, 70% in group II, and 18% in group III had a response greater than 36 RIA units. The magnitude of the response was significantly different in groups I, II, and III (19,456 vs 8,326 vs 153 RIA units, respectively; P less than 0.05, group I vs III). In those who did not respond, a significant (P less than 0.02) lower helper/inducer (T4) class of lymphocytes was observed as compared to patients who exhibited an adequate response. These observations suggest: (1) that the response to hepatitis B vaccine is a T-cell-dependent event and (2) that in this population, using the existing vaccine, postvaccination evaluations of antibody concentrations are needed before protection against hepatitis B infection can be assumed.

102 consecutive alcoholics attending an outpatient alcoholic clinic were tested for hepatitis B virus (HBV) markers in serum. HBsAg was found in 21, anti-HBs in 22 and anti-HBc in 42; at least 1 marker was present in 49. These results were significantly higher than in a matched control population. Out of 21 HBsAg positive cases 7 had markers of ongoing viral replication as judged by the presence of HBeAg and HBV DNA.

Alcoholic liver cirrhosis is a leading cause of morbidity and mortality in alcohol dependence. A common precursor to cirrhosis is alcoholic hepatotoxicity evident clinically by elevated serum liver enzymes. In this study 50 male patients with significant (greater than two times upper limits of normal) elevation of liver enzymes attending a veterans inpatient alcohol treatment center were matched by age and time since last drink to 50 male veterans without elevated liver enzymes. Patients with elevated liver enzymes were found to be more likely to be daily drinkers, less likely to indulge in binge drinking patterns or have alcoholic blackouts, and showed a trend towards a less severe pattern of alcoholism. Significant gamma glutamyl transferase (GGT) elevations were found in patients consuming an average of 7 beers/day for 5 years, and significant aspartate aminotransferase (AST) elevations were found in patients consuming a threshold of 12 beers/day for 10 years. These findings are consistent with current research suggesting alcoholic cirrhosis is a result of a threshold exposure to alcohol in alcoholics with an additional environmental or genetic risk factor.

A study was carried out to confirm the pathogenetic role of ethanol in the development of chronic active hepatitis (CAH) and to assess if previous or current superimposed hepatitis B virus (HBV) infection could be relevant to the course of alcoholic liver disease (ALD). We examined clinical and laboratory reports of 57 alcoholics with biopsy-proven CAH. Serum and/or tissue HBV markers and the presence or absence of cirrhosis were investigated. Alcohol was the only aetiological factor present in a small group of CAH, with or without histological findings suggestive of alcoholic damage. Age, sex and survival were similar among the subgroups of CAH with and without previous or current HBV infection and among the subgroups of CAH with and without associated histological alcoholic features. Among the laboratory data, the AST/ALT ratio was higher in CAH without previous or current HBV infection. The mean age was comparable in CAH patients with and without cirrhosis, whereas the cumulative 5-year survival was worse in CAH with cirrhosis (87% vs. 49%). These data suggest a difference in alcohol susceptibility in our subjects.

The male-female ratio in 186 hepatocellular carcinoma (HCC) Chinese patients was 5:1. The clinical presentation, biochemical parameters, and histologic findings were the same in both sexes except for a higher proportion of underlying cirrhosis (P = 0.02), and spider naevi (P = 0.04) in the men. There were also more smokers and alcohol drinkers among the men. Over 75% of both sexes were positive for the hepatitis B surface antigen. The possible contributory factors to the predominance of males to females in HCC included: the association with the hepatitis B virus, the higher proportion of male cirrhotics, smoking, and alcohol drinking. The survival probability for both sexes was equally poor; the median survival was 8 weeks for males and 10 weeks for females.

In this long-term follow-up evaluation of chronic alcoholics without established cirrhosis we investigated the influence of alcohol on the progression of fibrosis and the prognostic significance of histological features. We were unable to confirm results of retrospective cross-sectional analysis suggesting a linear relationship between alcohol intake and the development of cirrhosis. Alcoholic hepatitis, advanced fibrosis, central hyaline necrosis and central vein sclerosis were unfavorable signs for the further course of the disease. All but one of the patients with central vein sclerosis who progressed to advanced fibrosis also had an alcoholic hepatitis in one of their biopsies. Two patients had an acute alcoholic hepatitis initially, and later showed the mixed histological pattern of an alcohol-induced chronic active hepatitis, a pattern which was also seen in four other patients, all progressing to cirrhosis. This may be taken as evidence that immunological factors contribute in some patients to progression of fibrosis.

Serum and tissue hepatitis B virus (HBV) markers were compared in 35 alcoholic and 23 non-alcoholic subjects affected by chronic liver disease. Seventeen point one per cent of alcoholic and 21.7% of non-alcoholic subjects had HBV tissue markers, but not serum markers, for this virus. It is therefore concluded that showing the presence of HBV tissue markers permits a better aetiological definition of hepatitis B surface antigen (HBsAg) negative chronic liver disease, both in alcoholic and non-alcoholic subjects.