Viral Hepatitis

You have full text access to this OnlineOpen article

Hepatitis C — identifying patients with progressive liver injury†

  1. Jordan J. Feld,
  2. T. Jake Liang*

Article first published online: 30 JAN 2006

DOI: 10.1002/hep.21065

Issue

Hepatology

Hepatology

Special Issue: 25th Anniversary Issue

Volume 43, Issue S1, pages S194–S206, February 2006

Additional Information

How to Cite

Feld, J. J. and Liang, T. J. (2006), Hepatitis C — identifying patients with progressive liver injury. Hepatology, 43: S194–S206. doi: 10.1002/hep.21065

Author Information

  1. Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD

*NIH, 10 CenterDrive, Room 9B16, Bethesda, MD, 20892

  1. †

    Potential conflict of interest: Nothing to report.

Publication History

  1. Issue published online: 30 JAN 2006
  2. Article first published online: 30 JAN 2006

Funded by

  • Intramural Research Program of the NIH, National Institute of Diabetes and Digestive and Kidney Diseases

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (280K)

References

  • 1
    Seeff LB, Hoofnagle JH. Appendix: The National Institutes of Health Consensus Development Conference Management of Hepatitis C 2002. Clin Liver Dis 2003; 7: 261-287.
  • 2
    Heller T, Rehermann B. Acute hepatitis C: a multifaceted disease. Semin Liver Dis 2005; 25: 7-17.
  • 3
    Kleiner DE. The liver biopsy in chronic hepatitis C: a view from the other side of the microscope. Semin Liver Dis 2005; 25: 52-64.
  • 4
    Poynard T, Bedossa P, Opolon P. Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Lancet 1997; 349: 825-832.
  • 5
    McCaughan GW, George J. Fibrosis progression in chronic hepatitis C virus infection. Gut 2004; 53: 318-321.
  • 6
    Ghany MG, Kleiner DE, Alter H, Doo E, Khokar F, Promrat K, et al. Progression of fibrosis in chronic hepatitis C. Gastroenterology 2003; 124: 97-104.
  • 7
    Ryder SD, Irving WL, Jones DA, Neal KR, Underwood JC. Progression of hepatic fibrosis in patients with hepatitis C: a prospective repeat liver biopsy study. Gut 2004; 53: 451-455.
  • 8
    Kenny-Walsh E. Clinical outcomes after hepatitis C infection from contaminated anti-D immune globulin. Irish Hepatology Research Group. N Engl J Med 1999; 340: 1228-1233.
  • 9
    Wiese M, Berr F, Lafrenz M, Porst H, Oesen U. Low frequency of cirrhosis in a hepatitis C (genotype 1b) single-source outbreak in germany: a 20-year multicenter study. Hepatology 2000; 32: 91-96.
    Direct Link:
  • 10
    Seeff LB, Hollinger FB, Alter HJ, Wright EC, Cain CM, Buskell ZJ, et al. Long-term mortality and morbidity of transfusion-associated non-A, non-B, and type C hepatitis: A National Heart, Lung, and Blood Institute collaborative study. Hepatology 2001; 33: 455-463.
    Direct Link:
  • 11
    Tremolada F, Casarin C, Alberti A, Drago C, Tagger A, Ribero ML, et al. Long-term follow-up of non-A, non-B (type C) post-transfusion hepatitis. J Hepatol 1992; 16: 273-281.
  • 12
    Koretz RL, Abbey H, Coleman E, Gitnick G. Non-A, non-B post-transfusion hepatitis. Looking back in the second decade. Ann Intern Med 1993; 119: 110-115.
  • 13
    Hopf U, Moller B, Kuther D, Stemerowicz R, Lobeck H, Ludtke-Handjery A, et al. Long-term follow-up of posttransfusion and sporadic chronic hepatitis non-A, non-B and frequency of circulating antibodies to hepatitis C virus (HCV). J Hepatol 1990; 10: 69-76.
  • 14
    Di Bisceglie AM, Goodman ZD, Ishak KG, Hoofnagle JH, Melpolder JJ, Alter HJ. Long-term clinical and histopathological follow-up of chronic posttransfusion hepatitis. Hepatology 1991; 14: 969-974.
    Direct Link:
  • 15
    Asselah T, Boyer N, Guimont MC, Cazals-Hatem D, Tubach F, Nahon K, et al. Liver fibrosis is not associated with steatosis but with necroinflammation in French patients with chronic hepatitis C. Gut 2003; 52: 1638-1643.
  • 16
    Wright M, Goldin R, Fabre A, Lloyd J, Thomas H, Trepo C, et al. Measurement and determinants of the natural history of liver fibrosis in hepatitis C virus infection: a cross sectional and longitudinal study. Gut 2003; 52: 574-579.
  • 17
    Minola E, Prati D, Suter F, Maggiolo F, Caprioli F, Sonzogni A, et al. Age at infection affects the long-term outcome of transfusion-associated chronic hepatitis C. Blood 2002; 99: 4588-4591.
  • 18
    Vogt M, Lang T, Frosner G, Klingler C, Sendl AF, Zeller A, et al. Prevalence and clinical outcome of hepatitis C infection in children who underwent cardiac surgery before the implementation of blood-donor screening. N Engl J Med 1999; 341: 866-870.
  • 19
    Tovo PA, Pembrey LJ, Newell ML. Persistence rate and progression of vertically acquired hepatitis C infection. European Paediatric Hepatitis C Virus Infection. J Infect Dis 2000; 181: 4194-4124.
  • 20
    Jara P, Resti M, Hierro L, Giacchino R, Barbera C, Zancan L, et al. Chronic hepatitis C virus infection in childhood: clinical patterns and evolution in 224 white children. Clin Infect Dis 2003; 36: 275-280.
  • 21
    Casiraghi MA, De Paschale M, Romano L, Biffi R, Assi A, Binelli G, et al. Long-term outcome (35 years) of hepatitis C after acquisition of infection through mini transfusions of blood given at birth. Hepatology 2004; 39: 90-96.
    Direct Link:
  • 22
    Castellino S, Lensing S, Riely C, Rai SN, Davila R, Hayden RT, et al. The epidemiology of chronic hepatitis C infection in survivors of childhood cancer: an update of the St. Jude Children's Research Hospital hepatitis C seropositive cohort. Blood 2004; 103: 2460-2466.
  • 23
    Tillmann HL, Manns MP, Rudolph KL. Merging models of hepatitis C virus pathogenesis. Semin Liver Dis 2005; 25: 84-92.
  • 24
    Wali M, Harrison RF, Gow PJ, Mutimer D. Advancing donor liver age and rapid fibrosis progression following transplantation for hepatitis C. Gut 2002; 51: 248-252.
  • 25
    Ostapowicz G, Fontana RJ, Schiodt FV, Larson A, Davern TJ, Han SH, et al. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann Intern Med 2002; 137: 947-954.
  • 26
    Tong MJ, el-Farra NS, Reikes AR, Co RL. Clinical outcomes after transfusion-associated hepatitis C. N Engl J Med 1995; 332: 1463-1466.
  • 27
    Degos F, Christidis C, Ganne-Carrie N, Farmachidi JP, Degott C, Guettier C, et al. Hepatitis C virus related cirrhosis: time to occurrence of hepatocellular carcinoma and death. Gut 2000; 47: 131-136.
  • 28
    Di Martino V, Lebray P, Myers RP, Pannier E, Paradis V, Charlotte F, et al. Progression of liver fibrosis in women infected with hepatitis C: long-term benefit of estrogen exposure. Hepatology 2004; 40: 1426-1433.
    Direct Link:
  • 29
    Yasuda M, Shimizu I, Shiba M, Ito S. Suppressive effects of estradiol on dimethylnitrosamine-induced fibrosis of the liver in rats. Hepatology 1999; 29: 719-27.
    Direct Link:
  • 30
    Kim WR, Poterucha JJ, Benson JT, Therneau TM. The impact of competing risks on the observed rate of chronic hepatitis C progression. Gastroenterology 2004; 127: 749-755.
  • 31
    Harris DR, Gonin R, Alter HJ, Wright EC, Buskell ZJ, Hollinger FB, et al. The relationship of acute transfusion-associated hepatitis to the development of cirrhosis in the presence of alcohol abuse. Ann Intern Med 2001; 134: 120-124.
  • 32
    Seeff LB, Buskell-Bales Z, Wright EC, Durako SJ, Alter HJ, Iber FL, et al. Long-term mortality after transfusion-associated non-A, non-B hepatitis. The National Heart, Lung, and Blood Institute Study Group. N Engl J Med 1992; 327: 1906-1911.
  • 33
    Corrao G, Arico S. Independent and combined action of hepatitis C virus infection and alcohol consumption on the risk of symptomatic liver cirrhosis. Hepatology 1998; 27: 914-919.
    Direct Link:
  • 34
    Donato F, Tagger A, Gelatti U, Parrinello G, Boffetta P, Albertini A, et al. Alcohol and hepatocellular carcinoma: the effect of lifetime intake and hepatitis virus infections in men and women. Am J Epidemiol 2002; 155: 323-331.
  • 35
    Wiley TE, McCarthy M, Breidi L, Layden TJ. Impact of alcohol on the histological and clinical progression of hepatitis C infection. Hepatology 1998; 28: 805-809.
    Direct Link:
  • 36
    Safdar K, Schiff ER. Alcohol and hepatitis C. Semin Liver Dis 2004; 24: 305-315.
  • 37
    Sata M, Fukuizumi K, Uchimura Y, Nakano H, Ishii K, Kumashiro R, et al. Hepatitis C virus infection in patients with clinically diagnosed alcoholic liver diseases. J Viral Hepat 1996; 3: 143-148.
    Direct Link:
  • 38
    Pessione F, Degos F, Marcellin P, Duchatelle V, Njapoum C, Martinot-Peignoux M, et al. Effect of alcohol consumption on serum hepatitis C virus RNA and histological lesions in chronic hepatitis C. Hepatology 1998; 27: 1717-1722.
    Direct Link:
  • 39
    Oshita M, Hayashi N, Kasahara A, Hagiwara H, Mita E, Naito M, et al. Increased serum hepatitis C virus RNA levels among alcoholic patients with chronic hepatitis C. Hepatology 1994; 20: 1115-1120.
    Direct Link:
  • 40
    Perlemuter G, Letteron P, Carnot F, Zavala F, Pessayre D, Nalpas B, et al. Alcohol and hepatitis C virus core protein additively increase lipid peroxidation and synergistically trigger hepatic cytokine expression in a transgenic mouse model. J Hepatol 2003; 39: 1020-1027.
  • 41
    Hezode C, Lonjon I, Roudot-Thoraval F, Mavier JP, Pawlotsky JM, Zafrani ES, et al. Impact of smoking on histological liver lesions in chronic hepatitis C. Gut 2003; 52: 126-129.
  • 42
    Hezode C, Roudot-Thoraval F, Nguyen S, Grenard P, Julien B, Zafrani ES, et al. AS. Daily cannabis smoking as a risk factor for progression of fibrosis in chronic hepatitis C. Hepatology 2005; 42: 63-71.
    Direct Link:
  • 43
    Julien B, Grenard P, Teixeira-Clerc F, Van Nhieu JT, Li L, Karsak M, Zimmer A, et al. Antifibrogenic role of the cannabinoid receptor CB2 in the liver. Gastroenterology 2005; 128: 742-755.
  • 44
    Diwakaran HH, Befeler AS, Britton RS, Brunt EM, Bacon BR. Accelerated hepatic fibrosis in patients with combined hereditary hemochromatosis and chronic hepatitis C infection. J Hepatol 2002; 36: 687-691.
  • 45
    Ardalan FA, Osquei MR, Toosi MN, Irvanloo G. Synergic effect of chronic hepatitis C infection and beta thalassemia major with marked hepatic iron overload on liver fibrosis: a retrospective cross-sectional study. BMC Gastroenterol 2004; 4: 17.
  • 46
    Siagris D, Giannakoulas N, Christofidou M, Tsamandas A, Lekkou A, Thomopoulos K, et al. Virological, immunological and histological aspects in adult beta-thalassemic patients with chronic hepatitis C virus infection. Liver Int 2004; 24: 204-209.
    Direct Link:
  • 47
    Tung BY, Emond MJ, Bronner MP, Raaka SD, Cotler SJ, Kowdley KV. Hepatitis C, iron status, and disease severity: relationship with HFE mutations. Gastroenterology 2003; 124: 318-326.
  • 48
    Erhardt A, Maschner-Olberg A, Mellenthin C, Kappert G, Adams O, Donner A, et al. HFE mutations and chronic hepatitis C: H63D and C282Y heterozygosity are independent risk factors for liver fibrosis and cirrhosis. J Hepatol 2003; 38: 335-342.
  • 49
    Lebray P, Zylberberg H, Hue S, Poulet B, Carnot F, Martin S, et al. Influence of HFE gene polymorphism on the progression and treatment of chronic hepatitis C. J Viral Hepatol 2004; 11: 175-182.
    Direct Link:
  • 50
    Thorburn D, Curry G, Spooner R, Spence E, Oien K, Halls D, et al. The role of iron and haemochromatosis gene mutations in the progression of liver disease in chronic hepatitis C. Gut 2002; 50: 248-252.
  • 51
    Theurl I, Zoller H, Obrist P, Datz C, Bachmann F, Elliott RM, et al. Iron regulates hepatitis C virus translation via stimulation of expression of translation initiation factor 3. J Infect Dis 2004; 190: 819-825.
  • 52
    Fillebeen C, Rivas-Estilla AM, Bisaillon M, Ponka P, Muckenthaler M, Hentze MW, et al. Iron inactivates the RNA polymerase NS5B and suppresses subgenomic replication of hepatitis C Virus. J Biol Chem 2005; 280: 9049-9057.
  • 53
    Fargion S, Fracanzani AL, Rossini A, Borzio M, Riggio O, Belloni G, et al. Iron reduction and sustained response to interferon-alpha therapy in patients with chronic hepatitis C: results of an Italian multicenter randomized study. Am J Gastroenterol 2002; 97: 1204-1210.
  • 54
    Di Bisceglie AM, Bonkovsky HL, Chopra S, Flamm S, Reddy RK, Grace N, et al. Iron reduction as an adjuvant to interferon therapy in patients with chronic hepatitis C who have previously not responded to interferon: a multicenter, prospective, randomized, controlled trial. Hepatology 2000; 32: 135-138.
    Direct Link:
  • 55
    Fontana RJ, Israel J, LeClair P, Banner BF, Tortorelli K, Grace N, et al. Iron reduction before and during interferon therapy of chronic hepatitis C: results of a multicenter, randomized, controlled trial. Hepatology 2000; 31: 730-736.
    Direct Link:
  • 56
    Pawlotsky JM. Pathophysiology of hepatitis C virus infection and related liver disease. Trends Microbiol 2004; 12: 96-102.
  • 57
    Soriano V, Sulkowski M, Bergin C, Hatzakis A, Cacoub P, Katlama C, et al. Care of patients with chronic hepatitis C and HIV co-infection: recommendations from the HIV-HCV International Panel. Aids 2002; 16: 813-828.
  • 58
    Bica I, McGovern B, Dhar R, Stone D, McGowan K, Scheib R, et al. Increasing mortality due to end-stage liver disease in patients with human immunodeficiency virus infection. Clin Infect Dis 2001; 32: 492-497.
  • 59
    Rosenthal E, Poiree M, Pradier C, Perronne C, Salmon-Ceron D, Geffray L, et al. Mortality due to hepatitis C-related liver disease in HIV-infected patients in France (Mortavic 2001 study). Aids 2003; 17: 1803-9.
  • 60
    Soriano V, Puoti M, Sulkowski M, Mauss S, Cacoub P, Cargnel A, et al. Care of patients with hepatitis C and HIV co-infection. Aids 2004; 18: 1-12.
  • 61
    Graham CS, Baden LR, Yu E, Mrus JM, Carnie J, Heeren T, et al. Influence of human immunodeficiency virus infection on the course of hepatitis C virus infection: a meta-analysis. Clin Infect Dis 2001; 33: 562-569.
  • 62
    Benhamou Y, Bochet M, Di Martino V, Charlotte F, Azria F, Coutellier A, et al. Liver fibrosis progression in human immunodeficiency virus and hepatitis C virus coinfected patients. The Multivirc Group. Hepatology 1999; 30: 1054-1058.
    Direct Link:
  • 63
    Sterling RK, Sulkowski MS. Hepatitis C virus in the setting of HIV or hepatitis B virus coinfection. Semin Liver Dis 2004; 24( Suppl 2): 61-68.
  • 64
    Tural C, Fuster D, Tor J, Ojanguren I, Sirera G, Ballesteros A, et al. Time on antiretroviral therapy is a protective factor for liver fibrosis in HIV and hepatitis C virus (HCV) co-infected patients. J Viral Hepat 2003; 10: 118-125.
    Direct Link:
  • 65
    Peffault de Latour R, Levy V, Asselah T, Marcellin P, Scieux C, Ades L, et al. Long-term outcome of hepatitis C infection after bone marrow transplantation. Blood 2004; 103: 1618-1624.
  • 66
    Aroldi A, Lampertico P, Montagnino G, Lunghi G, Passerini P, Villa M, et al. Natural history of hepatitis C virus infection in adult renal graft recipients. Transplant Proc 2005; 37: 940-941.
  • 67
    Berenguer M, Ferrell L, Watson J, Prieto M, Kim M, Rayon M, Cordoba J, et al. HCV-related fibrosis progression following liver transplantation: increase in recent years. J Hepatol 2000; 32: 673-684.
  • 68
    Neumann UP, Berg T, Bahra M, Seehofer D, Langrehr JM, Neuhaus R, et al. Fibrosis progression after liver transplantation in patients with recurrent hepatitis C. J Hepatol 2004; 41: 830-836.
  • 69
    Charlton M, Seaberg E, Wiesner R, Everhart J, Zetterman R, Lake J, et al. Predictors of patient and graft survival following liver transplantation for hepatitis C. Hepatology 1998; 28: 823-830.
    Direct Link:
  • 70
    Bozorgzadeh A, Jain A, Ryan C, Ornt D, Zand M, Mantry P, et al. Impact of hepatitis C viral infection in primary cadaveric liver allograft versus primary living-donor allograft in 100 consecutive liver transplant recipients receiving tacrolimus. Transplantation 2004; 77: 1066-1070.
  • 71
    Berenguer M, Crippin J, Gish R, Bass N, Bostrom A, Netto G, et al. A model to predict severe HCV-related disease following liver transplantation. Hepatology 2003; 38: 34-41.
    Direct Link:
  • 72
    Chopra KB, Demetris AJ, Blakolmer K, Dvorchik I, Laskus T, Wang LF, et al. Progression of liver fibrosis in patients with chronic hepatitis C after orthotopic liver transplantation. Transplantation 2003; 76: 1487-1491.
  • 73
    Powell EE, Jonsson JR, Clouston AD. Steatosis: co-factor in other liver diseases. Hepatology 2005; 42: 5-13.
    Direct Link:
  • 74
    Negro F. Hepatitis C virus and liver steatosis: is it the virus? Yes it is, but not always. Hepatology 2002; 36: 1050-1052.
    Direct Link:
  • 75
    Barba G, Harper F, Harada T, Kohara M, Goulinet S, Matsuura Y, et al. Hepatitis C virus core protein shows a cytoplasmic localization and associates to cellular lipid storage droplets. Proc Natl Acad Sci U S A 1997; 94: 1200-1205.
  • 76
    Adinolfi LE, Gambardella M, Andreana A, Tripodi MF, Utili R, Ruggiero G. Steatosis accelerates the progression of liver damage of chronic hepatitis C patients and correlates with specific HCV genotype and visceral obesity. Hepatology 2001; 33: 1358-1364.
    Direct Link:
  • 77
    Hourigan LF, Macdonald GA, Purdie D, Whitehall VH, Shorthouse C, Clouston A, et al. Fibrosis in chronic hepatitis C correlates significantly with body mass index and steatosis. Hepatology 1999; 29: 1215-1219.
    Direct Link:
  • 78
    Westin J, Nordlinder H, Lagging M, Norkrans G, Wejstal R. Steatosis accelerates fibrosis development over time in hepatitis C virus genotype 3 infected patients. J Hepatol 2002; 37: 837-842.
  • 79
    Rubbia-Brandt L, Fabris P, Paganin S, Leandro G, Male PJ, Giostra E, et al. Steatosis affects chronic hepatitis C progression in a genotype specific way. Gut 2004; 53: 406-412.
  • 80
    Patton HM, Patel K, Behling C, Bylund D, Blatt LM, Vallee M, et al. The impact of steatosis on disease progression and early and sustained treatment response in chronic hepatitis C patients. J Hepatol 2004; 40: 484-490.
  • 81
    Fartoux L, Poujol-Robert A, Guechot J, Wendum D, Poupon R, Serfaty L. Insulin resistance is a cause of steatosis and fibrosis progression in chronic hepatitis C. Gut 2005; 54: 1003-1008.
  • 82
    Gordon A, McLean CA, Pedersen JS, Bailey MJ, Roberts SK. Hepatic steatosis in chronic hepatitis B and C: predictors, distribution and effect on fibrosis. J Hepatol 2005; 43: 38-44.
  • 83
    Hui JM, Sud A, Farrell GC, Bandara P, Byth K, Kench JG, et al. Insulin resistance is associated with chronic hepatitis C virus infection and fibrosis progression [corrected]. Gastroenterology 2003; 125: 1695-1704.
  • 84
    Ratziu V, Munteanu M, Charlotte F, Bonyhay L, Poynard T. Fibrogenic impact of high serum glucose in chronic hepatitis C. J Hepatol 2003; 39: 1049-1055.
  • 85
    Paradis V, Perlemuter G, Bonvoust F, Dargere D, Parfait B, Vidaud M, et al. High glucose and hyperinsulinemia stimulate connective tissue growth factor expression: a potential mechanism involved in progression to fibrosis in nonalcoholic steatohepatitis. Hepatology 2001; 34: 738-744.
    Direct Link:
  • 86
    Svegliati-Baroni G, Ridolfi F, Di Sario A, Casini A, Marucci L, Gaggiotti G, et al. Insulin and insulin-like growth factor-1 stimulate proliferation and type I collagen accumulation by human hepatic stellate cells: differential effects on signal transduction pathways. Hepatology 1999; 29: 1743-1751.
    Direct Link:
  • 87
    Ong JP, Younossi ZM, Speer C, Olano A, Gramlich T, Boparai N. Chronic hepatitis C and superimposed nonalcoholic fatty liver disease. Liver 2001; 21: 266-271.
    Direct Link:
  • 88
    Clouston AD, Jonsson JR, Purdie DM, Macdonald GA, Pandeya N, Shorthouse C, et al. Steatosis and chronic hepatitis C: analysis of fibrosis and stellate cell activation. J Hepatol 2001; 34: 314-320.
  • 89
    Day CP. Pathogenesis of steatohepatitis. Best Pract Res Clin Gastroenterol 2002; 16: 663-678.
  • 90
    Sanyal AJ, Campbell-Sargent C, Mirshahi F, Rizzo WB, Contos MJ, Sterling RK, et al. Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology 2001; 120: 1183-1192.
  • 91
    Paradis V, Mathurin P, Kollinger M, Imbert-Bismut F, Charlotte F, Piton A, Opolon P, Holstege A, Poynard T, Bedossa P. In situ detection of lipid peroxidation in chronic hepatitis C: correlation with pathological features. J Clin Pathol 1997; 50: 401-406.
  • 92
    Lonardo A, Adinolfi LE, Loria P, Carulli N, Ruggiero G, Day CP. Steatosis and hepatitis C virus: mechanisms and significance for hepatic and extrahepatic disease. Gastroenterology 2004; 126: 586-597.
  • 93
    Walsh MJ, Vanags DM, Clouston AD, Richardson MM, Purdie DM, Jonsson JR, et al. Steatosis and liver cell apoptosis in chronic hepatitis C: a mechanism for increased liver injury. Hepatology 2004; 39: 1230-1238.
    Direct Link:
  • 94
    Canbay A, Feldstein AE, Higuchi H, Werneburg N, Grambihler A, Bronk SF, et al. Kupffer cell engulfment of apoptotic bodies stimulates death ligand and cytokine expression. Hepatology 2003; 38: 1188-1198.
    Direct Link:
  • 95
    Okuda M, Li K, Beard MR, Showalter LA, Scholle F, Lemon SM, et al. Mitochondrial injury, oxidative stress, and antioxidant gene expression are induced by hepatitis C virus core protein. Gastroenterology 2002; 122: 366-375.
  • 96
    Hickman IJ, Jonsson JR, Prins JB, Ash S, Purdie DM, Clouston AD, et al. Modest weight loss and physical activity in overweight patients with chronic liver disease results in sustained improvements in alanine aminotransferase, fasting insulin, and quality of life. Gut 2004; 53: 413-419.
  • 97
    Puoti C, Castellacci R, Montagnese F, Zaltron S, Stornaiuolo G, Bergami N, et al. Histological and virological features and follow-up of hepatitis C virus carriers with normal aminotransferase levels: the Italian prospective study of the asymptomatic C carriers (ISACC). J Hepatol 2002; 37: 117-123.
  • 98
    Kyrlagkitsis I, Portmann B, Smith H, O'Grady J, Cramp ME. Liver histology and progression of fibrosis in individuals with chronic hepatitis C and persistently normal ALT. Am J Gastroenterol 2003; 98: 1588-1593.
    Direct Link:
  • 99
    Hui CK, Belaye T, Montegrande K, Wright TL. A comparison in the progression of liver fibrosis in chronic hepatitis C between persistently normal and elevated transaminase. J Hepatol 2003; 38: 511-517.
  • 100
    Jacobson IM, Ahmed F, Russo MW, Lebovics E, Dieterich DT, Esposito SP, et al. Interferon alfa-2b [correction of alpha-2b]and ribavirin for patients with chronic hepatitis C and normal ALT. Am J Gastroenterol 2004; 99: 1700-1705.
    Direct Link:
  • 101
    Hui CK, Monto A, Belaye T, Lau E, Wright TL. Outcomes of interferon alpha and ribavirin treatment for chronic hepatitis C in patients with normal serum aminotransaminases. Gut 2003; 52: 1644-1648.
  • 102
    Chou R, Clark EC, Helfand M. Screening for hepatitis C virus infection: a review of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2004; 140: 465-479.
  • 103
    Alter MJ, Seeff LB, Bacon BR, Thomas DL, Rigsby MO, Di Bisceglie AM. Testing for hepatitis C virus infection should be routine for persons at increased risk for infection. Ann Intern Med 2004; 141: 715-717.
  • 104
    Crespo J, Lozano JL, de la Cruz F, Rodrigo L, Rodriguez M, San Miguel G, et al. Prevalence and significance of hepatitis C viremia in chronic active hepatitis B. Am J Gastroenterol 1994; 89: 1147-1151.
  • 105
    Gaeta GB, Stornaiuolo G, Precone DF, Lobello S, Chiaramonte M, Stroffolini T, et al. Epidemiological and clinical burden of chronic hepatitis B virus/hepatitis C virus infection. A multicenter Italian study. J Hepatol 2003; 39: 1036-1041.
  • 106
    Cacciola I, Pollicino T, Squadrito G, Cerenzia G, Orlando ME, Raimondo G. Occult hepatitis B virus infection in patients with chronic hepatitis C liver disease. N Engl J Med 1999; 341: 22-26.
  • 107
    Kao JH, Chen PJ, Lai MY, Chen DS. Occult hepatitis B virus infection and clinical outcomes of patients with chronic hepatitis C. J Clin Microbiol 2002; 40: 4068-4071.
  • 108
    Fabris P, Brown D, Tositti G, Bozzola L, Giordani MT, Bevilacqua P, de Lalla F, et al. Occult hepatitis B virus infection does not affect liver histology or response to therapy with interferon alpha and ribavirin in intravenous drug users with chronic hepatitis C. J Clin Virol 2004; 29: 160-166.
  • 109
    Torbenson M, Kannangai R, Astemborski J, Strathdee SA, Vlahov D, Thomas DL. High prevalence of occult hepatitis B in Baltimore injection drug users. Hepatology 2004; 39: 51-57.
    Direct Link:
  • 110
    Paterlini P, Gerken G, Nakajima E, Terre S, D'Errico A, Grigioni W, et al. Polymerase chain reaction to detect hepatitis B virus DNA and RNA sequences in primary liver cancers from patients negative for hepatitis B surface antigen. N Engl J Med 1990; 323: 80-85.
  • 111
    Shintani Y, Yotsuyanagi H, Moriya K, Fujie H, Tsutsumi T, Takayama T, et al. The significance of hepatitis B virus DNA detected in hepatocellular carcinoma of patients with hepatitis C. Cancer 2000; 88: 2478-2486.
    Direct Link:
  • 112
    Vento S, Garofano T, Renzini C, Cainelli F, Casali F, Ghironzi G, et al. Fulminant hepatitis associated with hepatitis A virus superinfection in patients with chronic hepatitis C. N Engl J Med 1998; 338: 286-290.
  • 113
    Bianco E, Stroffolini T, Spada E, Szklo A, Marzolini F, Ragni P, et al. Case fatality rate of acute viral hepatitis in Italy:1995-2000. An update. Dig Liver Dis 2003; 35: 404-408.
  • 114
    McHutchison JG, Nainan OV, Alter MJ, Sedghi-Vaziri A, Detmer J, Collins M, et al. Hepatitis C and G co-infection: response to interferon therapy and quantitative changes in serum HGV-RNA. Hepatology 1997; 26: 1322-1327.
  • 115
    Watanabe H, Saito T, Kawamata O, Shao L, Aoki M, Terui Y, et al. Clinical implications of TT virus superinfection in patients with chronic hepatitis C. Am J Gastroenterol 2000; 95: 1776-1780.
    Direct Link:
  • 116
    Asti M, Martinetti M, Zavaglia C, Cuccia MC, Gusberti L, Tinelli C, et al. Human leukocyte antigen class II and III alleles and severity of hepatitis C virus-related chronic liver disease. Hepatology 1999; 29: 1272-1279.
    Direct Link:
  • 117
    Kuzushita N, Hayashi N, Moribe T, Katayama K, Kanto T, Nakatani S, et al. Influence of HLA haplotypes on the clinical courses of individuals infected with hepatitis C virus. Hepatology 1998; 27: 240-244.
    Direct Link:
  • 118
    Renou C, Halfon P, Pol S, Cacoub P, Jouve E, Bronowicki JP, et al. Histological features and HLA class II alleles in hepatitis C virus chronically infected patients with persistently normal alanine aminotransferase levels. Gut 2002; 51: 585-590.
  • 119
    Hue S, Cacoub P, Renou C, Halfon P, Thibault V, Charlotte F, et al. Human leukocyte antigen class II alleles may contribute to the severity of hepatitis C virus-related liver disease. J Infect Dis 2002; 186: 106-109.
  • 120
    Tillmann HL, Chen DF, Trautwein C, Kliem V, Grundey A, Berning-Haag A, et al. Low frequency of HLA-DRB1*11 in hepatitis C virus induced end stage liver disease. Gut 2001; 48: 714-718.
  • 121
    Yee LJ. Host genetic determinants in hepatitis C virus infection. Genes Immun 2004; 5: 237-245.
  • 122
    Thursz M, Yallop R, Goldin R, Trepo C, Thomas HC. Influence of MHC class II genotype on outcome of infection with hepatitis C virus. The HENCORE group. Hepatitis C European Network for Cooperative Research. Lancet 1999; 354: 2119-2124.
  • 123
    Kuzushita N, Hayashi N, Kanto T, Takehara T, Tatsumi T, et al. Involvement of transporter associated with antigen processing 2 (TAP2) gene polymorphisms in hepatitis C virus infection. Gastroenterology 1999; 116: 1149-1154.
  • 124
    Romero-Gomez M, Montes-Cano MA, Otero-Fernandez MA, Torres B, Sanchez-Munoz D, Aguilar F, et al. SLC11A1 promoter gene polymorphisms and fibrosis progression in chronic hepatitis C. Gut 2004; 53: 446-450.
  • 125
    Hellier S, Frodsham AJ, Hennig BJ, Klenerman P, Knapp S, Ramaley P, et al. Association of genetic variants of the chemokine receptor CCR5 and its ligands, RANTES and MCP-2, with outcome of HCV infection. Hepatology 2003; 38: 1468-1476.
  • 126
    Goulding C, Murphy A, MacDonald G, Barrett S, Crowe J, Hegarty J, et al. The CCR5-delta32 mutation: impact on disease outcome in individuals with hepatitis C infection from a single source. Gut 2005; 54: 1157-1161.
  • 127
    Promrat K, McDermott DH, Gonzalez CM, Kleiner DE, Koziol DE, Lessie M, et al. Associations of chemokine system polymorphisms with clinical outcomes and treatment responses of chronic hepatitis C. Gastroenterology 2003; 124: 352-360.
  • 128
    Muhlbauer M, Bosserhoff AK, Hartmasnn A, Thasler WE, Weiss TS, Herfarth H. et al. A novel MCP-1 gene polymorphism is associated with hepatic MCP-1 expression and severity of HCV-related liver disease. Gastroenterology 2003; 125: 1085-1093.
  • 129
    Glas J, Torok HP, Tonenchi L, Schiemann U, Folwaczny C. The −2518 promotor polymorphism in the MCP-1 gene is not associated with liver cirrhosis in chronic hepatitis C virus infection [Correspondence]. Gastroenterology 2004; 126: 1930-1932.
  • 130
    Bonkovsky HL, Salek J. No role of the −2518 promoter polymorphism of monocyte chemotactic protein-1 in chronic hepatitis C [Correspondence]. Gastroenterology 2005; 128: 1361-1362.
  • 131
    Knapp S, Hennig BJ, Frodsham AJ, Zhang L, Hellier S, Wright M, et al. Interleukin-10 promoter polymorphisms and the outcome of hepatitis C virus infection. Immunogenetics 2003; 55: 362-369.
  • 132
    Powell EE, Edwards-Smith CJ, Hay JL, Clouston AD, Crawford DH, Shorthouse C, et al. Host genetic factors influence disease progression in chronic hepatitis C. Hepatology 2000; 31: 828-833.
    Direct Link:
  • 133
    Tokushige K, Tsuchiya N, Hasegawa K, Hashimoto E, Yamauchi K, Komatsu T, et al. Influence of TNF gene polymorphism and HLA-DRB1 haplotype in Japanese patients with chronic liver disease caused by HCV. Am J Gastroenterol 2003; 98: 160-166.
    Direct Link:
  • 134
    Goyal A, Kazim SN, Sakhuja P, Malhotra V, Arora N, Sarin SK. Association of TNF-beta polymorphism with disease severity among patients infected with hepatitis C virus. J Med Virol 2004; 72: 60-65.
    Direct Link:
  • 135
    Sonzogni L, Silvestri L, De Silvestri A, Gritti C, Foti L, Zavaglia C, et al. Polymorphisms of microsomal epoxide hydrolase gene and severity of HCV-related liver disease. Hepatology 2002; 36: 195-201.
    Direct Link:
  • 136
    Wright M, Goldin R, Hellier S, Knapp S, Frodsham A, Hennig B, et al. Factor V Leiden polymorphism and the rate of fibrosis development in chronic hepatitis C virus infection. Gut 2003; 52: 1206-1210.
  • 137
    Richardson MM, Powell EE, Barrie HD, Clouston AD, Purdie DM, Jonsson JR. A combination of genetic polymorphisms increases the risk of progressive disease in chronic hepatitis C. J Med Genet 2005; 42: e45.
  • 138
    Chou AH, Tsai HF, Wu YY, Hu CY, Hwang LH, Hsu PI, et al. Hepatitis C virus core protein modulates TRAIL-mediated apoptosis by enhancing Bid cleavage and activation of mitochondria apoptosis signaling pathway. J Immunol 2005; 174: 2160-2166.
  • 139
    Abdalla MY, Ahmad IM, Spitz DR, Schmidt WN, Britigan BE. Hepatitis C virus-core and non structural proteins lead to different effects on cellular antioxidant defenses. J Med Virol 2005; 76: 489-497.
    Direct Link:
  • 140
    Abdalla MY, Britigan BE, Wen F, Icardi M, McCormick ML, LaBrecque DR, et al. Down-regulation of heme oxygenase-1 by hepatitis C virus infection in vivo and by the in vitro expression of hepatitis C core protein. J Infect Dis 2004; 190: 1109-1118.
  • 141
    Friedman SL. Cytokines and fibrogenesis. Semin Liver Dis 1999; 19: 129-140.
  • 142
    Perlemuter G, Sabile A, Letteron P, Vona G, Topilco A, Chretien Y, et al. Hepatitis C virus core protein inhibits microsomal triglyceride transfer protein activity and very low density lipoprotein secretion: a model of viral-related steatosis. FASEB J 2002; 16: 185-194.
  • 143
    Yang SH, Lee CG, Lee CW, Choi EJ, Yoon SK, Ahn KS, et al. Hepatitis C virus core inhibits the Fas-mediated p38 mitogen activated kinase signaling pathway in hepatocytes. Mol Cells 2002; 13: 452-62.
  • 144
    Soguero C, Joo M, Chianese-Bullock KA, Nguyen DT, Tung K, Hahn YS. Hepatitis C virus core protein leads to immune suppression and liver damage in a transgenic murine model. J Virol 2002; 76: 9345-9354.
  • 145
    Bantel H, Lugering A, Heidemann J, Volkmann X, Poremba C, Strassburg CP, et al. Detection of apoptotic caspase activation in sera from patients with chronic HCV infection is associated with fibrotic liver injury. Hepatology 2004; 40: 1078-1087.
    Direct Link:
  • 146
    Majumder M, Ghosh AK, Steele R, Zhou XY, Phillips NJ, Ray R, et al. Hepatitis C virus NS5A protein impairs TNF-mediated hepatic apoptosis, but not by an anti-FAS antibody, in transgenic mice. Virology 2002; 294: 94-105.
  • 147
    Girard S, Vossman E, Misek DE, Podevin P, Hanash S, Brechot C, et al. Hepatitis C virus NS5A-regulated gene expression and signaling revealed via microarray and comparative promoter analyses. Hepatology 2004; 40: 708-718.
    Direct Link:
  • 148
    Bataller R, Paik YH, Lindquist JN, Lemasters JJ, Brenner DA. Hepatitis C virus core and nonstructural proteins induce fibrogenic effects in hepatic stellate cells. Gastroenterology 2004; 126: 529-540.
  • 149
    Marshall A, Rushbrook S, Davies SE, Morris LS, Scott IS, Vowler SL, et al. Relation between hepatocyte G1 arrest, impaired hepatic regeneration, and fibrosis in chronic hepatitis C virus infection. Gastroenterology 2005; 128: 33-42.
  • 150
    Dharancy S, Malapel M, Perlemuter G, Roskams T, Cheng Y, Dubuquoy L, et al. Impaired expression of the peroxisome proliferator-activated receptor alpha during hepatitis C virus infection. Gastroenterology 2005; 128: 334-342.
View Full Article (HTML) Get PDF (280K)