Quantitative serum HBV DNA levels during different stages of chronic hepatitis B infection

The goals of this retrospective study were to determine whether there is a threshold hepatitis B virus (HBV) DNA value associated with spontaneous or antiviral therapy—related hepatitis B e antigen (HBeAg) clearance. We also investigated whether there is an HBV DNA value that can be used for differentiating inactive carriers from patients with HBeAg-negative chronic hepatitis B. HBV DNA levels in sequential serum samples of 165 Chinese patients with different stages of chronic HBV infection were quantified by a polymerase chain reaction (PCR)—based assay. Our results showed that almost all of the patients (89%) who remained HBeAg-positive had HBV DNA levels that were persistently above 10 5 copies/mL. Serum HBV DNA levels decreased by a mean of 3 log 10 in patients with HBeAg loss, but 51% had levels above 10 5 copies/mL at the time HBeAg first became undetectable. Mean serum HBV DNA levels were significantly lower in HBeAg-negative patients. HBV DNA value above 10 5 copies/mL would exclude all inactive carriers, but 45% of patients with HBeAg-negative chronic hepatitis would also be excluded if testing were only performed at presentation and 30% would be excluded if testing were performed on 3 occasions. In conclusion, serum HBV DNA levels decreased significantly in patients with HBeAg loss, but there was no threshold HBV DNA level associated with HBeAg clearance. Given the fluctuating course of HBeAg-negative chronic hepatitis, it is not possible to define a single cutoff HBV DNA value for differentiating inactive carriers from patients with HBeAg-negative chronic hepatitis. (H EPATOLOGY 2002;36:1408–1415).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38414/1/1840360617_ftp.pd

HBV genotype B is associated with better response to interferon therapy in HBeAg( + ) chronic hepatitis than genotype C

Hepatitis B virus (HBV) genotype and precore/core promoter mutations have been implicated in spontaneous and interferon alfa (IFN-Α)—related hepatitis B e antigen (HBeAg) seroconversion. We performed a retrospective analysis of a previously reported randomized controlled trial to determine the effects of HBV genotype and precore/core promoter mutations on IFN-Α response in patients with HBeAg-positive chronic hepatitis. Clinical data and stored sera from 109 (95%) patients in the original trial were analyzed. Seventy-three patients received IFN-Α and 34 received no treatment (controls). Almost all patients had HBV genotypes B (38%) and C (60%). Antiviral response was achieved in 39% and 17% of IFN-Α—treated patients ( P = 0.03) and in 10% and 8% of untreated controls ( P = 0.88) with HBV genotype B and C, respectively. Multivariate analysis identified HBV genotype B, elevated pretreatment alanine aminotransferase (ALT) levels, and low pretreatment HBV-DNA levels but not IFN-Α treatment as independent factors associated with antiviral response. Among the 66 patients with elevated pretreatment ALT level, antiviral response was achieved in 57% and 21% of IFN-Α—treated patients ( P = 0.019), and in 25% and 8% of untreated controls ( P = 0.45) with HBV genotype B and C, respectively. Multivariate analysis showed that genotype B and low pretreatment HBV-DNA levels were independent predictors of antiviral response. In conclusion, our data showed that HBV genotype B was associated with a higher rate of IFN-induced HBeAg clearance compared with genotype C. Stratification for HBV genotypes should be considered in future clinical trials of antiviral therapy of chronic hepatitis B. (H EPATOLOGY 2002;36:1425–1430).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38415/1/1840360619_ftp.pd

Hepatitis B e antigen–negative chronic hepatitis b in Hong Kong

Hepatitis B e antigen–negative chronic hepatitis B (e−CHB) has been reported in Asia but its prevalence and clinical significance have not been determined. The aims of this study were to determine the prevalence of e−CHB in Hong Kong and the frequency of precore and core promoter mutations in these patients. A cross-sectional study was performed in 350 consecutive Chinese patients (230 men and 120 women; mean age ±SD, 42 ± 13 years) with chronic hepatitis B virus infection. A total of 243 (69%) patients were hepatitis B e antigen (HBeAg)-negative of whom 15% had clinical cirrhosis. In the remaining 85% of patients, 63% had normal and 22% had elevated transaminases. Serum hepatitis B virus (HBV) DNA was detectable using branched DNA assay in 46% of HBeAg-negative patients with clinical cirrhosis/elevated transaminases. Forty-five percent of the patients with e−CHB had the precore stop codon mutation, and an additional 41% had core promoter changes. There was no correlation between the presence of precore/core promoter mutations and liver disease or HBV-DNA levels. Overall, 17% of HBeAg-negative patients were viremic and had evidence of chronic liver disease (e−CHB) with mean HBV-DNA levels comparable with that in HBeAg-positive patients. In summary, we found that e−CHB may be present in up to 17% of HBeAg-negative patients seen in a tertiary referral center in Hong Kong. e−CHB may be a heterogenous condition and is not invariably associated with the precore HBV mutant. Population studies are needed to determine the true prevalence of e−CHB in Asia and to assess its natural course and response to treatment.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34778/1/510310330_ftp.pd

Hepatitis B infection in patients with acute liver failure in the United States

Occult hepatitis B virus (HBV) infection has been reported in 30% to 50% of patients with acute liver failure (ALF) in small case series. The aim of this study was to determine the prevalence of occult HBV infection in a large series of ALF patients in the United States and the prevalence of precore and core promoter variants in patients with ALF caused by hepatitis B. Sera from patients in the US ALF study and liver, when available, were tested using nested polymerase chain reaction (PCR) with primers in the HBV S and precore regions. PCR-positive samples were sequenced. Sera and/or liver from 139 patients (39 males, 100 females; mean age, 42 years) enrolled between January 1998 and December 1999 were studied. Twelve patients were diagnosed with hepatitis B, 1 with hepatitis B+C+D coinfection, and 22 had indeterminate etiology. HBV DNA was detected in the sera of 9 (6%) patients; all 9 had ALF caused by hepatitis B. HBV genotypes A, B, C, and D were present in 4, 3, 1, and 1 patients, respectively. Seven of these 9 patients had precore and/or core promoter variants. Liver from 19 patients were examined. HBV DNA was detected in the liver of 3 patients with ALF caused by hepatitis B, but in none of the remaining 16 patients with non-B ALF. Contrary to earlier reports, occult HBV infection was not present in this large series of ALF patients in the United States. HBV precore and/or core promoter variants were common among US patients with ALF caused by hepatitis B. (H EPATOLOGY 2001;33:972-976.)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34782/1/510330426_ftp.pd

Evolution of hepatitis B virus polymerase gene mutations in hepatitis B e Antigen–negative patients receiving lamivudine therapy

Lamivudine has been shown to be effective in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B, but its long-term efficacy and the rate of resistant mutations in patients with HBeAg-negative chronic hepatitis B is less clear. Twenty-nine patients with HBeAg-negative chronic hepatitis B, who have received lamivudine for at least 1 year were studied to determine the antiviral response, the rate and pattern of lamivudine-resistant mutations, and the effect of lamivudine-resistant mutations on HBeAg status. The mean duration of treatment was 21 ± 7 months. Before treatment, core promoter variant was detected in 16 (55%) patients and precore stop codon variant in 18 (62%) patients. Serum hepatitis B virus (HBV) DNA was detected by solution hybridization assay in 62%, 4%, and 24% and by polymerase chain reaction (PCR) assay in 100%, 31%, and 40% at months 0, 6, and 24, respectively. The cumulative rates of detection of lamivudine-resistant mutations after 1 and 2 years of treatment were 10% and 56%, respectively. In addition to the duration of treatment, core promoter mutation was associated with the selection of lamivudine-resistant mutants. Three patients with lamivudine-resistant mutations had reversion of the precore stop codon mutation; in 2 patients this was accompanied by the reappearance of HBeAg. We found that lamivudine-resistant mutants were detected at similar rates in patients with HBeAg-negative as in patients with HBeAg-positive chronic hepatitis B. Additional changes in other parts of the HBV genome may restore the replication fitness of lamivudine-resistant mutants.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34780/1/510320535_ftp.pd

Hepatitis B virus genotypes, precore and core promoter variants among predominantly Asian patients with chronic HBV infection in a Canadian center

The epidemiology of hepatitis B virus (HBV) infection in North America may be changing as a result of immigration from endemic countries. The purpose of this study was to determine the prevalence of HBV genotypes, precore (PC) and core promoter (CP) variants, and the proportion of patients meeting treatment criteria for HBV. Methods : A cross-sectional study of consecutive HBV patients attending a Canadian tertiary liver center was conducted. HBV DNA was quantified by polymerase chain reaction assay. HBV genotypes and variants were determined using a line probe assay. Results : Two hundred and seventy-two patients were enrolled; 200 were not receiving treatment at enrollment, of whom 116 were men and 84 women with a mean age 42±14 years. Among this group, 177 (88%) patients were Asian and 19 (10%) were Caucasian and 69 (35%) patients were hepatitis B e antigen (HBeAg) positive. Genotypes B and C were found in 42% and 50% untreated patients, respectively; while CP and PC were detected in 52% and 43% patients, respectively. Approximately 20% patients not receiving treatment (29% HBeAg positive, 14% HBeAg negative) met AASLD guidelines for antiviral therapy. If lower cutoff values for alanine aminotransferase and HBV DNA levels were used, 49% patients would qualify for treatment. Conclusions : The vast majority of patients at a Canadian tertiary referral center were Asian. Virological and clinical characteristics of these patients reflect their country of origin. Our findings highlight the need to monitor the changing patterns of HBV infection in countries with large immigrant populations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71778/1/j.1478-3231.2006.01297.x.pd