Clinical, Virologic and Histologic Outcome Following Seroconversion From Hbeag to Anti–Hbe in Chronic Hepatitis Type B

Abstract

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.

Extended lamivudine retreatment for chronic hepatitis B: Maintenance of viral suppression after discontinuation of therapy

“…[20][21][22][23][24][25][26][27][28][29] In addition, histological assessments of patients in other studies of lamivudine have shown that liver biopsy features improve significantly during lamivudine-induced suppression of HBV replication. 5,30,31 Further controlled trials of prolonged lamivudine treatment are in progress to define the efficacy and safety of lamivudine therapy and maintenance of virological responses after drug withdrawal.…”

Chronic hepatitis B

“…The majority of carriers eventually lose HBeAg and develop antibody to HBeAg (anti-HBe). [29][30][31][32][33] In most patients who have undergone seroconversion from HBeAg to anti-HBe, levels of HBV DNA decrease below detection by unamplified assays (ϳ10 5 copies/ mL), aminotransferase (ALT) levels normalize, and necroinflammation decreases. 29,32 However, in some patients, liver disease persists or relapses after a period of inactivity.…”

“…15,41 Very little longitudinal data is available on the latter patients, but liver disease is generally present in patients with high HBV DNA levels. 30,32,42 Among adults in Asia and the Oceania with elevated ALT levels and carriers of all ages with childhood or adult-acquired HBV infection, the rate of clearance of HBeAg averages between 8% and 12% per year. [29][30][31][32][33]43 The rate of clearance of HBeAg is much lower in Asian children (most of whom have normal ALT levels) 34,35 and in immunocompromised subjects.…”

“…30,32,42 Among adults in Asia and the Oceania with elevated ALT levels and carriers of all ages with childhood or adult-acquired HBV infection, the rate of clearance of HBeAg averages between 8% and 12% per year. [29][30][31][32][33]43 The rate of clearance of HBeAg is much lower in Asian children (most of whom have normal ALT levels) 34,35 and in immunocompromised subjects. 28,44 The largest prospective follow-up study conducted in Alaska of 1,536 carrier children and adults, followed for 12 years, showed that spontaneous HBeAg clearance occurred in 45% of carriers in 5 years and in 80% after 10 years.…”

Durability of Serologic Response After Lamivudine Treatment of Chronic Hepatitis B

“…Whether spontaneous or associated with antiviral therapy, HBeAg responses appear to reflect a change in the level of HBV replication that tends to be sustained and to be associated with clinical improvement. [15][16][17] One of the benefits of antiviral therapy, therefore, lies in its ability to increase the frequency, or hasten the occurrence, of HBeAg responses. [4][5][6][7]11 In the present study, patients with reappearance of hepatitis B markers who were retreated with lamivudine experienced favorable clinical outcomes, including HBeAg seroconversion, ALT normalization, and HBV DNA loss.…”