Low HBV-DNA Levels Research Articles

Identification of factors associated with YMDD mutation in patients with chronic hepatitis B receiving lamivudine treatment

To identify factors associated with YMDD mutation in patients with chronic hepatitis B before and after lamivudine treatment in Zunyi region. 53 patients with chronic hepatitis B were enrolled in this study, HBV DNA,HBV markers, ALT, AST, TBil, albumin in the serum were examined at 0, 3, 6, 12, 18 and 24 months after lamivudine treatment. HBV genotype and YMDD mutation were determined by sequencing before lamivudine treatment. YMDD mutation was checked again if serum HBV DNA rebound to more than 1 x 10(4) copies/ml after the initial decrease. HBV genotype in Zunyi region is constitute of B, C and B+C genotype. YMDD mutation occurred in 18 cases after lamivudine treatment, the rate of YMDD mutation was 15.1%, and 34.0% after 1 year and 2 years treatment. There are four types of mutation: rtL180M/M204V, rtL180M/M204I, rtM204I, rtL180M. rtM204V mutation in C gene was always accompanied by rtL180M mutation (100%). The rate of rtL180M/M204V mutation in genotype C group was significantly higher than that in genotype B group (77.8% to 25.0%), the same was true for the rtL180M/ M204I mutation (22.2% to 12.5%). There was no point mutation in genotype C group. The point mutation of rtM204I and rtL180M appeared only in genotype B group. Gender, nation, family history of hepatitis B and HBeAg were not associated with YMDD mutation (P more than 0.05), while the mutation rate was associated with the disease course and severity of disease. YMDD mutation did not occur in patients with low HBV DNA level (less than 10(5) copies/ml). YMDD mutation after lamivudine therapy is associated with HBV genotype and P gene mutation type, and prolonged treatment increases the the mutation rate. In order to reduce the incidence of YMDD mutation, patients with shorter disease course, lower HBV DNA level, more serious liver damage should be treated with lamivudine.

Negative correlation between viral load and HBsAg levels in chronic HBV-infected patients

The objective of this study is to reveal the relationship between viral load (as HBV DNA) and HBsAg levels. Ninety-two chronically HBV-infected patients were included in the study. The patients were divided in two different groups: the cirrhotic group (n = 32) and the non-cirrhotic group (n = 60). The correlation between study groups was also examined with regard to HBeAg status. Hepatitis B viral markers (HBsAg, HBeAg, Anti-HBs, anti-HBc and anti-HBe) and HBV viral load of the patients were measured. A significant negative correlation between HBV DNA and HBsAg levels was found in the non-cirrhotic group (p < 0.01). The anti-HBc level was higher in the non-cirrhotic group than in the cirrhotic group (p < 0.016). The viral load was significantly higher in HBeAg (+) patients in comparison with HBeAg (-) cases (p < 0.0001). The HBsAg level was low in HBeAg (+) patients, whereas it was higher in HBeAg (-) cases (p < 0.001). In conclusion, a significant negative correlation between viral load and HBsAg levels was detected in the non-cirrhotic chronically HBV-infected group. Therefore, concomitantly low HBsAg and HBV DNA levels may indicate a better prognosis compared to high HBsAg and low HBV DNA levels.

The relationship between the levels of HBV DNA loads and both the clinical characteristics and 48-week prognosis in patients with decompensated cirrhosis due to hepatitis B

To evaluate the relationship between the levels of HBV DNA loads and both the clinical characteristics and 48-week prognosis in patients with decompensated cirrhosis due to hepatitis B. One hundred and forty-three patients with decompensated cirrhosis of hepatitis B virus infection were divided into low level HBV DNA group [HBV DNA < 10(5) copies/ml = (46 cases) and high-level HBV-DNA group (HBV DNA > or = 10(5) copies/ml) (97 cases)]. 21 cases in low-level group and 52 cases in high-level group treated with nucleoside analog. There was no significant difference between the two groups on the demography and the baseline in ALT, ALB, TBil, CHE before treatment, while in AST and HBeAg were statistically different. At 48-week, there was no significant difference between the two groups on the liver function. The mortality rate in low-level group was similar to that in high level group. In the low-level HBV DNA patients, hepatocellular carcinoma, spontaneous peritonitis and gastrointestinal hemorrhage were higer than that in the high-level HBV DNA patients. In patients with decompensated cirrhosis due to hepatitis B, those who were in low-level HBV DNA had not got better than that in high-level HBV DNA, which indicated that earlier treatment was also needed in low-level HBV DNA patients.

Identification of low HBV-DNA levels by nucleic acid amplification test (NAT) in blood donors

To evaluate the presence of HBV-DNA in 22,765 consecutive blood donors, who donated blood in the period from January 2006 to August 2007 at a transfusion centre in Lazio, a region in central Italy with low HBV endemicity. Each donation was individually tested using immunoenzymatic assays and nucleic acid amplification technologies (NAT). Samples that were reactive to generic NAT, Procleix Ultrio Assay were tested for HBV-DNA, HCV-RNA and HIV1-RNA by Discriminatory Procleix Ultrio NAT Assay. In samples that were reactive to generic NAT and negative for HBsAg, HCV-RNA and HIV1-RNA, HBV-DNA was further tested using Cobas TaqMan and an in-house nested PCR following an ultracentrifugation step. Sequence analysis confirmed HBV-DNA positivity. Generic NAT identified 31 (0.13%) reactive sera. HBV-DNA discriminatory NAT identified 15 positive sera; HBsAg was positive in 12 sera. Of the 5 generic NAT-reactive/discriminatory NAT-negative/HBsAg-negative sera and of the 3 HBsAg-negative/HBV-DNA discriminatory NAT-positive sera, 7 were positive to Cobas TaqMan or the in-house PCR after ultracentrifugation. The overall HBV-DNA positivity was 0.083% [19 of 22,765 donors: 12 HBsAg-positive (HBV-DNA range 10(2)-10(4) IU/mL), 7 HBsAg-negative/anti-HBc positive (HBV-DNA< 6 IU/mL)]. For blood transfusion safety, the significance of the finding of very low HBV-DNA levels should be further investigated. Our data indicate that in areas with a low HBV endemicity, single NAT assays may not always identify blood donations with very low HBV-DNA levels.

High rates of HBsAg seroconversion in HBeAg-positive chronic hepatitis B patients responding to interferon: A long-term follow-up study

To assess the HBsAg seroconversion rate and its impact on the long-term outcome in chronic hepatitis B patients treated with conventional interferon, and to analyze the serum HBsAg concentration prior to seroconversion. Ninety-seven HBeAg-positive patients were retrospectively evaluated. Sustained virological response (SVR) was defined as HBeAg seroconversion and undetectable serum HBV-DNA 48 weeks after treatment discontinuation. HBsAg level was assessed at yearly intervals until seroconversion in SVRs. Twenty-five patients (26%) achieved SVR. By multivariate analysis, SVR was associated with low serum HBV DNA level and severe liver fibrosis. During a median follow-up of 14 years (range, 5-20 years), 28 patients (29%) developed HBsAg seroconversion including 16 SVRs (64%) and 12 non-SVRs (16%), p < 0.001. HBsAg quantification showed a major decrease (median = 46%, range = 19-100%) in the first year after interferon starting in SVR patients. Six patients developed hepatocellular carcinoma, none of them had undergone HBsAg seroconversion. Liver fibrosis improved in 70% of patients with HBsAg seroconversion compared to 30% of those without HBsAg seroconversion (p < 0.01). HBsAg seroconversion is achieved with a high steady rate in patients responding to interferon, and associated with excellent outcome. Prospective studies are needed to clarify the utility of on-treatment quantitative serum HBsAg in interferon-based therapy.

A short course of add‐on adefovir dipivoxil treatment in lamivudine‐resistant chronic hepatitis B patients

The aims of the study were to investigate the efficacy of rescue therapy with lamivudine (LAM) and adefovir (ADV) combination for 6 months followed by ADV monotherapy in lamivudine-resistant chronic hepatitis B (LAM-R CHB) patients, and to analyze the frequency of ADV resistance mutant development in such patients. A total of 170 consecutive LAM-R CHB patients (male/female: 130/40, mean age: 42.9+/-13.4 years) with viral breakthrough under LAM therapy were analyzed. A total of 68 had HBeAg-positive. Patients received rescue therapy with LAM [100 mg (qd)]+ADV [10 mg (qd)] for 6 months after which LAM was discontinued. HBV-DNA was assessed with the HBV-DNA 3.0 bDNA assay. ADV-resistant mutations were identified by sequencing the reverse transcriptase region. The median duration of rescue therapy was 24 months. Cumulative probability of becoming HBV-DNA undetectable was 33.8%, 59.6% and 68.2% after 24, 48 and 96 weeks of treatment, respectively. These figures were 43.2%, 58.0% and 73.1% for ALT normalization. Among 68 HBeAg-positive CHB patients, 10 patients had an e-antigen seroconversion. Low baseline HBV-DNA level (<10(7) copies/mL) was a significant predictor of response to ADV treatment (P<0.01). Cumulative probability of ADV resistance was 1.2%, 15.1% and 37.3% at 12, 24 and 36 months of therapy, respectively. By multivariate analysis, baseline high viral load and primary nonresponse to treatment at week 24 predicted ADV resistance. The data indicate that a time limited add-on strategy does not provide benefit over the switch strategy with respect emergence of ADV resistant mutants in LAM-R CHB patients.

On‐treatment monitoring of adefovir therapy in chronic hepatitis B: virologic response can be assessed at 24 weeks

Patients with chronic hepatitis B (CHB) who will and those who will not respond to adefovir (ADV) monotherapy need to be identified at an early stage in order to adjust treatment and prevent future development of antiviral resistance. In a single-centre cohort study, we investigated 76 CHB patients [50% hepatitis B e antigen (HBeAg)-positive] treated with long-term ADV monotherapy. During a median follow-up of 122 (24-185) weeks, 42 (55%) patients achieved virologic response (VR), defined as HBV-DNA levels <10(3) copies/mL, and 10 patients (13%) developed genotypic ADV resistance. Independent baseline predictors of VR were HBeAg negativity [hazard ratio (HR) 2.98; 95% confidence interval (CI) 1.24-7.19; P = 0.02], high alanine aminotransferase (ALT) levels (HR 1.11; 95% CI 1.05-1.18; P = 0.001), and low HBV-DNA levels (HR 0.56; 95% CI 0.41-0.75; P < 0.001). HBV-DNA at week 24 demonstrated a higher predictive value for VR than HBV-DNA at week 48. Important predictors of genotypic resistance were presence of cirrhosis (HR 6.54; 95% CI 1.39-30.9; P = 0.018), and not achieving VR during treatment (HR 6.60; 95% CI 1.35-32.4; P = 0.008). Patients without VR at week 24 already demonstrated a trend towards the emergence of ADV resistance (P = 0.07). HBV-DNA at week 24 was a better on-treatment predictor of VR than HBV-DNA at week 48, and ADV-resistant mutations developed more frequently in patients without VR at week 24. Therefore, our study suggests that virologic response to ADV therapy can be assessed at 24 weeks, instead of the generally recommended 48 weeks.

Early hepatitis B virus DNA reduction in hepatitis B e antigen–positive patients with chronic hepatitis B

This study was undertaken to compare the early antiviral activity and viral kinetic profiles of entecavir (ETV) versus adefovir (ADV) in hepatitis B e antigen positive nucleoside-naïve adults with chronic hepatitis B (CHB). Sixty-nine nucleoside-naïve CHB patients with baseline HBV DNA of 10(8) copies/mL or more were randomized 1:1 to open-label treatment with entecavir 0.5 mg/day or adefovir 10 mg/day for a minimum of 52 weeks. The primary efficacy analysis compared mean reduction in HBV DNA at week 12 adjusted for baseline levels using linear regression. Entecavir was superior to adefovir for mean change from baseline in HBV DNA at week 12 (-6.23 log(10) copies/mL versus -4.42 log(10) copies/mL, respectively; mean difference -1.58 log(10) copies/mL; P < 0.0001). Both drugs demonstrated biphasic viral kinetics, with a first phase of rapid decline lasting 10 days. A significant difference favoring ETV was reached at day 10 (day 10 ETV-ADV difference estimate: -0.66 log(10) copies/mL; 95% CI [-0.30, -0.01]). Early virological response was found to be predictive of subsequent virological response, with those having lower HBV DNA levels at day 10 being more likely to achieve HBV DNA of less than 300 copies/mL at week 48. In addition, there was considerably less variability in the extent of HBV DNA reductions in patients treated with entecavir versus adefovir. Both the mean decrease in serum HBV DNA and the proportion of patients achieving HBV DNA less than 300 copies/mL were greater in entecavir-treated than adefovir-treated patients at weeks 2, 4, 8, 12, 24, and 48. At week 48, one (3%) ETV-treated versus 15 (47%) ADV-treated patients had HBV DNA of 10(5) copies/mL or more. Both antivirals were well tolerated. Entecavir therapy resulted in earlier and superior reduction in HBV DNA compared with adefovir in nucleoside-naïve HBeAg-positive patients with CHB.

Hepatitis B vaccine non-response and occult hepatitis B virus infection

Aims: Low levels of HBV DNA can remain detectable after serological recovery from Hep. B. This so called occult HBV infection is thought to maintain HBV-specific T-cell responses witch in turn is preventing HBV reactivation. However HCV-specific CTLs may also target B-cells presenting HBV antigens and thereby inhibiting the production of antibodies. In mouse models it has been shown that this mechanism can lead to an impaired humeral immune response.

Management of hepatitis virus infections

Management of hepatitis virus infections

Relationship between liver pathological characteristics and serum HBeAg and HBV DNA in 1057 patients with chronic hepatitis B

To study the relationship between liver pathological changes and serum HBeAg and HBV DNA in 1057 patients with chronic hepatitis B. Liver puncture biopsy for histopathological examinations were performed in 1057 patients with chronic hepatitis B. The quantitative analysis of serum HBV DNA by fluorogenic quantitative PCR and HBeAg by chemoluminescence were also conducted. The inflammatory grade and fibrosis stage were higher in HBeAg-negative patients (G4 and S4 were 7.83% and 12.17% respectively) than in HBeAg-positive patients (G4 and S4 were 3.39% and 5.44% respectively). The inflammatory grade and fibrosis stage were higher in HBeAg-positive patients with low-level HBV DNA (G3G4 was 45.64% and S3S4 was 30.20% for HBV DNA104-105), whereas they were higher in HBeAg-negative patients with high-level HBV DNA (G3G4 was 54.55% for HBV DNA106-107 and S3S4 was 42.85% for HBV DNA108-109). There were some correlation between the liver pathological changes and serum HBeAg and HBV DNA levels in patients with chronic hepatitis B. It is important to perform the liver pathological examination and antiviral therapy as early as possible in patients with HBeAg-negative chronic hepatitis B.

Adefovir and lamivudine in combination compared with adefovir monotherapy in HBeAg-negative adults with chronic hepatitis B virus infection and clinical or virologic resistance to lamivudine: A retrospective, multicenter, nonrandomized, open-label study

The aim of this study was to assess the therapeutic effectiveness of adefovir dipivoxil (ADV), administered in combination with lamivudine (LAM) or as monotherapy, and the rate of resistance to ADV, in hepatitis B e antigen (HBeAg)-negative adult patients with chronic hepatitis B virus (HBV) infection and clinical or virologic resistance to LAM. Furthermore, we evaluated in these selected patients the clinical co-variates associated with a sustained virologic response. Data from adult outpatients aged >18 years with chronic HBV infection and clinical or virologic resistance to LAM were used in this retrospective, multicenter, nonrandomized, open-label study. Patients were selected if they received ADV 10 mg PO QD + LAM 100 mg QD PO or ADV 10 mg PO QD as monotherapy for 24 to 32 months between June 2003 and July 2006. End points were the proportions of patients who achieved virologic response (undetectable HBV-DNA [<3.3 log(10) copies/mL]) and biochemical response (normalization [<40 IU/L] of alanine aminotransferase [ALT]), and the proportions in whom resistance to ADV (rebound serum HBV-DNA >1 log(10) copies/mL compared with on-treatment nadir, as confirmed on molecular analysis) was found. HBV-DNA and ALT levels were checked every month during the first 3 months of treatment and every 3 months thereafter until 28 months. Data from each center were stored in a centralized database and analyzed by a blinded independent investigator. Data from 70 patients were included (48 men, 22 women; median age, 51 years; ADV + LAM, 36 patients; ADV monotherapy, 34). The median duration of the pharmacologic treatment in the 2 groups of patients was 28 months (range, 24-32 months). By month 3, virologic response was achieved in 30 patients (83%) in the ADV + LAM group and in 26 patients (76%) in the ADV monotherapy group. At 12 months, virologic response was achieved in 5 additional patients in the ADV + LAM group and 2 additional patients in the ADV monotherapy group. Biochemical response was found to be time dependent: in the 2 groups, the rates of biochemical response were, respectively, 56% and 54% at month 3, 80% and 71% at month 6, and 96% and 79% at month 12, persisting up to the end of the study period. The rates of clinical resistance to ADV were 3% with ADV + LAM and 18% with ADV monotherapy (with a 6% rate of resistance due to rtA181 mutation in the monotherapy group). Logistic regression analysis found that pre-treatment levels of HBV-DNA <5 log(10) copies/mL, ALT levels >150 IU/L, an inflammation score >7, and a fibrosis score <2 were the strongest covariates independently associated with a sustained virologic response in both groups of patients. No adverse events were reported in any of the patients. ADV, administered in combination with LAM or as monotherapy, appeared to be effective in this small, selected group of HBeAg-negative patients with clinical or virologic resistance to LAM, especially in those with low pretreatment HBV-DNA levels, high ALT levels, and low fibrosis scores.

What is the clinical significance of the high prevalence of occult hepatitis B in US liver transplant patients with chronic hepatitis C?

What is the clinical significance of the high prevalence of occult hepatitis B in US liver transplant patients with chronic hepatitis C?

Treatment of Chronic Hepatitis B in Children

Chronic hepatitis B in children is mainly asymptomatic, but they are at life long risk for severe complications. Treatment is considered to suppress the virus and to prolong the survival by preventing the progression to cirrhosis and HCC. Therapeutic options for children are interferon-alpha (IFN-alpha) with antiviral, antiproliferative and immuno-modulatory effects and lamivudine (LAM) which inhibits HBV replication and increases cellular immune response. IFN-alpha, 5 MU/m(2), thrice weekly for 6 months is used in patients with high ALT levels which is associated with virologic response rate of 30-40%. Predictors of response are high ALT levels, low HBVDNA levels and high histological activity index. The response is sustained in 85%-90% of responders. Adverse events include flu-like syndrome, bone marrow suppression, hair loss, and psychiatric side effects, induction of autoimmunity and temporarily suppression of weight gain and growth velocity. LAM, a nucleoside anolog, leads to a virologic response rate of 20-30% when used for 12 months. High ALT levels, low HBVDNA levels and high histological activity index predict better response. Maintenance of HBeAg seroconversion is 56-80%. Longer courses of treatment with LAM increases the seroconversion rate but with high mutation rate and viral resistance. Except for causing mutations, LAM doesn't have serious adverse events. Different timing and durations of combination treatment with IFN and LAM were also evaluated without any significant superiority over monotherapy. In conclusion, the best approach for treatment of chronic HBV infection in children haven't been determined yet. Future developments concerning new drugs and different treatment strategies are needed.

Hepatitis B Virus Genotype-Associated Variability in Antiviral Response to Adefovir Dipivoxil Therapy in Chinese Han Population

It is well known that different genotypes of hepatitis B virus (HBV) have a different sensitivity to interferon-alpha or lamivudine (nucleoside analogue) antiviral therapy. However, for adefovir dipivoxil (ADV, a nucleotide analogue), the antiviral response of the different genotypes remains to be clarified. In order to evaluate the response of HBV genotypes to ADV therapy and to identify factors that might affect initial virological response, we performed a retrospective analysis on patients with chronic hepatitis B (CHB) in Chinese Han population. The study included 183 patients, who had been tested positive for hepatitis B e antigen (HBeAg) and had been treated with ADV (10 mg/day) for 48 weeks. The numbers of patients infected with HBV genotype B and genotype C were 98 and 75 cases, respectively, and the remaining 10 patients were mixture infection of genotypes B plus C or genotypes B plus D. The mean HBV-DNA reduction and HBV-DNA seroclearance of genotypes B and C at 48 weeks were 3.6 log(10) and 3.1 log(10) copies/ml (p < 0.05) and 41.8% and 34.6% (p < 0.05), respectively. There were no statistically significant differences between genotypes B and C in terms of HBeAg loss, anti-HBe seroconversion and normalization of serum alanine aminotransferase (ALT). Multivariate analysis showed that young age, low pretreatment HBV-DNA and/or elevated ALT level might be independent predictive factors associated with initial virological response. Thus, in Han CHB patients who are HBeAg-positive, HBV genotype B shows a better virological response to ADV therapy than does genotype C.

Hepatitis B virus DNA in serum of ‘anti-HBc only’-positive healthy Lebanese blood donors: significance and possible implications

Transmission of HBV infection through transfusion of HBsAg-negative blood has been documented. It is evident that low levels of HBV-DNA remain detectable in serum and liver tissue of some patients who clear HbsAg, and that the detection rate is highest in individuals who are 'anti-HBc positive alone'. This study was designed to assess the frequency and clinical significance of 'anti-HBc alone' in Lebanese blood donors. A total of 5511 blood donor samples from three major hospitals representing most regions of the country were tested for anti-HBc, amongst other screening tests. Samples positive for 'anti-HBc alone' were then tested for HBV-DNA and any positive for HBV-DNA were then genotyped and investigated for hepatitis B viral load. The study showed that 203 (3.7%) of randomly selected Lebanese blood donors were confirmed as 'anti-HBc alone'. Of these, 11 (5.4%) were HBV-DNA positive as detected by nested PCR. All samples had HBV-DNA levels below 400 copies/ml and all were genotype D. It can be concluded that HBV was present, although the circulating amount of virus was below the detectable limit for the assay used. Therefore, routine screening for anti-HBc may be required in Lebanese blood donation centres as an additional preventive measure for controlling transmission of HBV via blood transfusion.

Viral genotype and baseline load predict the response to adefovir treatment in lamivudine-resistant chronic hepatitis B patients

To determine the factors associated with virological response (VR), HBeAg loss or the emergence of adefovir (ADV)-related mutations in ADV-treated chronic hepatitis B (CHB) patients with lamivudine (LAM) resistance. Fifty-four LAM-resistant CHB patients (46% HBeAg-positive) were treated with ADV monotherapy (n=28) or ADV plus LAM (n=26) for a mean of 30.4 months. Thirty-eight patients (70.4%) achieved VR defined as HBV-DNA levels <10(4)copies/ml within the first 12 months of treatment. Six (24%) of 25 HBeAg-positive patients exhibited HBeAg loss and 20% seroconverted to anti-HBe. Eight patients (14.8%) developed ADV-related mutations. In the multivariate analysis, female gender (HR=0.20, 95% CI: 0.05-0.76, p=0.018), HBeAg-negative (HR=0.37, 95% CI: 0.14-0.96, p=0.040) and low baseline HBV-DNA levels (HR=0.65, 95% CI: 0.45-0.95, p=0.027) were independent predictors of VR, whereas low HBV-DNA levels (HR=0.36, 95% CI: 0.11-1.20, p=0.095) and HBV-genotype D (HR=0.06, 95% CI: 0.004-0.84, p=0.037) independently predicted HBeAg loss. ADV therapy suppresses viral replication in more than 70% of LAM-R patients. Factors associated with virologic response are female gender, HBeAg-negative status and low baseline serum HBV-DNA levels. Genotype D HBV infection and low baseline HBV-DNA levels independently predict HBeAg loss.

HBV-DNA Levels in HBsAg-positive Blood Donors and its Relationship With Liver Histology

The clinical meaning of viremia, especially at low levels, in chronic hepatitis B virus (HBV)-infected patients remains unknown. The objective of the present study was to determine serum HBV-DNA levels and its relationship with liver histology in HBsAg-positive blood donors. A cross-sectional study was conducted on 78 blood donors, with alanine aminotransferase (ALT) and HBeAg evaluation and quantitative determination of HBV-DNA by polymerase chain reaction (Amplicor, HBV Monitor, Roche; lower limit of sensitivity 1,000 copies/mL). Liver biopsy was obtained from all patients with detectable viremia irrespective of ALT and HBV-DNA levels. Among 78 blood donors, serum HBV-DNA was detected in 47 (60%) patients; 39 (83%) were males; mean age 37.6+/-10.4 years; 31 (66%) were HBeAg-negative, and ALT was elevated in 26 (55%). The median of HBV-DNA levels was 24,000 copies/mL and 31 (40%) subjects had no detectable serum HBV-DNA. Although the histologic lesions were mild in the majority of patients, HBV-DNA levels were significantly higher in patients with chronic hepatitis or cirrhosis when compared with patients without histologic liver disease (25,260,000 vs. 9480 copies/mL; P<0.001). There was a significant correlation between HBV-DNA levels and necroinflammatory score (r=0.59) and fibrosis (r=0.50); however, in the subset of HBeAg-negative patients with HBV-DNA levels below 30,000 copies/mL, 25% presented histologic disease related to HBV. Most HBsAg-positive blood donors show low viral load. There is a significant association between viral replication and liver damage; however, low HBV-DNA levels do not exclude the presence of histologic disease.

HBsAg non-reactive HBV infection in blood donors: Transmission and pathogenicity

Five blood donors with occult persistent and one donor with an early window phase HBV infection were identified. They were negative in regular HBsAg screening and had low levels of HBV DNA that were probably not detectable by current mini-pool nucleic acid amplification testing. In four donors several mutations were found located in the HBs antigen loop. In three donors the mutations were predominantly outside the “a” determinant; one donor had a wild type HBsAg sequence. Fifty-five recipients of donations from the persistently infected donors could be tested for previous or ongoing HBV infection and of them 53% (29/55) were anti-HBc positive. Based on the prevalence of anti-HBc in Germany (7%), it was assumed that four of those recipients had already been positive before transfusion. In 22 cases, it was assumed that they acquired infection by the donations, but the infection remained asymptomatic and was resolved. In three cases transmission was proven by the time course of the acute infection and sequence identity The resulting infection was fatal and associated with immunological disorders at the time of transmission: in one case sepsis and in the other two cases immunosuppression. In a further asymptomatic case of proven transmission from the early window phase donation passively administered anti-HBs could not prevent spread of wildtype HBV but antiviral treatment lead to resolution. Surprisingly the typical acute hepatitis B was not observed in a single one of the 26 cases of assumed or proven transmission. J. Med. Virol. 79:S32–S36, 2007. © 2007 Wiley-Liss, Inc.

Effect of Initial Virologic Response to Adefovir on the Development of Resistance to Adefovir in Lamivudine-resistant Chronic Hepatitis B

Adefovir dipivoxil (ADV) resistance in patients with lamivudine-resistant chronic hepatitis B is not well understood. This study examined the initial virologic response (IVR) to ADV, the rate of ADV resistance and the factors associated with ADV resistance. Eighty one lamivudine-resistant HBeAg-positive patients were enrolled in this study. IVR was defined as HBV DNA < 4 log10 copies/mL after 6 months of therapy. IVR was observed in 37/81(45.7%) patients and it was associated with higher pretreatment ALT (P=0.002), and low pretreatment HBV DNA level (P=0.015). The HBV DNA levels were significantly higher in the non-IVR patients than the IVR patients at 12, 18 and 24 months (4.73 vs 2.59, 4.53 vs 2.31, 4.39 vs 2.40 log10 copies/mL, respectively; P<0.01). During the follow-up period, 17(21.0%) patients showed phenotypic resistance to ADV and 9 (11.1%) patients had ADV-resistant mutations. The cumulative probabilities of the phenotypic resistance to ADV at 12 and 24 months were 8.7% and 32.5%, respectively. The cumulative probabilities of the genotypic resistance to ADV at 12 and 24 months were 0% and 14.6%, respectively. Resistance to ADV was associated with a higher pretreatment HBV DNA (P=0.019), and non-IVR (P<0.001). The cumulative probabilities of the phenotypic and genotypic resistance to ADV at 24 months were 32.5% and 14.6%. The high pretreatment HBV DNA and non-IVR (HBV DNA >/= 4 log10 copies/mL after 6 months of therapy) were associated with ADV resistance.