Mary C. Kuhns

A Randomized, Controlled Trial of Interferon Alfa-2b Alone and after Prednisone Withdrawal for the Treatment of Chronic Hepatitis B

Abstract Background and Methods. Chronic hepatitis B is a common and often progressive liver disorder for which there is no accepted therapy. To assess the efficacy of treatment with interferon, we randomly assigned patients with chronic hepatitis B to one of the following regimens: prednisone for 6 weeks followed by 5 million units of recombinant interferon alfa-2b daily for 16 weeks; placebo followed by 5 million units of interferon daily for 16 weeks; placebo followed by 1 million units of interferon daily for 16 weeks; or observation with no treatment. Results. Hepatitis B e antigen and hepatitis B viral DNA disappeared from serum significantly more often in the patients given prednisone plus interferon (16 of 44 patients, or 36 percent) or 5 million units of interferon alone (15 of 41; 37 percent) than in the untreated controls (3 of 43; 7 percent; P<0.001); the difference between those given 1 million units of interferon (7 of 41; 17 percent) and the controls was not significant. The strongest indep...

Frequency of HBV DNA detection in US blood donors testing positive for the presence of anti-HBc: implications for transfusion transmission and donor screening

BACKGROUND: An estimate of the rate of HBV DNA‐positive, anti‐HBc‐positive units is important for evaluating the need for anti‐HBc donor screening, especially in the context of HBV NAT.

Prednisone Withdrawal Followed by Recombinant Alpha Interferon in the Treatment of Chronic Type B Hepatitis: A Randomized, Controlled Trial

STUDY OBJECTIVE To determine the efficacy of a short course of prednisone followed by recombinant interferon treatment in patients with chronic type B hepatitis. DESIGN Randomized, controlled trial with a 5-month treatment phase and a 9-month observation period after treatment. SETTING Two referral-based university-affiliated medical centers. PATIENTS Thirty-nine clinically stable patients with chronic type B hepatitis, all of whom were positive for hepatitis B antigen, hepatitis B virus-associated-DNA (HBV-DNA), and DNA polymerase for at least 6 months before entry. Patients included 20 heterosexuals and 19 male homosexuals. INTERVENTIONS Eighteen patients were treated with a 6-week tapered regimen of prednisone, followed by 90 days treatment with recombinant interferon alpha-2b; 21 patients were untreated controls. Paired liver biopsy specimens of 27 patients (pretreatment and 9 months after treatment) were blindly evaluated. MEASUREMENTS AND MAIN RESULTS Nine treated patients had a sustained loss of HBV-DNA. In addition, eight treated patients lost hepatitis B e antigen and four became negative for hepatitis B surface antigen (HBsAg). When compared with controls the differences were statistically significant for clearance of HBV-DNA and HBsAg (P = 0.035 and 0.037, respectively). Treated patients who had a sustained loss of HBV-DNA had higher initial alanine aminotransferase lower initial DNA and DNA polymerase levels, and were more frequently heterosexual. Patients who responded to treatment with the disappearance of hepatitis B e antigen and HBV-DNA had normal liver function tests and markedly improved liver histology during follow-up. CONCLUSIONS The immunologic priming provided by a short course of prednisone used with alpha interferon may be an effective treatment for selected patients with chronic type B hepatitis.

Serum and liver hepatitis B virus DNA in chronic hepatitis B after sustained loss of surface antigen

Polymerase chain reaction (PCR) was used to detect hepatitis B virus DNA in the sera and livers of nine patients with chronic hepatitis B after treatment-induced or spontaneous loss of serum hepatitis B surface antigen. Patients were evaluated at intervals ranging from 3 to 67 months after disappearance of hepatitis B surface antigen. PCR was performed using primer pairs from the surface and core gene regions, and surface gene products were quantitated. Liver tissue was also evaluated by in situ hybridization to assess viral transcription. Five of the nine patients had viral DNA detectable in serum by PCR. Quantitation of polymerase chain reaction products in serum and liver showed that the DNA levels tended to decline progressively after antiviral therapy. Six of seven surface antigen-negative patients tested had detectable viral DNA in the liver, and four of the six DNA-positive patients were negative for DNA in serum by PCR. None had surface gene messenger RNA. Thus, it is concluded that hepatitis B virus DNA may be detectable by PCR in liver tissue years after the disappearance of hepatitis B surface antigen, even in the absence of detectable hepatitis B virus DNA in serum.

Lack of correlation between HBsAg and HBV DNA levels in blood donors who test positive for HBsAg and anti-HBc: implications for future HBV screening policy

BACKGROUND:  Studies showing a significant correlation between hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels have focused on the HBV seroconversion window period.

Current incidence and residual risk of hepatitis B infection among blood donors in the United States

BACKGROUND: This study used two approaches to estimate the current incidence of hepatitis B virus (HBV) in a US donor population.

New strategies for blood donor screening for hepatitis B virus: nucleic acid testing versus immunoassay methods.

Serologic testing for hepatitis B virus (HBV) surface antigen (HBsAg) and antibody to HBV core antigen (anti-HBc) has historically been the foundation of blood screening, while HBV nucleic acid testing (NAT) was recently developed to detect HBsAg-negative, anti-HBc-negative blood units donated during early acute infection. Comparison data on seroconversion panels using HBsAg assays of varying sensitivities and pooled- or single-sample NAT, along with viral load estimates corresponding to HBsAg assay detection limits, have provided information on the theoretical benefits of NAT relative to HBsAg. Model-derived estimates have generally been predictive of the yields of DNA-positive, HBsAg-negative window period blood units detected in a number of studies from Europe, Japan, and the US. Studies indicate that the added benefit of pooled-sample NAT is relatively small in areas of low endemicity, with greater yields in areas highly endemic for HBV. Single-sample NAT would offer more significant early window period closure and could prevent a moderate number of residual HBV transmissions not detected by HBsAg assays; however, no fully automated single-sample HBV NAT systems are currently available.Even single-sample HBV NAT may not substitute for anti-HBc screening, as indicated by studies of donors with isolated anti-HBc who have extremely low DNA levels undetectable by standard single-sample NAT and who have been associated with transfusion-transmitted HBV. Moreover, HBsAg testing may still be needed even in the setting of combined anti-HBc and NAT screening. HBsAg-positive units from donors in the chronic stage of infection may contain very low or intermittently detectable DNA levels that single-sample NAT would miss. Although such donors are usually anti-HBc reactive and would be interdicted by anti-HBc screening, some lack anti-HBc. Extensive parallel testing will be needed to determine whether single-sample NAT in combination with anti-HBc might be sufficient to detect all the infectious donors currently interdicted by HBsAg testing. In countries that do not screen for anti-HBc, HBsAg testing would be the only means of detecting donations from chronically infected individuals with low/intermittently detectable DNA, since even single-donor NAT would not identify these potentially infectious blood units.In the future, the current fully automated HBsAg assays may incorporate significant sensitivity improvements, and automated single-sample HBV NAT may become a reality. Each country will need to develop its blood screening strategy based on HBV endemicity, yields of infectious units detected by different serologic/NAT screening methods, and cost effectiveness of test methods in ensuring blood safety.

Serum HBeAg quantitation during antiviral therapy for chronic hepatitis B

Hepatitis Be antigen (HBeAg) seroconversion is considered the principal short‐term goal of antiviral therapy in chronic hepatitis B. To test whether the pre‐ and per‐treatment HBeAg quantitation has a higher predictive value than that of hepatitis B virus DNA (HBV‐DNA) quantitation for the outcome of antiviral therapy in chronic hepatitis B. A quantitative measurement of HBV‐DNA and HBeAg (AxSYM HBe 2.0 Quantitative, Abbott Laboratories) was undertaken in serial serum samples from 30 patients with 16‐week interferon‐α (IFN‐α) treatment (follow‐up 36 weeks; 14 responders) and from 15 patients with 24‐week lamivudine treatment (follow‐up 24 weeks; 2 responders).

Cytokine and Chemokine Responses in the Acute Phase of Hepatitis B Virus Replication in Naive and Previously Vaccinated Blood and Plasma Donors

BACKGROUND Blood and plasma donor screening for hepatitis B virus (HBV) DNA, HBV surface antigen (HBsAg), and antibodies to surface (anti-HBs) and core (anti-HBc) antigens allows identification of individuals who acquired HBV despite previous HBV vaccination. METHODS Of 14 HBV acute infection donor panels (HBV-DNA-positive/anti-HBc-negative), 6 donors were previously vaccinated (anti-HBs+). We investigated the differences in viral kinetics and immune responses in vaccinated and nonvaccinated individuals. Serial specimens were characterized for HBV DNA and serological markers and 39 cytokines. RESULTS The rate of viral load increase was blunted, and virus was cleared more rapidly in vaccinated individuals (P = .004). In unvaccinated individuals, induced protein 10 (IP-10), interleukin 10 (IL-10), macrophage inflammatory protein 1β (MIP-1β), and soluble interleukin 2Rα (sIL-2Rα) levels were commonly elevated at the time of peak viremia. In contrast, vaccinated individuals had earlier peaks in IL-10 and IP-10 responses that occurred at much lower viral loads and coincided with anamnestic anti-hepatitis B surface (HBs) responses and clearance of viremia. CONCLUSION There is earlier engagement of innate and adaptive immunity in infected subjects with previous vaccination, possibly explaining suppressed viremia in vaccine breakthrough infections. Although breakthrough infections occur in partially protected vaccine recipients, vaccination likely contributes to early control of replication, limiting immune activation and preventing development of clinically significant acute and chronic HBV infection.

Clinical and Laboratory Features of Acute Community-acquired Non-A, Non-B, Non-C Hepatitis

Hepatitis C virus (HCV) infection, the main cause of post-transfusion non-A, non-B hepatitis worldwide, appears much less commonly in community-acquired non-A, non-B (CA-NANB) hepatitis. To further define the role of HCV or other known hepatitis viruses, we studied a well-defined cohort of 71 patients with acute CA-NANB hepatitis in Athens, Greece. Four of 46 biopsied cases were classified as chronic hepatitis. HCV was responsible for only 10 of 67 (14.9%) acute cases. Clinically and histologically, severe hepatitis was exclusively observed in non-A, non-B, non-C (NANBNC) (20/36 or 55.6% vs 0/6, P = 0.014) cases. Progression to chronic hepatitis was more frequent in anti-HCV-positive (6/10 or 60%) than in anti-HCV-negative (15/57 or 26.3%) cases (P = 0.044). Six of the 9 biopsied chronic NANBNC cases developed cirrhosis within 10–21 months. Seven NANBNC cases were tested for anti-HEV as well as HCV RNA and HBV DNA in serum and liver, and all were found to be negative. In conclusion, this study indicates that HCV is implicated in a minority of cases of acute CA-NANB hepatitis in Greece. Based on clinical severity and rate of chronicity, acute CA-NANBNC hepatitis differs from acute HCV infection. CA-NANBNC hepatitis is not caused by any known hepatitis virus. Although the viral etiology of the non-(A-E) hepatitis remains to be proven, this study lends further support to the existence of hitherto unkown hepatitis viruses.