Abstract
Purpose
To elucidate the long-term natural course following the onset of cirrhosis in patients with chronic hepatitis B.
Methods
Ninety-three patients with chronic hepatitis B who had developed cirrhosis during regular follow-up were included in this long-term follow-up study. At the time of cirrhosis detection, 30% of the patients were seropositive for hepatitis B e antigen (HBeAg) and 73% had a HBV-DNA level >104 copies/ml. Follow-up studies included liver biochemistry, viral markers, α-fetoprotein and ultrasonography every 3–6 months.
Results
During a mean follow-up period of 102 ± 60 (12–246; median 97) months, 32 patients (34.4%) experienced 55 episodes of hepatitis flare (7.0%/year), 15 (53.6%) of 28 HBeAg-positive patients seroconverted to anti-HBe (6.3%/yr) and 12 (12.9%) lost HBsAg (1.5%/year). Overall disease progression was observed in 25 (26.9%, 3.2%/year) patients: 12 (12.9%, 1.5%/year) hepatic decompensation, 21 (22.6%, 2.7%/year) hepatocellular carcinoma and 11 (11.8%, 1.4%/year) died. Multivariate analysis showed that age at onset of cirrhosis (P = 0.015) and persistent HBeAg seropositivity (P = 0.019) were the independent factors for overall disease progression.
Conclusions
These results suggest that patients with older age at onset of cirrhosis and persistent HBeAg seropositivity following the onset of cirrhosis were independent factors for the disease progression in the first 10-year after the development of cirrhosis in patients with chronic hepatitis B.
Keywords: Hepatitis flare, Hepatic decompensation, Hepatocellular carcinoma, HBeAg seroconversion, HBsAg seroconversion
Abbreviations
- HBV
Hepatitis B virus
- HCC
Hepatocellular carcinoma
- HBeAg
Hepatitis e antigen
- HBsAg
Hepatitis B surface antigen
- HCV
Hepatitis C virus
- HDV
Hepatitis D virus
- AFP
α-Fetoprotein
- ALT
Alanine aminotransferase
- ULN
Upper limit of normal
- PCR
Polymerase chain reaction
- PT
Prothrombin time
Footnotes
This work was supported by grants from National Science Council, Taiwan (NSC95-2314-B-182A-032) and the Prosperous Foundation, Taipei, Taiwan.
Contributor Information
Yi-Cheng Chen, Email: yicheng@cgmh.org.tw.
Chia-Ming Chu, Email: chu0066@cgmh.org.tw.
Chau-Ting Yeh, Email: chauting@adm.cgmh.org.tw.
Yun-Fan Liaw, Phone: +886-3-3281200, FAX: +886-3-3282824, Email: liveryfl@so-net.net.tw.
References
- 1.Lavanchy D. Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat 2004;11:97–107 [DOI] [PubMed]
- 2.Liaw YF, Tai DI, Chu CM, Chen TJ. The development of cirrhosis in patients with chronic type B hepatitis: a prospective study. Hepatology 1988;8:493–6 [DOI] [PubMed]
- 3.Liaw YF, Tai DI, Chu CM, Lin DY, Sheen IS, Chen TJ, Pao CC. Early detection of hepatocellular carcinoma in patients with chronic type B hepatitis. Gastroenterology 1986;90: 263–7 [DOI] [PubMed]
- 4.Liaw YF, Lin DY, Chen TJ, Chu CM. Natural course after the development of cirrhosis in patients with chronic type B hepatitis: a prospective study. Liver 1989;9:235–41 [DOI] [PubMed]
- 5.Yu MW, Hsu FC, Sheen IS, Chu CM, Lin DY, Chen CJ, Liaw YF. Prospective study of hepatocellular carcinoma and liver cirrhosis in asymptomatic chronic hepatitis B virus carriers. Am J Epidemiol 1997;145:1039–47 [DOI] [PubMed]
- 6.Benvegnu L, Gios M, Boccato S, Alberti A. Natural history of compensated viral cirrhosis: a prospective study on the incidence and hierarchy of major complications. Gut 2004;53:744–9 [DOI] [PMC free article] [PubMed]
- 7.de Jongh FE, Janssen HL, de Man RA, Hop WC, Schalm SW, van Blankenstein M. Survival and prognostic indicators in hepatitis B surface antigen-positive cirrhosis of the liver. Gastroenterology 1992;103:1630–5 [DOI] [PubMed]
- 8.Fattovich G, Giustina G, Schalm SW, Hadziyannis S, Sanchez-Tapias J, Almasio P, Christensen E, et al. Occurrence of hepatocellular carcinoma and decompensation in western European patients with cirrhosis type B. The EUROHEP Study Group on Hepatitis B Virus and Cirrhosis. Hepatology 1995;21:77–82 [DOI] [PubMed]
- 9.Hui AY, Chan HL, Leung NW, Hung LC, Chan FK, Sung JJ. Survival and prognostic indicators in patients with hepatitis B virus-related cirrhosis after onset of hepatic decompensation. J Clin Gastroenterol 2002;34:569–72 [DOI] [PubMed]
- 10.Liaw YF, Tai DI, Chu CM, Pao CC, Chen TJ. Acute exacerbation in chronic type B hepatitis: comparison between HBeAg and antibody-positive patients. Hepatology 1987;7:20–3 [DOI] [PubMed]
- 11.Lok ASF, Lai CL. Acute exacerbation in Chinese patients with chronic hepatitis B virus (HBV) infection. Incidence, predisposing factors and etiology. J Hepatol 1990;10:29–34 [DOI] [PubMed]
- 12.Liaw YF, Chen JJ, Chen TJ. Acute exacerbation in patients with liver cirrhosis: a clinicopathological study. Liver 1990;10:177–84 [DOI] [PubMed]
- 13.Liaw YF. Hepatitis flares and hepatitis B e antigen seroconversion: implication in anti-hepatitis B virus therapy. J Gastroenterol Hepatol 2003;18:246–52 [DOI] [PubMed]
- 14.Chen YC, Sheen IS, Chu CM, Liaw YF. Prognosis following spontaneous HBsAg seroclearance in chronic hepatitis B patients with or without concurrent infection. Gastroenterology 2002;123:1084–9 [DOI] [PubMed]
- 15.Lin DY, Sheen IS, Chiu CT, Lin SM, Kuo YC, Liaw YF. Ultrasonographic changes of early liver cirrhosis in chronic hepatitis B: a longitudinal study. J Clin Ultrasound 1993;21:303–8 [DOI] [PubMed]
- 16.Liaw YF, Sheen IS, Chen TJ, Chu CM, Pao CC. Incidence, determinants and significance of delayed clearance of serum HBsAg in chronic hepatitis B virus infection: a prospective study. Hepatology 1991;13:627–31 [DOI] [PubMed]
- 17.Ikeda K, Arase Y, Kobayashi M, Someya T, Saitoh S, Suzuki Y, Suzuki F, et al. Consistently low hepatitis B virus DNA saves patients from hepatocellular carcinogenesis in HBV-related cirrhosis. A nested case–control study using 96 untreated patients. Intervirology 2003;46:96–104 [DOI] [PubMed]
- 18.Mahmood S, Niiyama G, Kamei A, Izumi A, Nakata K, Ikeda H, Suehiro M, et al. Influence of viral load and genotype in the progression of Hepatitis B-associated liver cirrhosis to hepatocellular carcinoma. Liver Int 2005;25: 220–5 [DOI] [PubMed]
- 19.Fattovich G, Pantalena M, Zagni I, Realdi G, Schalm SW, Christensen E. Effect of hepatitis B and C virus infections on the natural history of compensated cirrhosis: a cohort study of 297 patients. Am J Gastroenterol 2002;97:2886–95 [DOI] [PubMed]
- 20.Chu CM, Liaw YF. Hepatitis B virus-related cirrhosis: natural history and treatment. Semin Liver Dis 2006;26: 142–52 [DOI] [PubMed]
- 21.Lin SM, Yu ML, Lee CM, Chien RN, Sheen IS, Chu CM, Liaw YF. Interferon therapy in HBeAg positive chronic hepatitis reduces cirrhosis and hepatocellular carcinoma. J Hepatol 2007;46:45–52 [DOI] [PubMed]
- 22.Liaw YF. Hepatitis B virus replication and liver disease progression: the impact of antiviral therapy. Antivir Ther 2006;11:669–79 [PubMed]