Low HBV-DNA Levels Research Articles

485 PREVALENCE AND CLINCAL SIGNIFICANCE OF OCCULT HEPATITIS B INFECTION IN PATIENTS WITH CHRONIC HEPATITIS C INFECTION

stopping NA treatment. Nobody had HBsAg loss. Of the patients with undetectable HBcrAg, 39% had HBsAg level of <100 IU/ml. Of the patients with HBsAg level of <100 IU/ml, 63% had undetectable HBcrAg. Only 7.6% of all patients had undetectable HBV DNA, HBcrAg, and HBsAg level of <100 IU/ml after NA treatment. Patients with undetectable HBcrAg were older, and tended to be treated longer by NA, and had significantly lower HBV DNA level at baseline. All patients with undetectable HBcrAg were HBeAg negative and anti-HBe positive at baseline. Patients with HBsAg level of <100 IU/ml had no significant difference of background at baseline, however, HBcrAg level during NA treatment was significantly lower (3.1±0.3 vs. 4.3±1.0 log U/ml). Conclusions: Despite HBV DNA suppression, decline of HBcrAg and/or HBsAg after NA treatment was rare in Japanese patients with chronic genotype C HBV infection. HBcrAg and HBsAg provide a viral marker which is independent of HBV DNA, but not same way for monitoring NA treatment.

Hepatitis B virus genotypes, precore mutations, and basal core promoter mutations in HBV-infected Chinese patients with persistently normal alanine aminotransferase and low serum HBV-DNA levels

Hepatitis B virus (HBV) genotype and precore and basal core promoter (BCP) mutants in the patients with persistently normal alanine aminotransferase (ALT) and low serum HBV-DNA levels are unclear. The aim of this study was to determine HBV genotypes, precore and BCP mutations, and their association with chronic hepatitis and liver fibrosis in HBV-infected patients with persistently normal ALT, and low serum HBV-DNA levels in northeast China. Patients (n = 89) with normal ALT and serum HBV-DNA levels below 20000 IU/mL but detectable with real-time PCR were included in this study. HBV genotypes were determined by real-time PCR. The precore and BCP mutations were detected by sequencing. All the patients had biopsy results. Of the 89 patients, 11 (12.4%) were genotype B and 78 (87.6%) were genotype C. The most common mutations were G1896A (23.6%), G1764A (9.0%), and A1762T (6.7%). The prevalence of precore mutation was significantly higher in genotype B patients than in genotype C patients (54.5% vs. 19.2%, p < 0.01). There was no significant difference in the prevalence of BCP mutations between genotype B and genotype C (18.2% vs. 10.2%). Multivariate analysis showed that old age (> 40 years) and BCP mutations were independent predictors of liver necroinflammation and fibrosis. Thus, BCP mutations may be associated with liver necroinflammation and fibrosis in patients with persistently normal ALT and low serum HBV-DNA levels in northeast China.

Effect and Predictive Elements for 52 Weeks’ Telbivudine Treatment on Naïve HBeAg Positive Chronic Hepatitis B

: Background: Antiviral treatment with nucleoside analogs has been used for chronic hepatitis B (CHB). each kind of nucleoside analog has its own characteristics and suitability for patients. Telbivudine (LdT, brand name: Sebivo, Beijing novartis pharma Ltd) is the newest nucleoside analog, with strong and rapid viral suppression. However, its resistance rate is relatively high during long-term application, due to low genetic barriers to resistance. So, it is necessary to increase the effect and reduce resistance with effective management, according to baseline factors and early on-treatment responses. Objectives: To reveal possible predictive factors of the effect of telbivudine (LdT) treatment on naïve HBeAg-positive chronic hepatitis B (CHB) patients to optimize treatment. Patients and Methods: A total 71 naïve chronic hepatitis B (CHB) patients who met the inclusion criteria were enrolled. All patients were treated with LdT 600 mg Qd for at least 52 weeks. Multiple logistic regression analyses were done to investigate the predictive values of baseline factors and responses at Week 24. Results: The reduction in hepatitis virus B (HBV) DnA level was 6.44 ± 2.38 lg copies/mL at Week 52 compared with baseline. The complete virus response (CVR), biochemical response (BR), serological response (SR), and drug resistance (DR) were 61.99%, 77.46%, 35.21%, and 8.45% respectively. By multiple regression analysis, baseline alanine aminotransferase (ALT) levels significantly affected CVR (P = 0.024, oR = 1.008), and baseline ALT and baseline HBV DnA levels were independent compact factors of SR (P = 0.012, oR = 1.007; P = 0.001, oR = 0.423). The differences in CVR, SR, and DR in patients with ALT > 120 Iu/mL compared with patients with ALT ≤ 120 Iu/mL were statistically significant. The differences in SR in patients with HBV DnA > 107 copies/mL compared with patients with HBV DnA ≤ 107 copies/mL were statistically significant. Additionally, CVR, BR, and SR were differed significantly between patients with HBV DnA lower than 300 copies/mL at Week 24 and patients with HBV DnA higher than 300 copies/mL (P = 0.000, P = 0.0016, and P = 0.000, respectively). Conclusions: There were more responders among naïve HBeAg-positive chronic hepatitis B patients with lower HBV DnA levels (especially lower than 107 copies/mL) and higher ALT values (especially higher than 120 Iu/mL at baseline) to LdT treatment. Adjustments for treatment strategy should be considered if HBV DnA > 300 copies/mL at Week 24 is observed.

Hepatitis B virus genotypes, precore mutations, and basal core promoter mutations in HBV-infected Chinese patients with persistently normal alanine aminotransferase and low serum HBV-DNA levels

Hepatitis B virus (HBV) genotype and precore and basal core promoter (BCP) mutants in the patients with persistently normal alanine aminotransferase (ALT) and low serum HBV-DNA levels are unclear. The aim of this study was to determine HBV genotypes, precore and BCP mutations, and their association with chronic hepatitis and liver fibrosis in HBV-infected patients with persistently normal ALT, and low serum HBV-DNA levels in northeast China. Patients (n = 89) with normal ALT and serum HBV-DNA levels below 20000 IU/mL but detectable with real-time PCR were included in this study. HBV genotypes were determined by real-time PCR. The precore and BCP mutations were detected by sequencing. All the patients had biopsy results. Of the 89 patients, 11 (12.4%) were genotype B and 78 (87.6%) were genotype C. The most common mutations were G1896A (23.6%), G1764A (9.0%), and A1762T (6.7%). The prevalence of precore mutation was significantly higher in genotype B patients than in genotype C patients (54.5% vs. 19.2%, p < 0.01). There was no significant difference in the prevalence of BCP mutations between genotype B and genotype C (18.2% vs. 10.2%). Multivariate analysis showed that old age (> 40 years) and BCP mutations were independent predictors of liver necroinflammation and fibrosis. Thus, BCP mutations may be associated with liver necroinflammation and fibrosis in patients with persistently normal ALT and low serum HBV-DNA levels in northeast China.

Effect and Predictive Elements for 52 Weeks’ Telbivudine Treatment on Naïve HBeAg positive Chronic Hepatitis B

Antiviral treatment with nucleoside analogs has been used for chronic hepatitis B (CHB). Each kind of nucleoside analog has its own characteristics and suitability for patients. Telbivudine (LdT, brand name: Sebivo, Beijing Novartis Pharma Ltd) is the newest nucleoside analog, with strong and rapid viral suppression. However, its resistance rate is relatively high during long-term application, due to low genetic barriers to resistance. So, it is necessary to increase the effect and reduce resistance with effective management, according to baseline factors and early on-treatment responses. To reveal possible predictive factors of the effect of telbivudine (LdT) treatment on naïve HBeAg-positive chronic hepatitis B (CHB) patients to optimize treatment. A total 71 naïve chronic hepatitis B (CHB) patients who met the inclusion criteria were enrolled. All patients were treated with LdT 600 mg Qd for at least 52 weeks. Multiple logistic regression analyses were done to investigate the predictive values of baseline factors and responses at Week 24. The reduction in hepatitis virus B (HBV) DNA level was 6.44 ± 2.38 lg copies/mL at Week 52 compared with baseline. The complete virus response (CVR), biochemical response (BR), serological response (SR), and drug resistance (DR) were 61.99%, 77.46%, 35.21%, and 8.45% respectively. By multiple regression analysis, baseline alanine aminotransferase (ALT) levels significantly affected CVR (P = 0.024, OR = 1.008), and baseline ALT and baseline HBV DNA levels were independent compact factors of SR (P = 0.012, OR = 1.007; P = 0.001, OR = 0.423). The differences in CVR, SR, and DR in patients with ALT > 120 Iu/mL compared with patients with ALT ≤ 120 Iu/mL were statistically significant. The differences in SR in patients with HBV DNA > 107 copies/mL compared with patients with HBV DNA ≤ 107 copies/mL were statistically significant. Additionally, CVR, BR, and SR were differed significantly between patients with HBV DNA lower than 300 copies/mL at Week 24 and patients with HBV DNA higher than 300 copies/mL (P = 0.000, P = 0.0016, and P = 0.000, respectively). There were more responders among naïve HBeAg-positive chronic hepatitis B patients with lower HBV DNA levels (especially lower than 107 copies/mL) and higher ALT values (especially higher than 120 Iu/mL at baseline) to LdT treatment. Adjustments for treatment strategy should be considered if HBV DNA > 300 copies/mL at Week 24 is observed.

Factors Predicting the Effi cacy of Adefovir Dipivoxil on Treatment-Naïve Chronic Hepatitis B Patients at 48 Weeks

Background/AimsTo reveal possible factors predicting the effect of adefovir dipivoxil (ADV) treatment on chronic hepatitis B (CHB) and optimize the utilization of ADV.MethodsIn total, 168 treatment-naïve CHB patients were enrolled, including 117 hepatitis B e antigen (HBeAg)-positive patients and 51 HBeAg-negative patients who met the inclusion criteria. All patients were treated with ADV 10 mg per day for 48 weeks. Multiple logistic regression analyses were used to investigate baseline factors, and responses at weeks 12 and 24 were analyzed as predictive values.ResultsMultiple regression analyses showed that baseline HBeAg status and HBV DNA levels significantly affected the virological response (VR) (p<0.05), baseline ALT levels were an independent predictor of serological response (SR) (p<0.05) and the body mass index (BMI) may affect the biochemical response (BR) (p<0.05). There was a statistically significant difference in the VR and SR between patients with a primary nonresponse (PNR) at week 12 and those with a VR at week 12 (p<0.01). Additionally, the VR was significantly different between patients with HBV DNA lower than 103 copies/mL at week 24 and those with greater than 103 copies/mL (p<0.01).ConclusionsPatients with negative HBeAg, lower HBV DNA levels and higher ALT values at baseline are more suitable for ADV treatment, whereas patients with lower BMIs may be more amenable to ALT normalization. Adjustments for treatment strategy should be considered if PNR at week 12 or HBV DNA ≥103 copies/mL at week 24 is observed.

Occult hepatitis B infection and HBV replicative activity in patients with cryptogenic cause of hepatocellular carcinoma

We aimed to investigate the incidence of occult hepatitis B infection (OBI) in patients with "cryptogenic" hepatocellular carcinoma (HCC) and to study the HBV replicative activity in these patients. Tumorous and adjacent nontumorous liver tissues were obtained from 33 cryptogenic HCC patients and 28 HCC patients with identifiable causes (13 with chronic hepatitis B [CHB], six with chronic hepatitis C, and nine alcohol-related). OBI was identified by nested polymerase chain reaction (PCR). Intrahepatic HBV DNA, covalently closed circular DNA (cccDNA), and pregenomic RNA (pgRNA) were quantified by real-time PCR and reverse-transcription PCR (RT-PCR), respectively. OBI was identified in 24 (73%) cryptogenic HCC patients, one (17%) HCC patient with HCV, and five (56%) patients with alcohol-related HCC. In HCC patients with OBI, HBV DNA were detected in ≥2 HBV genomic regions more often in nontumorous tissues than in tumorous tissues (90% versus 57%, respectively; P = 0.007). Cryptogenic HCC patients with OBI had lower intrahepatic total HBV DNA levels than HCC patients with CHB (median: 0.010 versus 3.19 copies/cell, respectively; P < 0.0001). Only six (26%) cryptogenic HCC patients with OBI had detectable cccDNA (median: <0.0002 copies/cell), which was significantly lower than that of the CHB patients (median: 0.005 copies/cell; P < 0.0001). HBV pgRNA were detectable in 12 (52%) cryptogenic HCC patients with OBI (median: 0.0001 copies/cell), which was significantly lower than that of the CHB patients (median: 2.90 copies/cell; P < 0.001). 73% of patients with apparently unidentifiable causes for HCC were HBV-related. The detection rate was higher in nontumorous tissues than tumorous tissues. The low intrahepatic HBV DNA and pgRNA levels indicated that persistent viral replication and possibly HBV integration are the likely causes of HCC in OBI patients.

Entecavir Monotherapy Is Effective in Suppressing Hepatitis B Virus After Liver Transplantation

We investigated the efficacy of entecavir, a cyclopentyl guanosine nucleoside analogue, as monoprophylaxis in patients with chronic hepatitis B who received a liver transplant. We studied data from 80 consecutive patients who received a liver transplant (47 from living donors and 33 from deceased donors) for hepatitis B-related disease and entecavir monotherapy as prophylaxis. None of the patients received hepatitis B immunoglobulin. Indications for transplant included decompensation from cirrhosis (27.5%), acute-on-chronic hepatitis B (47.5%), and hepatocellular carcinoma (25%). The median follow-up time was 26 months (range, 5-40 months). Before transplant, 33 patients were not on antiviral therapy and 47 were on oral therapy (18 had received less than 3 months of treatment). At the time of transplant, the median log HBV DNA level was 3.5 copies/mL (range, 1.54-8.81); 21 patients (26%) had undetectable levels of HBV DNA. The cumulative rate of hepatitis B surface antigen (HBsAg) loss was 86% and 91% after 1 and 2 years, respectively. Ten patients had reappearance of HBsAg. Eighteen patients (22.5%) were HBsAg positive at the time of their last examination; 17 of these had undetectable levels of HBV DNA, and the remaining patient had a low level of HBV DNA (217 copies/mL). There was no evidence of mutations at sites that confer resistance to entecavir among patients who were HBsAg positive. Although only 26% of patients had complete viral suppression at the time of transplant, 91% lost HBsAg, with 98.8% achieving undetectable levels of HBV DNA. A hepatitis B immunoglobulin-free regimen of entecavir monotherapy is effective after liver transplantation for chronic hepatitis B.

HBV lamivudine resistance among hepatitis B and HIV coinfected patients starting lamivudine, stavudine and nevirapine in Kenya

Widespread use of lamivudine in antiretroviral therapy may lead to hepatitis B virus resistance in HIV-HBV coinfected patients from endemic settings where tenofovir is not readily available. We evaluated 389 Kenyan HIV-infected adults before and for 18 months after starting highly active antiretroviral therapy with stavudine, lamivudine and nevirapine. Twenty-seven (6.9%) were HBsAg positive and anti-HBs negative, 24 were HBeAg negative, and 18 had HBV DNA levels ≤ 10,000 IU/mL. Sustained HBV suppression to <100 IU/mL occurred in 89% of 19 evaluable patients. Resistance occurred in only two subjects, both with high baseline HBV DNA levels. Lamivudine resistance can emerge in the setting of incomplete HBV suppression but was infrequently observed among HIV-HBV coinfected patients with low baseline HBV DNA levels.

Surveillance and Treatment Protocols to Detect and Treat Hepatitis B Virus Reactivation in Hepatitis B Surface Antigen–Negative/Antibody to Hepatitis B Core Antigen–Positive Patients Receiving Chemotherapy for Onco-Hematologic Malignancies

TO THE EDITOR: We read with interest the article by Niitsu et al, and we compliment the authors for having focused their attention on the group of hepatitis B surface antigen–negative/antibody to hepatitis B core antigen–positive patients who are undergoing chemotherapy for onco-hematologic malignancies and who are at high risk for hepatitis B reactivation, especially if receiving rituximab-based protocols. In this setting, the risks of hepatitis B virus (HBV) reactivation and development of difficult-to-treat acute hepatitis characterized by high mortality rates need to be clarified, and appropriate screening and managing protocols should be developed. However, some specific questions regarding the article do arise. What is the cost of monthly dosing of HBV-DNA and the antibody to the hepatitis B surface antigen titer? Has the cost-effectiveness profile of this approach been addressed or compared with alternative strategies? What HBV-DNA levels were detected at reactivation? It would be interesting to provide this information, given that the decision to use a high-potency/high-genetic barrier antiviral such as entecavir to treat low-level HBV-DNA reactivation might be excessive. Actually, in patients with reactivation that is characterized by low levels of HBVDNA, lamivudine still presents an attractive treatment solution, given its relative availability, effectiveness, and low cost. The use of other, more potent antivirals such as entecavir could be considered for the management of patients with higher levels of HBV-DNA or acute hepatitis that develops as a result of HBV reactivation. In addition, the strategy of lamivudine prophylaxis in selected high-risk groups may present an additional option to be considered in the setting of immunosuppression during the treatment of onco-hematologic malignancies. Answers to these questions are crucial to define the applicability of the authors’ findings to everyday practice, especially in countries in which the availability of high-cost medications and surveillance protocols might hamper the feasibility of this approach. Definition of surveillance strategies for isolated patients with an antibody to the hepatitis B core antigen who are undergoing chemotherapy and are at risk for HBV reactivation, and how to manage the manifestations of reactivation, which range from isolated increases of HBV-DNA to severe acute hepatitis and liver failure, still remain debated issues.

P72 Low rates of testing for delta hepatitis amongst a large hepatitis B cohort

IntroductionDelta hepatitis is frequently neglected amongst hepatitis guidelines and publications. There are limited data on the prevalence of delta in the UK and this is likely to be a rapidly...

The prevalence of “anti‐HBc alone” and HBV DNA detection among anti‐HBc alone in Korea

The "anti-HBc alone" is a frequent serological finding in clinical laboratories, making it difficult to determine whether the HBV infection has resolved. The objectives of this study were to investigate the prevalence of anti-HBc alone and HBV DNA detection (occult HBV infection) among anti-HBc alone, and to describe the demographic and clinical characteristics of anti-HBc alone. A total of 17,677 sera referred from the Health Promotion Center (HPC group, 4,014 sera) as well as all the hospital clinical departments (Patient group, 13,663 sera) were tested for HBs Ag, anti-HBc, and anti-HBs. HBV DNA test using real-time PCR was performed on 230 anti-HBc alone. The prevalence of anti-HBc alone was 8.9%, significantly higher in the Patient group than in the HPC group. The prevalence of anti-HBc was higher in men than women and was increased with age. Very low levels of HBV DNA were found in only 4 (1.7%) out of 230 subjects with anti-HBc alone. They were patients with conditions unrelated to chronic liver disease. Considering the high prevalence of anti-HBc alone, the frequency of occult HBV infection among anti-HBc alone was unexpectedly low. In addition, HBV viral load was low in these patients. Further studies are required to determine the clinical significance and infectivity of anti-HBc alone, in conjunction with very low levels of HBV DNA and to standardize the detection methodology for both anti-HBc alone and HBV DNA.

A Personalized Approach to Optimize Hepatitis B Treatment in Treatment-naive Patients

In a treatment-naive patient with chronic hepatitis B, a personalized approach allows treatment efficacy to be optimized. Firstly, the selection of good candidates for therapy is crucial. Patients with chronic active hepatitis B--with relatively low levels of HBV DNA replication (<10(9) copies/ml) and relatively high alanine aminotransferase (ALT) levels--are good candidates for therapy. By contrast, patients with chronic hepatitis B in the immunotolerance phase, who have high levels of HBV DNA and persistently normal ALT levels, as well as inactive hepatitis B surface antigen (HBsAg) carriers with low HBV DNA and normal ALT levels do not have an indication for therapy as they are poor responders. Secondly, the characteristics of the patient (for example, gender, age, immune status, general health status and comorbidities), the characteristics of the liver disease (for example, presence of cirrhosis and liver function) and the characteristics of the virus (for example, genotype) are important when assessing the chance of success and when choosing the best therapeutic strategy (nucleoside/nucleotide analogue or interferon). Thirdly, during therapy, the antiviral effect--assessed by decrease in HBV DNA level--allows an individualized response-guided approach. In addition, quantification of HBsAg after 3-6 months of interferon therapy appears to be a good predictor of sustained virological response after treatment and HBsAg clearance. Continuing interferon therapy until week 48 is justified in patients with a significant decrease in HBsAg. Ongoing and future studies will provide useful information regarding prolonging interferon therapy beyond 48 weeks in some patients in order to increase efficacy, and also regarding the role of combination therapy with interferon and potent nucleoside/nucleotide analogues, such as entecavir or tenofovir disoproxil fumarate.

Prevalence and impact of occult hepatitis B infection in chronic hepatitis C patients treated with pegylated interferon and ribavirin

The prevalence of occult hepatitis B, defined by absence of HBsAg and HBV DNA, ranges widely in patients with hepatitis C. This may influence the treatment of hepatitis C and the severity of liver disease. Sensitive and specific real-time PCR techniques are available commercially and can detect more reliably low HBV DNA levels. The aim of this study was to determine the prevalence of occult hepatitis B virus infection using the COBAS Taqman assay (Roche Diagnostics, Meylan, France) in the serum and liver of HBsAg negative patients with chronic hepatitis C and to evaluate its clinical consequences on liver pathology and its impact on the response to treatment with peg-IFNalpha and Ribavirin. HBV DNA detection was assessed retrospectively on 140 sera and 113 liver biopsies of HCV positive/HBsAg negative patients before treatment. A 4.4% (5/113) prevalence of occult hepatitis B was recorded in liver samples and in none of the sera. Anti-HBc was not detected in one, three of whom were sustained virological responders to treatment, one was relapsed responder and one was non-responder. Furthermore, in this cohort composed of 12% anti-HBs negative/anti-HBc positive and 20% anti-HBs positive/anti-HBc positive patients, anti-HBc was not associated with pre-therapeutic viral load, ALT serum levels, and histological activity or fibrosis. Using a commercial real-time PCR assay, we observed a low prevalence of occult B hepatitis. This, just as anti-HBC status, had no clinical impact in a large cohort of hepatitis C patients. It therefore does not appear useful to screen for occult hepatitis B in these patients with this test before beginning HCV treatment.

Incidence of hepatocellular carcinoma in patients with chronic hepatitis B virus infection who have normal alanine aminotransferase values

The importance of alanine aminotransferase (ALT) levels in the progression of hepatitis B virus (HBV) infection remains a subject of debate. This study sought to identify independent risk factors involved in development of hepatocellular carcinoma (HCC), particularly in patients with chronic HBV infection who have normal ALT values. Data from 381 consecutive hepatitis B patients were analyzed with average ALT integration values < or = 40 IU/L and follow-up periods of > 3 years. Integration values were calculated from biochemical tests, and serological markers associated with the cumulative incidence of HCC were analyzed. HCC developed in 17 of the 381 patients (4.5%) during the follow-up period. Male sex (hazard ratio, 6.011 [95% confidence interval: 1.353-26.710], P = 0.018), high HBV-DNA levels (> or = 5.0 log copies/ml; 5.125 [1.880-13.973], P = 0.001), low platelet counts (< 15.0 x 10(4)/mm(3); 4.803 [1.690-13.647], P = 0.003), and low total cholesterol levels (< 130 mg/dl; 5.983 [1.558-22.979], P = 0.009) were significantly associated with greater incidence of HCC development. High HBV-DNA levels and low platelet counts are associated with the development of HCC in patients infected with hepatitis B who have normal ALT values. Therefore, maintenance of low HBV-DNA levels is important for the prevention of HCC in patients with low platelet counts, particularly in patients whose ALT values fall within the current normal range.

Expression profile of immune effector molecules in natural killer cells in patients with chronic hepatitis B

To investigate the expression profile of immune effector molecules in peripheral natural killer cells (NK) in patients with chronic hepatitis virus B. According to the infection status, patients were divided into four experiment groups: normal hepatic function and high HBV DNA level group, normal hepatic function and low HBV DNA level group, abnormal hepatic function and high HBV DNA level group and abnormal hepatic function and low HBV DNA level group. The expression of perforin (PF), granzyme B (Gr B), granulysin (GNLY), tumor necrosis factor alpha (TNFa) and interferon gamma (IFNr) in NK cells were detected by flow cytometer. Compared with control group (31.50%+/-27.64%), the expression of GNLY was significantly increased in normal hepatic function and high HBV DNA level group (59.74%+/-30.82%) and normal hepatic function and low HBV DNA level group (61.89%+/-33.30%); the expression of IFNr in normal hepatic function and high HBV DNA level group (39.89%+/-21.30%) and abnormal hepatic function and high HBV DNA level group (37.54%+/-18.79%) was lower than that in normal control group (57.38%+/-23.69%); the expression of PF, GrB, GNLY in abnormal hepatic function and high HBV DNA level group (35.47%+/-29.64%, 66.55%+/-22.92%, 42.03%+/-33.17%) was lower than that in normal hepatic function and high HBV DNA level group (56.98%+/-38.34%, 81.53%+/-19.58%, 59.74%+/-30.82%) and normal hepatic function and low HBV DNA level groups (62.95%+/-31.98%, 84.51%+/-14.57%, 61.89%+/-33.3%); there were positive correlations between ef PF, Gr B, GNLY, TNFa, and IFNr. The expression of IFNr in NK cells from patients with high HBV DNA replication level is lower than that in normal control group; the expression of PF, Gr B and GNLY in NK cells from patients with normal hepatic function is higher than that in NK cells from patients with abnormal hepatic function.

Efficacy and predictors of the virologic response to entecavir therapy in nucleoside-naïve patients with chronic hepatitis B

The aim of this study was to elucidate the antiviral efficacy and the predictors of entecavir treatment in nucleoside-naive chronic hepatitis B patients. A total of 160 patients treated with entecavir (0.5 mg daily) for at least 24 weeks were consecutively enrolled. The virologic response (HBV DNA<2,000 copies/mL), biochemical response (ALT< or = upper limit of normal), and virologic breakthrough (>1 log(10) copies/mL increase in HBV DNA level above nadir on two consecutive occasions) were retrospectively analyzed. The mean follow-up duration was 58.8 weeks, and 85 patients (53.1%) showed HBeAg positivity. The median pretreatment levels of serum ALT and HBV DNA were 99 IU/L and 7.6 log(10) copies/mL, respectively. The cumulative rates at 12, 24, 48, and 72 weeks were 37.5%, 68.1%, 87.4%, and 95.8%, respectively, for the virologic response; 40.0%, 66.2%, 84.5%, and 92.7% for the biochemical response; 10.6%, 18.8%, 27.0%, and 34.5% for HBeAg loss; and 3.5%, 7.1%, 9.0%, and 13.2% for HBeAg seroconversion. There was no case of virologic breakthrough. An absence of HBeAg and a low serum HBV DNA level (<8 log(10) copies/mL) at baseline were significant predictors of the virologic response in a multivariate analysis (P<0.01). Entecavir therapy showed excellent efficacy in nucleoside-naive chronic hepatitis B patients. The predictors of a virologic response were an absence of HBeAg and a low baseline HBV DNA level.

Emerging infections in Asia and its possible global effects.

Emerging infections in Asia and its possible global effects.

Frequencies and characterization of HBV-specific cytotoxic T lymphocytes in self-limited and chronic hepatitis B viral infection in China

Hepatitis B virus (HBV)-specific cytotoxic T lymphocytes (CTLs) are believed to play a major role in viral clearance and disease pathogenesis during HBV infection. To clarify the differences in host immune responses between self-limited and chronic HBV infections, we constructed three HLA-A*0201/HBV tetramers with immunodominant epitopes of core18-27, polymerase 575-583 and envelope 335-343, and analyzed the HBV-specific CTLs in peripheral blood mononuclear cells (PBMCs) from patients infected with HBV. The frequencies and expansion ability of HBV-specific CD8(+) T cells in most self-limited HBV infected individuals were higher than those in chronic HBV-infected patients. HBV-specific CD8(+) T cells could be induced by in vitro peptide stimulation from chronic patients with a low level of serum HBV-DNA but not from those with a high level of serum HBV-DNA. In chronic infection, no significant correlation was found either between the frequencies of HBV-specific CD8(+) T cells and the viral load, or between the frequencies and the levels of alanine transaminase. Our results suggested that the frequencies of HBV-specific CTLs are not the main determinant of immune-mediated protection in chronic HBV infection and immunotherapeutic approaches should be aimed at not only boosting a HBV-specific CD8(+) T response but also improving its function.

Factors That Predict Response of Patients With Hepatitis B e Antigen–Positive Chronic Hepatitis B to Peginterferon-Alfa

Therapy with pegylated interferon (PEG-IFN)-alfa results in sustained response in a minority of patients with chronic hepatitis B virus (HBV) infection and has considerable side effects. We analyzed data from the 2 largest global trials of hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B to determine which are most likely to respond to PEG-IFN-alfa therapy. The study included 542 patients treated with PEG-IFN-alfa-2a (180 microg/wk, 48 wk) and 266 patients treated with PEG-IFN-alfa-2b (100 microg/wk, 52 wk). Eighty-seven patients were excluded, leaving 721 patients for analysis. A sustained response was defined as HBeAg loss and HBV-DNA level less than 2.0 x 10(3) IU/mL 6 months after treatment. Logistic regression analysis was used to identify predictors of sustained response and a multivariable model was constructed. HBV genotype, high levels of alanine aminotransferase (ALT; >or=2 x upper limit of normal), low levels of HBV DNA (<2.0 x 10(8) IU/mL), female sex, older age, and absence of previous IFN therapy predicted a sustained response. Genotype A patients with high ALT and/or low HBV-DNA levels had a high predicted probability (>30%) of a sustained response. The strongest predictors of response were a high level of ALT in genotype B patients and a low level of HBV DNA in genotype C patients. Genotype D patients had a low chance of sustained response, irrespective of ALT or HBV-DNA levels. The best candidates for a sustained response to PEG-IFN-alfa are genotype A patients with high levels of ALT or low levels of HBV DNA, and genotypes B and C patients who have both high levels of ALT and low HBV DNA. Genotype D patients have a low chance of sustained response.