Natural course following the onset of cirrhosis in patients with chronic hepatitis B: a long-term follow-up study

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 >10 4 copies/ml. Follow-up studies included liver biochemistry, viral markers, a-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.

Factors Associated with Progression to Hepatocellular Carcinoma and to Death from Liver Complications in Patients with HBsAg-Positive Cirrhosis

“…The development of cirrhosis is associated with repeated bouts of viral and biochemical flares and less commonly by superinfection with HDV or HCV [16,19,23]. Hepatitis B viral markers may influence cirrhosis development.…”

“…At enrollment, and every 3-6 months thereafter, all patients had complete blood counts and liver tests, which included serum bilirubin, albumin, and ALT levels. Hepatitis flares were defined as levels of ALT two-fold above the baseline level or over five times the upper limits of normal [ULN, 45 U/L] [19]. Surveillance for HCC was performed by serial measurements of AFP and abdominal ultrasound examinations every 6 months.…”

Management of HBV and HBV/HDV-Associated Liver Cirrhosis

“…In patients with cirrhosis the incidence of HCC is estimated to be between 1.2 and 2.7% per year in the natural course [52,53]; however, the incidence is strongly influenced by region, age, stage of the liver disease, and other comorbidities.…”

Role of antiviral therapy in the natural history of hepatitis B virus-related chronic liver disease

“…The prevalence of HBsAg is high amongst patients with HCC and HBsAg carriers HBeAg negative/HBV DNA negative patients (4%, P = 0.04) [34] . Persistent HBeAg seropositivity was shown to be significantly (P = 0.035) associated with the probability of decompensation in a study analyzing 93 patients with newly developed cirrhosis, and patients in whom HBeAg was persistently positive had a 6 times higher risk of decompensation compared to HBeAg seronegative subjects at entry, during a mean follow-up period of 102 mo [35] . Although it is recommended to commence antiviral treatment as soon as CHB is diagnosed, IFN use, even at low doses, increases the risk of bacterial infections and may provoke an episode of hepatic decompensation.…”