Hepatitis B Virus Co-infected Patients Research Articles

Transplantation of hepatitis D virus patients: Lifelong hepatitis B immunoglobulins?

The introduction of Hepatitis B Immunoglobulins (HBIg) prophylaxis at and after liver transplantation (LT) facilitated excellent long-term survival of transplant patients with chronic hepatitis B virus (HBV) infection. Several studies suggested that only short-term (i.e. 4-8 weeks) HBIg prophylaxis after LT followed by the long-term administration of HBV polymerase inhibitors prevents HBV recurrence. In hepatitis D virus (HDV)/HBV co-infected patients, the need for long-term HBIg prophylaxis on top of HBV polymerase inhibitors is unknown. HDV requires HBV surface antigen (HBsAg) for uptake into hepatocytes to subsequently establish HDV replication. Data on HDV recurrence and its impact on outcomes after LT are limited. In this review, we evaluated the available data on post-LT recurrence of HBV and/or HDV. Overall, HBIg prophylaxis was effective, but 10-13% of patients became HBsAg positive after LT. Only a single study from Turkey reported HDV recurrence, which was not observed in other LT centres. Since all studies administered continuous HBIg prophylaxis, the post-LT recurrence rates without HBIg prophylaxis remain unknown. In a German study, the clinical course and histopathological aspects of liver injury (inflammation, fibrosis and steatosis) were similar in post-LT patients on continuous HBIg and those who stopped HBIg after a median of 72 months. Discontinuation of HBIg in stable patients after LT for HBV/HDV co-infection did not lead to impaired overall survival or a higher recurrence rate in this long-term follow-up. In summary, discontinuation of HBIg after liver transplantation for HBV/HDV liver disease seems safe, but randomized controlled studies are needed before it can be generally recommended.

Hepatitis B Virus Genotypes and Antiviral Resistance Mutations in Romanian HIV-HBV Co-Infected Patients.

Background and Objectives: Romania has one of the highest prevalence of hepatitis B virus (HBV) infection in human immunodeficiency virus (HIV) patients, mostly in those parenterally infected during childhood; nevertheless, there are scarce data on the virological profile of co-infection. The objective of this study was to assess the prevalence of HBV genotypes and antiviral resistance-associated mutations (RAMs) in these co-infected patients, in order to monitor the viral factors associated with the evolution of liver disease. Materials and Methods: HBV genotypes and RAMs were detected using nested PCR and line probe assays (INNO-LiPA HBV genotyping assay, and INNO-LiPA HBV DR v2, Innogenetics). Results: Out of 117 co-infected patients, 73.5% had detectable HBV-DNA, but only 38.5% presented an HBV viral load >1000 IU/mL. HBV genotype A was present in 66.7% of the cases and was dominant in patients parenterally infected during early childhood, who experienced multiple treatment regimens, with a mean therapy length of 15.25 years, and present numerous mutations associated with lamivudine (LAM) resistance, but very rarely active liver disease. HBV genotype D was detected in 33.3% of the cases, mostly in recently diagnosed injecting drug users who are treatment naïve, but, nevertheless, present RAMs in 63.5% of the cases, suggesting transmitted drug resistance, and display more frequently advanced liver fibrosis (36.1% vs. 12.3%; p = 0.033). The most frequently encountered RAMs are M204V/I: 48.8%, L180M: 33.3%, L80V: 28.8%, and V173L: 42.2%. There are no significant differences in the distribution of RAMs in patients infected with different HBV genotypes, except for the L80V and N236T mutations, which were more frequently found in HBV genotype A infections (p = 0.032 and p = 0.004, respectively). Conclusions: HBV genotypes A and D are the only genotypes present in HIV–HBV co-infected patients from Romania, with different distributions according to the infection route, and are frequently associated with multiple RAMs, conferring extensive resistance to LAM.

Clinical and demographic predictors of antiretroviral efficacy in HIV-HBV co-infected patients.

The clinical and demographic characteristics that predict antiretroviral efficacy among patients co-infected with HIV and hepatitis B virus (HBV) remain poorly defined. We evaluated HIV virological suppression and rebound in a cohort of HIV-HBV co-infected patients initiated on antiretroviral therapy. A retrospective cohort analysis was performed with Canadian Observation Cohort Collaboration data. Cox proportional hazards models were used to determine the factors associated with time to virological suppression and time to virological rebound. HBV status was available for 2,419 participants. A total of 8% were HBV co-infected, of whom 95% achieved virological suppression. After virological suppression, 29% of HIV-HBV co-infected participants experienced HIV virological rebound. HBV co-infection itself did not predict virological suppression or rebound risk. The rate of virological suppression was lower among patients with a history of injection drug use or baseline CD4 cell counts of <199 cells per cubic millimetre. Low baseline HIV RNA and men-who-have-sex-with-men status were significantly associated with a higher rate of virological suppression. Injection drug use and non-White race predicted viral rebound. HBV co-infected HIV patients achieve similar antiretroviral outcomes as those living with HIV mono-infection. Equitable treatment outcomes may be approached by targeting resources to key subpopulations living with HIV-HBV co-infection.

Clinical characteristics of COVID-19 patients with hepatitis B virus infection - a retrospective study.

The outbreak of coronavirus disease 2019 (COVID-19) has been declared a pandemic. Although COVID-19 is caused by infection in the respiratory tract, extrapulmonary manifestations including dysregulation of the immune system and hepatic injury have been observed. Given the high prevalence of hepatitis B virus (HBV) infection in China, we sought to study the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and HBV coinfection in patients. Blood samples of 50 SARS-CoV-2 and HBV coinfected patients, 56 SARS-CoV-2 mono-infected patients, 57 HBeAg-negative chronic HBV patient controls and 57 healthy controls admitted to Renmin Hospital of Wuhan University were collected in this study. Complete blood count and serum biochemistry panels including markers indicative of liver functions were performed. Cytokines including IFN-γ, TNF-α, IL-2, IL-4, IL-6 and IL-10 were evaluated. T cell, B cell and NK cell counts were measured using flow cytometry. SARS-CoV-2 and HBV coinfection did not significantly affect the outcome of the COVID-19. However, at the onset of COVID-19, SARS-CoV-2 and HBV coinfected patients showed more severe monocytopenia and thrombocytopenia as well as more disturbed hepatic function in albumin production and lipid metabolism. Most of the disarrangement could be reversed after recovery from COVID-19. While chronic HBV infection did not predispose COVID-19 patients to more severe outcomes, our data suggest SARS-CoV-2 and HBV coinfection poses a higher extent of dysregulation of host functions at the onset of COVID-19. Thus, caution needs to be taken with the management of SARS-CoV-2 and HBV coinfected patients.

SARS-CoV-2 May Not Aggravate Liver Injury in Patients with Hepatitis B Virus Infection

COVID-19 has become a global pandemic and garnered international attention. Although the clinical features of COVID-19 related liver injury have been investigated, there have been no reports and studies on the clinical characteristics of COVID-19 patients co-infected with Hepatitis B Virus (HBV). This study was aimed to evaluate whether SARS-CoV-2/HBV co-infection could influence liver function and the disease outcome. All 326 confirmed COVID-19 cases in Shanghai Public Health Clinical Center (The COVID-19 designated hospital in Shanghai, China) from January 20, 2020 to February 24, 2020 were enrolled and followed up until February 29 in this study. The clinical, laboratory data and the length of stay were collected and analyzed retrospectively. 20 patients with HBV co-infection (6.1%) and 306 patients (93.9%) without HBV infection showed no differences in the level of liver function parameters. However, compared with HBsAg- patients [145.4 mg/L (103.9-179.2)], HBsAg+ patients had a lower level of prealbumin [(102.3 mg/L (76.22-160.2), P=.0367]. There were also no significant differences for the discharge rate and the length of stay between two groups. Our study is the first to elaborate on the clinical characteristics of SARS-CoV-2/HBV co-infection patients and no evidence shows SARS-CoV-2/HBV co-infection could aggravate liver injury or extend hospitalization time. Funding Statement: This study was funded by the first-class discipline construction project of Fudan university (ISF162005),Shanghai Science and Technology Development Fund (No.17411969500), National Science and Technology Major Project (2017ZX10203202-003-007) and Shanghai Public Health Clinical Center Fund (2020YJKY01, XKJS-2019HBV-06, KY-GW-2019-32) joined in hepatitis prevention and control procedures. Declaration of Interests: All authors declare that they have no competing interests. Ethics Approval Statement: This study was approved by the Ethics Committee of the Shanghai Public Health Clinical Center (2019-S047-02, Review date: Jan 13, 2020) and was exempted from the need for informed consent from patients.

The role of hepatitis B infection in anti-tuberculosis drug-induced liver injury: a meta-analysis of cohort studies.

Drug-induced liver injury (DILI) is a common adverse drug reaction leading to the interruption of tuberculosis (TB) therapy. We aimed to identify whether the hepatitis B virus (HBV) infection would increase the risk of DILI during first-line TB treatment. A meta-analysis of cohort studies searched in PubMed, Web of Science and China National Knowledge Infrastructure was conducted. Effect sizes were reported as risk ratios (RRs) and 95% confidence intervals (CIs) and calculated by R software. Sixteen studies with 3960 TB patients were eligible for analysis. The risk of DILI appeared to be higher in TB patients co-infected with HBV (RR 2.66; 95% CI 2.13-3.32) than those without HBV infection. Moreover, patients with positive hepatitis B e antigen (HBeAg) were more likely to develop DILI (RR 3.42; 95% CI 1.95-5.98) compared to those with negative HBeAg (RR 2.30; 95% CI 1.66-3.18). Co-infection with HBV was not associated with a higher rate of anti-TB DILI in latent TB patients (RR 4.48; 95% CI 0.80-24.99). The effect of HBV infection on aggravating anti-TB DILI was independent of study participants, whether they were newly diagnosed with TB or not. Besides, TB and HBV co-infection patients had a longer duration of recovery from DILI compared to non-co-infected patients (SMD 2.26; 95% CI 1.87-2.66). To conclude, the results demonstrate that HBV infection would increase the risk of DILI during TB therapy, especially in patients with positive HBeAg, and close liver function monitoring is needed for TB and HBV co-infection patients.

Risk Factors for the Co-infection with HIV, Hepatitis B and C Virus in Syphilis Patients.

Syphilis, human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) share transmission routes. Syphilis infection can increase the risk of acquiring and transmitting HIV in key populations. The aims of this study were to investigate the risk factors and co-infection patterns for HIV, HBV and HCV in patients with syphilis. A retrospective study was conducted of 2,412 patients with syphilis (1,922 (79.68%) with latent syphilis, 336 (13.93%) with secondary syphilis, 78 (3.23%) with primary syphilis, 72 (2.99%) with tertiary syphilis, and 4 (0.17%) with congenital syphilis). Positive results were observed in 8.21% (134/1,620) of patients tested for HIV, 5.75% (82/1,427) for HBV, and 1.02% (14/1,374) for HCV, respectively. Multivariate logistic regression analysis found that male sex (adjusted odds ratio (AOR) 26.03; 95% confidence interval (CI) 10.37–65.36), age < 55 years, especially age group 25–34-years (AOR 8.06; 95% CI 4.16–15.61), diagnosed at the Department of Infectious Disease (AOR 19.16; 95% CI 9.74–37.69), patients from Southern China, which is a geographical area south of the Qinling-Huaihe line (AOR 1.86; 95% CI 1.06–3.26) and having a rapid plasma reagin titre ≥ 1:32 (AOR 1.88; 95% CI 1.12–3.15) were independently associated with HIV infection. Risk factors for HBV co-infection in patients with syphilis, including male sex (AOR 1.78; 95% CI 1.12–2.83) and living in Southern China (AOR 4.66; 95% CI, 2.36–9.17) were also identified.

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.

Comparative effectiveness of anti-viral drugs with dual activity for treating hepatitis B and HIV co-infected patients: a network meta-analysis

BackgroundThere are randomized trials assessing a variety of antiviral drugs for hepatitis B virus (HBV), but the relative effectiveness of these drugs in the treatment of patients co-infected with human immunodeficiency virus (HIV) remains unclear. The objectives of the current study were to estimate and rank the relative effectiveness of antiviral drugs for treating HBV and HIV co-infected patients.MethodsRandomized trials, assessing the efficacy of antiviral drugs for HBV and HIV co-infected patients were searched in health-related databases. The methodological quality of the included trials was evaluated using the Cochrane risk of bias tool. Main outcome in this meta-analysis study was the success of treatment by antivirals as determined by virologic response. We performed pairwise and network meta-analysis of these trials and assessed the quality of evidence using the GRADE approach.ResultsSeven randomized trials (329 participants) were included in this network meta-analysis study. A network geometry was formed with six treatment options including four antiviral drugs, adefovir (ADV), emtricitabine (FTC), lamivudine (LMV) and tenofovir disoproxil fumarate (TDF), combination treatment of TDF plus LMV, and placebo. The weighted percentage contributions of each comparison distributed fairly equally in the entire network of evidence. An assumption of consistency required for network meta-analysis was not violated (the global Wald test for inconsistency: Chi2(4) = 3.63, p = 0.46). The results of estimates showed no differences between the treatment regimens in terms of viral response for treating HBV and HIV co-infected patients, which spanned both benefit and harm (e.g. LMV vs TDF plus LMV: OR: 0.37, 95%CI: 0.06–2.41). Overall, the certainty of evidence was very low in all comparisons (e.g. LMV vs TDF plus LMV: 218 fewer per 1000,121 more to 602 fewer, very low certainty). Therefore, we remained uncertain to the true ranking of the antiviral treatments in HBV/ HIV co-infected patients.ConclusionsThe findings suggest that the evidence is insufficient to provide guidance to the relative effectiveness of currently available antiviral drugs with dual activity in treating co-infection of HBV/HIV. Well-designed, large clinical trials in this field to address other important outcomes from different epidemiological settings are recommended.

Effect of hepatitis B virus (HBV) surface-gene variability on markers of replication during treated human immunodeficiency virus-HBV infection in Western Africa.

Replication markers exhibit substantial variation during chronic hepatitis B virus (HBV) infection, part of which can be explained by mutations on the surface (S) gene. We aimed to identify S-gene mutations possibly influencing the quantification of HBV replication markers (MUPIQH) in HBV genotype E infection, common to Western Africa. Seventy-three antiretroviral treatment (ART)-naïve human immunodeficiency virus (HIV)-HBV co-infected patients from Côte d'Ivoire, initiating anti-HBV-containing ART, had available HBV S-gene sequences. S-gene MUPIQHs were screened at ART initiation based on lower HBV-DNA or HBsAg quantification (qHBsAg) compared to wildtype. Their association with HBV virological response and qHBsAg slope during treatment was evaluated. Genotype E was predominant (95.9%). At ART initiation, median HBV-DNA was 7.27 log10 copies/mL (IQR = 5.26-8.33) and qHBsAg 4.08 log10 IU/mL (IQR = 3.49-4.61). Twelve S-gene MUPIQHs were identified among 21 patients (28.8%): sS140L (n = 4), sD144A (n = 1), sS167L (n = 2), sS174N (n = 6), sP178Q (n = 2), sG185L (n = 2), sW191L (n = 2), sP203Q/R (n = 2), sS204N/I/R/K/T/G (n = 7), sN207T (n = 2), sF212C (n = 1) and sV224A/Y (n = 7). MUPIQHs at positions s185+s191+s224 and s178+s204 were within highly covarying networks of S-gene mutations. Older age (P = 0.02), elevated transaminases (P = 0.03) and anti-hepatitis B "e" antibody-positive serology (P = 0.009) were significantly associated with prevalent MUPIQHs at ART initiation. During treatment, baseline MUPIQHs were not associated with time-to-undetectable HBV-DNA (P = 0.7) and qHBsAg levels decreased at similar rates between those with vs without MUPIQHs (P = 0.5). Several novel S-gene mutations were associated with reductions in replication markers among West African co-infected patients. These mutations, however, do not affect response during antiviral treatment. Their diagnostic and clinical consequences need clarification.

Clinical Correlates of Hepatitis B or Hepatitis C Coinfections in People Living with HIV/AIDS (PLHIV)

Introduction: Hepatitis B virus (HBV) coinfected HIV patients are likely to have chronic hepatitis B infection and associated severe liver disease, however effect of hepatitis B on HIV has not been proven to be off any effect. Similarly in HIV/HCV co-infection majority of the studies have shown no significant influence of hepatitis C on the course of HIV infection, although some studies have demonstrated an association between HCV infection and faster HIV disease progression.14,15 Therefore, further studies are needed to study the impact of HBV/HCV co-infection on course of HIV, specially, in India. Aims and Objectives: To study the clinical, biochemical and immunological profile of PLHIV co-infected with either hepatitis B or hepatitis C virus, the severity of liver disease and hepatitis B and hepatitis C viral loads in these co-infected PLHIV and the association of WHO stage of HIV and immunosuppression with hepatitis B and hepatitis C viral loads as well as severity of liver disease. Method: It was an observational cross-sectional study, involving 30 PLHIV co-infected with either hepatitis B or C. A detailed history and physical examination was done. Complete Haemogram, Liver function tests, kidney function tests, Ultrasonography abdomen, CD4 cell counts, hepatitis B surface antigen (HBsAg), hepatitis B envelope antigen (HBeAg), hepatitis B Viral DNA (HBV DNA) and HCV RNA levels were done. Severity of liver disease was assessed by FIB 4 SCORE. Results: Among the 30 PLHIV subjects 30% were co-infected with HCV 70% were co-infected with HBV (HBsAg positive). All the subjects were asymptomatic for their liver disease. All the subjects were on Anti-Retroviral Therapy (ART) and 80% were in Early WHO stage (T1 and T2) and 20% were in Advanced WHO stage (T3 and T4). It was similar in both HBV and HCV co-infected group. The mean CD4 count of the subjects was 416.70±189.50 cells/mm3 with the range of 69 – 909 cells/mm3. Five subjects (16.67%) had a CD4 count 3.25). In HCV co-infected subjects 3 of 9 (33.33%) had severe liver fibrosis and only 1 of 21 (4.7%) among HBV co-infected had severe liver fibrosis.Among the 9 HCV co-infected subjects, 3 (33.33%) had undetectable HCV RNA. More number of subjects with detectable hepatitis C viral load had severe liver disease as compared to undetectable viral load.In HIV and HBV co-infected subjects the HBeAg positivity was seen in 42.86% subjects and 38.1% subjects had detectable HBV DNA load. Significant correlation was seen between HBeAg positivity and HBV DNA load. No correlation could be found between FIB 4 score and hepatitis B envelope antigen (HBeAg) positivity or HBV DNA load.No correlation between severity of liver disease (FIB 4) score and WHO staging or CD4 count could be seen. WHO staging and CD4 count also did not correlated with HCV RNA load, HBeAg positivity and HBV DNA load. Conclusions: There is no correlation of CD4 count and WHO stage with liver disease severity or hepatitis viral load in patients on HAART. In HIV and HBV co-infected patients high prevalence of HBeAg positivity is seen. Thus it becomes important to look for deranged liver enzymes and HBeAg positivity in PLHIV coinfected with hepatitis B so that ART can be initiated in these patients irrespective of CD4 count. Hepatitis C co-infected subjects are more likely to have severe liver disease inspite of good CD4 count, so specific treatment for hepatitis C virus should be considered.

Low incidence of hepatitis B virus reactivation and subsequent hepatitis in patients with chronic hepatitis C receiving direct-acting antiviral therapy.

To determine the clinical characteristics of hepatitis B virus (HBV) reactivation in patients undergoing interferon-free antihepatitis C virus (HCV) therapy, we examined HBV DNA in 25 HBV co-infected patients and 765 patients with resolved HBV infection during and after treatment with direct-acting antiviral agents (DAAs). Among those with HCV genotype 1, asunaprevir plus daclatasvir was administered to 160 patients, sofosbuvir (SOF) plus ledipasvir to 438 patients and paritaprevir plus ombitasvir and ritonavir to 25 patients. In total, 167 patients with genotype 2 were treated with SOF plus ribavirin. Three patients with an HBV DNA level ≥2000IU/mL were treated with entecavir before anti-HCV therapy, without reactivation of HBV. In 3 of 22 (12%) HBV surface antigen (HBsAg)-positive patients with an HBV DNA level <2000IU/mL, the viral load increased during treatment. However, hepatitis flare did not occur in these patients. There was no significant difference in clinical history between patients with and without HBV reactivation. Among 765 patients with resolved HBV infection, HBV reactivation occurred in 1 (0.1%) patient after initial resolution, whose HBV DNA level spontaneously decreased after DAA therapy. We compared anti-HBs titres at baseline with those at post-DAA therapy in 123 patients without HBsAg. There was no significant difference in anti-HBs levels between the two points (P=.79). In conclusion, HBV reactivation was rare in HBsAg-negative patients treated with DAA therapy. Additionally, hepatitis did not occur in HBV-reactivated patients with a baseline HBV DNA level <2000IU/mL before DAA therapy.

Evolution of the serologic and virologic course of occult HBV infection in therapy experienced HIV co-infected patients.

We investigated how the natural course of occult hepatitis B virus (HBV) infection (OBI) may evolve during HIV co-infection and long term HBV-active HAART. From a cohort of 181 HIV infected patients who were consecutively recruited over a 5 year period, 28 HBV co-infected patients with sequential sera (n = 98) were identified. Iterative HBV serology and viral loads were determined before and during treatment. The viral HBsAg gene was then serially amplified, directly sequenced, and molecularly characterized. Persistent detection of anti-HBs did not result in a modification to the clinical course of OBI. In contrast, reactivation of chronic HBV infection, hepatic enzymatic flares and cases of HBV reinfection were evident among anti-HBs negative OBI patients, and this was a notable finding. Of the 14 chronic HBV infected patients, eight progressed to persistent OBI after initiation of HBV-active HAART, increasing the number of patients with OBI in the study. Long term HBV-active HAART was not found to have a notable impact on low level viremia during OBI. While the HBsAg gene sequences isolated from chronic HBV infection were genetically stable over time, OBI-associated variants (sP111R, sT127P, sY161F) were neither stable nor predominant during the course of infection. This study is the first of its kind from South Africa to show the occurrence of hepatic enzymatic flares, HBV reactivation, and reinfection in HAART-exposed HIV co-infected patients with OBI. Among the cases studied, there was further evidence that OBI-associated variants may not play a significant role in the pathogenesis of OBI.

Recurrent Hepatitis B and D Virus Infection in a Liver Transplant Recipient

Hepatitis B virus (HBV) and hepatitis delta virus (HDV) co-infections progress rapidly and lead to cirrhosis. In Japan, the prevalence of HBV and HDV co-infected patients is low. Therefore, there are few reports of patients with HBV and HDV co-infection having undergone liver transplantation. Herein, we report a rare case of recurrence of HBV and HDV in a 41-year-old man who underwent living donor liver transplantation 4 years prior.

Magnitude of Hepatitis B Virus and Hepatitis C Virus among HAART Taking Patients and Association with Liver and Renal Function and CD4+ T Cells Level

Background: Co-infection of Hepatitis B virus (HBV) and Hepatitis C virus (HCV) are very prevalent and the primary cause for morbidity and mortality among patients with Human immunodeficiency Virus (HIV). The aim of this study was to assess the magnitude of HBV and HCV infection and its association with liver and renal function, and CD4+ T cell levels of highly active anti-retroviral therapy (HAART) taking patients. Method: A hospital based cross sectional study was conducted at Zewditu Memorial Hospital. Participants’ sociodemographic and clinical information were collected from the anti-retroviral therapy (ART) database. Blood samples were collected from 384 volunteer, patients taking HAART for at least 1 year to investigate CD4, HBSAg, HCVAb, liver and renal function. Data was entered and analyzed by SPSS version 20 and p value less than 0.05 was taken as statistically significant. Results: Of the 384 participants, 222 (57.81%) were females, and 168 (43.75%) were in age group 30-39 years. Overall burden of HBV and HCV were 21 (5.7%). Co-infection rates of HBV-HIV, HCV-HIV and HBV-HCV-HIV were 18 (4.7%), 4 (1%) and 1 (0.2%), respectively. Co-infected study participants had significantly raised mean liver enzyme levels (AST, ALT and ALP) than mono-infected ones. There was no statistically significant difference for renal function parameters between mono-infected and co-infected HAART taking patients. Co-infected HIV patients had lower mean level of CD4 compared to mono-infected ones. Conclusion: HBV and HCV co-infected HIV patients are more likely to have abnormal liver enzyme levels and tend to have low mean CD4 count than mono-infected HIV patients. Large scale cohort study is recommended for consolidating the current findings.

Baseline characteristics of HIV & hepatitis B virus (HIV/HBV) co-infected patients from Kolkata, India.

Background & objectives:Hepatitis B virus (HBV) and HIV co-infection has variable prevalence worldwide. In comparison to HBV mono-infection, the course of chronic HBV infection is accelerated in HIV/HBV co-infected patients. The present study was carried out to analyse the baseline characteristics (clinical, biochemical, serological and virological) of treatment naïve HIV/HBV co-infected and HIV mono-infected patients.Methods:Between July 2011 and January 2013, a total number of 1331 HIV-seropositive treatment naïve individuals, enrolled in the ART Centre of Calcutta School of Tropical Medicine, Kolkata, India, were screened for hepatitis B surface antigen (HBsAg). A total of 1253 HIV mono-infected and 78 HIV/HBV co-infected patients were characterized. The co-infected patients were evaluated for HBeAg and anti-HBe antibody by ELISA. HIV RNA was quantified for all co-infected patients. HBV DNA was detected and quantified by real time-PCR amplification followed by HBV genotype determination.Results:HIV/HBV co-infected patients had proportionately more advanced HIV disease (WHO clinical stage 3 and 4) than HIV mono-infected individuals (37.1 vs. 19.9%). The co-infected patients had significantly higher serum bilirubin, alanine aminotransferase (ALT), alkaline phosphatase and ALT/platelet ratio index (APRI). CD4 count was non-significantly lower in co-infected patients. Majority (61.5%) were HBeAg positive with higher HIV RNA (P<0.05), HBV DNA (P<0.001) and APRI (P<0.05) compared to those who were HBeAg negative. HBV/D was the predominant genotype (73.2%) and D2 (43.7%) was the commonest subgenotype.Interpretation & conclusions:HIV/HBV co-infected patients had significantly higher serum bilirubin, ALT, alkaline phosphatase and lower platelet count. HBeAg positive co-infected patients had higher HIV RNA and HBV DNA compared to HBeAg negative co-infected patients. Prior to initiation of antiretroviral treatment (ART) all patients should be screened for HBsAg to initiate appropriate ART regimen.

Liver function biomakers in Malaria and Hepatitis B co-infection among patients with febrile illness

Introduction: Malaria and Hepatitis B Virus (HBV) co-infections present major threat to public health throughout tropical and Sub-Saharan Africa. This study was carried out to analyze the status of liver enzymes and serum protein in HBV and malaria co-infected patients in Murtala Muhammed Specialist Hospital (MMSH) Kano. Methods: Standard microscopy and rapid diagnostic test (RDT) were used separately to screen for mono and co-infections among 200 outpatients presented with fever. Their serum protein and liver enzymes were investigated. Results: Among the total subjects studied 25.5% were malaria positive. Females had higher rate of malaria infection (18%) than males (7.5%). Age group 15-24 had the highest malaria prevalence (11%). Thirteen (6.5%) subjects were HBV positive. Males had higher rate of infection (4.5%) than females (2.0%). Male subjects had higher prevalence of co-infection representing 4.5% and age groups 25-34 were observed to have highest co-infection rate of 1.5%. Biochemical parameters analyzed on all the categories of subjects shows significant difference in their mean values as compared to other groups (P<0.05). However no significant difference was observed in the value of ALP in all the groups. Statistical difference was also established in ALB values between the co-infection and malaria groups (P=0.037) and between malaria and control group (P=0.022). There is also a statistical difference in the mean value of total bilirubin among the groups P<0.05 and mean value of DB between HBV and control groups (P=0.022). Conclusion: The study showed that co-infection of malaria and HBV infection had no profound effect on the level of serum protein and liver enzyme activities in the serum.

Molecular epidemiology of Hepatitis B virus in Córdoba, Argentina

BackgroundThe analysis of the genomes of hepatitis B virus (HBV) identifies phylogenetic variants called genotypes, which may lead to distinct biological and clinical behaviors. ObjectivesThe aim of this study was to describe the current molecular epidemiology and genetic diversity of HBV in Córdoba, Argentina. Study designA total of 52 HBV samples, 40 from HBV mono-infected and 12 from human immunodeficiency virus (HIV)-HBV co-infected patients, were sequenced in the S gene and in the basal core promoter-precore (BCP-pC) region. ResultsPresence of subgenotypes F1b (35%) and F4 (17.5%), subgenotype A2 (37.5%), C (5.0%) (subgenotype could not be defined) and D (5.0%) (subgenotype D2, and the other could not be defined) were observed among mono-infected patients. The co-infected individuals displayed a different genotype distribution: sub-genotype A2 was the most common (75.0%), followed by subgenotype F1b (25.0%). ConclusionsThese results showed two epidemiologic scenarios: the mono-infected population may represent the ethnic composition of the current human population of Córdoba, where the Amerindian (genotype F) and European origins (subgenotype A2) account for the 90% of the samples; for the co-infected patients, the high prevalence of subgenotype A2 resemble previous analyses from Buenos Aires. In addition, mutations in hepatitis B surface antigen (HBsAg), polymerase and BCP-pC regions were identified, mainly in chronic or co-infected patients.

Transaminase [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] Activity of HIV and HBV Co-Infected Female Patients on Drugs and Female Patients Not on Drugs

Human immunodeficiency virus-1 (HIV) and hepatitis B virus (HBV) co-infection is a major threat, especially to liver damage. 100 female patients referred to Virology department of the Jos University teaching Hospital (JUTH), were selected by physicians on the basis of the following criteria: documented HIV infection, no alcohol abuse (≤ 20 g alcohol daily and no history of chronic alcohol consumption), no history of hereditary and autoimmune liver disease, no evidence of hemochromatosis. Data on demographics, drug or alcohol use, and history of liver diseases were obtained at first visit. A month-by-month documentation of the prescribed drug combination allowed a calculation of each patient's individual cumulative drug exposure. Subjects were then classified into control (30), co-infected; on drugs (35) and co-infected; not on drugs (35). The test for HIV antibodies, HBsAg were carried out on day one (at first visit) serum ALT and serum AST were determined three (3) months after detection (day 90; after HIV antigen confirmatory test). Thirty-five (35) patients started medication at day-one, and 35 decided not to start medication until after confirmatory test (three months later).The serum ALT levels of the HIV-HBV co-infected patients on drugs (M=43.60, SD=1.83) was significantly higher than the serum ALT levels of the control group (M=29.17, SD=6.17), t (63) =12, p< .0001 at p <.05 confidence level. In a similar trend, the serum ALT levels of the HIV-HBV co-infected patients not on drugs (M=37.74, SD=3.70) was significantly higher than the serum ALT levels of the control group (M=29.17, SD=6.17), t (63) =6.5, p< .0001 at p <.05 confidence level. On comparison, the serum ALT levels of the HIV- HBV co-infected patients on drugs (M=43.60, SD=1.83) was significantly higher than the serum ALT levels of the HIV-HBV co-infected patients not on drugs (M=37.74, SD=3.70), t (68) =8.40, p< .0001 at p <.05 confidence level. The serum AST levels of the HIV-HBV co-infected patients on drugs (M=43.54, SD=2.74) was significantly higher than the serum AST levels of the control group (M=32.23, SD=5.93), t (63) =10, p< .0001 at p <.05 confidence level. In a similar manner, the serum AST levels of the HIV-HBV co-infected patients not on drugs (M=37.66, SD=2.11) was significantly higher than the serum AST levels of the control group (M=32.23, SD=5.93), t (63) =5.1, p< .0001 at p <.05 confidence level. On comparison, the serum AST levels of the HIV-HBV co-infected patients on drugs (M=43.54, SD=2.74) was significantly higher than the serum AST levels of the HIV-HBV co-infected patients not on drugs (M=37.66, SD=2.11), t (68) =10.07, p< .0001 at p <.05 confidence level. HIV-HBV infection causes liver damage with more damage caused by drugs taken to manage these infections. A correlation analysis between ALT and AST levels shows a non-significant correlation.