Lucio Brollo

Long-term effect of low dose recombinant interferon therapy in patients with chronic hepatitis B

Thirty three heterosexual chronic hepatitis B virus (HBV) carriers were randomized, with stratification for disease activity, to receive intramuscular recombinant interferon alpha-2a (r-IFN) at doses of 4.5 megaunits thrice weekly for 4 months, or no treatment. During r-IFN treatment, serum HBV-DNA levels fell in all, but 2 patients. Final evaluation at 16 months after randomization revealed that the rate of complete response, i.e., loss of both HBV-DNA and HBeAg with ALT normalization was 22.2% (2 of 9 cases) in patients on interferon and 12.5% (1 of 8 cases) in untreated patients for the group with high serum alanine aminotransferase (ALT) and with piecemeal necrosis on liver biopsy on entry. The corresponding value was 25% (2 of 8 cases) in treated and 12.5% (1 of 8 cases) in untreated patients with low liver disease activity. Overall, a complete response was thus observed in 23.5% of treated patients and in 12.5% of controls. None of the patients on therapy became HBsAg negative. It is concluded that treatment of heterosexual patients with chronic hepatitis B with r-IFN in the dose regimen used here was not associated with a significant higher rate of serologic and clinical response compared to controls, independently of pretreatment biochemical and histologic activity of liver disease.

LEVAMISOLE THERAPY IN CHRONIC TYPE B HEPATITIS

A double-blind, randomized, controlled trial has been undertaken to evaluate treatment of chronic hepatitis type B with levamisole. Ten patients received levamisole (150 mg/day, 3 days/wk) and 10 received placebo until seroconversion to antibody to hepatitis B e antigen eventually occurred, or for a maximum of 18 mo. Final evaluation at 24 mo after starting treatment revealed that 60% of the patients in the levamisole group had become hepatitis B e antigen negative, 90% were hepatitis B virus-deoxyribonucleic acid negative in serum, and 8 of 9 (89%) patients had cleared hepatitis B core antigen from the liver. On the other hand, in the placebo group only 4 of the 10 subjects (40%) were hepatitis B e antigen and hepatitis B virus-deoxyribonucleic acid negative in serum and 3 of 8 (37.5%) of them became hepatitis B core antigen free in the liver. Moreover, in 8 patients of the treated group and in 4 of the control cases aminotransferase activities fell into the normal range. A liver biopsy specimen was obtained after treatment in 17 patients and 7 of 9 levamisole recipients showed marked improvement in hepatic histology, compared with 3 of 8 placebo recipients. These data show that patients treated with long-term levamisole therapy have a tendency toward normalization of aminotransferase activities and suppression of hepatitis B virus replication, suggesting that the drug may be of benefit in chronic hepatitis B e antigen-positive hepatitis.

Chronic persistent hepatitis type B can be a progressive disease when associated with sustained virus replication

In 44 hepatitis B virus (HBV) carriers with chronic persistent hepatitis (CPH), serial liver biopsies were available. At presentation 38 patients had HBV-DNA in their serum including 31 HBeAg positive and seven anti-HBe positive cases. The remaining six patients were anti-HBe positive and HBV-DNA negative. During a mean histologic follow-up of 4.2 years, 12 (32%) of the 38 HBV-DNA positive patients progressed to chronic active hepatitis (six cases) or to active cirrhosis (six cases), while 26 patients showed either unchanged features of CPH (21 cases), or histologic improvement to normal liver (five cases). Persistence of HBV-DNA in serum, independently of HBeAg/anti-HBe events, was significantly (p less than 0.01) associated with deterioration of liver disease, while termination of HBV replication correlated significantly (p less than 0.05) with spontaneous biochemical remission and with unchanged or improved histology. None of the six anti-HBe positive patients without serologic markers of hepatitis B virus replication showed histologic deterioration. These findings indicate that continuing HBV replication is a marker which predicts unfavourable evolution of chronic persistent hepatitis and frequent transition to chronic active hepatitis or cirrhosis.

Induction of autoantibodies during alpha interferon treatment in chronic hepatitis B.

Thirty-two patients with chronic hepatitis B treated with alpha interferon were tested for 12 different antibodies. Only a minority (18%) of cases developed antinuclear antibodies and none developed clinical signs of autoimmune disease. These data suggest that, at the dose regimen used, interferon therapy of chronic hepatitis B is not associated with triggering of autoimmunity.