Five-year survival predictive factors in patients with excessive alcohol intake and cirrhosis. Effect of alcoholic hepatitis, smoking and abstinence.

AIM: To evaluate 5-year survival predictive factors in hospitalised patients with excessive alcohol intake and cirrhosis, including in a multivariate analysis the severity of the liver disease, gastrointestinal bleeding, concomitant viral B or C infection, smoking status, presence of alcoholic hepatitis at inclusion and abstinence from alcohol during follow-up. METHODS: In a non-concurrent cohort study, 122 patients with excessive alcohol intake and cirrhosis were followed up at least five years or till death. Two patients were lost to follow-up. RESULTS: The 5-year survival rates were 43% in the 122 patients and 66%, 50% and 25% in Child-Pugh class A, B and C patients, respectively. In multivariate analysis, age (P = 0.01), Child-Pugh score (P = 0.0001), gastrointestinal bleeding (P = 0.01), presence of HBs Ag and/or anti-HCV (P = 0.03), smoking (P = 0.01), absence of histologically proven alcoholic hepatitis (P = 0.05) and persistent alcohol intake (P = 0.002) were associated with significantly increased risk ratios of death. CONCLUSIONS: In hospitalised patients with excessive alcohol intake and cirrhosis: (1) age, liver failure, gastrointestinal bleeding, concomitant viral B or C infection and persistent alcohol intake are independent poor prognostic markers, (2) smoking may contribute to the aggravation of cirrhosis, and (3) alcoholic hepatitis, being a potentially reversible cause of liver failure, has a favourable prognostic significance.

Cigarette smoking and hepatic lesions in patients with chronic hepatitis C.

A possible hepatotoxicity of cigarette smoke has been recently suggested by epidemiological and experimental studies. Our aim was to study the possible relationships between smoking and liver fibrosis and activity in patients with chronic hepatitis C. A cross-sectional study was performed in a group of 310 patients with chronic hepatitis C consecutively hospitalized for their first liver biopsy. The relationships between age, gender, alcohol consumption, route of contamination, tobacco consumption, and Knodell fibrosis and activity scores were examined in univariate, age-adjusted, and multivariate analyses. One hundred and seventy-six patients (57%) were current smokers. Smokers were younger (P <.001), more often of male gender (P =.001), more often alcohol consumers (P =.001), and more often had a history of intravenous drug use (P =.0001) than never smokers. Smoking was related to increased fibrosis and activity scores in age-adjusted (P =.009 and P =.005, respectively) and multivariate analyses (P =.03 and P =.04, respectively). Smoking increases the severity of hepatic lesions in patients with chronic hepatitis C.

[Screening of cancerous and precancerous lesions of the oral mucosa in an at-risk population]. / Dépistage des lésions cancéreuses et pré-cancéreuses de la muqueuse buccale dans une population à risque.

Early diagnosis of oral carcinomas allows a limitation of functional consequences of surgical treatment. A prospective study was designed in 270 alcoholic patients. We practiced a clinical examination of the oral cavity by a stomatologist followed by a Toluidin blue test. The clinical examination permitted to detect 1 carcinoma and 23 leukoplakias. The Toluidin blue test revealed one more carcinoma and two leukoplakias more. The early diagnosis of oral carcinomas in alcoholics patients gives them a better survival. The Toluidin blue test could be proposed as an aid to early diagnosis of these carcinomas.

[Evaluation of drug treatment of primary alcoholism]. / Evaluation des traitements médicamenteux de l'alcoolodépendance psychique primaire.

Clinical improvement (abstinence and sobriety) can be obtained in 30% of alcohol dependent (primary) patients at one year when therapy consists of meetings and talking with physicians. The association of drugs led to 40% clinical improvement in controlled studies. These drugs are acamprosate (Aotal), which is well tolerated and shown to be beneficial at one year, naltrexone (Revia), also well tolerated with a follow-up of 3 months, and lithium (Téralithe), to be used more cautiously, with a follow-up of one year. Disulfirame (Espéral), is poorly effective in its usual oral prescription, but is useful when prescribed with the assistance of a close relation. The authors propose an individual drug approach to each patient, with assessment of results at a set date.

Effect of alcohol consumption on serum hepatitis C virus RNA and histological lesions in chronic hepatitis C.

The role of alcohol intake in the occurrence of severe liver disease in chronic hepatitis C virus (HCV) carriers is still debated. A cross-sectional study has been conducted in 233 chronic hepatitis C virus carriers. Weekly self-reported alcohol consumption (SRAC) was evaluated, serum HCV RNA levels were measured by a branched DNA technique (Quantiplex 2.0) and HCV genotypes were determined. A liver biopsy was performed simultaneously and liver lesions were graded with the Knodell histological activity index. Data were examined by uni- and multivariate analyses. Alcohol consumption was relatively low (< 140 g/per week in 193/233 patients [80%]). We found a highly significant correlation between SRAC and serum HCV RNA levels (r = .26, P = .001). Fibrosis was significantly correlated with age and alcohol consumption. These results suggest that in HCV carriers, alcohol consumption, even with low alcohol intake, increases viremia and hepatic fibrosis. Chronic HCV carriers should be advised to avoid regular alcohol intake.

Survival and prognostic factors in patients with severe alcoholic hepatitis treated with prednisolone.

BACKGROUND & AIMS: Corticosteroids have been shown to significantly decrease short-term mortality in patients with severe alcoholic hepatitis. However, independent factors associated with a favorable outcome and long-term survival are unknown. The aim of this study was to examine prognostic factors and long-term survival in patients with biopsy-proven severe alcoholic hepatitis. METHODS: Of 183 patients studied, 61 had been randomized in a previous trial; 32 of them were treated with prednisolone (group I) and 29 were not treated (group II); 61 were treated from the end of this randomized trial (group III); and 61 were simulated (group IV). RESULTS: At 1 year, survival in group I (69%; confidence interval [CI], 57%-81%) and group III (71%; CI, 55%-87%) was better than in the nontreated groups (group II, 41%; CI, 23%-59%; P = 0.01) (group IV, 50%; CI, 37%-63%; P = 0.05). At 2 years, survival was not significantly different. Treated patients with marked liver polymorphonuclear infiltrate had better 1-year survival (76%; CI, 64%-88%) than the others (53%; CI, 35%-71%; P = 0.05). Treated patients with polymorphonuclear counts of > 5500/mm3 had better 1-year survival (77%; CI, 65%-89%) than the others (40%; CI, 14%-66%; P = 0.003). In the 93 treated patients, liver polymorphonuclear infiltrate (P < 0.03) and polymorphonuclear count (P < 0.001) were independently correlated with 1-year survival. CONCLUSIONS: Prednisolone reduced mortality by at least 1 year. Liver polymorphonuclear infiltrate and polymorphonuclear count were independent prognostic factors.

Improving hypertension control among excessive alcohol drinkers: a randomised controlled trial in France. The WALPA Group.

OBJECTIVES: To improve blood pressure control among hypertensive ( > 140/90 mmHg) excessive alcohol drinkers. DESIGN: Fourteen worksite physicians were randomised onto an intervention group and a control group. The intervention was based on training the worksite physicians and follow up of those hypertensive subjects defined as excessive drinkers. Follow up was based on self monitoring of alcohol consumption by the subject, in view of the results of their gamma glutamyl transferase (GGT) activity determination. SETTING: Fourteen workplaces in France - mainly in the industrial sector. SUBJECTS: Altogether 15 301 subjects were screened by the 14 physicians: 129 of these were included in the study. MAIN OUTCOME MEASURES: This was the difference between the initial systolic blood pressure (SBP) and the SBP one year later (delta BP). Secondary criteria were the difference between the initial and final diastolic blood pressure (delta DBP) and delta BP at two years; antihypertensive treatment; state alcohol consumption (delta AC); delta GGT; and body mass index (delta BMI). RESULTS: The decrease in SBP levels was significantly larger in the intervention group than in the control group: at one year, delta SBP values were -11.9 (15.6) mmHg and -4.6 (13.8) respectively (p < 0.05). This benefit was still observed after two years of follow up (-13.8 (17.4) mmHg v -7.5 (14.2) mmHg (p < 0.05)). No difference was observed in DBP. The percentage of treated subjects did not differ between groups. At one year, delta AC was larger in the intervention group (-2.8 (5.2) U/d) than in the control group (-1.6 (3.4) (p < 0.1)). delta GGT and delta BMI did not differ between the two groups. A weak positive correlation was observed between delta AC and delta SBP (r = 0.16). CONCLUSION: An intervention aimed at the hypertensive excessive drinkers in a working population was found to be effective in reducing SBP on a long term basis (two years). The mechanisms of reduction in alcohol consumption and improved drug compliance cannot be ascertained in this pragmatic study. From a public health point of view, reducing the excess cardiovascular risk among a "hard to reach" population seems feasible with a strategy specifically designed for this high risk group.

Parental history of alcoholism: a risk factor for alcohol-related peripheral neuropathies.

The aim of this study was to identify the risk factors of alcohol-related peripheral neuropathies. A case-control study was performed to compare two groups of alcoholic patients, one with peripheral neuropathy and the other without, but with alcohol-related cirrhosis, pancreatitis or cardiomyopathy. Ninety patients were recruited in four in-patient units of a French hospital: 32 patients had a peripheral neuropathy and 58 patients did not. Univariate analysis showed no differences between the two groups for sex, age, body mass index and duration of the alcoholic disease. Peripheral neuropathies were associated with a higher frequency of parental history of alcoholism, severity of alcohol dependence, heavier alcohol consumption and more alcohol-related somatic diseases. Multivariate analysis showed a strong relationship between a parental history of alcoholism and the presence of a neuropathy, when the severity of the alcoholic disease was taken into account (adjusted OR = 6.8, IC95% [2.2-21.6], P < 0.001). The hypothesis that neuropathy may be a marker of an inherited susceptibility to alcoholism is discussed.

Relationship between alcohol and tobacco dependencies among alcoholics who smoke.

Outpatients followed in an alcoholic clinic and who fulfilled DSM-III-R criteria for alcohol dependence and had used both tobacco (at least one cigarette every day) and alcohol in the preceding week were studied. For each patient, two experimenters assessed: (1) the amount of tobacco and alcohol used; (2) the severity of dependence for each product. Results showed that: (a) The prevalence of smoking in this population of current alcohol dependents was 88%; (b) 91.6% of this sample of smoker alcoholics were dependent on nicotine; (c) the amount of tobacco smoked was correlated to the amount of alcohol consumed and the severity of alcohol dependence; and (d) there was a correlation between the severity of alcohol and nicotine dependencies. The results of this study may help to clarify the difficulty of treating tobacco dependence in alcoholics.

Prompting alcoholics to be referred to an alcohol clinic: the effectiveness of a simple letter.

Many patients received in emergency units (EU) of hospitals present alcohol-related problems. Most are alcohol dependent or abusers and enter for drunkenness, stay a few hours and return home. To assess the effectiveness of a letter referring these patients to an outpatient alcoholism treatment clinic, we performed a randomized study. For 6 months, all the patients who had been diagnosed as alcoholic, who had an address and who had not consulted a physician for alcoholism in the 6 previous months were selected from the records of the EU of a French university hospital. At least 2 days after their stay in the EU, we sent a letter to 181 patients of an experimental group (group E) suggesting they make an appointment with a physician specializing in alcoholism. No letter was sent to 181 patients in a control group (group C). Six months later, 21 patients (11.2%) of group E had called the outpatient alcoholism treatment clinic to make an appointment and came to a consultation. Two of the 181 patients of group C came to the consultation. The effectiveness of this method for referring alcoholics to a clinic had been controlled by another prospective study. We concluded that sending a letter 2 days after the passage of an alcoholic to an EU for drunkenness is a useful method of referral to an outpatient alcoholism treatment clinic.

A multidimensional case-control study of dietary, alcohol, and tobacco habits in alcoholic men with chronic pancreatitis.

This study compared diet, type of alcoholism, and smoking in three groups of alcoholic men, with chronic pancreatitis (n = 56), with histological cirrhosis (n = 50), and without pancreatitis or cirrhosis (controls; n = 50) by a multidimensional analysis. Only patients in whom the first symptom of pancreatitis or cirrhosis was present for < 1 year before the interview were included. Patients with pancreatitis consumed more nonalcohol calories than cirrhotics (p < 0.05). The percentage of calories taken as proteins (p < 0.0003) and lipids (p < 0.0001) was higher and the percentage of calories taken as alcohol (p < 0.0003) was lower in patients with pancreatitis than in cirrhotics and control patients. There was no difference among the three groups for total calories/basal energy expenditure ratio, total nonalcohol calories/basal energy expenditure ratio, mineral and vitamin intake, or tobacco consumption. The duration of excessive alcohol consumption and the total alcohol consumption in patients with pancreatitis was similar to that of controls but lower than that of cirrhotics (p < 0.002 and p < 0.05, respectively). Three parameters were found to be independently different in the three groups by discriminant analysis: percentage of calories taken as lipids (p < 0.0001), duration of excessive alcohol consumption (p < 0.002), and percentage of calories taken as proteins (p < 0.08). These three parameters explained 24% of the variance. We conclude that the reasons alcoholic men develop chronic pancreatitis may be explained partly by dietary habits.(ABSTRACT TRUNCATED AT 250 WORDS)

Deleterious influence of pyrazinamide on the outcome of patients with fulminant or subfulminant liver failure during antituberculous treatment including isoniazid.

Isoniazid and pyrazinamide are well-known hepatotoxic drugs, often used in combination. The aim of this study was to assess the prognostic influence of pyrazinamide on the outcome of fulminant or subfulminant liver failure caused by antituberculous therapy. Eighteen patients with fulminant or subfulminant liver failure due to antituberculous therapy were studied. Nine patients received isoniazid and rifampicin without pyrazinamide (group 1), and nine patients received isoniazid and rifampicin together with pyrazinamide (group 2). The severity of fulminant and subfulminant liver failure, as judged by the prevalence of coma and the lowest level of factor V, was similar in the two groups. Spontaneous survival was greater in group 1 (eight of nine) than in group 2 (two of nine) (P < .02). The authors conclude that pyrazinamide co-administration was associated with an increased mortality in patients with fulminant or subfulminant hepatitis occurring during antituberculous therapy. In these patients, pyrazinamide administration and an interval of more than 15 days between the onset of antituberculous treatment and jaundice, combined with grade III encephalopathy and factor V below 20%, predicted death without liver transplantation.

Effect of clonidine on liver oxygen extraction during alcohol withdrawal in man.

Since catecholamines can alter splanchnic oxygen transport and extraction, the suppression of sympathetic overactivity during alcohol withdrawal might improve hepatic oxygen extraction. Therefore, this study investigated the effects of clonidine, a centrally-acting alpha 2-agonist which reduces sympathetic nervous outflow, on splanchnic oxygen transport and extraction in 13 patients with chronic alcoholism during alcohol withdrawal. All patients had elevated transaminases and steatosis at liver biopsy and were withdrawn from alcohol 51 +/- 15 h (mean +/- SD) before the study. Hepatic blood flow, cardiac output and the oxygen contents were measured in the radial and pulmonary arteries and in the hepatic veins before and 45 min after intravenous administration of clonidine, 150 micrograms. Basal hepatic blood flow was inversely correlated with norepinephrine plasma concentrations (r = -0.63, p < 0.025). After clonidine administration, the decrease in plasma norepinephrine correlated with the norepinephrine basal value (r = 0.889, p < 0.001), and splanchnic oxygen extraction increased (from 40 +/- 15 to 49 +/- 17%, p < 0.025). After clonidine administration, splanchnic oxygen extraction was correlated with the decrease in plasma norepinephrine (r = 0.72, p < 0.01). Arterial lactate concentration decreased (from 0.74 +/- 0.20 to 0.64 +/- 0.23 mmol/l, p < 0.01). These results suggest that defective liver oxygen extraction might occur during alcohol withdrawal as a result of sympathetic nervous hyperactivity. Alterations in the hepatic microcirculation during withdrawal might be related to catecholamine secretion and be controlled by pharmacological manipulation.

Medical treatment for alcoholic liver disease.

The most effective treatment for alcoholic liver disease is abstinence from alcohol and it is the only treatment for patients with alcoholic fatty liver. Although many empirical therapeutic agents have been studied in the short-term and long-term treatment of alcoholic hepatitis, results have been mainly inconclusive. To date, only corticosteroids have proved to decrease the short-term mortality rate of patients with severe forms of acute alcoholic hepatitis. Corticosteroids are not beneficial to the majority of patients with mild or moderate forms of acute alcoholic hepatitis; such patients improve with abstinence from alcohol and general supportive measures and do not need a specific short-term treatment. Most long-term trials have only showed that most patients with alcoholic liver disease were neither abstinent nor compliant, and that long-term survival was strongly correlated to abstinence from alcohol. In one study, propylthiouracil decreased the long-term mortality rate of compliant patients with severe alcoholic liver disease who reduced their alcohol intake; however, further clinical trials are needed before propylthiouracil can be recommended. In another study, colchicine decreased the long-term mortality rate of cirrhotic patients, 45% of whom had alcoholic cirrhosis. Results were highly significant, and the need for further clinical trials of colchicine in the long-term treatment of alcoholic and non-alcoholic cirrhosis is imperative. Enteral nutrition should also be studied in severely malnourished cirrhotic patients, since it was shown to decrease the short-term mortality rate of such patients in a recent study.

Herpesvirus infection of the respiratory tract in patients with alcoholic hepatitis.

Respiratory herpesvirus infections have rarely been described in alcoholics. We report four cases of severe respiratory herpesvirus infections in patients with alcoholic liver disease. Two were related to Herpes Simplex Virus and two to Cytomegalovirus. Both chronic alcoholism and severe liver disease induce immunosuppression, which might account for these unusual herpesvirus infections of the respiratory tract. These cases suggest that infections with herpesviruses should be considered in patients with alcoholic liver disease and pulmonary or tracheobronchial disease unresponsive to standard antibiotic therapy. Bronchoscopy, viral culture, and serological tests appear warranted, particularly given the existence of specific therapy.

A randomized trial of prednisolone in patients with severe alcoholic hepatitis.

BACKGROUND: Controlled trials have yielded inconsistent results with regard to the efficacy of corticosteroids in the treatment of alcoholic hepatitis. Three meta-analyses suggest that they may be effective in patients with encephalopathy who have severe liver disease. METHODS: We conducted a randomized, double-blind trial comparing 28 days of prednisolone treatment (40 mg per day) with placebo in 61 patients with biopsy-proved alcoholic hepatitis and either spontaneous hepatic encephalopathy (n = 19) or a discriminant-function value higher than 32. The discriminant function used was as follows: 4.6 (prothrombin time-control time [in seconds]) + serum bilirubin (in micromoles per liter)/17. Fifty-seven of the patients had evidence of cirrhosis on biopsy. The primary end point was death within two months. RESULTS: One patient was lost to follow-up after 56 days. Treatment was discontinued in two patients because of drug toxicity. By the 66th day after randomization, 16 of 29 placebo recipients had died (mean [+/- SE] survival, 45 +/- 8 percent), as compared with 4 of 32 prednisolone recipients (survival, 88 +/- 5 percent) (log-rank test, 10.9; P = 0.001). The survival advantage for prednisolone persisted after stratification according to center and the presence of encephalopathy, and after adjustment for prognostic factors in a proportional-hazards model. CONCLUSIONS: Treatment with prednisolone improves the short-term survival of patients with severe biopsy-proved alcoholic hepatitis.

[Atrium-related hepatitis. Report of four cases]. / Hépatites au cours de l'administration d'Atrium. Observation de quatre cas.

Four patients developed acute hepatitis after receiving Atrium, an association of phenobarbital, febarbamate and difebarbomate, for the treatment of tremor or for the prevention of alcohol withdrawal symptoms. Hepatitis occurred 1 to 3 months after treatment. Asthenia was the unique clinical manifestation. Marked increase in serum aminotransferases and gamma-glutamyltranspeptidase levels were the main biological features. Histological examination showed liver cell necrosis in two cases, prominent in the centrolobular area in one case. There was no case of hepatic failure. Atrium withdrawal was followed by complete recovery within 6 to 12 weeks. The mechanism of Atrium hepatotoxicity remains unknown.

[Prevalence of alcoholic diseases. At a teaching hospital of the Paris suburbs]. / Prévalence des maladies alcooliques. Dans un hôpital universitaire de la banlieue parisienne.

During the last 15 days of January 1989, the 757 patients admitted for more than 48 hours in any of the departments of Hôpital Beaujon (Clichy) were investigated for diseases that were certainly or probably related to alcoholism, and in order to detect drinkers at high risk, the amount of alcohol consumed in a week was recorded. The prevalence of alcohol-related diseases was 14.7 per cent (range: 12.2 per cent-17.2 per cent) and that of alcohol consumers at high risk was 4.2 per cent (range: 2.8 per cent-5.6 per cent).