Abstract
This paper describes the correlation of hepatitis C genotypes detected in liver tissue with histological grading (inflammatory activity) and staging (degree of fibrosis/cirrhosis). The viral genotype was analysed by type-specific polymerase chain reaction (PCR) and correlated with histology and age of patients. In 69 patients with chronic hepatitis C (HCV) infection, genotypes 1a and 1b were detected in 13 (18.8%) and 31 (44.9%) liver biopsies, respectively. Genotypes 2a and 2b were each detected once (1.5%) and 12 (17.4%) tissue samples showed a mixed infection with two genotypes. In 11 (15.9%) biopsies, no genotype could be established. The liver specimens were grouped according to the presence or absence of genotype 1b: group A consisted of specimens infected with genotypes 1a, 2a, and 2b (n=16), Group B contained biopsies infected with genotype 1b (n=42), and group C were biopsies with no detectable genotype (n=11). Activity (grade) of chronic hepatitis was not different in these three groups. However, advanced fibrosis/cirrhosis was observed in 16 (38.1%) biopsies in group B (containing genotype 1b), compared with none in group A (P=0.01). The mean age of patients in group B was significantly higher than that in group A (P=0.038), and the mean age of patients with advanced fibrosis was higher than that of patients with low fibrosis scores within these two groups (P=0.004). Stepwise logistic regression revealed an independent association of age and genotype 1b (group B) with advanced fibrosis/cirrhosis. These data indicate that patients infected with genotype 1b have an higher risk of developing cirrhosis than do patients with other genotypes.
Similar content being viewed by others
References
Alter HJ, Purcell RH, Shih JW, Melpolder JC, Houghton M, Choo QL, Kuo G (1989) Detection of antibody to hepatitis C virus in prospectively followed transfusion recipients with acute and chronic non-A, non-B hepatitis. N Engl J Med 321:1494–1500
Andonov A, Chaudhary RK (1994) Genotyping of Canadian hepatitis C virus isolates by PCR. J Clin Microbiol 32:2031–2034
Bach N, Thung SN, Schaffner F (1992) The histological features of chronic hepatitis C and autoimmune chronic hepatitis: a comparative analysis. Hepatology 15:572–577
Bianchi L, Gudat F (1994) Chronic hepatitis. In: Mc Sween RNM, Anthony PP, Scheuer PJ, Portmann B, Burt AD (eds) Pathology of the liver. Churchill Livingstone, Edinburgh, pp 349–395
Bianchi L, Desmet VJ, Popper H, Scheuer PJ, Aledort LM, Berk P (1987) Histological patterns of liver disease in hemophiliacs, with special reference to morphological characteristics of non-A, non-B hepatitis. Semin Liver Dis 7:203–209
Chan SW, McOmish F, Holmes EC, Dow B, Peutherer JF, Follett E, Yap PL, Simmonds P (1992) Analysis of a new hepatitis C virus type and its phylogenetic relationship to existing variants. J Gen Virol 73:1131–1141
Chemello L, Alberti A, Rose K, Simmonds P (1994) Hepatitis C serotype and response to interferon therapy (letter). N Engl J Med 330:143
Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156–159
Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M (1989) Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 244:359–362
Desmet JV, Gerber M, Hoofnagle JH, Manns M, Scheuer PJ (1994) Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology 19:1513–1520
Dienes HP, Popper H, Arnold W, Lobeck H (1982) Histologic observations in human hepatitis non-A, non-B. Hepatology 2:562–571
Dusheiko GM, Schmilovitz Weiss H, Brown D, McOmish F, Yap PL, Sherlock S, McIntyre N, Simmonds P (1994) Hepatitis C virus genotypes: an investigation of type-specific differences in geographic origin and disease. Hepatology 13–18
Esteban JI, Esteban R, Viladomiu L, Lopez TJC, Gonzalez A, Hernandez JM, Roget M, Sanchez C, Vargas V, Genesca J, Buti M (1989) Hepatitis C virus antibodies among risk groups in Spain. Lancet II:294–296
Feray C, Gigou M, Samuel D, Paradis V, Mishiro S, Maertens G, Reynes M, Okamoto H, Bismuth H, Brechot C (1995) Influence of the genotypes of hepatitis C virus on the severity of recurrent liver disease after liver transplantation (see comments). Gastroenterology 108:1088–1096
Garson JA, Ring C, Tuke P, Tedder RS (1990) Enhanced detection by PCR of hepatitis C virus RNA. Lancet 337:878–879
Gerber MA, Krawczynski K, Alter MJ, Sampliner RE, Margolis HS (1992) Histopathology of community acquired chronic hepatitis C. The Sentinel Counties Chronic Non-A, Non-B Hepatitis Study Team. Mod Pathol 5:483–486
Giannini C, Thiers V, Nousbaum J-B, Stuyver L, Maertens G, Brechot C (1995) Comparative analysis of two assays for genotyping hepatitis C virus based on genotype-specific primers or probes. J Hepatol 23:246–253
Hosoda K, Omata M, Yokosuka O, Kato N, Ohto M (1992) Non-A, non-B chronic hepatitis is chronic hepatitis C: a sensitive assay for the detection of hepatitis C virus RNA in the liver. Hepatology 15:777–781
Ishak KG (1994) Chronic hepatitis: morphology and nomenclature. Mod Pathol 7:690–713
Kiyosawa K, Sodeyama T, Tanaka E, Gibo Y, Yoshizawa K, Nakano Y, Furuta S, Akahane Y, Nishioka K, Purcell RH, Alter HJ (1990) Interrelationship of blood transfusion, non-A, non-B hepatitis and hepatocellular carcinoma: analysis by detection of antibody to hepatitis C virus. Hepatology 12:671–675
Kobayashi Y, Watanabe S, Konishi M, Yokoi M, Kakehashi R, Kaito M, Kondo M, Hayashi Y, Jomori T, Suzuki S (1993) Quantitation and typing of serum hepatitis C virus RNA in patients with chronic hepatitis C treated with interferon-beta. Hepatology 18:1319–1325
Kuo G, Choo QL, Alter HJ, Gitnick GL, Redeker AG, Purcell RH, Miyamura T, Dienstag JL, Alter MJ, Stevens CE, Tegtmeier GE, Bonino F, Colombo M, Lee WS, Kuo C, Berger K, Shuster JR, Weiner AJ, Overby LR, Bradley DW, Houghton M (1989) An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis. Science 244:362–364
Lau JY, Mizokami M, Kolberg JA, Davis GL, Prescott LE, Ohno T, Perrillo RP, Lindsay KL, Gish RG, Qian KP, et al (1995) Application of six hepatitis C virus genotyping systems to sera from chronic hepatitis C patients in the United States. J Infect Dis 171:281–289
Lefkowitch JH, Schiff ER, Davis GL, Perrillo RP, Lindsay K, Bodenheimer HCJ, Balart LA, Ortego TJ, Payne J, Dienstag JL, Gibas A, Jacobson IM, Tamburro CH, Carey W, O'Brien C, Sampliner R, vanThiel D, Feit D, Albrecht J, Meschievitz C, Sanghvi B, Vaughan RD, group Hit (1993) Pathological diagnosis of chronic hepatitis C: a multicenter comparative study with chronic hepatitis B. The Hepatitis Interventional Therapy Group. Gastroenterology 104:595–603
Matsumoto A, Tanaka E, Suszuki T, Ogata H, Kiyosawa K (1994) Viral and host factors that contribute to efficacy of Interferon-alpha 2a therapy in patients with chronic hepatitis C. Dig Dis Sci 39:1273–1280
Miller RH, Purcell RH (1990) Hepatitis C virus shares amino acid sequence similarity with pestiviruses and flaviviruses as well as members of two plant virus supergroups. Proc Natl Acad Sci 87:2057–2061
Mita E, Hayashi N, Hagiwara H, Ueda K, Kanazawa Y, Kasahara A, Fusamoto H, Kamada T (1994) Predicting interferon therapy efficacy from hepatitis C virus genotype and RNA titer. Dig Dis Sci 39:977–982
Mita E, Hayashi N, Kanazawa Y, Hagiwara H, Ueda K, Kasahara A, Fusamoto H, Kamada T (1994) Hepatitis C virus genotype and RNA titer in the progression of type C chronic liver disease. J Hepatol 21:468–473
Nakagawa H, Shimomura H, Hasui T, Tsuji H, Tsuji T (1994) Quantitative detection of hepatitis C virus genome in liver tissue and circulation by competitive reverse transcription-polymerase chain reaction. Dig Dis Sci 39:225–233
Nousbaum J-B, Pol S, Nalpas B, Landais P, Berthelot P, Bréchot C, group atcs (1995) Hepatitis C virus type 1b (II) infection in France and Italy. Ann Intern Med 122:161–168
Okamoto H, Kurai K, Okada S, Yamamoto K, Lizuka H, Tanaka T, Fukuda S, Tsuda F, Mishiro S (1992) Full-length sequence of a hepatitis C virus genome having poor homology to reported isolates: comparative study of four distinct genotypes. Virology 188:331–341
Okamoto H, Sugiyama Y, Okada S, Kurai K, Akahane Y, Sugai Y, Tanaka T, Sato K, Tsuda F, Miyakawa Y, Mayumi M (1992) Typing hepatitis C virus by polymerase chain reaction with type-specific primers: application to clinical surveys and tracing infectious sources. J Gen Virol 73:673–679
Pistello M, Maggi F, Vatteroni L, Cecconi N, Panicucci F, Bresci GP, Gambardella L, Taddei M, Bionda A, Tuoni M, Bendinelli M (1994) Prevalence of hepatitis C virus genotypes in Italy. J Clin Microbiol 32:232–234
Poulsen H, Christoffersen P (1972) Abnormal bile duct epithelium in chronic aggressive hepatitis and cirrhosis. A review of morphology and clinical biochemical and immunological features. Hum Pathol 3:227–235
Pozzato G, Moretti M, Franzin F, Crocè LS, Titribelli C, Masayu T, Kaneko S, Unoura M, Kobayashi K (1991) Severity of liver disease with different hepatitis C viral clones. Lancet 338:509
Ravaggi A, Zonaro A, Marin MG, Puoti M, Albertini A, Cariani E (1994) Distribution of viral genotypes in Italy determined by hepatitis C virus typing by DNA immunoassay. J Clin Microbiol 2280–2284
Scheuer PJ, Ashrafzadeh P, Sherlock S, Brown D, Dusheiko GM (1992) The pathology of hepatitis C. Hepatology 15:567–571
Shieh YSC, Shim K-S, Lampertico P, Balart LA, Jeffers LJ, Thung SN, Regenstein F, Reddy KR, Farr G, Schiff ER, Gerber MA (1991) Detection of hepatitis C virus sequences in liver tissue by the polymerase chain reaction. Lab Invest 65:408–411
Simmonds P, Alberti A, Alter HJ, Bonino F, Bradley DW, Brechot C, Brouwer JT, Chan S-W, Chayama K, Chen D-S, Choo Q-L, Colombo M, Cuypers HTM, Date T, Dusheiko GM, Esteban JI, Fay O, Hadziyannis SJ, Han J, Hatzakis A, Holmes EC, Hotta H, Houghton M, Irvine B, Kohara M, Kolberg JA, Kuo G, Lau JYN, Lelie PN, Maertens G, McOmish F, Miyamura T, Mizokami M, Nomoto A, Prince AM, Reesink HW, Rice C, Roggendorf M, Schalm SW, Shikata T, Shimotohno K, Stuyver L, Trepo C, Weiner A, Yap PL, Urdea MS (1994) A proposed system for the nomenclature of hepatitis C viral genotypes. Hepatology 19:1321–1324
Takada N, Takase S, Takada A, Date T (1993) Differences in the hepatitis C virus genotypes in different countries. J Hepatol 17:277–283
Tsubota A, Chayama K, Ikeda K, Yasuji A, Koida I, Saitoh S, Hashimoto M, Iwasaki S, Kobayashi M, Hiromitsu K (1994) Factors predictive of response to interferon-alpha therapy in hepatitis C virus infection. Hepatology 19:1088–1094
Yamada G, Takahashi M, Miyamoto R, Tsuji T, Yoshizawa H, Okamoto H (1994) Prediction of interferon effect in chronic hepatitis C by both quantification and genotyping of HCV-RNA (letter). Dig Dis Sci 39:441
Yamada M, Kakumu S, Yoshioka K, Higashi Y, Tanaka K, Ishikawa T, Takayanagi M (1994) Hepatitis C virus genotypes are not responsible for development of serious liver disease. Dig Dis Sci 39:234–239
Yoshioka K, Kakumu S, Wakita T, Ishikawa T, Itoh Y, Takayanagi M, Higashi Y, Shibata M, Morishima T (1992) Detection of hepatitis C virus by polymerase chain reaction and response to interferon-alpha therapy: relationship to genotypes of hepatitis C virus. Hepatology 16:293–299
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Cathomas, G., McGandy, C.E., Terracciano, L.M. et al. Detection and typing of hepatitis C RNA in liver biopsies and its relation to histopathology. Vichows Archiv A Pathol Anat 429, 353–358 (1996). https://doi.org/10.1007/BF00198439
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00198439