Undetectable Hepatitis B Virus Viral Load Research Articles

High Prevalence of Hepatitis B Virus Drug Resistance Mutations to Lamivudine among People with HIV/HBV Coinfection in Rural and Peri-Urban Communities in Botswana.

(1) Background: We aimed to determine the prevalence of hepatitis B virus (HBV) resistance-associated mutations (RAMs) in people with HBV and human immunodeficiency virus (HBV/HIV) in Botswana. (2) Methods: We sequenced HBV deoxyribonucleic acid (DNA) from participants with HBV/HIV from the Botswana Combination Prevention Project study (2013-2018) using the Oxford Nanopore GridION platform. Consensus sequences were analyzed for genotypic and mutational profiles. (3) Results: Overall, 98 HBV sequences had evaluable reverse transcriptase region coverage. The median participant age was 43 years (IQR: 37, 49) and 66/98 (67.4%) were female. Most participants, i.e., 86/98 (87.8%) had suppressed HIV viral load (VL). HBV RAMs were identified in 61/98 (62.2%) participants. Most RAMs were in positions 204 (60.3%), 180 (50.5%), and 173 (33.3%), mostly associated with lamivudine resistance. The triple mutations rtM204V/L180M/V173L were the most predominant (17/61 [27.9%]). Most participants (96.7%) with RAMs were on antiretroviral therapy for a median duration of 7.5 years (IQR: 4.8, 10.5). Approximately 27.9% (17/61) of participants with RAMs had undetectable HBV VL, 50.8% (31/61) had VL < 2000 IU/mL, and 13/61 (21.3%) had VL ≥ 2000 IU/mL. (4) Conclusions: The high prevalence of lamivudine RAMs discourages the use of ART regimens with 3TC as the only HBV-active drug in people with HIV/HBV.

Entecavir add-on Peg-interferon therapy plays a positive role in reversing hepatic fibrosis in treatment-naïve chronic hepatitis B patients: a prospective and randomized controlled trial.

BackgroundThe efficacy of entecavir (ETV) add-on peg-interferon therapy compared with ETV monotherapy in treatment-naïve hepatitis B virus (HBV) patients remains controversial. We investigated whether adding peg-interferon to ongoing ETV treatment leads to a better curative effect or not.MethodsAll patients have been recruited between August 2013 and January 2015 from the Shanghai Public Health Clinical Center and Zhongshan Hospital (China). Eligible HBV patients (n = 144) were randomly divided (1:1) to receive either ETV monotherapy (n = 70) or peg-interferon add-on therapy from week 26 to 52 (n = 74). Patients were followed-up for at least 2 years. Indexes including hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) seroconversion rate, sustained virologic response, transient elastography value, and histological scores were evaluated every 3 months until the end of the study. The rate of patients with HBsAg loss was defined as the primary endpoint criteria.ResultsAt week 26, no patient achieved HBsAg seroconversion in either group. At week 52, one patient in the monotherapy group was HBsAg-negative but there was none in the combination therapy group. The monotherapy group showed significantly better liver function recovery results than the combination therapy group. At week 78, one patient in the combination group had HBsAg seroconverted. At week 104, only three patients in the combination therapy group were HBsAg-negative compared with one patient in monotherapy. The mean alanine aminotransferase and aspartate aminotransferase levels and transient elastography values decreased significantly compared with baseline. Both groups showed a favorable decrease in alpha-fetoprotein (monotherapy: 4.5 [2.8, 7.1] vs. 2.2 [1.8, 3.1] ng/mL, P < 0.001; combination therapy: 5.7 [3.0, 18.8] vs. 3.2 [2.0, 4.3] ng/mL, P < 0.001) and an improved result of liver biopsy examination scores. The combination group showed a better improvement in histology compared with the monotherapy group (mean transient elastography value 6.6 [4.9, 9.8] vs. 7.8 [5.4, 11.1] kPa, P = 0.028). But there was no significant difference in HBsAg conversion rate (1.8% [1/56] vs. 4.1% [3/73], P = 0.809) and HBeAg conversion rate (12.5% [7/56] vs. 11.0% [8/73], P = 0.787), as well as HBV-DNA, sustained virologic response (93.2% vs. 98.5%, P = 0.150) between the two groups.ConclusionsBoth therapies supported liver function recovery and histology improvement. Combination therapy did not show better anti-viral efficacy in HBsAg or HBeAg seroconversion compared with monotherapy. However, combination therapy played a more positive role in reversing hepatic fibrosis compared with monotherapy.Trial registrationClinicalTrials.gov: NCT02849132; https://clinicaltrials.gov/ct2/show/NCT02849132

The reasons to include the serology of human T-lymphotropic virus types 1 and 2 (HTLV-1 and HTLV-2) in the clinical follow-up of patients with viral hepatitis B and C in Brazil.

BackgroundThe WHO established targets for 2030 to globally reduce new viral hepatitis B and C infections by 90% and deaths by 65% and recommends searching for coinfections that increase the progression of chronic liver infections towards cirrhosis and hepatocellular carcinoma.Aims and methodologyThis study aimed to add information concerning the influence of human T-lymphotropic virus type 1 (HTLV-1) and type 2 (HTLV-2) infections in hepatitis B and C, since in Brazil, these human retroviruses are endemic but neglected. Serum samples from 1,910 patients with hepatitis B and 1,315 with hepatitis C from São Paulo, southeast Brazil, that were previously tested and grouped for HIV and HTLV-1/-2 coinfections were analyzed for hepatitis B virus (HBV) and hepatitis C virus (HCV) loads measurements and subsequent clearance using data from laboratory records.Key resultsBriefly, the lowest HBV viral load (VL) was detected in HBV/HTLV-2 coinfected patients, regardless of whether they were infected with HIV (all comparisons p<0.05). In contrast, higher HCV VL was detected in HCV/HIV, HCV/HIV/HTLV-1/-2 coinfected patients (all p<0.05), and the lowest HCV VL was detected in HCV/HTLV-2 coinfected patients. Curiously, 61.1% of the patients with HBV/HTLV-2 coinfection had an undetectable HBV VL at the beginning of the study versus 21.4% in the patients with HBV/HTLV-1 coinfection. Although the percentages of undetectable HCV loads in HCV/HTLV-1 and HCV/HTLV-2 coinfected patients were quite similar, during follow-up, more HCV clearance was detected in patients with HCV/HTLV-2 coinfection [OR 2.65; 95% IC (1.17–5.99)].Major conclusionsHTLV-2 positively impacts HBV and HCV viral loads and HCV clearance, while HIV and/or HTLV-1 negatively impacts HCV viral load. Thus, the search for HTLV-1/-2 in viral hepatitis B and C infected patients has virological prognostic value, which is a strong reason to suggest including HTLV serology in the follow-up of patients.

Effect of Treatment of Hepatitis C by Directly Acting Antivirals (DAA) on Chronic Hepatitis C, B Coinfected Patients

Background: Persons with hepatitis C virus (HCV) who are co-infected with hepatitis B virus (HBV) may be at risk for reactivation of HBV infection during or following HCV treatment. HBV and HCV share similar modes of transmission, and co-infection with the two viruses does occur. Objectives: This study aimed to evaluate the effect of HCV anti-viral treatment (DAAS) on HBV in HCV and HBV Coinfected patients. Patients and methods: The study was performed in Internal Medicine Department (Outpatient Clinic and the Inpatient Ward), Mahalla Hepatology Teaching Hospital, Gharbia, Egypt during the period from August 2016 to November 2017 on 20 HCV and HBV co-infected patients ranged from 18-70 years old. Results: The age of patients ranging from 26 to 65 years old (median 44). Male represent 55% and female represent 45% which showed male predominance. Patients were treated by different types by Hcv antiviral treatment (DAAS) like (SOF+DAC), (SOF+SIM), (SOF+DAC+RBV). At baseline, 12 patients had detectable HBV viral load, 5 Patients had positive (HBsAg) and undetectable HBV viral load and 3 patients had negative (HBsAg) and undetectable HBV viral load. Total number of HBV reactivated cases were 12 patients, 3 of them reactivated by increasing HBV DNA, and 5 of them reactivated by both increasing HBVDNA and ALT flare. Conclusion: HBV reactivation is a severe, life-threatening consequence of chemotherapy and immunotherapy in patients with chronic hepatitis B infection. Reactivation may be associated with DAA therapy in patients with HCV/HBV co-infection. HBV reactivation can be prevented through the use of pretreatment screening and anti-HBV prophylactic treatment.

Effect of Treatment of Hepatitis C by Directly Acting Antivirals (DAA) on Chronic Hepatitis C, B Coinfected Patients

Background: Persons with hepatitis C virus (HCV) who are co-infected with hepatitis B virus (HBV) may be at risk for reactivation of HBV infection during or following HCV treatment. HBV and HCV share similar modes of transmission, and co-infection with the two viruses does occur. Objectives: This study aimed to evaluate the effect of HCV anti-viral treatment (DAAS) on HBV in HCV and HBV Coinfected patients. Patients and methods: The study was performed in Internal Medicine Department (Outpatient Clinic and the Inpatient Ward), Mahalla Hepatology Teaching Hospital, Gharbia, Egypt during the period from August 2016 to November 2017 on 20 HCV and HBV co-infected patients ranged from 18-70 years old. Results: The age of patients ranging from 26 to 65 years old (median 44). Male represent 55% and female represent 45% which showed male predominance. Patients were treated by different types by Hcv antiviral treatment (DAAS) like (SOF+DAC), (SOF+SIM), (SOF+DAC+RBV). At baseline, 12 patients had detectable HBV viral load, 5 Patients had positive (HBsAg) and undetectable HBV viral load and 3 patients had negative (HBsAg) and undetectable HBV viral load. Total number of HBV reactivated cases were 12 patients, 3 of them reactivated by increasing HBV DNA, and 5 of them reactivated by both increasing HBVDNA and ALT flare. Conclusion: HBV reactivation is a severe, life-threatening consequence of chemotherapy and immunotherapy in patients with chronic hepatitis B infection. Reactivation may be associated with DAA therapy in patients with HCV/HBV co-infection. HBV reactivation can be prevented through the use of pretreatment screening and anti-HBV prophylactic treatment.

Hepatitis B virus coinfection is associated with high early mortality in HIV-infected Tanzanians on antiretroviral therapy

There is limited data on the effect of antiviral therapies on clinical outcomes in HIV and hepatitis B virus (HBV)-infected individuals in sub-Saharan Africa. Single center, prospective longitudinal cohort study at Management and Development for Health supported HIV Care and Treatment clinics in Dar es Salaam, Tanzania. Between April 2014 and December 2015, HIV-infected, HBV-infected and HIV/HBV-coinfected, treatment naïve, Tanzanian adults more than 18 years of age were eligible for enrollment and followed for 10-18 months after initiating antivirals. All HIV-infected and HIV/HBV-coinfected participants received tenofovir, lamivudine and efavirenz; HBV-infected participants received lamivudine. Multivariate regression models were constructed to identify factors associated with mortality in HIV-infected and HIV/HBV-coinfected participants. A total of 265 HIV-infected, 165 HBV-infected and 64 HIV/HBV-coinfected participants were analyzed. At baseline, HBV-infected participants were younger and had a higher BMI than HIV-infected and HIV/HBV-coinfected participants. After a median of 371 (interquartile range 50) days on treatment, there were 40 deaths. Mortality was significantly higher among HIV/HBV-coinfected participants compared with HIV and HBV-infected participants [HIV/HBV-coinfected 12 of 64 (19%) vs. HIV-infected 26 of 265 (10%) and HBV-infected two of 265 (1%), P < 0.01]. High baseline HIV RNA and low hemoglobin levels, but not HBV coinfection were independently associated with early mortality in multivariate analyses of HIV-infected participants. High rates of early mortality were observed after treatment initiation in HIV/HBV-coinfected individuals compared with participants with HIV or HBV alone, despite robust aspartate aminotransferase to platelet ratio index declines and high rates of virologic suppression. HIV rather than HBV-related factors are more important contributors to mortality in these individuals.

Field performance of the Determine HBsAg point-of-care test for diagnosis of hepatitis B virus co-infection among HIV patients in Zambia

BackgroundWe evaluated the field performance of a rapid point-of-care (POC) test for hepatitis B surface antigen (HBsAg) that could support decentralization and scale-up of hepatitis B virus (HBV) diagnosis in Africa. ObjectiveTo determine the field performance of the Determine HBsAg POC test for diagnosis of HBV co-infection among HIV patients in Zambia. Study designBetween 2013–2014, we screened HIV-infected adults for HBsAg at two urban clinics in Zambia. A subset were tested with the POC Determine HBsAg (Alere, USA) by finger prick in the clinic and HBsAg serology (Access2Analyzer, Beckman Coulter) at a reference laboratory. If either test was reactive, we determined HBV viral load (VL) and genotype. We described patient demographic and clinical characteristics (including liver fibrosis) and assessed the sensitivity, specificity, positive and negative predictive values (PPV and NPV) of the Determine test. In secondary analyses, we assessed sensitivity among patients with replicating HBV (i.e., VL>20 IU/ml) and with high HBV VL (i.e.,>20,000IU/ml). ResultsAmong 412 participants with both HBsAg tests, median age was 34 years, 51% were women, and median CD4 was 208 cells/mm3. By serology, 66 (16%) were HBsAg-positive. Overall Determine had 87.9% sensitivity, 99.7% specificity, 98.3% PPV, and 97.7% NPV. Six of 8 patients with false negative results had undetectable HBV VL and no evidence of significant liver fibrosis. Test sensitivity was 95.9% among the 51 with replicating HBV and 100% among the 28 with high HBV VL. ConclusionsDetermine HBsAg is a cheaper alternative HBV testing option compared to the gold standard ELISA and has high specificity and good sensitivity in the field among HIV-infected individuals.

Hepatitis B Virus Reactivation Associated With Direct-Acting Antiviral Therapy for Chronic Hepatitis C Virus: A Review of Cases Reported to the U.S. Food and Drug Administration Adverse Event Reporting System.

Direct-acting antiviral agents (DAAs) are used increasingly to treat hepatitis C virus (HCV) infection. Reports were published recently on hepatitis B virus (HBV) reactivation (HBV-R) in patients with HBV-HCV co-infection. Hepatitis B virus reactivation, defined as an abrupt increase in HBV replication in patients with inactive or resolved HBV infection, may result in clinically significant hepatitis. To assess whether HBV-R is a safety concern in patients receiving HCV DAAs. Descriptive case series. U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). 29 patients with HBV-R receiving HCV DAAs. Clinical and laboratory data. The FDA identified 29 unique reports of HBV-R in patients receiving DAAs from 22 November 2013 to 15 October 2016. Two cases resulted in death and 1 case in liver transplantation. Patients in whom HBV-R developed were heterogeneous regarding HCV genotype, DAAs received, and baseline HBV characteristics. At baseline, 9 patients had a detectable HBV viral load, 7 had positive results on hepatitis B surface antigen (HBsAg) testing and had an undetectable HBV viral load, and 3 had negative results on HBsAg testing and had an undetectable HBV viral load. For the remaining 10 patients, data points were not reported or the data were uninterpretable. Despite provider knowledge of baseline HBV, HBV-R diagnosis and treatment were delayed in 7 cases and possibly 7 others. The quality of information varied among reports. Because reporting is voluntary, HBV-R associated with DAAs likely is underreported. Hepatitis B virus reactivation is a newly identified safety concern in patients with HBV-HCV co-infection treated with DAAs. Patients with a history of HBV require clinical monitoring while receiving DAA therapy. Studies would help determine the risk factors for HBV-R, define monitoring frequency, and identify patients who may benefit from HBV prophylaxis and treatment. DAAs remain a safe and highly effective treatment for the management of HCV infection. None.

FIELD PERFORMANCE OF POINT-OF-CARE TO DETERMINE HBSAG TEST FOR DIAGNOSIS OF ACTIVE HEPATITIS B VIRUS INFECTION IN ZAMBIA

BackgroundIn Zambia, we evaluated the field performance of a rapid point-of-care test for hepatitis B surface antigen (HBsAg) which could support decentralisation and scale-up of care and treatment of chronic...

Assessment of Adherence to Prescribed Therapy in Patients with Chronic Hepatitis B.

IntroductionEvidence shows that treatment for hepatitis B virus (HBV) can suppress viral load. Among the factors directly linked to therapeutic success is adherence to the treatment. Several instruments to assess adherence are available, but they are not validated for use in chronic hepatitis B. The purpose of this paper was to adapt and validate the “Assessment of Adherence to Antiretroviral Therapy Questionnaire—HIV” (CEAT-VIH) for patients with chronic hepatitis B (referred to herein as CEAT-HBV).MethodsThe validity of the adapted questionnaire evidence was established through concurrent, criterion, and construct validities.ResultsWe found negative and significant correlation between the domain “degree of compliance to antiviral therapy” assessed by CEAT-HBV and the Morisky test (r = −0.62, P < 0.001) and between the domain “barriers to adherence” and HBV viral load (r = −0.42, P < 0.001). In terms of the construct’s discriminative capacity, scores greater than or equal to 80 detected antiviral therapy success, which are necessary for the prediction of an undetectable HBV viral load. Thus, a cutoff value of 80.5 was set with a value of 81% for sensitivity and 67% for specificity.ConclusionThe CEAT-HBV identified 43% (n = 79) non-adherent patients and was shown to be a useful tool in clinical practice.Electronic supplementary materialThe online version of this article (doi:10.1007/s40121-015-0101-y) contains supplementary material, which is available to authorized users.

Randomized Controlled Trial of Entecavir Prophylaxis for Rituximab-Associated Hepatitis B Virus Reactivation in Patients With Lymphoma and Resolved Hepatitis B

The role of antiviral prophylaxis in preventing hepatitis B virus (HBV) reactivation before rituximab-based chemotherapy in patients with lymphoma and resolved hepatitis B is unclear. Eighty patients with CD20(+) lymphoma and resolved hepatitis B were randomly assigned to receive either prophylactic entecavir (ETV) before chemotherapy to 3 months after completing chemotherapy (ETV prophylactic group, n = 41) or to receive therapeutic ETV at the time of HBV reactivation and hepatitis B surface antigen (HBsAg) reverse seroconversion since chemotherapy (control group, n = 39). Fifty-eight patients (72.5%) were positive for hepatitis B surface antibody, and HBV DNA was undetectable in 50 patients (62.5%). During a mean 18-month follow-up period, one patient (2.4%) in the ETV prophylactic group and seven patients (17.9%) in the control group developed HBV reactivation (P = .027). The cumulative HBV reactivation rates at months 6, 12, and 18 after chemotherapy were 8%, 11.2%, and 25.9%, respectively, in the control group, and 0%, 0%, and 4.3% in the ETV prophylactic group (P = .019). Four patients (50%) in the control group had HBsAg reverse seroconversion after HBV reactivation. The cumulative HBsAg reverse seroconversion rates at months 6, 12, and 18 since chemotherapy were 0%, 6.4%, and 16.3% in the control group, respectively, which were significantly higher than those in the ETV prophylactic group (P = .032). Patients with detectable or undetectable viral load could develop HBV reactivation and HBsAg reverse seroconversion. Undetectable HBV viral load before chemotherapy did not confer reactivation-free status. Antiviral prophylaxis can potentially prevent rituximab-associated HBV reactivation in patients with lymphoma and resolved hepatitis B.

Hepatitis B and C

Hepatitis B and C