[Alcoholic hepatitis]. / Hépatite alcoolique aiguë

Alcoholic hepatitis is one of the most severe presentations of alcoholic liver disease. It is usually revealed by the recent onset of jaundice in a patient with alcoholic cirrhosis. Maddrey's discriminant function can help to recognize patients with poor prognosis (the 6-month mortality is above 50% when it exceeds 32). Corticosteroids increase survival in those patients with high risk of death. Other treatments (pentoxifylline, N-acetyl-cysteine or enteral nutrition) need to be investigated further before to recommend their routine use instead of, or in association with, corticoids. Liver transplantation can be proposed to highly selected patients who do not respond to medical therapy. In any case, long-term prognosis will primarily depend on the maintenance of alcohol abstinence.

Triggering of acute alcoholic hepatitis by alpha-interferon therapy.

BACKGROUND/AIMS: Alcohol may induce autoimmunity by recognition of acetaldehyde-modified proteins which may be implicated in the pathogenicity of acute alcoholic hepatitis. We report here the potential role of alpha-interferon, a potent inducer of the autoimmunity process, in inducing alcoholic hepatitis. METHODS: We analyzed clinical, biological, virological and histological features in two cases where alpha-interferon treatment for HCV-related hepatitis led to a marked increase in aminotransferase activities. RESULTS: alpha-interferon as treatment of HCV-related hepatitis seemed to exacerbate acute alcoholic hepatitis despite moderate alcohol consumption. In Case 1, moderate daily alcohol intake of 40 g during therapy led to biopsy-proven acute alcoholic hepatitis, while the same consumption before therapy did not. In Case 2, before treatment, the liver biopsy showed mild acute alcoholic hepatitis; aminotransferases increased during alpha-interferon therapy, although no increase in alcohol intake was observed. CONCLUSION: alpha-interferon therapy by its immunomodulatory properties could be implicated in alteration of the course of acute alcoholic hepatitis. These observations emphasize that the decision to treat with alpha-interferon when there is even moderate alcohol consumption should be carefully weighted in HCV-infected patients.

ESBRA 1997 Award lecture: relationship between excessive alcohol drinking and viral infections.

Several epidemiological studies suggest that chronic alcoholics are at risk of viral infections. Clinical and basic research has demonstrated that alcohol not only worsens the natural history of chronic viral hepatitis, but also seems to interact with the viral replication cycle leading to an unusual serum virological profile and/or modification in the serum concentration of viral particles. Infections with hepatitis B and C viruses are a major risk for the development of hepatocellular carcinoma in excessive drinkers who should be protected against these viruses.

A comparative study between carbohydrate-deficient transferrin and gamma-glutamyltransferase for the diagnosis of excessive drinking in a liver unit.

AIM: To compare the efficacy of carbohydrate-deficient transferrin and gamma-glutamyltransferase for the diagnosis of excessive alcohol intake in patients admitted in a liver unit. METHODS: The 346 patients were divided into three groups of alcoholics: 57 patients (31 men, 26 women) with a normal liver, 77 patients (51 men, 26 women) with non-cirrhotic alcoholic liver disease, and 61 patients (43 men, 18 women) with alcoholic cirrhosis; and three groups of non-alcoholics: 35 abstainers (21 men, 14 women), and 58 healthy blood donors (26 men, 32 women), and 58 patients (32 men, 26 women) who had a non-alcoholic liver disease. Carbohydrate-deficient transferrin and gamma-glutamyltransferase were measured at admission using commercially available kits. RESULTS: Carbohydrate-deficient transferrin was more sensitive than gamma-glutamyltransferase in patients without alcoholic liver disease, in both men (85 vs 54%) and women (64 vs 36%). Carbohydrate-deficient transferrin sensitivity decreased slightly but not significantly according to the severity of the liver disease in men and women. The sensitivity of gamma-glutamyltransferase which was low in men and women without alcoholic liver disease, improved in groups with moderate or severe alcoholic liver disease: not less than 80% in men and up to 100% in women. The specificity of carbohydrate-deficient transferrin in patients with non-alcoholic liver disease was consistently higher than that of gamma-glutamyltransferase (80% vs 60%). CONCLUSIONS: In liver units, carbohydrate-deficient transferrin can help to identify excessive drinkers without liver disease with a higher efficacy than that of gamma-glutamyltransferase; carbohydrate-deficient transferrin can also be used to distinguish between alcoholics with moderate liver disease and patients with non-alcoholic liver diseases.

[Sero-epidemiology of hepatitis A: alcoholic patients are a group at risk]. / Séro-épidémiologie de l'hépatite A: les alcooliques sont un groupe à risque.

OBJECTIVES: The possibility of "community-acquired" viral infection has been suggested in alcoholics. In order to assess this hypothesis, we evaluated the prevalence of antibodies against hepatitis A virus, a oro-fecally transmitted virus, in heavy drinkers. PATIENTS AND METHODS: We retrospectively studied 258 heavy drinkers, 188 males and 70 females, divided into sub-groups of increasing age, and compared them to 277 similarly classified blood donors. RESULTS: The prevalence of serum anti-hepatitis A antibodies was significantly higher in alcoholics than in controls (64.7 vs 52.3%, P < 0.01). The difference was particularly marked in patients younger than 45 years old (56.2 vs 39.1%, P < 0.01). In the alcoholics, there was no correlation between the prevalence of anti-hepatitis A antibodies and the socioeconomic level, the quantity of alcohol ingested, or the severity of the underlying liver disease. CONCLUSION: These results suggest that alcoholism is, per se, a risk factor for viral infections.

Clinical impact of drug addiction in alcoholics.

Careful interviewing of alcoholics who wish to undergo alcohol withdrawal programmes reveals that some are past intravenous drug abusers. As these two potentially hepatotoxic types of substance abuse could cause liver disease or influence its clinical course, we studied biological, histological and virological features in 26 alcoholics with a past history of intravenous (i.v.) drug abuse, compared with paired controls (alcoholics without i.v. drug abuse). There were no differences with regard to routine liver test results. In contrast, the former drug abusers had a significantly higher prevalence of serum markers of hepatitis C (76.9%) and hepatitis B viruses (76.9%) than the other patients (16.7 and 12.5%, respectively). Eight patients, all of whom were HBs Ag negative, were positive for serum HBV-DNA; three were former drug abusers and five were not, giving an overall prevalence of HBV markers in the two groups of 80.8 and 25%, respectively. Two former drug abusers had anti-HIV antibodies and one had anti-hepatitis delta virus antibodies. Ten of the 17 former drug abusers who underwent liver biopsy had histological signs of viral infection. These data underline the need for careful interviews of alcoholic patients, together with serological tests for viral infections and histological analysis of the liver, as some will have liver-damaging viral diseases and may be candidates for anti-viral (i.e. interferon) treatment.

Red blood cell deformability and alcohol dependence in humans.

Studies of DPH fluorescence polarization and deformability have shown that alcohol induces rigidification of the red blood cell (RBC) membrane. We investigated a possible link between RBC membrane fluidity and deformability by studying both parameters simultaneously in samples from alcohol-dependent patients (group 1, N = 19), social drinkers (group 2, N = 12) and long-term abstaining alcoholics (group 3, N = 8). The active drinkers showed disturbances of several RBC membrane parameters, including abnormal microorganization of the membrane surface, a decrease in sialic acid content, and resistance to the fluidizing effect of ethanol, that were not completely corrected in the abstinent alcoholics. The RBC transit time was significantly longer in the active drinkers than in the abstainers but not the social drinkers. There were no significant differences between the groups with regard to membrane lipid core fluidity. The main abnormality (fluidization) in RBC from the active alcoholics involved the polar surface of the membrane (probed using TMA-DPH), and correlated with the decrease in sialic acid content but not with RBC deformability.

Secondary immune response to hepatitis B virus vaccine in alcoholics.

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.

Hepatitis C viremia and anti-HCV antibodies in alcoholics.

We determined serum hepatitis C status using a RIBA2 kit and a sensitive PCR procedure in 62 chronic alcoholics, 36 of whom had anti-HCV antibodies (Ab) detectable in an ELISA1 assay. Anti-HCV antibodies were detected in 22 patients using RIBA2. HCV RNA was detected by means of PCR in 18 patients who were RIBA2 positive and in none who were RIBA2 negative. Liver biopsies, available for 12 HCV RNA-positive patients, revealed histological features of purely alcohol-related lesions in seven and mixed alcohol-viral lesions in five. These results indicate that HCV replication is maintained in most alcoholics who score positive for anti-HCV Ab in the RIBA2 test, and that HCV viremia can be associated with histological features typical of alcoholic liver disease.

[Alcohol dependence. Financial aspect and socio-occupational consequences]. / La dépendance à l'alcool. Aspect financier et conséquences socio-professionnelles.

The financial cost of alcohol dependence was evaluated in 133 alcoholic patients. The main amount of money spent daily on alcoholic beverages was 94 French francs, a figure that was unrelated to the patients' monthly incomes and highest in those living alone and in those drinking exclusively out of home. These results suggest that the economic cost of alcohol dependence plays a key role in the socio-professional degradation of alcoholics.