The incidence and contributing factors of cirrhosis developing in patients with chronic type B hepatitis were assessed prospectively in 684 clinicopathologically verified patients, of which 509 were HBeAg positive and 175 were anti-HBe positive at entry into the study. During an average follow-up period of 35.3 months, cirrhosis occurred 6 to 64 months after entry in 35 HBeAg-positive and 7 anti-HBe positive patients with a calculated annual incidence of 2.4 and 1.3%, respectively (p greater than 0.05). The incidence increased significantly with the increasing age at entry. Patients who had experienced (a) hepatic decompensation, (b) repeated episodes of severe acute exacerbation (with alpha-fetoprotein greater than 100 ng per ml and/or bridging hepatic necrosis), (c) severe acute exacerbation not accompanied by subsequent HBeAg seroconversion and (d) hepatitis B virus reactivation (particularly those with HBeAg reappearance) were found to develop cirrhosis much more frequently (p less than 0.001). Contrary to general belief, patients who had hepatitis delta virus superinfection and patients with chronic active hepatitis were not particularly prone to develop cirrhosis. We conclude that in addition to age factor, the extent, severity, duration, frequency and etiology of the hepatic lobular alterations are important factors for the development of cirrhosis in patients with chronic type B hepatitis.

To investigate the incidence, determinants and significance of delayed clearance of serum HBsAg in chronic hepatitis B virus infection, a prospective follow-up study was conducted in two consecutive groups of patients. Group I consisted of 984 patients (859 men and 125 women) with biopsy-proven chronic type B hepatitis, whereas group II consisted of 1,598 asymptomatic chronic carriers (998 men and 600 women) with normal serum aminotransferase activity. During a mean follow-up period of 4.0 +/- 2.3 yr, 19 patients (1.9%) of group I cleared HBsAg from their serum, whereas 35 patients (2.2%) in group II did so in a mean follow-up period of 2.7 +/- 1.4 yr. The annual incidence of delayed serum HBsAg clearance was 0.5% in group I and 0.8% in group II (p less than 0.02). The cumulative probability of HBsAg clearance was also higher in group II than in group I (p less than 0.007). Antibodies to HBsAg developed in 9 patients (47.4%) with chronic hepatitis and in 11 (31.4%) asymptomatic carriers who cleared serum HBsAg. Those who were HBeAg negative and those older than 40 at entry and those who exhibited cirrhosis during follow-up had a higher incidence of delayed HBsAg clearance. Gender, initial histological changes and hepatitis delta virus infection did not influence the occurrence of HBsAg clearance. Serum HBV DNA was not detectable by slot-blot hybridization but was still detectable by polymerase chain reaction in serum specimens collected within 1 yr of HBsAg clearance. Liver biopsy performed later in 10 patients showed no significant hepatitis activity or tissue HBV DNA, HBsAg or HBcAg.(ABSTRACT TRUNCATED AT 250 WORDS)

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The incidence, clinicopathological features and etiology of acute exacerbation occurring in patients with chronic type B hepatitis were assessed prospectively among 385 patients who had HBeAg and 279 who had anti-HBe in serum. During an average follow-up of 23.5 months, acute exacerbations occurred in 197 HBeAg-positive patients and in 56 anti-HBe positive patients, with a calculated annual incidence of 28.6 and 10.3%, respectively (p less than 0.001). The clinical and laboratory findings of acute exacerbations were similar in the HBeAg-positive and anti-HBe positive patients. The mean serum bilirubin and alpha-fetoprotein levels were higher in anti-HBe positive patients (p less than 0.01), but actual differences were small. The histologic features of acute exacerbations were also similar in the HBeAg-positive patients and anti-HBe positive patients. Lobular alterations were the main histologic findings; in addition, one-fourth of patients had bridging necrosis and one-fourth had piecemeal necrosis. Spontaneous reactivation of hepatitis B was the major cause of these exacerbations in both HBeAg-positive patients (91.5%) as well as anti-HBe positive patients (62.5%). Hepatitis delta virus superinfection accounted for a higher percentage of exacerbations in anti-HBe positive patients (14.3%) than in HBeAg-positive cases (6.5%). Hepatitis A and possibly non-A, non-B virus superinfections also contributed to some episodes of exacerbation. Thus, acute exacerbations of disease occurred more frequently in HBeAg-positive patients than in anti-HBe positive patients with chronic type B hepatitis, but the clinicopathological features and etiologies were similar.

ABSTRACT— To examine the early stage of the natural course of liver cirrhosis, a prospective follow‐up study was conducted in a series of 76 patients with recent development of cirrhosis during the course of chronic type B hepatitis. During a mean follow‐up period of 34.4 months, 45 episodes of acute exacerbation were recorded; the majority of the episodes occurred within 2 years after entry. The calculated annual incidence of acute exacerbation was significantly higher in patients seropositive for hepatitis B e antigen (HBeAg) and/or hepatitis B virus (HBV)‐DNA (25.9%) than in those without these markers (11.9%). Three‐fourths of the acute exacerbations were attributable to the reactivation of HBV. Spontaneous HBeAg seroconversion to anti‐HBe also occurred in the early phase, but less than 30% of the events were preceded by acute exacerbation. Late hepatitis B surface antigen clearance occurred in two patients. Hepatic decompensation, esophageal variceal bleeding and hepatocellular carcinoma developed relatively late in the course of the disease with a calculated annual incidence of 2.3%, 2.3% and 2.8%, respectively. Seven patients (9.2%) died of hepatic failure or variceal bleeding, usually more than 3 years after entry. The estimated 5‐year survival rate was 80%. The results suggest that the natural events of chronic HBV infection, including exacerbation, seroconversion and its sequelae could occur after the development of cirrhosis. In addition, these events might be responsible for the clinicopathological changes and the outcomes of these cirrhotic patients.