Types Of Alcoholic Liver Disease Research Articles

A review: Alcoholic liver disease pathophysiology, current molecular and clinical perspectives

Alcohol-related liver damage (ALD) is a term used for a variety of liver conditions comprising cirrhosis, fibrosis, and steatohepatitis with chronic inflammation that is predominantly brought on by heavy alcohol consumption. ALD is currently regarded as one of the most common causes of liver disease-related mortality on a global scale. The majority of cirrhosis in the liver cases seen in district general hospitals in the UK are caused by alcohol, which is a key factor in the Western world. Alcoholic cirrhosis, acute alcoholic hepatitis, and alcoholic fatty liver (steatosis) are the three most widely recognized types of alcoholic liver disease. According to the National Institute on Alcohol Abuse and Alcoholism's the most recent surveillance report, liver cirrhosis was among the top twelve causes of death in the country, contributing to a total of 14,477 deaths in the year 2014.This page speaks about the various types of alcoholic liver damage (ALD), with a focus on cirrhosis because it is the type of liver diseases that is most frequently linked to alcohol misuse and has the most studies investigating it. Epidemiological studies have assessed the incidence of ALD and the factors who frequently cause the condition. Although excessive alcohol use is the main cause of ALD, gender and cultural variations also have a significant role in the prevalence of liver disease. Since the 1970s, cirrhosis-related mortality rates have decreased in the United States and certain other countries as well. This dip may have been caused by a variety of variables, including increasing enrollment in alcohol rehab facilities and in Alcoholics Anonymous, drops in alcohol consumption, and more

Enfermedad hepática inducida por alcohol

Excessive alcohol intake is a worldwide problem. A high percentage of worldwide morbidity-mortality rates are associated to alcoholic liver disease, which comprehend a very wide clinical spectrum. Screening strategies are more important in earliest stages, when symptomatology is non-specific. Once abusive alcohol intake is detected, interventions aimed at decreasing alcohol intake as well as diagnostic tests have to be performed. So, in recent years non-invasive methods for the diagnosis of liver fibrosis, like elastography, have gained relevance. Alcohol abstinence is the treatment of alcoholic liver disease, conditioning prognosis both in early cirrhosis and in decompensated cirrhosis. A special type of alcoholic liver disease is the alcoholic hepatitis and its typical biochemical and histological features. Currently, corticoids are the only possible treatment for severe alcoholic hepatitis (mortality rates are high). Because corticoid therapy only has beneficial effect at short term and shows a low response rate, nowadays new therapies are being researched.

A PROSPECTIVE OBSERVATIONAL STUDY ON EFFECTS OF HEPATOPROTECTIVE AGENTS IN ALCOHOLIC LIVER DISEASE AT A TERTIARY CARE HOSPITAL

Drug utilization evaluation of hepatoprotective drugs is important in view of the spectrum of effect and associated risks with their therapy. The study was designed to evaluate the effects and adverse effects of hepatoprotective agents. A prospective, observational study was carried out for a period of 6 months at Osmania General Hospital (a tertiary care hospital). 120 patients were evaluated receiving corticosteroids, pentoxifylline, ursodeoxycholic acid for observing a trend in hepatic parameters and its outcomes. Ursodeoxycholic acid (81.66%) was the most commonly prescribed drug in almost all cases of alcoholic liver diseases followed by pentoxifylline (10%) in hepatorenal syndrome and then prednisolone (8.33%) in fatty liver. 67 cases were reported to have the significant drop in liver transaminases and bilirubin levels. Ursodeoxycholic acid resulted in a drop of 25% serum bilirubin and 35% drop in serum ALT (alanine transaminase) and 33% drop in serum AST (aspartate transaminase) in patients in a time gap of 1 week. Among 120 cases 94 were males (78.05%) and 26 females (21.04%) and maximum patients with alcoholic liver disease belonged to age group of 30-40 years (27.6%). Ursodeoxycholic acid (300 mg once daily) is used as an off-label drug for all types of alcoholic liver disease and also for viral hepatitis. Though Ursodeoxycholic acid showed a significant drop in liver transaminases and serum bilirubin levels in cirrhotic patients a better alternative lie in liver transplantation as long as they remain abstinent from alcohol. Keywords: Alcoholic liver diseases, Hepatoprotective agents, Liver transaminases, Bilirubin, Paired t-test.

Serum Ubiquitin-Protein Conjugates in Normal Subjects and Patients With Alcoholic Liver Diseases: Immunoaffinity Isolation and Electrophoretic Mobility

Background We previously reported that levels of multiubiquitin chains, representing ubiquitin-protein conjugates, were significantly higher in sera of patients with alcoholic liver cirrhosis than in normal subjects and patients with other types of alcoholic liver disease. Methods To characterize them, ubiquitin-immunoreactive proteins were purified from sera of healthy human volunteers and patients with alcoholic liver diseases by using affinity chromatography on a Sepharose column containing an immobilized monoclonal antibody recognizing conjugated ubiquitin. Results SDS-PAGE analysis followed by Western blotting revealed that the immunoaffinity-purified proteins mainly contained multiple components with molecular masses greater than 60 kDa, almost all of which were immunostained with the ubiquitin antibody. This size heterogeneity was in agreement with the property of ubiquitin-protein conjugates in all cells examined. These results indicate that the immunoaffinity-purified serum proteins are polyubiquitinated proteins presumably derived from some somatic cells. These ubiquitinated proteins obtained from the alcoholic cirrhosis patients were stained more strongly than those from the normal subjects and patients with other types of alcoholic liver disease, although equal amounts of multiubiquitin chains were analyzed simultaneously. In addition, marked differences were observed in the two-dimensional PAGE pattern of the ubiquitin-protein conjugates purified from the alcoholic cirrhosis patient serum compared with those from the normal human serum: four distinct broad spots (presumably polyubiquitin-protein complexes) were observed only in the former. Conclusions This is the first report on isolation of ubiquitin-protein conjugates from human serum, and it indicates that not only their levels, but also their molecular compositions, were greatly affected by alcoholic cirrhosis.

Serum Ubiquitin‐Protein Conjugates in Normal Subjects and Patients With Alcoholic Liver Diseases: Immunoaffinity Isolation and Electrophoretic Mobility

Background We previously reported that levels of multiubiquitin chains, representing ubiquitin‐protein conjugates, were significantly higher in sera of patients with alcoholic liver cirrhosis than in normal subjects and patients with other types of alcoholic liver disease.Methods To characterize them, ubiquitin‐immunoreactive proteins were purified from sera of healthy human volunteers and patients with alcoholic liver diseases by using affinity chromatography on a Sepharose column containing an immobilized monoclonal antibody recognizing conjugated ubiquitin.Results SDS‐PAGE analysis followed by Western blotting revealed that the immunoaffinity‐purified proteins mainly contained multiple components with molecular masses greater than 60 kDa, almost all of which were immunostained with the ubiquitin antibody. This size heterogeneity was in agreement with the property of ubiquitin‐protein conjugates in all cells examined. These results indicate that the immunoaffinity‐purified serum proteins are polyubiquitinated proteins presumably derived from some somatic cells. These ubiquitinated proteins obtained from the alcoholic cirrhosis patients were stained more strongly than those from the normal subjects and patients with other types of alcoholic liver disease, although equal amounts of multiubiquitin chains were analyzed simultaneously. In addition, marked differences were observed in the two‐dimensional PAGE pattern of the ubiquitin‐protein conjugates purified from the alcoholic cirrhosis patient serum compared with those from the normal human serum: four distinct broad spots (presumably polyubiquitin‐protein complexes) were observed only in the former.Conclusions This is the first report on isolation of ubiquitin‐protein conjugates from human serum, and it indicates that not only their levels, but also their molecular compositions, were greatly affected by alcoholic cirrhosis.

Changes in laminin content in livers of patients with alcoholic liver disease

An increase in serum laminin levels has been reported in patients with liver disease; however, the mechanisms for this increase have not yet been clarified. In the present study, the laminin content of liver biopsy specimens obtained from patients with alcoholic liver disease and non-alcoholic liver disease was determined with a one-step sandwich enzyme-immunoassay system, using monoclonal antibodies for human placental laminin. Hepatic laminin content was significantly higher in patients with liver disease than in normal controls. In alcoholic liver disease, the content in patients with mild fibrosis was lower than in patients with advanced types of alcoholic liver disease. In non-alcoholic liver disease, the hepatic laminin content tended to increase in parallel with the progression of fibrosis. The laminin content in alcoholic liver disease was significantly higher than in the corresponding type of non-alcoholic liver disease. The ratio of laminin to total collagen content was highest in alcoholic liver disease showing mild fibrosis and decreased in parallel with the progression of fibrosis. In contrast, the ratio was low in all types of nonalcoholic liver disease. The ratio in patients with alcoholic liver disease was significantly higher than these with the corresponding non-alcoholic liver disease. Hepatic laminin content increased in parallel with the increase in hepatic type IV collagen in alcoholic liver disease, and the correlation was statistically significant. However, similar correlation was not found in non-alcoholic liver disease. These results indicate that the response to laminin synthesis to alcoholic liver disease is strong in mild fibrosis and reached a plateau at a relatively early stage of fibrosis. The stimulation for laminin synthesis in non-alcoholic liver disease is different from that in alcoholic liver disease.

Changes in type IV collagen content in livers of patients with alcoholic liver disease

An increase of serum type IV collagen levels in patients with liver disease has been reported; however, the mechanisms of this increase are not yet well known. We recently developed an assay system for type IV collagen content in liver biopsy specimens. In this study, type IV collagen content in the livers and sera of patients with alcoholic liver disease and nonalcoholic liver disease was determined. Serum and hepatic type IV collagen contents were measured with a one-step sandwich enzyme immunoassay system using monoclonal antibodies for human type IV collagen. Hepatic type IV collagen content increased significantly in liver disease. In alcoholic liver disease, type IV collagen content in patients with mild fibrosis was lower than that in advanced types of alcoholic liver disease. In nonalcoholic liver disease, hepatic type IV collagen content tended to increase with the progression of fibrosis. Type IV collagen content in alcoholic liver disease was significantly higher than that in the corresponding type of nonalcoholic liver disease. Hepatic total collagen content increased significantly in parallel with the progression of fibrosis in both alcoholic liver disease and nonalcoholic liver disease. The total collagen content in each type of alcoholic liver disease was significantly lower than that in the corresponding type of nonalcoholic liver disease. The ratio of type IV collagen to total collagen content was the highest in livers showing mild fibrosis, both in alcoholic liver disease and nonalcoholic liver disease, and decreased in parallel with the progression of fibrosis. The ratio in patients with alcoholic liver disease was significantly higher than that in those with the corresponding nonalcoholic liver disease. Hepatic type IV collagen content correlated with the intensity of the staining reactions for type IV collagen only around the sinusoidal walls in alcoholic liver disease, but not in nonalcoholic liver disease. A significant correlation was found between serum and liver type IV collagen content, although the coefficient value was not very high. These results indicate that the response of type IV collagen synthesis to liver injury is strong in mild fibrosis and reaches a plateau at a relatively early stage of fibrosis; then the content of the other types of collagen increases gradually with the progression of fibrosis. The stimulation for type IV collagen synthesis is more prominent in alcoholic liver disease than in nonalcoholic liver disease, especially at intralobular areas.

Changes in type IV collagen content in livers of patients with alcoholic liver disease

An increase of serum type IV collagen levels in patients with liver disease has been reported; however, the mechanisms of this increase are not yet well known. We recently developed an assay system for type IV collagen content in liver biopsy specimens. In this study, type IV collagen content in the livers and sera of patients with alcoholic liver disease and nonalcoholic liver disease was determined. Serum and hepatic type IV collagen contents were measured with a one-step sandwich enzyme immunoassay system using monoclonal antibodies for human type IV collagen. Hepatic type IV collagen content increased significantly in liver disease. In alcoholic liver disease, type IV collagen content in patients with mild fibrosis was lower than that in advanced types of alcoholic liver disease. In nonalcoholic liver disease, hepatic type IV collagen content tended to increase with the progression of fibrosis. Type IV collagen content in alcoholic liver disease was significantly higher than that in the corresponding type of nonalcoholic liver disease. Hepatic total collagen content increased significantly in parallel with the progression of fibrosis in both alcoholic liver disease and nonalcoholic liver disease. The total collagen content in each type of alcoholic liver disease was significantly lower than that in the corresponding type of nonalcoholic liver disease. The ratio of type IV collagen to total collagen content was the highest in livers showing mild fibrosis, both in alcoholic liver disease and nonalcoholic liver disease, and decreased in parallel with the progression of fibrosis. The ratio in patients with alcoholic liver disease was significantly higher than that in those with the corresponding nonalcoholic liver disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatitis C Virus Antibody in Alcoholic Patients

To evaluate the relationship between hepatitis C viral infection and alcoholic liver disease. Case-comparison study. Bronx (NY) Veterans Affairs Medical Center. Forty-seven consecutive alcoholic patients undergoing diagnostic liver biopsy. Serum was obtained at the time of liver biopsy and assayed for antibodies to hepatitis C virus using enzyme-linked immunosorbent assay, recombinant immunoblot assay, and hepatitis C virus neutralization methods. Antibody to hepatitis C virus, as confirmed by the recombinant immunoblot assay, was strongly associated with the presence of portal and/or lobular inflammation (91% seropositivity) but was only present in 16% of patients without this histologic finding (P < .001). In patients without portal or lobular hepatitis, recombinant immunoblot assay seropositivity was seen in 27% of patients with cirrhosis and 20% of patients with alcoholic hepatitis and was absent in patients with steatosis and/or perivenular fibrosis. In the subgroup of alcoholic patients who were without known risk factors for hepatitis C virus infection (ie, no history of intravenous drug use or blood transfusions), antibody to hepatitis C virus was present in 78% of subjects with portal and/or lobular hepatitis but was absent in those with other types of alcoholic liver disease. Finally, anti-hepatitis C virus-seropositive patients had a significantly greater mean necroinflammatory score as compared with anti-hepatitis C virus-seronegative alcoholic patients (2.1 vs 1.2; P < .001). In contrast, there was no significant difference in the mean fibrosis score between the two groups. The presence of portal and/or lobular inflammation is strongly associated with antibodies to hepatitis C virus in alcoholic patients, even in the absence of known risk factors. This association indicates that hepatitis C virus is responsible, at least in part, for the portal and/or lobular hepatitis associated with alcoholic liver disease.

Clinical and pathological features, and the mechanism of development in severe alcoholic hepatitis, especially in comparison with acute type fulminant hepatitis.

Among the patients with alcoholic hepatitis, the patients with severe alcoholic hepatitis (SAH) were distinguished by clinical course, laboratory data and histological findings. The aim of this study was to clarify the clinicopathological features, pathological condition and pathogenesis of SAH. Twenty-four SAH patients were compared with 55 patients with acute type fulminant hepatitis (FH) and the other types of alcoholic liver disease. SAH showed a very poor prognosis with a survival rate of 25% and was complicated by multiple organ failure earlier than FH. IgA class lipid A antibody, endotoxin (Et) and tumor necrosis factor-alpha (TNF-alpha) levels in the blood well reflected the pathological condition and severity of SAH. The white blood cell count in the peripheral blood was thought to be the simplest indicator for the prediction of the prognosis of SAH. In conclusion, SAH involves hyper-endotoxemia due to dysfunction of the reticuloendothelial system in the liver, and cytokines including TNF-alpha and neutrophils play an important role in the severity of liver injury.

Alcoholic liver disease in heterozygotes of mutant and normal aldehyde dehydrogenase-2 genes

To clarify the pathogenetic role of acetaldehyde in the development of alcoholic liver disease, genotyping of aldehyde dehydrogenase-2 genes was performed and the clinical features of the alcoholic liver disease patients with different genotypes were compared. Genotyping of aldehyde dehydrogenase-2 was performed in 47 patients with alcoholic liver disease using the polymerase chain reaction and slot-blot hybridization. Of the 47 patients with alcoholic liver disease, 40 were homozygous for the normal aldehyde dehydrogenase-2 gene and the remaining seven cases were heterozygous for the normal and mutant aldehyde dehydrogenase-2 genes. No homozygote was found for the mutant aldehyde dehydrogenase-2 genes. Daily alcohol intake was less than 100 gm in all heterozygotes without relation to the type of alcoholic liver disease. On the other hand, all but four patients homozygotic for the normal aldehyde dehydrogenase-2 gene drank more than 100 gm alcohol/day. The mean daily alcohol intake in the heterozygotes was significantly lower than that in the normal homozygotes. The incidence of alcoholic fibrosis tended to be lower in the heterozygotes than in the normal homozygotes (14.2% vs. 52.5%). On the other hand, the incidence of alcoholic hepatitis and/or cirrhosis tended to be higher in the heterozygotes than in the normal homozygotes. These results indicate that alcoholic liver disease develops even with moderate amounts of alcohol intake in heterozygotes of the aldehyde dehydrogenase-2 genes, in which acetaldehyde metabolism in the liver is impaired and liver damage in the heterozygotes is more severe than that in the normal homozygotes, suggesting that habitual drinkers who are heterozygotes of the aldehyde dehydrogenase-2 genes may be at high risk for alcoholic liver disease.

An experimental study on the severe type of alcoholic liver disease

An experimental study on the severe type of alcoholic liver disease

Alcoholic Liver Disease in Japan

From these discussions, it is apparent that: Alcoholic liver disease is increasing at a rapid rate in conjunction with an increase of annual gross and per capita consumption of alcohol. Alcoholic hepatitis and alcoholic hyaline are much less common in Japan compared to western countries. Alcoholic hepatic fibrosis and chronic hepatitis are the common types of alcoholic liver disease in Japan. Alcoholic hepatic fibrosis may be a pathological process or entity independent of fatty liver, alcoholic hepatitis, and alcoholic cirrhosis. It is not clear at the present time whether heavy alcohol consumption per se or non-A, non-B hepatitis virus is the cause of chronic hepatitis seen in HBsAg negative alcoholics.

Severity of alcohol dependence in patients with alcoholic liver disease.

To determine the severity of dependence on alcohol in patients with alcoholic liver disease the severity of alcohol dependence questionnaire was administered to 193 patients with various types of alcoholic liver disease established histologically, in whom a detailed history of lifetime alcohol consumption was also obtained. Only 34 patients (18%) were classified as being severely dependent compared with 56% of patients without overt liver disease who were attending a neighbouring alcohol treatment unit. There was a significant correlation between the severity of dependence and mean daily alcohol consumption (r = 0.45 and 0.39 for men and women, respectively) but not duration of drinking. Dependence scores tended to be lower in patients with cirrhosis than in those with precirrhotic liver disease, but this difference reached significance only in women. These findings confirm that patients who develop chronic alcoholic liver disease are usually only mildly dependent on alcohol and support the hypothesis that patients who escape florid symptoms of alcohol dependence are at greater risk of developing liver damage because they are able to sustain a continual consumption of alcohol over many years.

Liver membrane antibodies in alcoholic liver disease. II. Antibodies to ethanol-altered hepatocytes.

Using an indirect immunofluorescence technique, circulating liver membrane antibodies against normal rabbit hepatocytes and ethanol-altered rabbit hepatocytes have been sought in a series of patients with histologically confirmed alcoholic liver disease. Liver membrane antibodies against normal hepatocytes were found in 18 (28%) of the 65 sera examined, but with ethanol-altered hepatocytes as substrate liver membrane antibodies were found in 48 (74%) of the sera. Isolation of F(ab')2 fragments confirmed that the positive results were due to antibody binding. Liver membrane antibodies against ethanol-altered hepatocytes are peculiar to alcoholic liver disease, and there is a similar incidence in the various histological types of alcoholic liver disease. Absorption studies suggest that the liver membrane antibodies are directed against new or altered antigens which are not present in normal hepatocytes. These new or altered antigens may also appear after pretreatment with other primary alcohols and seem likely to be induced by a haptenic effect of the alcohol or a metabolic break-down product. These studies represent a novel approach to the further investigation of the possible role of immunological mechanisms in alcohol-induced liver injury.

Lymphocyte cytotoxicity to autologous hepatocytes in alcoholic liver disease.

Cytotoxicity of peripheral blood lymphocytes for autologous hepatocytes has been studied in 18 patients with different histological types of alcoholic liver disease. Cytotoxicity was significantly increased in five of ten patients with cirrhosis and/or alcoholic hepatitis but in only one of eight with fatty infiltration or minor histological changes. The cytotoxic effect of T-and non-T-effector cells was separately evaluated in 11 cases. Of six patients with alcoholic hepatitis, non-T lymphocyte cytotoxicity was increased in five and T-cell in only one. These preliminary results are consistent with the concept that autoimmune reactions may play a role in the development and progression of alcoholic hepatitis and cirrhosis, although it is likely that direct hepatotoxic effects of ethanol or its metabolites are also important in determining the pattern of liver injury and perhaps in initiating the immune reactions observed in this study.

Serum Ethanol Estimations in the Control of Alcohol Abstinence in Patients with Liver Disease

Eighty-eight patients with a non-alcoholic and 105 patients with an alcoholic liver disease were warned against alcohol consumption. On three consecutive ambulatory visits, serum ethanol was measured and compared with patients' admission of alcohol intake. None in the non-alcoholic group had a positive serum ethanol test, whereas 60 samples from 40 patients with alcoholic liver disease were positive. The serum ethanol values were higher in women than in men. Continuation of drinking was unrelated to sex, age, or type of alcoholic liver disease. Twenty-seven of the 40 patients with ethanol in serum denied alcohol consumption. The reliability of the patients was unrelated to sex, age, or type of alcoholic liver disease. Serum ethanol was more valuable than aspartate aminotransferase, alkaline phosphatase, bilirubin, and coagulation factors in pointing out the patients who continued drinking.