A Review of the Natural History of Chronic Hepatitis C Infection
Keywords:
chronic hepatitis C infection, anti-HCV antibodies, morbidity, mortalityAbstract
The burden of chronic hepatitis C infection worldwide is significant. Approximately 4.1 million people in the United States have anti-HCV antibodies. The prevalence worldwide varies, but reaches greater than 3.5% in some regions (North African, East Asia). The burden of hepatitis C virus is reflected in the morbidity and mortality of this disease, as well as the societal costs. The morbidity and mortality associated with chronic hepatitis c infection is mostly related to the rate of fibrosis and associated progression to cirrhosis. The natural history of this progression is a complex and dynamic process related to individual characteristics (age, sex, race, genetics), viral characteristics (genotype), behavioral (smoking, alcohol), metabolic factors (insulin resistance, obesity), and co-infection (Hepatitis B and HIV). This review describes the current literature on how these factors interact with chronic hepatitis C infection and impact the natural history of this disease and progression to fibrosis and cirrhosis.
References
Armstrong GL, Wasley A, Simard EP, McQuillan GM, Kuhnert WL, Alter MJ. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med. 2006;144(10):705-714.
Farci P, Alter HJ, Wong D, et al. A long-term study of hepatitis C virus replication in non-A, non-B hepatitis. N Engl J Med. 1991;325(2):98-104.
Barrera JM, Bruguera M, Ercilla MG, et al. Persistent hepatitis C viremia after acute self-limiting posttransfusion hepatitis C. Hepatology. 1995;21(3):639-644.
Ly KN, Xing J, Klevens RM, Jiles RB, Ward JW, Holmberg SD. The increasing burden of mortality from viral hepatitis in the United States between 1999 and 2007. Ann Intern Med. 2012;156(4):271-278.
Wong JB, McQuillan GM, McHutchison JG, Poynard T. Estimating future hepatitis C morbidity, mortality, and costs in the United States. Am J Public Health. 2000;90(10):1562-1569.
Liang TJ, Rehermann B, Seeff LB, Hoofnagle JH. Pathogenesis, natural history, treatment, and prevention of hepatitis C. Ann Intern Med. 2000;132(4):296-305.
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(9055):825-832.
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(1):91-96.
Tong MJ, el-Farra NS, Reikes AR, Co RL. Clinical outcomes after transfusion-associated hepatitis C. N Engl J Med. 1995;332(22):1463-1466.
Yano M, Kumada H, Kage M, et al. The long-term pathological evolution of chronic hepatitis C. Hepatology. 1996;23(6):1334-1340.
Dienstag JL, Ghany MG, Morgan TR, et al. A prospective study of the rate of progression in compensated, histologically advanced chronic hepatitis C. Hepatology. 2011;54(2):396-405.
Niederau C, Lange S, Heintges T, et al. Prognosis of chronic hepatitis C: results of a large, prospective cohort study. Hepatology. 1998;28(6):1687-1695.
Fattovich G, Giustina G, Degos F, et al. Morbidity and mortality in compensated cirrhosis type C: a retrospective follow-up study of 384 patients. Gastroenterology. 1997;112(2):463-472.
Adinolfi LE, Giordano MG, Andreana A, et al. Hepatic fibrosis plays a central role in the pathogenesis of thrombocytopenia in patients with chronic viral hepatitis. Br J Haematol. 2001;113(3):590-595.
Merican I, Sherlock S, McIntyre N, Dusheiko GM. Clinical, biochemical and histological features in 102 patients with chronic hepatitis C virus infection. Q J Med. Feb 1993;86(2):119-125.
Hu KQ, Tong MJ. The long-term outcomes of patients with compensated hepatitis C virus-related cirrhosis and history of parenteral exposure in the United States. Hepatology. Apr 1999;29(4):1311-1316.
Bruno S, Crosignani A, Maisonneuve P, Rossi S, Silini E, Mondelli MU. Hepatitis C virus genotype 1b as a major risk factor associated with hepatocellular carcinoma in patients with cirrhosis: a seventeen-year prospective cohort study. Hepatology. Nov 2007;46(5):1350-1356.
Minola E, Prati D, Suter F, et al. Age at infection affects the long-term outcome of transfusion-associated chronic hepatitis C. Blood. Jun 15 2002;99(12):4588-4591.
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(3):451-455.
Casiraghi MA, De Paschale M, Romano L, et al. Long-term outcome (35 years) of hepatitis C after acquisition of infection through mini transfusions of blood given at birth. Hepatology. Jan 2004;39(1):90-96.
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(2):419-424.
Maasoumy B, Wedemeyer H. Natural history of acute and chronic hepatitis C. Best Pract Res Clin Gastroenterol. 2012;26(4):401-412.
Poynard T, Ratziu V, Charlotte F, Goodman Z, McHutchison J, Albrecht J. Rates and risk factors of liver fibrosis progression in patients with chronic hepatitis c. J Hepatol. 2001;34(5):730-739.
Deuffic-Burban S, Poynard T, Valleron AJ. Quantification of fibrosis progression in patients with chronic hepatitis C using a Markov model. J Viral Hepat. 2002;9(2):114-122.
Massard J, Ratziu V, Thabut D, et al. Natural history and predictors of disease severity in chronic hepatitis C. J Hepatol. 2006;44(1 Suppl):S19-24.
Missiha SB, Ostrowski M, Heathcote EJ. Disease progression in chronic hepatitis C: modifiable and nonmodifiable factors. Gastroenterology. 2008;134(6):1699-1714.
Seeff LB. Natural history of hepatitis C. Hepatology. 1997;26(3 Suppl 1):21S-28S.
Marabita F, Aghemo A, De Nicola S, et al. Genetic variation in the interleukin-28B gene is not associated with fibrosis progression in patients with chronic hepatitis C and known date of infection. Hepatology. 2011;54(4):1127-1134.
Ratziu V, Munteanu M, Charlotte F, Bonyhay L, Poynard T. Fibrogenic impact of high serum glucose in chronic hepatitis C. J Hepatol. 2003;39(6):1049-1055.
Yasuda M, Shimizu I, Shiba M, Ito S. Suppressive effects of estradiol on dimethylnitrosamine-induced fibrosis of the liver in rats. Hepatology. 1999;29(3):719-727.
Bissell DM. Sex and hepatic fibrosis. Hepatology. 1999;29(3):988-989.
Naugler WE, Sakurai T, Kim S, et al. Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production. Science. 2007;317(5834):121-124.
Lavanchy D. The global burden of hepatitis C. Liver international : official journal of the International Association for the Study of the Liver. 2009;29 (Suppl 1):74-81.
Centers for Disease Control and Prevention. Hepatitis C Information for Health Professionals. Centers for Disease Control and Prevention 2008; http://www.cdc.gov/hepatitis/hcv/.
Armstrong GL, Wasley A, Simard EP, McQuillan GM, Kuhnert WL, Alter MJ. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med. 2006;144(10):705-714.
NIH consensus statement on management of hepatitis C: 2002. NIH consensus and state-of-the-science statements. 2002;Vol 192002:1-46.
Alter MJ, Kruszon-Moran D, Nainan OV, et al. The prevalence of hepatitis C virus infection in the United States, 1988 through 1994. N Engl J Med. 1999;341(8):556-562.
Crosse K, Umeadi OG, Anania FA, et al. Racial differences in liver inflammation and fibrosis related to chronic hepatitis C. Clin Gastroenterol Hepatol. 2004;2(6):463-468.
Wiley TE, Brown J, Chan J. Hepatitis C infection in African Americans: its natural history and histological progression. Am J Gastroenterol. 2002;97(3):700-706.
Sterling RK, Stravitz RT, Luketic VA, et al. A comparison of the spectrum of chronic hepatitis C virus between Caucasians and African Americans. Clin Gastroenterol Hepatol. 2004;2(6):469-473.
Bonacini M, Groshen MD, Yu MC, Govindarajan S, Lindsay KL. Chronic hepatitis C in ethnic minority patients evaluated in Los Angeles County. Am J Gastroenterol. 2001;96(8):2438-2441.
D'Souza R, Glynn MJ, Ushiro-Lumb I, et al. Prevalence of hepatitis C-related cirrhosis in elderly Asian patients infected in childhood. Clin Gastroenterol Hepatol. 2005;3(9):910-917.
Ge D, Fellay J, Thompson AJ, et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature. 2009;461(7262):399-401.
Ryan CK, Johnson LA, Germin BI, Marcos A. One hundred consecutive hepatic biopsies in the workup of living donors for right lobe liver transplantation. Liver Transpl. 2002;8(12):1114-1122.
Hwang SJ, Luo JC, Chu CW, et al. Hepatic steatosis in chronic hepatitis C virus infection: prevalence and clinical correlation. J Gastroenterol Hepatol. 2001;16(2):190-195.
Fiore G, Fera G, Napoli N, Vella F, Schiraldi O. Liver steatosis and chronic hepatitis C: a spurious association? Eur J Gastroenterol Hepatol. 1996;8(2):125-129.
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(6):1358-1364.
Ohata K, Hamasaki K, Toriyama K, et al. Hepatic steatosis is a risk factor for hepatocellular carcinoma in patients with chronic hepatitis C virus infection. Cancer. 2003;97(12):3036-3043.
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(6):837-842.
Hui JM, Sud A, Farrell GC, et al. Insulin resistance is associated with chronic hepatitis C virus infection and fibrosis progression [corrected]. Gastroenterology. 2003;125(6):1695-1704.
McCaughan GW, George J. Fibrosis progression in chronic hepatitis C virus infection. Gut. 2004;53(3):318-321.
Romero-Gomez M, Del Mar Viloria M, Andrade RJ, et al. Insulin resistance impairs sustained response rate to peginterferon plus ribavirin in chronic hepatitis C patients. Gastroenterology. 2005;128(3):636-641.
Friedenberg F. Hepatitis C and diabetes: an update from the National Health and Nutrition Examination Survey (abstr). Gastroenterology. 2007;132(A775).
Arciello M, Gori M, Balsano C. Mitochondrial Dysfunctions and Altered Metals Homeostasis: New Weapons to Counteract HCV-Related Oxidative Stress. Oxid Med Cell Longev. 2013;2013:971024.
Haque S, Chandra B, Gerber MA, Lok AS. Iron overload in patients with chronic hepatitis C: a clinicopathologic study. Hum Pathol. 1996;27(12):1277-1281.
Bonkovsky HL, Banner BF, Rothman AL. Iron and chronic viral hepatitis. Hepatology. 1997;25(3):759-768.
Olynyk JK, Reddy KR, Di Bisceglie AM, et al. Hepatic iron concentration as a predictor of response to interferon alfa therapy in chronic hepatitis C. Gastroenterology. 1995;108(4):1104-1109.
Fargion S, Fracanzani AL, Rossini A, 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(5):1204-1210.
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(5):687-691.
Yano M, Hayashi H, Wakusawa S, et al. Long term effects of phlebotomy on biochemical and histological parameters of chronic hepatitis C. Am J Gastroenterol. 2002;97(1):133-137.
Di Bisceglie AM, Bonkovsky HL, Chopra S, 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(1):135-138.
Tirnitz-Parker JE, Glanfield A, Olynyk JK, Ramm GA. Iron and hepatic carcinogenesis. Crit Rev Oncog. 2013;18(5):391-407.
Hamed MA, Ali SA. Non-viral factors contributing to hepatocellular carcinoma. World J Hepatol. 2013;5(6):311-322.
Zarski JP, Mc Hutchison J, Bronowicki JP, et al. Rate of natural disease progression in patients with chronic hepatitis C. J Hepatol. Mar 2003;38(3):307-314.
Monto A, Patel K, Bostrom A, et al. Risks of a range of alcohol intake on hepatitis C-related fibrosis. Hepatology. 2004;39(3):826-834.
Hezode C, Lonjon I, Roudot-Thoraval F, et al. Impact of smoking on histological liver lesions in chronic hepatitis C. Gut. 2003;52(1):126-129.
Dev A, Patel K, Conrad A, Blatt LM, McHutchison JG. Relationship of smoking and fibrosis in patients with chronic hepatitis C. Clin Gastroenterol Hepatol. 2006;4(6):797-801.
Hezode C, Roudot-Thoraval F, Nguyen S, et al. Daily cannabis smoking as a risk factor for progression of fibrosis in chronic hepatitis C. Hepatology. 2005;42(1):63-71.
Freedman ND, Everhart JE, Lindsay KL, et al. Coffee intake is associated with lower rates of liver disease progression in chronic hepatitis C. Hepatology. 2009;50(5):1360-1369.
Altekruse SF, McGlynn KA, Reichman ME. Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005. J Clin Oncol. 2009;27(9):1485-1491.
Freedman ND, Curto TM, Lindsay KL, Wright EC, Sinha R, Everhart JE. Coffee consumption is associated with response to peginterferon and ribavirin therapy in patients with chronic hepatitis C. Gastroenterology. 2011;140(7):1961-1969.
Lane HC, Depper JM, Greene WC, Whalen G, Waldmann TA, Fauci AS. Qualitative analysis of immune function in patients with the acquired immunodeficiency syndrome. Evidence for a selective defect in soluble antigen recognition. N Engl J Med. 1985;313(2):79-84.
Kim AY, Schulze zur Wiesch J, Kuntzen T, et al. Impaired hepatitis C virus-specific T cell responses and recurrent hepatitis C virus in HIV coinfection. PLoS Med. 2006;3(12):e492.
Soriano V, Sulkowski M, Bergin C, et al. Care of patients with chronic hepatitis C and HIV co-infection: recommendations from the HIV-HCV International Panel. AIDS. 2002;16(6):813-828.
Eyster ME, Fried MW, Di Bisceglie AM, Goedert JJ. Increasing hepatitis C virus RNA levels in hemophiliacs: relationship to human immunodeficiency virus infection and liver disease. Multicenter Hemophilia Cohort Study. Blood. 1994;84(4):1020-1023.
Pol S, Lamorthe B, Thi NT, et al. Retrospective analysis of the impact of HIV infection and alcohol use on chronic hepatitis C in a large cohort of drug users. J Hepatol. 1998;28(6):945-950.
Merriman NA, Porter SB, Brensinger CM, Reddy KR, Chang KM. Racial difference in mortality among U.S. veterans with HCV/HIV coinfection. Am J Gastroenterol. 2006;101(4):760-767.
Qurishi N, Kreuzberg C, Luchters G, et al. Effect of antiretroviral therapy on liver-related mortality in patients with HIV and hepatitis C virus coinfection. Lancet. 2003;362(9397):1708-1713.
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(1):22-26.
Zarski JP, Bohn B, Bastie A, et al. Characteristics of patients with dual infection by hepatitis B and C viruses. J Hepatol. 1998;28(1):27-33.
Gaeta GB, Stornaiuolo G, Precone DF, et al. Epidemiological and clinical burden of chronic hepatitis B virus/hepatitis C virus infection. A multicenter Italian study. J Hepatol. 2003;39(6):1036-1041.
Marcellin P, Asselah T, Boyer N. Fibrosis and disease progression in hepatitis C. Hepatology. 2002;36(5 Suppl 1):S47-56.
Estrabaud E, Vidaud M, Marcellin P, Asselah T. Genomics and HCV infection: progression of fibrosis and treatment response. J Hepatol. 2012;57(5):1110-1125.
Okamoto K, Mimura K, Murawaki Y, Yuasa I. Association of functional gene polymorphisms of matrix metalloproteinase (MMP)-1, MMP-3 and MMP-9 with the progression of chronic liver disease. J Gastroenterol Hepatol. 2005;20(7):1102-1108.
Reynolds WF, Patel K, Pianko S, Blatt LM, Nicholas JJ, McHutchison JG. A genotypic association implicates myeloperoxidase in the progression of hepatic fibrosis in chronic hepatitis C virus infection. Genes Immun. 2002;3(6):345-349.
Paris AJ, Snapir Z, Christopherson CD, et al. A polymorphism that delays fibrosis in hepatitis C promotes alternative splicing of AZIN1, reducing fibrogenesis. Hepatology. 2011;54(6):2198-2207.
Trepo E, Pradat P, Potthoff A, et al. Impact of patatin-like phospholipase-3 (rs738409 C>G) polymorphism on fibrosis progression and steatosis in chronic hepatitis C. Hepatology. 2011;54(1):60-69.
Huang H, Shiffman ML, Friedman S, et al. A 7 gene signature identifies the risk of developing cirrhosis in patients with chronic hepatitis C. Hepatology. 2007;46(2):297-306.
Marcolongo M, Young B, Dal Pero F, et al. A seven-gene signature (cirrhosis risk score) predicts liver fibrosis progression in patients with initially mild chronic hepatitis C. Hepatology. 2009;50(4):1038-1044.
Baur K, Mertens JC, Schmitt J, et al. Combined effect of 25-OH vitamin D plasma levels and genetic vitamin D receptor (NR 1I1) variants on fibrosis progression rate in HCV patients. Liver Int. 2012;32(4):635-643.
Micallef JM, Kaldor JM, Dore GJ. Spontaneous viral clearance following acute hepatitis C infection: a systematic review of longitudinal studies. J Viral Hepat. 2006;13(1):34-41.
Doyle JS, Hellard ME, Thompson AJ. The role of viral and host genetics in natural history and treatment of chronic HCV infection. Best Pract Res Clin Gastroenterol. 2012;26(4):413-427.
Bochud PY, Cai T, Overbeck K, et al. Genotype 3 is associated with accelerated fibrosis progression in chronic hepatitis C. J Hepatol. 2009;51(4):655-666.
Backus LI, Boothroyd DB, Phillips BR, Belperio P, Halloran J, Mole LA. A sustained virologic response reduces risk of all-cause mortality in patients with hepatitis C. Clin Gastroenterol Hepatol. 2011;9(6):509-516.
Hue S, Cacoub P, Renou C, 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(1):106-109.
Tillmann HL, Chen DF, Trautwein C, et al. Low frequency of HLA-DRB1*11 in hepatitis C virus induced end stage liver disease. Gut. 2001;48(5):714-718.
Patel K, Norris S, Lebeck L, et al. HLA class I allelic diversity and progression of fibrosis in patients with chronic hepatitis C. Hepatology. 2006;43(2):241-249.
Okuda M, Li K, Beard MR, et al. Mitochondrial injury, oxidative stress, and antioxidant gene expression are induced by hepatitis C virus core protein. Gastroenterology. 2002;122(2):366-375.
Chou AH, Tsai HF, Wu YY, 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(4):2160-2166.
Pearlman BL, Traub N. Sustained virologic response to antiviral therapy for chronic hepatitis C virus infection: a cure and so much more. Clin Infect Dis. 2011;52(7):889-900.
Jacobson IM, McHutchison JG, Dusheiko G, et al. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med. 2011;364(25):2405-2416.
Lok AS, Gardiner DF, Lawitz E, et al. Preliminary study of two antiviral agents for hepatitis C genotype 1. N Engl J Med. 2012;366(3):216-224.
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(6):969-974.
Gordon SC, Bayati N, Silverman AL. Clinical outcome of hepatitis C as a function of mode of transmission. Hepatology. 1998;28(2):562-567.
Rerksuppaphol S, Hardikar W, Dore GJ. Long-term outcome of vertically acquired and post-transfusion hepatitis C infection in children. J Gastroenterol Hepatol. 2004;19(12):1357-1362.