One hundred and five hepatitis B surface antigen (HBsAg) positive patients presenting with chronic persistent hepatitis (n=46) or chronic active hepatitis without cirrhosis (n= 59) were followed longitudinally for one to 16 years (mean 5.5 years) and underwent follow up biopsy. During a mean histological follow up of 3*7 years, active cirrhosis developed in 21 (20%) patients one to 13 years after entry to the study with a calculated annual incidence of 5.9%/o. The probability of evolution to cirrhosis was significantly higher in patients with chronic active hepatitis and bridging hepatic necrosis than in those with moderate chronic active hepatitis or chronic persistent hepatitis (p<0*0001). Cox multiple regression analysis showed that the following three variables independently implied poor prognosis: older age, presence of bridging hepatic necrosis, and persistence of hepatitis B virus DNA in serum (p<0-0001). These findings indicate that patients with severe chronic active hepatitis and persistent hepatitis B virus replication are at very high risk of rapid progression to cirrhosis.

ClinicalTrials.gov Identifier: NCT01657695.

No abstract

H epatitis B virus (HBV) and hepatitis C virus (HCV) infections account for the majority of liver disease cases worldwide. They share modes of transmission, and their combined infection is a fairly frequent occurrence-particularly in areas where the two viruses are endemic and are found among subjects with a high risk of parenteral infection. [1][2][3][4][5][6] The classic form of chronic HBV/HCV infection-identified by the contemporaneous positivity of the HBV surface antigen (HBsAg) and the antibody to HCV (anti-HCV)-occurs in a sizable proportion of chronic hepatitis patients, 1,3,5,[7][8][9] and is generally considered a condition favoring the progression of liver fibrosis and the establishment of cirrhosis. [10][11][12] It also represents one of the most important risk factors for the development of hepatocellular carcinoma, 13-16 even more significant than that observed in the case of single HBV or HCV infection. 17,18 Despite its considerable clinical importance, scant information is currently available on the treatment of the HBV/HCV coinfected population, 19 although the few available studies in the field agree that this form of chronic viral hepatitis is difficult to cure. [20][21][22][23][24] In this context, it is noteworthy to focus attention on the several reports suggesting that HBV and HCV interact in the case of coinfection (reviewed by Alberti et al. 5 and Liaw 11 ). In Abbreviations: HBV, hepatitis B virus; HCV, hepatitis C virus; HDV, hepatitis Delta virus; HBsAg, hepatitis B surface antigen; anti-HCV, antibody to HCV; ALT, alanine aminotransferase; anti-HDV, antibody to HDV; HBeAg, hepatitis B e antigen; anti-HBe, antibody to hepatitis B e antigen. From the

Seventy consecutive HBsAg- and HBeAg-positive patients with biopsy-proven chronic hepatitis were followed prospectively with serial determinations of SGPT levels and hepatitis B virus serum markers including HBsAg, HBeAg, anti-HBe and hepatitis B virus DNA. During a period of 1 to 11 years (mean +/- S.D.: 5.0 +/- 2.3 years), 28 patients remained persistently HBeAg positive, most with continuing biochemical and histologic activity, while 41 cases seroconverted to anti-HBe. One patient became HBeAg and anti-HBe negative. After seroconversion, 87.8% of the cases showed sustained normalization of SGPT, and clearance of hepatitis B virus DNA from serum and histologic improvement was documented in 79% of the cases who had a control liver biopsy, while 15.8% developed cirrhosis. In two patients (4.9%), the disease remained active despite seroconversion, and both cases had evidence of continuing hepatitis B virus replication. Finally, reactivation of liver damage and of hepatitis B virus replication was observed in three additional patients (7.3%) who had transiently normalized SGPT after seroconversion. All 70 patients were analyzed for hepatitis delta virus markers, and only two persistently HBeAg-positive cases were found positive for antibody to hepatitis delta virus in serum, one also having hepatitis delta antigen in the liver. These findings indicate that, in chronic hepatitis type B, termination of virus replication is associated in most patients with biochemical and histologic regression of inflammatory activity. After anti-HBe seroconversion has occurred, virus replication and liver disease may persist or reactivate in a small proportion of patients thus giving origin to the well-recognized group of anti-HBe positive, hepatitis B virus DNA-positive chronic hepatitis type B.