thymosin and Alcoholism

Despite improvements in the treatment of chronic hepatitis C virus (HCV) infection, nearly half of all patients do not respond to initial therapy. Retreatment of these patients with pegylated interferon and ribavirin has been successful in only a limited percentage of cases. Factors associated with sustained virologic response (SVR) following retreatment include prior treatment with interferon monotherapy, HCV genotype 2 or 3, a low serum HCV RNA level, and the absence of cirrhosis. Fewer than 6% of nonresponders who were previously treated with interferon and ribavirin and who have cirrhosis, genotype 1, and a high viral load achieve SVR following retreatment with pegylated interferon and ribavirin. No therapy has been shown to yield SVR in patients who do not respond to pegylated interferon and ribavirin. Long-term maintenance therapy with pegylated interferon is currently being evaluated in nonresponders with advanced fibrosis and cirrhosis. Its use should be considered investigational at this time.

Topics: Adjuvants, Immunologic; Alcoholism; Amantadine; Antiviral Agents; Black or African American; Clinical Trials as Topic; Counseling; Drug Therapy, Combination; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Infusions, Intravenous; Injections, Subcutaneous; Interferons; Liver Cirrhosis; Meta-Analysis as Topic; Oligonucleotides, Antisense; Patient Compliance; Ribavirin; RNA, Viral; Thymalfasin; Thymosin; Time Factors; White People

Liver regeneration is regulated by the orderly activation of growth-related genes. Although ethanol impairs induction of liver regeneration by partial hepatectomy, we have not identified ethanol-associated differences in the hepatic mRNA levels of several proto-oncogenes, including c-myc, which peaks 3-6 hr post-partial hepatectomy. Prothymosin alpha, a gene encoding a ubiquitous nuclear protein, is activated by c-myc in resting fibroblasts and has been implicated as a regulator of cell proliferation. Prothymosin alpha mRNA levels reportedly increase 12-32 hr post-partial hepatectomy, several hours after c-myc induction. We sought to determine if chronic ethanol intake alters the expected induction post-partial hepatectomy of prothymosin alpha steady-state mRNA expression and protein levels. Comparing rats chronically fed ethanol with pair-fed controls, we found no significant differences in steady-state levels of prothymosin alpha mRNA; however, we did see a delay in the increase of prothymosin immunoreactive peptide in rats chronically fed alcohol. This suggests that the inhibition in protein levels in ethanol fed rats is not due to lower steady-state mRNA levels, but may occur post-transcriptionally. Further data are needed to determine if this finding is important in the inhibition in cell growth following partial hepatectomy in rats chronically fed ethanol.

Topics: Alcoholism; Animals; Cell Division; DNA Probes; Ethanol; Gene Expression Regulation; Liver Regeneration; Male; Protein Precursors; Proto-Oncogene Proteins c-myc; Rats; Rats, Inbred WF; RNA, Messenger; Thymosin