Search

BACKGROUND & AIMS: There is no histologic classification system to determine prognoses of patients with alcoholic hepatitis (AH). We identified histologic features associated with disease severity and created a histologic scoring system to predict short-term (90-day) mortality. METHODS: We analyzed data from 121 patients admitted to the Liver Unit (Hospital Clinic, Barcelona, Spain) from January 2000 to January 2008 with features of AH and developed a histologic scoring system to determine the risk of death using logistic regression. The system was tested and updated in a test set of 96 patients from 5 academic centers in the United States and Europe, and a semiquantitative scoring system called the Alcoholic Hepatitis Histologic Score (AHHS) was developed. The system was validated in an independent set of 109 patients. Interobserver agreement was evaluated by weighted κ statistical analysis. RESULTS: The degree of fibrosis, degree of neutrophil infiltration, type of bilirubinostasis, and presence of megamitochondria were independently associated with 90-day mortality. We used these 4 parameters to develop the AHHS to identify patients with a low (0-3 points), moderate (4-5 points), or high (6-9 points) risk of death within 90 days (3%, 19%, and 51%, respectively; P < .0001). The AHHS estimated 90-day mortality in the training and test sets with an area under the receiver operating characteristic value of 0.77 (95% confidence interval, 0.71-0.83). Interrater agreement values were 0.65 for fibrosis, 0.86 for bilirubinostasis, 0.60 for neutrophil infiltration, and 0.46 for megamitochondria. Interestingly, the type of bilirubinostasis predicted the development of bacterial infections. CONCLUSIONS: We identified histologic features associated with the severity of AH and developed a patient classification system that might be used in clinical decision making.

Introduction. Alcoholic cirrhosis is one of the most common indications for liver transplantation (LT) in western countries. A major concern about transplant patients due to alcoholic liver disease (ALD) is alcoholic recidivism. Data concerning psycho-social characteristics of patients with 6 months of abstinence at initial evaluation for LT is scarce. Objectives. The aims of this study were 1) To evaluate the psycho-social profile of a cohort of patients with alcoholic cirrhosis being evaluated for LT. 2) Determine factors associated with abstinence from alcohol at initial psycho-social evaluation for LT and 3) To evaluate the potential impact of alcohol-free beer consumption on 6-month abstinence. Material and methods. Ninety patients referred to the Alcohol Unit of the Hospital Clinic of Barcelona (January 1995-December 1996) were included. Univariate and multivariate logistic regression analyses were used to identify the factors associated with cessation in alcohol consumption and with 6-month abstinence. Results. Factors associated with cessation in alcohol consumption were awareness of alcohol toxicity (OR = 5.84, CI 1.31-26.11, p = 0.02) and family recognition (OR = 3.81, CI 1.27-11.41, p = 0.01). Cessation of alcohol consumption at knowledge of ALD (OR = 5.50, CI 1.52-19.81, p = 0.009), awareness of alcohol toxicity (OR = 2.99, CI 1.029.22, p = 0.05) and family recognition (OR = 5.21, CI 1.12-24.15, p = 0.03) were the independent factors associated with 6-month abstinence previous to psycho-social evaluation for LT. Conclusion. In conclusion awareness of alcohol toxicity and family recognition are the independent factors that influence cessation in alcohol consumption and 6-month abstinence in patients evaluated for LT. The use of alcohol-free beer was associated with a higher rate of abstinence in patients without alcohol cessation.

Nutritional factors, especially the protein and fat content of the diet, may change pancreatic morphology after ethanol induced injury. This study was performed to delineate the combined effects of a low fat diet and longterm ethanol ingestion on the rat pancreas. Male Sprague-Dawley rats were maintained with five different diets for 12 weeks and the pancreas removed on the day they were killed. Rats fed a very low fat diet without ethanol (5% of total calories as lipid) developed malnutrition, pancreatic steatosis, and reduction in zymogen granules content. Animals fed a 35% lipid diet with ethanol also developed pancreatic steatosis but changes in zymogen granules content were not detected. Both malnutrition and longterm ethanol consumption increased pancreatic cholesterol ester content, and their effects were additive. Pancreatic steatosis was accompanied with hypercholesterolaemia. Amylase, lipase, and cholesterol esterase content were reduced in malnourished rats; but longterm ethanol ingestion, regardless of the nutritional state, increased lipase content and decreased amylase. It is suggested that high serum cholesterol concentrations and increased pancreatic lipase activity could cause accumulation of cholesterol esters in acinar cells. Fat accumulation in the pancreas has been reported as the earliest histopathological feature in alcoholic patients and may be responsible for cytotoxic effects on the acinar cells at the level of the cell membrane. Although it is difficult to extrapolate results in this animal study to the human situation, the results presented in this work might explain the higher incidence of pancreatitis is malnourished populations as well as in alcoholic subjects that is reported in dietary surveys.

Background/Aims: It has been known for at least 50 years that alterations in methionine metabolism occur in human liver cirrhosis. However, the molecular basis of this alteration is not completely understood. In order to gain more insight into the mechanisms behind this condition, mRNA levels of methionine adenosyltransferase ( MAT1A ), glycine methyltransferase ( GNMT ), methionine synthase ( MS ), betaine homocysteine methyltransferase ( BHMT ) and cystathionine β-synthase ( CBS ) were examined in 26 cirrhotic livers, five hepatocellular carcinoma (HCC) tissues and ten control livers. Methods: The expression of the above-mentioned genes was determined by quantitative RT-PCR analysis. Methylation of MAT1A promoter was assessed by methylation-sensitive restriction enzyme digestion of genomic DNA. Results: When compared to normal livers MAT1A , GNMT, BHMT, CBS and MS mRNA contents were significantly reduced in liver cirrhosis. Interestingly, MAT1A promoter was hypermethylated in the cirrhotic liver. HCC tissues also showed decreased mRNA levels of these enzymes. Conclusions: These findings establish that the abundance of the mRNA of the main genes involved in methionine metabolism is markedly reduced in human cirrhosis and HCC. Hypermethylation of MAT1A promoter could participate in its reduced expression in cirrhosis. These observations help to explain the hypermethioninemia, hyperhomocysteinemia and reduced hepatic glutathione content observed in cirrhosis.

The severity of pancreatic fibrosis, a characteristic feature of patients with chronic pancreatitis (CP), can be assessed only by direct histologic analysis of pancreatic tissue. Since serum levels of the amino-terminal type III procollagen propeptide (PIIIP) can reflect the degree of fibrogenic activity in several diseases associated with fibrosis, the current study was aimed at investigating whether PIIIP are increased in chronic pancreatitis, the relationship between PIIIP and pancreatic fibrogenic activity, and the influence of pancreatectomy, pancreatic exocrine function, and duration of disease on PIIIP levels. Serum PIIIP was measured in 18 patients with CP (15 without liver disease and three with cholestasis) and in 21 healthy controls. The effect of pancreatectomy on PIIIP was evaluated in seven patients, in whom PIIIP was measured immediately before and 2 months after surgery. Prolylhydroxylase (PHase) activity as an index of pancreatic fibrogenesis was evaluated in pancreatic tissue from 11 patients who had undergone subtotal pancreatectomy and from 11 organ donors. The bentiromide (BT)-PABA test as an index of exocrine pancreatic function was measured in all patients. PIIIP was significantly higher in patients who had or had not undergone pancreatectomy (17.3 +/- 4.0 and 25 +/- 11.4 ng/ml, respectively) than in controls (12.3 +/- 3.1 ng/ml) (p < 0.001). PIIIP decreased significantly after pancreatectomy (before, 32.0 +/- 9.3 ng/ml; after, 18.4 +/- 4.8 ng/ml; p = 0.005). PHase was significantly higher in patients (773 +/- 250 cpm/mg protein) than in controls (405 +/- 121 cpm/mg protein) (p < 0.001). PIIIP was correlated with pancreatic PHase (r = 0.7, p = 0.001) but not with BT-PABA or with the duration of the disease. In conclusion, serum PIIIP levels are increased in patients with CP and reflect the severity of pancreatic fibrogenic activity. No relationship between the serum PIIIP levels and the pancreatic exocrine function and duration of disease was found.