No inflammation? No cancer! Clear HBV early and live happily

COMMENTARY ON:Clearance of Hepatitis B Surface Antigen and Risk of Hepatocellular Carcinoma in a cohort Chronically Infected with Hepatitis B Virus. Simonetti J, Bulkow L, McMahon BJ, Homan C, Snowball M, Negus S, Williams J, Livingston SE. Hepatology. 2009 Nov 30. [Epub ahead of print]. Copyright 2009. Reprinted with permission of John Wiley and Sons, Inc.Abstract: Some individuals who are chronically infected with hepatitis B virus (HBV) eventually lose hepatitis B surface antigen (HBsAg). Hepatocellular carcinoma (HCC) has been demonstrated to occur in a few patients after loss of HBsAg. Neither factors associated with loss of HBsAg nor the incidence of HCC thereafter have been clearly elucidated. We performed a prospective population-based cohort study in 1271 Alaska native persons with chronic HBV infection followed for an average of 19.6years to determine factors associated with loss of HBsAg and risk of developing HCC thereafter. HBsAg loss occurred in 158 persons for a rate of HBsAg clearance of 0.7%/year. Older age, but not sex, was associated with clearance of HBsAg, and loss of HBsAg was not associated with any particular HBV genotypes (A–D, and F) found in this population. Participants were followed for an average of 108.9months after HBsAg loss. Six patients, two with cirrhosis and four without, developed HCC a mean of 7.3years after HBsAg clearance (range, 2.0–15.5years). The incidence of HCC after clearance of HBsAg was 36.8 per 100,000 per year (95% CI 13.5–80.0) which was significantly lower than the rate in those who remained HBsAg-positive (195.7 cases per 100,000 person-years of follow-up [95% CI 141.1–264.5; P<0.001). After loss of HBsAg, HBV DNA was detected in the sera of 28 (18%) of those who cleared a median of 3.6years after clearance. Conclusion: HCC can occur in persons with chronic hepatitis B who have lost HBsAg, even in the absence of cirrhosis. These persons should still be followed with periodic liver ultrasound to detect HCC early

Influence of hepatitis delta virus infection on morbidity and mortality in compensated cirrhosis type B

BACKGROUND—The effect of hepatitis delta virus (HDV) infection on the clinical course of cirrhosis type B is poorly defined.
AIMS—To investigate the impact of HDV status on morbidity and mortality in cirrhosis type B.
PATIENTS/METHODS—Retrospective cohort study of 200 Western European patients with compensated cirrhosis type B followed for a median period of 6.6( )years.
RESULTS—At diagnosis, 20% of patients had antibodies to HDV (anti-HDV); median age was lower in anti-HDV positive cirrhotics (34 v 48 years respectively). Kaplan-Meier five year probability of hepatocellular carcinoma (HCC) was 6, 10, and 9% in anti-HDV positive/HBeAg negative, anti-HDV negative/HBeAg negative, and anti-HDV negative/HBeAg positive cirrhotics respectively; the corresponding figures for decompensation were 22, 16, and 19% and for survival they were 92, 89, and 83% respectively. Cox regression analysis identified age, albumin concentration, γ-globulin concentration, and HDV status as significant independent prognostic variables. After adjustment for clinical and serological differences at baseline, the risk (95% confidence interval) for HCC, decompensation, and mortality was increased by a factor of 3.2 (1.0 to 10), 2.2 (0.8( )to 5.7), and 2.0 (0.7 to 5.7) respectively in anti-HDV positive relative to HDV negative cirrhotic patients. The adjusted estimated five year risk for HCC was 13, 4, and 2% for anti-HDV positive/HBeAg negative, anti-HDV negative/HBeAg negative, and anti-HDV negative/HBeAg positive cirrhotics respectively; the corresponding figures for decompensation were 18, 8, and 14% and for survival 90, 95, and 93% respectively.
CONCLUSIONS—HDV infection increases the risk for HCC threefold and for mortality twofold in patients with cirrhosis type B.


Keywords: delta hepatitis; prognosis; hepatocellular carcinoma; decompensation; surviva

Natural history of hepatitis B.

The natural history of hepatitis B virus (HBV) infection is complex and variable and is greatly influenced by the age at infection, the level of HBV replication, and host immune status. Chronic HBV infection generally consists of an early replicative phase with active liver disease (hepatitis B e antigen [HBeAg]–positive chronic hepatitis) and a late low or nonreplicative phase with HBeAg seroconversion and remission of liver disease (inactive carrier state). After HBeAg seroconversion, some patients may have active hepatitis due to HBV variants not expressing HBeAg (HBeAg–negative chronic hepatitis). Morbidity and mortality are linked to development of cirrhosis and hepatocellular carcinoma. Survival is reasonably good (about 85% probability at 5 years) in compensated cirrhosis but very poor in decompensated cirrhosis. Both cirrhotic and noncirrhotic patients with sustained reduction of HBV replication and normalization of aminotransferase after interferon alfa therapy have a reduced risk for liver-related complicatio

Risk factors for hepatocellular carcinoma in HCV cirrhosis: what we know and what is missing.

Hepatocellular carcinoma (HCC) is a major health problem, being the fifth most common cancer worldwide with 626,000 new cases in 2002 [1]. The incidence and absolute mortality of HCC is increasing in Europe and the United States [2], and is currently the leading cause of death amongst cirrhotic patients [3,4]. Improvement of the overall outcome of these patients will come from prevention policies, early detection programs and advancement in the efficacy of therapies. Identification of the at-risk populations is particularly crucial to implement efficient prevention policies, and to engage the adequate populations in costeffective surveillance programs. Thus, the impact of the knowledge of at-risk populations in the surveillance strategy, and the relevance of these factors for the prevention and treatment strategies should be carefully analyzed