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BackgroundAs the era of interferon-alpha (IFN)-based therapy for hepatitis C ends, long-term treatment outcomes are now being evaluated.AimTo more fully understand the natural history of hepatitis C infection by following a multisite cohort of patients.MethodsPatients with chronic HCV were prospectively enrolled in 1999-2000 from 11 VA medical centers and followed through retrospective medical record review.ResultsA total of 2211 patients were followed for an average of 8.5 years after enrollment. Thirty-one percent of patients received HCV antiviral therapy, 15 % with standard IFN/ribavirin only, 16 % with pegylated IFN/ribavirin, and 26.7 % of treated patients achieved sustained virologic response (SVR). Cirrhosis developed in 25.8 % of patients. Treatment nonresponders had a greater than twofold increase in the hazard of cirrhosis and hepatocellular carcinoma, compared to untreated patients, whereas SVR patients were only marginally protected from cirrhosis. Nearly 6 % developed hepatocellular carcinoma, and 27.1 % died during the follow-up period. Treated patients, regardless of response, had a significant survival benefit compared to untreated patients (HR 0.58, CI 0.46-0.72). Improved survival was also associated with college education, younger age, lower levels of alcohol consumption, and longer duration of medical service follow-up-factors typically associated with treatment eligibility.ConclusionsAs more hepatitis C patients are now being assessed for all-oral combination therapy, these results highlight that patient compliance and limiting harmful behaviors contribute a significant proportion of the survival benefit in treated patients and that the long-term clinical benefits of SVR may be less profound than previously reported.

Background: Hepatic steatosis is common in patients infected with hepatitis C virus (HCV). The effect of steatosis on anti-HCV therapy efficacy is unclear. Methods: We studied host and viral factors associated with steatosis and the effect of steatosis on treatment efficacy using the database of a large prospective trial in patients with HCV genotypes 2 and 3. Results: Out of 885 patients assessed for steatosis, a total of 614 patients or 69% had steatosis. Patients with genotype 3 were more likely to have steatosis than those with genotype 2 (79 vs. 59%, P<0.001). Using the logistic regression model, steatosis was associated with genotype 3 ( P<0.0001), older age ( P=0.0025), heavier weight ( P<0.0001), higher HCV RNA ( P<0.0001), and higher ALT levels ( P=0.015). By univariate analysis, steatosis was associated with lower sustained virological response (SVR) in patients with genotype 3, but not in patients with genotype 2. When all factors associated with steatosis and SVR were evaluated by logistic regression analysis; genotype, age, bodyweight, histological diagnosis, ALT quotient, baseline HCV RNA and treatment duration were associated with the probability of SVR, but gender, race and steatosis were not. Further analysis showed that steatosis remained a non-significant factor while baseline viral load was significantly associated with the probability of an SVR. Conclusions: Steatosis did not influence the efficacy of treatment in our study population. Baseline viral load is a confounding factor, particularly in patients infected with genotype 3 and once baseline viral load was accounted for, the association between steatosis and SVR was not relevant. [ABSTRACT FROM AUTHOR]

Background: Infestation with Ascaris lumbricoides is seen worldwide. Recently, there has been much interest in the pancreatic-biliary complications of Ascaris infection. In this study, we present our experience of 300 patients seen in a tertiary referral center. Materials and Methods: Case charts of patients seen in the Department of Gastroenterology, University of Damascus, Syria, were analyzed, retrospectively, over a 5-yr period (September of 1988 to August of 1993). During this period, 1666 endoscopic retrograde cholangiopancreatographic studies were performed and pancreatic-biliary ascariasis was diagnosed in 300 patients (18%). Results: The most common presenting symptom was abdominal pain, seen in 98% of patients (294 patients). Complications observed were ascending cholangitis (48 patients; 16%), acute pancreatitis (13 patients; 4.3%), and obstructive jaundice (4 patients; 1.3%). History of worm emesis was present in 25% of patients (76 patients). Most patients (240 patients; 80%) had previously undergone a cholecystectomy or an endoscopic sphincterotomy (232 patients; 77%). Worms were successfully extracted endoscopically in all except two patients, and there were no procedure-related complications. Conclusions: in endemic countries, ascariasis should be suspected in patients with pancreatic-biliary disease, especially if a cholecystectomy or sphincterotomy has been performed in the past. Endoscopic management results in rapid resolution of symptoms and prevents development of complications. [ABSTRACT FROM AUTHOR]

The inhibitory effect of different drugs on pancreatic secretions was assessed in a patient with a posttraumatic pancreatic-cutaneous fistula. The various drugs examined were: pancreatic enzymes, competition, verapamil, propantheline, acetazolamide, and somatostatin analog octreotide. Only fasting and octreotide reduced pancreatic secretion. The optimum dose of octreotide was 50 μg bid given subcutaneously; increasing the dose up to 100 μg tid had no additional benefit. A stable pancreatic-cutaneous fistula is an excellent model to assess the effect of different therapeutic measures on pancreatic secretion. [ABSTRACT FROM AUTHOR]

Alcohol abuse and chronic hepatitis C virus (HCV) infection are two major causes of chronic liver disease in the United States. About 10%-15% of liver transplants performed in the United States are for patients with cirrhosis due to combined alcohol and HCV infection. Data on outcomes on graft and patient survival, HCV recurrence, and relapse of alcohol use comparing transplants in hepatitis C positive drinkers compared to alcohol abuse or hepatitis C alone are conflicting in the literature. Some studies report a slightly better overall outcome in patients who were transplanted for alcoholic cirrhosis vs those transplanted for HCV alone or for combined HCV and alcohol related cirrhosis. However, some other studies do not support these observations. However, most studies are limited to a retrospective design or small sample size. Larger prospective multicenter studies are needed to better define the outcomes in hepatitis C drinkers.

Hepatitis C virus (HCV) infection and alcohol abuse are two most important causes of chronic liver disease in the United States. Alcoholic hepatitis is a unique clinical syndrome among patients with chronic and active alcohol abuse with a potential for high short-term mortality. About 20% of patients presenting with alcoholic hepatitis have concomitant HCV infection. Mortality from alcoholic hepatitis is increased in the presence of concomitant hepatitis C due to synergistic interaction between HCV and alcohol in causing hepatocellular damage. Large prospective randomized studies are needed to develop guidelines on the use of corticosteroids among patients with alcoholic hepatitis and concomitant HCV infection. The impact of antiviral therapy on mortality and outcome in the setting of alcoholic hepatitis remains a novel area for future research.

Alcoholic cirrhosis remains the second most common indication for liver transplantation. A comprehensive medical and psychosocial evaluation is needed when making a decision to place such patients on the transplant list. Most transplant centers worldwide need a minimum of 6 mo of alcohol abstinence for listing these patients. Patients with alcohol dependence are at high risk for relapse to alcohol use after transplantation (recidivism). These patients need to be identified and require alcohol rehabilitation treatment before transplantation. Recidivism to the level of harmful drinking is reported in about 15%-20% cases. Although, recurrent cirrhosis and graft loss from recidivism is rare, occurring in less than 5% of all alcoholic cirrhosis-related transplants, harmful drinking in the post-transplant period does impact the long-term outcome. The development of metabolic syndrome with cardiovascular events and de novo malignancy are important contributors to non liver-related mortality amongst transplants for alcoholic liver disease. Surveillance protocols for earlier detection of de novo malignancy are needed to improve the long-term outcome. The need for a minimum of 6 mo of abstinence before listing makes transplant a nonviable option for patients with severe alcoholic hepatitis who do not respond to corticosteroids. Emerging data from retrospective and prospective studies has challenged the 6 mo rule, and beneficial effects of liver transplantation have been reported in select patients with a first episode of severe alcoholic hepatitis who are unresponsive to steroids.

General measures for treating patients with alcoholic hepatitis (AH) are similar irrespective of the disease severity. Alcohol abstinence is the cornerstone of treatment and can be achieved with appropriate social support, Alcoholics Anonymous and sometimes pharmacological therapy. Alcohol withdrawal should be anticipated and treatment initiated to prevent this complication. Treatment for complications of cirrhosis should be as for any other patient with cirrhosis. AH patients are particularly prone to infections and malnutrition. These should be identified and treated appropriately using broad spectrum antibiotics and nutritional support respectively.

Alcoholic liver disease (ALD) is a major cause of alcohol-related morbidity and mortality. Its presentation ranges from fatty liver to alcoholic hepatitis (AH), cirrhosis, and hepatocellular carcinoma. Although the amount and pattern of alcohol consumption is a well recognized predisposing factor for the development of serious liver pathology, environmental factors and the host's genetic make-up may also play significant roles that have not yet been entirely explored. Continuing alcohol consumption is a major factor that influences the survival of patients with AH. The presence of cirrhosis at presentation or its development on follow up is a major factor determining the outcome in the long run. This chapter deals with the epidemiology and magnitude of ALD in general and AH in particular.

Background: Hepatic steatosis is common in patients infected with hepatitis C virus (HCV). The effect of steatosis on anti-HCV therapy efficacy is unclear., Methods: We studied host and viral factors associated with steatosis and the effect of steatosis on treatment efficacy using the database of a large prospective trial in patients with HCV genotypes 2 and 3., Results: Out of 885 patients assessed for steatosis, a total of 614 patients or 69% had steatosis. Patients with genotype 3 were more likely to have steatosis than those with genotype 2 (79 vs. 59%, P<0.001). Using the logistic regression model, steatosis was associated with genotype 3 (P<0.0001), older age (P=0.0025), heavier weight (P<0.0001), higher HCV RNA (P<0.0001), and higher ALT levels (P=0.015). By univariate analysis, steatosis was associated with lower sustained virological response (SVR) in patients with genotype 3, but not in patients with genotype 2. When all factors associated with steatosis and SVR were evaluated by logistic regression analysis; genotype, age, bodyweight, histological diagnosis, ALT quotient, baseline HCV RNA and treatment duration were associated with the probability of SVR, but gender, race and steatosis were not. Further analysis showed that steatosis remained a non-significant factor while baseline viral load was significantly associated with the probability of an SVR., Conclusions: Steatosis did not influence the efficacy of treatment in our study population. Baseline viral load is a confounding factor, particularly in patients infected with genotype 3 and once baseline viral load was accounted for, the association between steatosis and SVR was not relevant.