Alcohol and hepatitis C virus (HCV) infection are recognized as independent causes of chronic liver disease and cirrhosis. Further, significant alcohol ingestion, defined variably as >30 gnvday (women) or >50-60 grnlday (men) has been associated with more severe histological disease, including cirrhosis and hepatocellular carcinoma and an accelerated rate of disease progression in patients with chronic HCV infection. The effect of more limited alcohol intake or non-daily drinking patterns on the progression of HCV disease are not known. In this study, we will establish a prospective cohort of at least 550 HCV-infected patients who drink varying amounts of alcohol at study entry. Total lifetime alcohol intake, patterns of alcohol ingestion, and periods of abstinence will be ascertained using validated questionnaires (Skinner, 1979; Russell, 1991) at study entry and annually for four years. Additional data collected at study entry include demographic, epidemiological and dietary history (including duration of HCV infection, mode of acquisition, use of iron supplements). A comprehensive evaluation of HCV RNA including viral titer in serum, liver and peripheral blood mononuclear cells (PBMCs), and baseline quasispecies complexity, will be obtained. Subjects with an alcohol intake of >30 gm/day (females) or >60 gm/day (males) will be counseled to completely abstain. A subset of 150 subjects drinking <15 gm/day (females) or <30 gm/day (males) of alcohol will be randomized to abstinence or no change in alcohol intake (control group). Annually we will readminister an alcohol questionnaire (12-month quantity/frequency questionnaire, National Alcohol Survey) and perform tests for ferritin, transfenin saturation, and serum aminotransferase activity. HCV viral quasispecies variability (assessed by heteroduplex mobility assay) HCV RNA quantitation and cytokine profiles will be compared in different tissue sources (serum, PBMCs and liver). Liver biopsies will be obtained at baseline and at the end of 4 years follow-up to assess severity and progression of liver disease. This study will determine 1) the quantity and pattern of alcohol intake associated with progression of HCV liver disease; 2) whether abstinence from alcohol among """"""""moderate"""""""" or """"""""light"""""""" drinkers reduces the rate of HCV disease progression; and 3) the host (including proinflammatory or profibrotic host genes which may be activated in the presence of alcohol) and viral factors (including quasispecies heterogeneity which may be altered by alcohol ingestion) which underlie the enhanced rate of disease progression in HCV-infected patients using alcohol.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA012879-05
Application #
6785229
Study Section
Special Emphasis Panel (ZAA1-DD (01))
Program Officer
Bryant, Kendall
Project Start
2000-09-30
Project End
2006-07-31
Budget Start
2004-08-01
Budget End
2006-07-31
Support Year
5
Fiscal Year
2004
Total Cost
$221,250
Indirect Cost
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Kort, Naomi S; Ford, Judith M; Roach, Brian J et al. (2017) Role of N-Methyl-D-Aspartate Receptors in Action-Based Predictive Coding Deficits in Schizophrenia. Biol Psychiatry 81:514-524
Pollak, T A; De Simoni, S; Barimani, B et al. (2015) Phenomenologically distinct psychotomimetic effects of ketamine are associated with cerebral blood flow changes in functionally relevant cerebral foci: a continuous arterial spin labelling study. Psychopharmacology (Berl) 232:4515-24
Stone, James; Kotoula, Vasileia; Dietrich, Craige et al. (2015) Perceptual distortions and delusional thinking following ketamine administration are related to increased pharmacological MRI signal changes in the parietal lobe. J Psychopharmacol 29:1025-8
DeLorenzo, Christine; DellaGioia, Nicole; Bloch, Michael et al. (2015) In vivo ketamine-induced changes in [¹¹C]ABP688 binding to metabotropic glutamate receptor subtype 5. Biol Psychiatry 77:266-275
Anticevic, Alan; Hu, Sien; Zhang, Sheng et al. (2014) Global resting-state functional magnetic resonance imaging analysis identifies frontal cortex, striatal, and cerebellar dysconnectivity in obsessive-compulsive disorder. Biol Psychiatry 75:595-605
Amorosa, Valerianna K; Luetkemeyer, Anne; Kang, Minhee et al. (2013) Addition of nitazoxanide to PEG-IFN and ribavirin to improve HCV treatment response in HIV-1 and HCV genotype 1 coinfected persons naïve to HCV therapy: results of the ACTG A5269 trial. HIV Clin Trials 14:274-83
Bacchetti, Peter; Boylan, Ross; Astemborski, Jacquie et al. (2011) Progression of biopsy-measured liver fibrosis in untreated patients with hepatitis C infection: non-Markov multistate model analysis. PLoS One 6:e20104
Ishida, Julie H; Peters, Marion G; Jin, Chengshi et al. (2008) Influence of cannabis use on severity of hepatitis C disease. Clin Gastroenterol Hepatol 6:69-75
Leandro, Gioacchino; Mangia, Alessandra; Hui, Jason et al. (2006) Relationship between steatosis, inflammation, and fibrosis in chronic hepatitis C: a meta-analysis of individual patient data. Gastroenterology 130:1636-42
Peters, Marion G; Terrault, Norah A (2002) Alcohol use and hepatitis C. Hepatology 36:S220-5