Coleman Smith

Survival in Chronic Hepatitis B: An Analysis of 379 Patients

Survival data from 379 patients with chronic hepatitis B were analyzed to determine life expectancy for the patient from the time of first contact. One hundred twenty-one patients had chronic persistent hepatitis, 128 had chronic active hepatitis, and 130 had chronic active hepatitis with cirrhosis. The frequency of symptoms (p less than 0.001), stigmata of chronic liver disease (p less than 0.001), and liver function test abnormalities (p less than 0.001) increased as the histologic features worsened, whereas the percentage of patients with circulating hepatitis B DNA polymerase declined (p less than 0.001). Women were uncommon in our series and had less severe disease than men (p less than 0.02). Fifty-one patients had died by the time of this analysis. The estimated 5-year survival rates were 97% for patients with chronic persistent hepatitis, 86% for those with chronic active hepatitis, and 55% for those with chronic active hepatitis with cirrhosis. The usual cause of death was liver failure and its sequelae. A multivariate analysis found age of 40 years or more, total bilirubin level of 1.5 mg/dL or more, ascites, and spider nevi to be factors that identified patients at a higher risk of death. The prognosis for patients with chronic hepatitis B is similar to that for patients with chronic hepatitis of other causes.

Effects of immunosuppressive therapy on viral markers in chronic active hepatitis B.

Hepatitis B virus associated DNA polymerase activity, hepatitis b surface antigen (HBsAg), and serum aspartate aminotransferase were followed in 21 patients with chronic active hepatitis while immunosuppressive therapy (prednisone +/- azathioprine) was being withdrawn. In every case, DNA polymerase activity fell within 6-10 wk of decreasing treatment and became undetectable in 8 patients. This was usually accompanied by a fall in HbsAg titer and a transient rise in serum aspartate aminotransferase activity. Four additional patients with previously untreated HbsAg positive chronic active hepatitis were placed on prednisone for 12 wk. There was a rise in DNA polymerase activity and HBsAg titer with a fall in serum aspartate aminotransferase values during treatment. Upon discontinuing therapy, DNa polymerase activity fell dramatically in all 3 patients who completed their course of prednisone and became undetectable in 1. These findings suggest that immunosuppressive therapy has a potentiating effect on hepatitis B viral replication in patients with chronic active hepatitis.

Prognostic factors and early predictability of sustained viral response with peginterferon alfa-2a (40KD)

BACKGROUND/AIMS Baseline factors and early decline in serum hepatitis C virus RNA are predictive of sustained virological response to interferon therapy in patients with chronic hepatitis C. We evaluated the prognostic value of baseline factors and early viral RNA among patients treated with peginterferon alfa-2a (40KD). METHODS Data were pooled from three randomized trials involving 814 patients treated with peginterferon alfa-2a (40KD) (90, 135, or 180 mirog). Stepwise and multiple logistic regression identified independent baseline factors associated with response. Receiver operating characteristic curves for both absolute values and log(10) decline in viral RNA at 4, 8, 12 and 24 weeks of therapy were created. RESULTS Independent prognostic factors for sustained virological response included viral genotype non-1, low pretreatment viral load, age (<40 years), no cirrhosis and body weight (<85 kg). In addition, alanine aminotransferase quotient (>3) and histological activity index score (>10) were also independently prognostic. Receiver operating characteristic curves showed that detectable or less than 2-log(10) decline in viral RNA at week 12 predicted sustained virological non-response (negative predictive value is 98%) . CONCLUSIONS In patients with chronic hepatitis C treated with peginterferon alfa-2a (40KD), the decision to continue or stop treatment can be made as early as week 12.

Adenine Arabinoside Monophosphate (Vidarabine Phosphate) in Combination with Human Leukocyte Interferon in the Treatment of Chronic Hepatitis B: A Randomized, Double-Blinded, Placebo-Controlled Trial

STUDY OBJECTIVE To determine the efficacy of adenine arabinoside monophosphate (Ara-AMP vidarabine phosphate) with or without human leukocyte interferon in chronic hepatitis B. STUDY DESIGN Randomized, double-blinded, placebo-controlled trial with 6-month treatment and an 18-month follow-up. SETTING Referral-based liver-disease clinics at three university medical centers. PATIENTS Twenty-five patients with chronic active hepatitis or cirrhosis and 39 with chronic persistent hepatitis. INTERVENTIONS Thirteen patients received intramuscular Ara-AMP, 2.5 mg/kg body weight, twice daily, alternated monthly for 6 months with subcutaneous human leukocyte interferon, 5 million units, twice daily. Painful paresthesia of the legs necessitated dosage reduction and early discontinuation of enrollment. Twenty-four patients received intramuscular Ara-AMP, 2.5 mg/kg, twice daily, alternated monthly for 6 months with a matching placebo given subcutaneously twice daily. Twenty-seven patients received placebo by intramuscular and subcutaneous injections twice daily for 6 months. MEASUREMENTS AND MAIN RESULTS Of the 64 patients, 95% had symptomatic and virologic data available and 64% had biopsies at 12 months; at 24 months, 77% had data available and 56% had repeat biopsies. The highest dropout rate was seen in the group receiving Ara-AMP. The group receiving the placebo was less symptomatic (Karnofsky score of 96% compared with 91% in the group receiving Ara-AMP/placebo and 92% in the group receiving Ara-AMP/human leukocyte interferon, p = 0.02) at 12 but not at 24 months. Loss of DNA polymerase, the hepatitis B e antigen, and the serum hepatitis B virus DNA was similar in all three groups. Histologically, erosion of the limiting plate and lobular activity favored Ara-AMP at 12 but not at 24 months and these differences did not result in differences in the histologic diagnosis. CONCLUSION These results do not support the use of Ara-AMP and human leukocyte interferon in chronic persistent or chronic active hepatitis B.

Preliminary studies of acyclovir in chronic hepatitis B

Three patients with HBsAg-positive and DNA-polymerase-positive chronic hepatitis were treated with increasing dosages of intravenous acyclovir. A fall in DNA polymerase activity was seen with all courses of acyclovir but no dose-response relationship was evident. In only one patient did DNA polymerase fall to zero where it has remained for five months. Two out of 10 courses were associated with significant side effects with the highest dosages of acyclovir but these promptly resolved when the agent was stopped. Acyclovirs apparently partial and transient action suggests that it will not have a role in the treatment of chronic hepatitis B virus infection.

Antiviral Response of HCV Genotype 1 to Consensus Interferon and Ribavirin Versus Pegylated Interferon and Ribavirin

Achieving an antiviral response at a reasonable cost is a challenge in the treatment of patients with chronic hepatitis C. A previous study indicated that consensus interferon with ribavirin had promising activity against hepatitis C virus (HCV) genotype 1. The objective of this study was to determine the virologic response with consensus interferon or pegylated interferon α-2b plus weight-ribavirin in patients chronically infected with HCV genotype 1. Intention-to-treat analysis showed response in 37% and 41% of subjects treated with consensus interferon/ribavirin or pegylated interferon/ribavirin, respectively, with response rates of 42% and 44% observed in analysis of the per-protocol population, not a significant difference. Tolerability of the two treatment regimens was similar. In conclusion, both treatment regimens were safe and gave a similar antiviral response. It is possible that if consensus interferon is administered daily rather than three times weekly, eradication of HCV could be achieved in a larger proportion of patients infected with HCV genotype 1.