Abstinence from alcohol and alcohol rehabilitation therapy in alcoholic liver disease: a population-based study.

Objective: Abstinence from alcohol is recommended in patients diagnosed with alcoholic hepatitis (AH) and alcoholic cirrhosis (AC). We aimed to determine the impact of alcohol abstinence on prognosis of patients with AC and AH.Methods: All incident AC and AH patients in Iceland 2001-2016 were identified. Cirrhosis was confirmed clinically, biochemically, with imaging and histologically. Abstinence, alcohol rehabilitation and survival were analyzed.Results: Overall, 169 patients with AC and/or AH were identified. Eleven died during index hospitalization, leaving 158 patients for final analysis, median (IQR) age 56 years (48-65), 72% males. Over all 61 patients (39%) had AC, 40 (25%) AH and 57 (36%) features of both. Thirty-nine percent of patients remained abstinent during follow-up and 63% underwent alcohol rehabilitation. Moderate to severe ascites at diagnosis (odds ratio (OR): 3.05, 95% confidence interval (CI): 1.37-7.02) and lack of alcoholic rehabilitation (OR: 5.28, 95% CI: 2.24- 14.11) were independent predictors of abstinence. Abstinence at one year of follow-up was not related to increased survival. Patients surviving one year, abstinence during follow-up was related to increased survival for both groups.Conclusion: Abstinence from alcohol following AC/AH diagnosis was achieved in 39% of patients. Abstinence was not related to increased survival for alcoholic liver disease patients at one-year, which might partly indicate that this might be a marker that some patients were 'too sick to drink'. AC and AH patients who survived one year and remained abstinent had a favorable long-term prognosis.

[Management of severe alcoholic hepatitis]. / Management bei schwerer alkoholischer Hepatitis.

Severe alcoholic hepatitis is still associated with high mortality and presence of liver failure manifested by jaundice, coagulopathy and encephalopathy is a poor prognostic indicator. The management of these patients includes at first hand several supportive measures as treatment of alcohol withdrawal, administration of fluid and vitamins and admission to an intensive care unit in the unstable patient. Glucocorticoids have been since decades the most intensively studied therapy in alcoholic hepatitis and are effective in certain subgroups. Indication for such a therapy is usually defined on a Maddrey Discriminant Function > 32. The Lille score at day 7 is used to decide whether corticosteroid therapy should be stopped or continued for a 1 month course. Nutritional supplementation is also likely to be beneficial. The main progress in better understanding its pathophysiology has come from cytokine studies. Various proinflammatory cytokines such as tumor necrosis factor-alpha (TNFα) or interleukin-1 (IL-1) have been proposed to play a role in this disease. This advancement has recently led to pilot studies investigating anti-TNF drugs such as pentoxifylline, infliximab (anti-TNF antibody) or etanercept in the treatment of this disease. These studies revealed besides for pentoxifylline rather negative results. Despite this fact, targeting of certain cytokines such as IL-1 remains an attractive treatment concept for this devastating disorder in the future.

Ethanol toxicity: rehabilitation of hepatic antioxidant defense system with dietary ginger.

The current investigation has been conducted to investigate the influence of ginger on hepatic antioxidant enzymes system in ethanol treated rats. Ethanol significantly decreased the superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione content while an increase of malondialdehyde (MDA) levels were estimated in the hepatic tissue. This effect was reversed by a treatment with 1% dietary ginger for 4 weeks in rats by improved antioxidant status which suggest that treatment of ginger may have protective role against the ethanol induced hepatotoxicity.

[Social-medical aspects of chronic liver diseases]. / Sozialmedizinische Aspekte chronischer Lebererkrankungen.

In our country liver diseases are frequent and have many different causes. They can often develop into cirrhosis of the liver with mortality beetween 13.5% and 24.5%. Hepatitis B and C-viral infections frequently play a significant role in the recognition of an occupational disease in the case of medical staff, with histological criteria of major importance in this respect. A consequence of cirrhosis of the liver may be the development of hepatoencephalopathia of varying degrees of severity. As it is then likely that a patient will no longer be able to drive motor vehicles, it is important that attending physicians inform their patients accordingly. Liver transplants are an acknowledged method of treatment in the therapy of advanced liver cirrhosis. Rehabilitation shortly after transplantation is highly important to help ensure a speedy return to work. Surprisingly, reintegration is more difficult in patients suffering from alcohol related liver disease than in those with non-alcohol-related liver disease.

Low serum amylase levels in drinking alcoholics.

BACKGROUND: We have reported that the serum level of amylase, different from other pancreatic enzymes, increases temporarily after abstinence in alcoholics. To elucidate the mechanism of this phenomenon, pancreatic isoamylase, salivary isoamylase, and amylase in urine were measured together with total serum amylase. METHODS: Total serum amylase, pancreatic isoamylase, and salivary isoamylase values were measured in 38 male patients admitted to the National Alcoholism Center, Kurihama Hospital, for alcoholism after abstinence. In an investigation of amylase secretion, amylase in urine was measured in some patients after abstinence. RESULTS: In the group with abnormally high total serum amylase on admission, levels were found to decrease after abstinence. In patients with pancreatic disorders in this group, abstinence leads to a decrease in total serum amylase, but in patients with no such disorders, total serum amylase increases temporarily due to increases in salivary isoamylase. In the group with normal total serum amylase on admission, levels increased sharply after abstinence, and both pancreatic isoamylase and salivary isoamylase contributed to the gains. In the group with low total serum amylase, a sharp increase of 2-fold or more was noted after abstinence, and a major contributor was pancreatic isoamylase. The ratio of urine amylase to total serum amylase gradually declined, indicating clearly that abstinence led to a decrease in the excretion of amylase in urine. CONCLUSIONS: In cases of heavy alcohol consumption, a decrease in the production or secretion of pancreatic isoamylase and salivary isoamylase while drinking could happen. It was thus suggested that the increase in serum amylase might be due to the fact that this situation is improved by abstinence, plus the fact that excretion of amylase in urine increases during alcohol consumption, and abstinence brings about a decline in such excretion. Measurement of total serum amylase is not appropriate for diagnosing pancreatitis in alcoholic patients or those who consume large quantities of alcohol.

Hyperhyaluronanemia in alcoholic hepatitis is associated with increased levels of circulating soluble intercellular adhesion molecule-1.

The purpose of this study was to evaluate the role of the sinusoidal endothelial cell (SEC) during the clinical course of alcoholic hepatitis. Twenty consenting patients (mean age: 49.4 +/- 11.0 years) with moderate or severe hepatitis were studied. The patients were selected and characterized according to their history of drinking and laboratory profile, including serum aminotransferases, bilirubin, total white blood cell and neutrophil count, and prothrombin times. C-reactive protein and interleukin-6 were also measured as markers of the hepatic acute phase response. A marker of the SEC functional state, the circulating level of hyaluronan, was measured in parallel with the circulating levels of soluble intercellular adhesion molecule (sICAM)-1 over a 6-month observation period. All patients were hospitalized for the first month and encouraged to abstain from drinking for the duration of the study. The initial increased levels of both hyaluronan (542 +/- 32 ng x ml(-1) serum) and sICAM-1 (488 +/- 70 ng x ml(-1) serum), gradually fell during the 6-month observation period, eventually reaching values close to those seen in healthy subjects. A positive correlation was obtained between changes in these two markers of SEC function/activation on the one hand, and between these two tests and bilirubin, on the other hand. These data indicate that abnormalities of SEC function/activation, as reflected by serum hyaluronan and siCAM-1, are prominent in alcoholic hepatitis, and these alterations improve within relatively short periods of time after cessation of alcohol consumption.

Abnormalities of peripheral blood T lymphocytes and natural killer cells in alcoholic hepatitis persist after a 3-month withdrawal period.

Present information about the behavior of the different lymphoid subsets in alcoholic hepatitis (AH), including cells displaying cytotoxic activity, is scanty and contradictory. The aim of this study was to gain further insight into knowledge of the immunological abnormalities involved in AH and the possible role of ethanol (EtOH) consumption in these changes. We analyzed the distribution of a wide range of peripheral blood (PB) lymphoid subsets, both during active EtOH intake and after a 3-month withdrawal period, using multiple stainings with monoclonal antibodies and flow cytometry, as well as natural killer (NK) cytotoxic activity. AH patients entering the study were selected strictly; only those undergoing their first episode of AH with no other lesions at liver biopsy were enrolled. Regarding the alcohol intake period, the most striking finding was a significant increase of the absolute number of PB T cells affecting both CD4+ and CD8+ lymphocytes. These changes were associated with a higher expression of T-cell activation antigens, such as HLA DR and CD11c. Simultaneously, a significant increase in both NK cells (CD3-/CD56+) and the cytotoxic T cells coexpressing the CD3 and the CD56 molecules together with an increased NK cytotoxic activity were observed. By contrast, the CD19+/CD5+ B-cell subset was significantly decreased. No significant changes were observed with EtOH withdrawal except in CD5+ B lymphocytes, which returned to normal values. Our results show that, in AH patients, a significant expansion of both activated T cells and NK lymphocytes occurs in the PB, which is associated with an increased NK cytotoxic activity. Interestingly these abnormalities persist during the withdrawal period.

Prognostic factors for short-term survival in alcoholic hepatitis in Japan: analysis by logistic regression.

Prognostic factors for the outcome of patients with alcoholic hepatitis were identified by logistic regression analysis. To predict the outcome immediately after admission, clinical data from 97 patients with alcoholic hepatitis on admission were introduced to multivariate analysis. Independent prognostic factors for favorable outcome were hepaplastin time, peripheral white blood cell count, age (40 to 60 years), and serum creatinine level (below 1.4 mg/dl). Sensitivity, specificity, positive predictive value, negative predictive value, and predictive accuracy were 0.78, 0.89, 0.78, 0.89, and 0.86, respectively. The resultant equation for the death rate was applied to another set of patients with alcoholic hepatitis as a validation study. Predictive accuracy estimated 0.95 in validation. The prognostic index derived was simple, accurate, and useful in the prediction of the outcome in patients with alcoholic hepatitis. Furthermore, it provides the clinician with an indication of the necessity for the intensive care of patients in a critical condition.

Fatty acid composition of liver total lipids in alcoholic patients with and without liver damage.

Alcohol ingestion may promote lipid peroxidation, and the presence of polyunsaturated fatty acids in liver lipids may be essential for the generation of liver damage through this mechanism. The aim of this study is to examine fatty acid composition of liver lipids in chronic alcoholics with and without histological liver damage. A percutaneous liver biopsy was performed to 28 patients hospitalized for treatment of their alcoholism. Liver total lipids were extracted from a portion of the tissue sample and fatty acid composition was measured by gas chromatography. Another piece of the sample was sent for histological study. Six patients had histological cirrhosis or alcoholic hepatitis in their biopsies, the rest of the patients had minimal changes. Patients with liver damage had higher levels of oleic acid and total monoenoic fatty acids, a higher 18:1/18:0 ratio, lower levels of polyunsaturated fatty acids, a lower 20:4/18:2 ratio, and a lower peroxidability index in liver total lipids, than patients without liver damage. Alcoholic patients with asymptomatic liver damage have less unsaturated fatty acids in liver total lipids than their counterparts with normal livers.

Relationship of protein calorie malnutrition to alcoholic liver disease: a reexamination of data from two Veterans Administration Cooperative Studies.

The relationship of protein calorie malnutrition (PCM) to alcoholic liver disease was studied in 666 patients enrolled in two Veterans Administration Cooperative Studies. Some findings of malnutrition could be detected early in 62% of the comparison patients (43 subjects who were alcoholic, but had not yet developed clinical or laboratory evidence of liver injury). In those who had progressed to the stage of liver injury sufficient to manifest clinical jaundice (536 patients), some findings of malnutrition were present in every patient (100%). The degree of malnutrition correlated closely with the development of all the serious complications of the liver disease (ascites, encephalopathy, and hepatorenal syndrome), as well as the overall mortality. The degree of malnutrition was also important in predicting response to some forms of treatment. When prednisolone, a catabolic adrenal steroid, was used, efficacy was independent of the level of malnutrition. However, a relationship was observed with the severity of the liver injury [quantified by the level of jaundice and coagulopathy, i.e., Maddrey's discriminant function (DF(Maddrey)]. For prednisolone, the response was seen only when the DF was 81-100 reducing mortality 45% When oxandrolone, an androgenic anabolic steroid treatment was given, efficacy was observed only in those with moderate malnutrition (PCM score 60-79% of normal) and maximized with adequate caloric intake reducing mortality 86%. To simplify the method of calculating the PCM score for predicting response to anabolic therapy, a multiple logistic regression model was developed from the parameters used to assess nutritional status: DF(PCM) = 0.098 (peripheral blood lymphocytes) + 0.078 (creatinine height index).(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatotoxicity is not increased in alcoholics with positive urinary cocaine metabolites.

Cocaine hepatotoxicity in mice has been reported by numerous investigators. Such hepatotoxicity in other animal models has been more difficult to produce. We prospectively assessed 1212 alcoholics admitted for detoxification for historical, clinical and laboratory evidence of concomitant cocaine/crack use and evidence of liver disease. The 470 cocaine positive subjects had both longer durations and higher average daily costs of cocaine/crack use than the 742 cocaine negative subjects, but had a shorter duration of alcohol use. Serum transaminases were higher in the cocaine negative group. There were no clinically severe cases of liver disease or rhabdomyolysis in either group. Serum hepatitis B surface antibody and hepatitis A antibody were more frequent in the cocaine positive subjects. In conclusion, in this large sample of alcoholics abusing cocaine, severe hepatotoxicity was not at all evident. The previous reports of hepatotoxicity may represent co-morbidity. Some possibilities include infection with a hepatitis or other virus, the presence of an adulterant, an idiosyncratic reaction or an enzymatic abnormality.

[Toxic alcohol-induced, acute intrahepatic cholestasis with reversible increase of the CA 19-9 tumor marker in chronic alcoholic hepatitis]. / Alkoholtoxische, akute intrahepatische Cholestase mit reversibler Erhöhung des Tumormarkers CA 19-9 bei chronischer Alkoholhepatitis.

The case report on an acute intrahepatic cholestasis caused by alcoholic intoxication in a 52-year-old medical laboratory assistant is given. In addition to extreme pathologic cholestasis parameters the increase of the tumor marker CA 19-9 was remarkable. By means of laparoscopy and histology, chronic fatty liver hepatitis due to alcoholic intoxication was found. The tumor marker CA 19-9 returned to normal following abstinence from alcohol parallel to the deline of the cholestasis parameters, which means the diagnostic importance of tumor markers in diseases with intrahepatic cholestasis is to be seen in relative terms.

Drug therapies as sources of information about alcoholism.

This report touched three aspects of drug therapy in alcoholics. The first topic consisted of a comparison between the effects of disulfiram treatment with the consequences of inborn deficiency of aldehyde dehydrogenase isozyme I; the comparison generated some concepts which might be subject to observational verification. The second topic was the citation of studies which suggest a selective decrease of the appetite for alcohol by drugs classified as serotonin uptake blockers. Finally, I cited the presently revealed success of propylthiouracil treatment of alcoholics suffering from liver damage, a success measured not only in laboratory terms but in terms of patient survival.