Biomedical subjects

Timothy R Morgan

Publications and source records attributed to Timothy R Morgan.

24 records · Page 2Linked to original sources

PubMed2004

Peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C who have failed prior treatment.

BACKGROUND & AIMS: The most effective therapy currently available for treatment of chronic hepatitis C virus (HCV) is the combination of peginterferon and ribavirin. This study evaluated the effectiveness of this treatment in patients who were nonresponders to previous interferon-based therapy. METHODS: The first 604 patients enrolled in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial were evaluated. All were HCV RNA positive, previous nonresponders to interferon, with or without ribavirin, and had bridging fibrosis or cirrhosis on liver biopsy (Ishak fibrosis stage 3-6). Patients were retreated with peginterferon alfa-2a 180 microg/wk plus ribavirin 1000-1200 mg/day. Those with no detectable HCV RNA in serum at week 20 continued treatment for a total of 48 weeks and were then followed for an additional 24 weeks. RESULTS: Thirty-five percent of patients had no detectable HCV RNA in serum at treatment week 20, and 18% achieved sustained virologic response (SVR). Factors associated with an SVR included previous treatment with interferon monotherapy, infection with genotypes 2 or 3, a lower AST:ALT ratio, and absence of cirrhosis. Reducing the dose of ribavirin from > or =80% to < or =60% of the starting dose during the first 20 weeks of treatment was associated with a decline in SVR from 21% to 11% (P < or = 0.05). In contrast, reducing the dose of peginterferon or reducing ribavirin after week 20, when HCV RNA was already undetectable, did not significantly affect SVR. CONCLUSIONS: Selected nonresponders to previous interferon-based therapy can achieve SVR following retreatment with peginterferon alfa-2a and ribavirin.

Adult↗

PubMed2004

Alcohol and hepatocellular carcinoma.

More than 18 million adults in the United States abuse alcohol, a prevalence 5 times higher than that of hepatitis C. Chronic alcohol use of greater than 80 g/day for more than 10 years increases the risk for hepatocellular carcinoma (HCC) approximately 5-fold; alcohol use of less than 80 g/day is associated with a nonsignificant increased risk for HCC. The risk for HCC in decompensated alcohol induced cirrhosis approaches 1% per year. The risk does not decrease with abstinence, and HCC can occur in a noncirrhotic liver. Alcohol use in chronic hepatitis C doubles the risk for HCC as compared with the risk in hepatitis C alone. Furthermore, there may be synergism between alcohol and hepatitis C in the development of HCC, and in these patients HCC may occur at an earlier age and the HCC may be histologically more advanced. Studies in the United States and Italy suggest that alcohol is the most common cause of HCC (accounting for 32%-45% of HCC). The mechanisms by which alcohol causes HCC are incompletely understood, but may include chromosomal loss, oxidative stress, a decreased retinoic acid level in the liver, altered DNA methylation, and genetic susceptibility. Alcohol use is increasing in many countries, suggesting that alcohol will continue to be a common cause of HCC throughout the world.

Alcohol Drinking↗

PubMed2004

Epidemiology of alcoholic liver disease.

Alcohol is one of the main causes of end-stage liver disease worldwide, and alcoholic liver disease is the second most common reason for liver transplantation in the United States. Beginning in the 1970s, there was a gradual decline in alcoholic cirrhosis-related mortality in many countries. However, in the past few years, alcoholic liver disease mortality rates in several countries have stabilized or started to increase. There are significant ethnic and gender differences in alcoholic cirrhosis-related mortality rates. Furthermore, alcohol use increases the risk for liver disease in those infected with hepatitis C. A better understanding of the epidemiology of alcoholic liver disease will allow for improved diagnosis and management of this common problem.

Adult↗

PubMed2003

Liver disease in alcohol and hepatitis C.

The prevalence of hepatitis C is 7-10-fold higher in alcoholics than it is in the general population. Among alcoholics, the prevalence of hepatitis C is higher in alcoholics with advanced liver disease. Serum ALT and hepatitis C viral load may improve if alcoholic patients with hepatitis C stop drinking for more than 4 months.Up to 60% of patients with hepatitis C have a past history of alcohol use. In patients with hepatitis C, chronic alcohol consumption of more than 5 drinks per day increases the rate of liver fibrosis. Hepatitis C patients who ingest more than 5 alcoholic drinks per day are at increased risk for cirrhosis, hepatocellular carcinoma and, possibly, death from liver disease. Recent alcohol use decreases the response rate to interferon treatment. The detrimental effects of small amounts (3 or fewer drinks per day) of alcohol consumption in patients with hepatitis C are not known.

Alcohol Drinking↗

PubMed2003

Hepatitis C and alcohol: fundamental and translational research directions.

Infection with hepatitis C and the alcohol abuse that frequently accompanies it, impose major worldwide healthcare burdens. The scientific knowledge base that would inform and direct the development of more effective treatment and intervention strategies for these linked pandemics is inadequate. Therefore, the National Institute on Alcohol Abuse and Alcoholism (NIAAA) organized a workshop in which a multidisciplinary group of experts was asked to review the state-of-the-science specific to alcohol in the context of hepatitis C infection. The panel was charged with identifying newly emerging areas likely to lead to advances in fundamental research and to identify those with the greatest potential for accelerating the development of more effective treatment options. The workshop panel made recommendations for research in four major categories: clinical studies of alcohol and HCV; virology and immunology; liver fibrosis and mechanisms of liver injury; and the development of model systems. This article summarizes the panel's deliberations and their recommendations for future research on alcohol and hepatitis C.

Alcohol Drinking↗

PubMed2002

Production of a cytochrome P450 2E1 transgenic mouse and initial evaluation of alcoholic liver damage.

Hepatic metabolism of ethanol by cytochrome P450 2E1 (CYP2E1) is believed to contribute to alcoholic liver damage. To further evaluate CYP2E1 in alcoholic liver disease, we created a transgenic mouse containing human CYP2E1 complementary DNA (cDNA) under the control of mouse albumin enhancer-promoter. Two experiments were performed. In the first experiment, transgenic and nontransgenic mice were fed normal chow. In the second experiment, transgenic and nontransgenic mice were pair fed a nutritionally complete liquid diet for 16 weeks. The liquid diet contained 30% of calories as ethanol (or dextrose) and 25% of calories as corn oil. Liver damage was assessed by measuring serum alanine aminotransferase (ALT) levels and examining liver histology. Transgenic animals reproduced and were phenotypically normal. Hepatic levels of CYP2E1 messenger RNA (mRNA), protein, and enzyme activity did not differ between chow-fed transgenic and nontransgenic mice. Livers from transgenic mice fed the alcohol diet contained significantly more CYP2E1 protein and enzyme activity than livers from nontransgenic mice fed the same diet. Transgenic mice receiving the alcohol diet had significantly higher serum ALT levels than nontransgenic mice. Histologic examination of the livers showed higher histologic scores in transgenic mice fed ethanol compared with nontransgenic mice fed ethanol. Ballooning hepatocytes were seen in livers from transgenic mice fed ethanol. Apoptosis, as determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay, did not differ between groups. In conclusion, we have produced a transgenic mouse that expresses human CYP2E1 in the liver. When fed a nutritionally complete alcohol diet, transgenic mice develop more liver damage than nontransgenic mice.

Alanine Transaminase↗