A new method of concentrating hepatitis B virus (HBV) DNA and HBV surface antigen: an application of the method to the detection of occult HBV infection

Background The risk of post‐transfusion hepatitis B virus (HBV) infection has been reduced after the implementation of HBV nucleic acid amplification technology (NAT). However, the problem of HBV DNA‐positive and HBV surface antigen (HBsAg)‐negative occult HBV infections remains to be solved. This is in part due to the HBV DNA load being too low to detect these occult HBV infections using mini‐pool NAT. In Japan, the assay for the antibody against the HBV core antigen (anti‐HBc) has not completely excluded occult HBV infection. To solve this problem, we have developed a new method of concentrating HBV DNA and HBsAg simultaneously to increase the sensitivity of detection tests. Methods Virus concentration is achieved by the enhancement of the agglutination of viruses using poly‐L‐lysine in the presence of a bivalent metal. Poly‐L‐lysine‐coated magnetic beads are used to shorten the time of each step of the concentration procedure. Seventy‐seven anti‐HBc‐positive and HBsAg‐negative donations were examined. HBsAg and anti‐HBc were tested by enzyme immunoassay (EIA) (AxSYM; Abbott) and haemagglutination inhibition test (Japanese Red Cross), respectively. Results HBV surface antigen and HBV DNA levels were concentrated up to four‐ to sevenfold. Using this method, 35 of the 77 anti‐HBc‐positive and HBsAg‐negative donors were HBV DNA‐positive by individual NAT and a further five donors became HBV DNA‐positive by HBV concentration. Twenty‐seven of 40 occult HBV infections became HBsAg‐positive by HBsAg concentration. Conclusion Our new method of concentrating HBV and HBsAg increased the sensitivities of EIA and HBV NAT, and enabled us to detect 27 of 40 occult HBV infections by HBsAg EIA.     

Association between occult hepatitis B infection and the risk of hepatocellular carcinoma: a meta‐analysis

Background: The association between occult hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) remains controversial. Aims: We conducted a meta‐analysis of prospective studies and retrospective studies to examine whether occult HBV infection increases the risk of HCC. Methods: Two independent reviewers searched databases for eligible studies published in English or Chinese dated from 1966 to 6 April 2010. The odds ratios or the relative risks (RRs) of each study were considered respectively. Results: We identified 16 eligible studies. A significantly increased risk of HCC was found in subjects with occult HBV infection in comparison with non‐infected controls in both retrospective [OR_unadjusted=6.08, 95% confidence interval (CI)=3.45–10.72] and prospective studies (RR_adjusted=2.86, 95% CI=1.59–4.13), and occult HBV increased the risk for HCC in both hepatitis C virus (HCV)‐infected populations (summary RR=2.83, 95% CI=1.56–4.10) and in non‐infected populations (OR_unadjusted=10.65, 95% CI=5.94–19.08). A higher prevalence of occult HBV was observed in individuals who were positive for anti‐HBs and anti‐HBc (OR_unadjusted=1.81, 95% CI=1.06, 3.09). Conclusion: Our findings suggest that occult HBV infection was associated with an increased risk of HCC. Occult HBV may serve as a cofactor in the development of HCV‐related HCC, and it may also play a direct role in promoting Non‐B and Non‐C HCC growth. Suggestive evidence indicates that individuals with a concomitant presence of anti‐HBs and anti‐HBc had an increased risk of occult HBV infection. However, further studies are needed to clarify these observations.     

Eighteen‐month lamivudine prophylaxis on preventing occult hepatitis B virus infection reactivation in patients with haematological malignancies receiving immunosuppression therapy

This study evaluated the long‐term efficacy and safety of an 18‐month lamivudine prophylaxis in 68 HBsAg‐negative/anti–HBc‐positive patients with oncohaematological disease. All 68 consecutive HBsAg‐negative/anti–HBc‐positive patients with an oncohaematological disease and naïve for chemotherapy observed from April 2008 to December 2012 at 2 Hematology Units in Naples were treated with lamivudine for 18 months after stopping chemotherapy and monitored for HBsAg at months 1 and 3 during chemotherapy and then every 3 months after its discontinuation. During follow‐up, 13 (19.1%) of the 68 patients died of complications related to their oncohaematological disease, and 3 (4%) showed a virological HBV reactivation (retroconversion to HBsAg positivity) 1‐7 months after the discontinuation of lamivudine prophylaxis (2 treated for chronic lymphocytic leukaemia and one for Waldenstrom's disease); of these, 2 showed a biochemical reactivation. Comparing the demographic and clinical characteristics of the 3 patients with a virological HBV reactivation to the 65 without, the former were older (median age and range: 67 years [75‐78] vs. 61 [24‐88]; P = .05) and were less frequently treated for B‐cell non‐Hodgkin lymphoma (B‐NHL) (0 vs. 70.7%, P = .03). In conclusion, a 18 months of lamivudine prophylaxis was effective in preventing HBV reactivation in HBsAg‐negative/anti–HBc‐positive patients treated for B‐NHL. However, in patients with chronic and severe immunodepression, such as those with chronic lymphocytic leukaemia and Waldenstrom's disease, prophylaxis should be continued for an indefinite period.     

多种肝脏疾病中隐匿性HBV感染检出率及其S基因MHR免疫逃逸相关突变特点分析

目的分析多种肝脏疾病中隐匿性HBV感染(occult HBV infection,OBI)检出率,并探讨OBI患者HBV S基因主要亲水区(major hydrophilic region,MHR)免疫逃逸相关突变特点。方法回顾性分析2005年1月—2017年12月就诊于中国人民解放军总医院第五医学中心的91037例HBV感染住院患者临床资料,筛选出OBI患者并扩增其HBV S基因序列,分析其HBV S基因MHR免疫逃逸相关突变特点。结果91037例住院患者中OBI总检出率为0.53%(487/91037),急性乙型肝炎患者中OBI检出率最高(9.26%,130/1404),肝硬化患者中OBI检出率最低(0.26%,78/29921)。62例OBI患者组与124例非OBI患者组相比,OBI患者组MHR免疫逃逸相关突变总体检出率显著高于非OBI患者组(59.68%vs.35.48%;P<0.05);OBI患者组MHR多个免疫逃逸相关突变的联合检出率显著高于非OBI患者组(43.55%vs.22.58%;P<0.05);其中,sT118K、sK122R和sV168A 3种单点突变的检出率显著高于非OBI患者组。结论本研究显示临床HBV感染患者中有较高的OBI检出率,而且不同肝脏疾病中OBI检出率不同。此外,HBV S基因MHR的免疫逃逸相关突变与临床实践中OBI的发生密切相关。     

Influence of anti‐HBc seropositivity on the risk of hepatocellular carcinoma in HCV‐infected patients after adjusting for confounding factors

Summary. It is controversial whether past hepatitis B virus infection constitutes an additional risk of hepatocellular carcinoma (HCC) among patients with hepatitis C virus (HCV). The incidence of HCC between 1994 and 2004 was analysed among 1262 patients who were only positive for HCV. The cumulative incidence of HCC was assessed by Kaplan–Meier analysis and the difference between two groups was assessed by the log‐rank test. The effect of anti‐HBc positivity on the risk of HCC was assessed with multivariate Cox proportional analysis. Anti‐HBc was positive in 522 (41.4%) patients. The proportion of male patients (56.7 vs 46.8%, P < 0.001) and mean age (60.8 vs 56.9 years, P < 0.001) were significantly higher in the anti‐HBc positive group. HCC developed in 339 patients (mean follow‐up 7.0 years), with cumulative incidence rates at 3, 5 and 10 years of 12.7, 24.5 and 41.9% in the anti‐HBc positive group and 10.6, 17.7 and 33.4% in the negative group, respectively (P = 0.005). However, anti‐HBc seropositivity did not reach statistical significance in multivariate analysis including age and gender (hazard ratio, 1.06; 95% CI, 0.85–1.31; P = 0.63). Anti‐HBc positivity and HCC incidence were confounded by male gender and older age.     

隐匿性乙型肝炎病毒感染的检测及临床特点分析

研究不明原因性肝炎患者中隐匿性乙型肝炎病毒（HBV）感染的巢式聚合酶链式反应（PCR）检测及HBV隐匿性感染的临床特点。不明原因性肝炎患者104例,收集临床资料及血清。HBV基因组S、X、C区分别设计2套巢式引物,比较扩增效率,挑选扩增效率高的引物巢式PCR扩增,检测出隐匿性HBV感染者。隐匿性HBV感染者与其它不明原因肝病患者易感因素、临床症状、体征、生化检查、影像学检查等方面比较分析。检测出隐匿性HBV感染13例。隐匿性HBV感染者较其它不明原因肝病患者年龄大,多为中老年患者,并且肝硬化比例明显高于后者。本组不明原因性肝炎患者中约有12.5%为隐匿性HBV感染。HBV隐匿性感染导致肝脏炎症,甚至肝硬化。     

Occult HBV infection in HIV‐infected adults and evaluation of pooled NAT for HBV

The study aimed to determine the prevalence of occult hepatitis B virus infection among HIV‐infected persons and to evaluate the use of a pooling strategy to detect occult HBV infection in the setting of HIV infection. Five hundred and two HIV‐positive individuals were tested for HBV, occult HBV and hepatitis C and D with serologic and nucleic acid testing (NAT). We also evaluated a pooled NAT strategy for screening occult HBV infection among the HIV‐positive individuals. The prevalence of HBV infection among HIV‐positive individuals was 32 (6.4%), and occult HBV prevalence was 10%. The pooling HBV NAT had a sensitivity of 66.7% and specificity of 100%, compared to HBV DNA NAT of individual samples. In conclusion, this study found a high prevalence of occult HBV infection among our HIV‐infected population. We also demonstrated that pooled HBV NAT is highly specific, moderately sensitive and cost‐effective. As conventional HBV viral load assays are expensive in resource‐limited settings such as India, pooled HBV DNA NAT might be a good way for detecting occult HBV infection and will reduce HBV‐associated complications.     

A weak association between occult HBV infection and non-B non-C hepatocellular carcinoma in Japan

Background In Japan, approximately 10% of hepatocellular carcinoma (HCC) patients are negative for both hepatitis B surface antigen (HBsAg) and antibodies to hepatitis C virus (anti-HCV), i.e., they constitute the so-called category of non-B non-C (NBNC) HCC. Little is known about the characteristics of NBNC-HCC. Methods Potential risk factors for carcinogenesis (including occult HBV infection [HBsAg is negative but HBV DNA is positive by polymerase chain reaction (PCR)], obesity, and diabetes) were assessed in 233 HCC patients grouped according to hepatitis virus serological status (152 with HCV-HCC, 36 with HBV-HCC, and 45 with NBNC-HCC). Results The prevalence of patients with obesity or diabetes was significantly higher in the NBNC-HCC group than in the HBV-HCC group. The same trend was observed even when patients with massive alcohol intake were excluded from the analysis. Only 8 patients (18%) in the NBNC-HCC group had detectable serum HBV DNA, and this was at very low levels (HBV/Ce/C2 and HBV/D were determined in 7 and 1 patients, respectively). In the NBNC-HCC group, the determined nucleotide sequences of the enhancer II/core promoter/precore/core region did not contain any HCC-associated mutations, whereas 25 of 30 patients in the HBV-HCC group carried strains with C1653T, T1753V, and/or A1762T/G1764A mutations. Conclusions A weak association between occult HBV infection and HCC development was observed in the NBNC patients. This study indicates that nonalcoholic steato-hepatitis should be further investigated to assess its contribution to HCC development in this category of patients.     

Hepatitis B virus genotypes and hepatitis B surface antigen mutations in family contacts of hepatitis B virus infected patients with occult hepatitis B virus infection

Background:  The association and profile of surface gene mutations with viral genotypes have been studied in patients with chronic hepatitis B virus (HBV) but not in subjects with occult HBV infection.
Aim:  This study aimed to investigate the association of surface gene mutations with viral genotypes in occult HBV infection.
Materials & Methods:  Of 293 family contacts of 90 chronic HBV index patients, 110 consented for the study. Of 110 subjects, 97 were hepatitis B surface antigen (HBsAg) negative. HBV genotyping was done using direct DNA sequencing. The S-gene was also sequenced in 13 chronic hepatitis B patients to serve as controls.
Results:  Twenty-eight (28.8%) of the 97 subjects had occult HBV infection. Bidirectional sequencing of partial S-gene was successful in 13 of them. Seven (53.8%) of the viral sequences are genotype A1, two (15.3%) each having genotypes D5&D2 and one each (7.6%) having D1&G genotypes. Seven (53.8%) of the 13 HBsAg positive patients, had genotype D&6 (46.1%) genotype A. A128V & T143M mutations were observed in 5 of 13 (38.4%) subjects and A128V & P127S in 2 of 13 (15.3%) patients ( P  = 0.385). A128V mutation was seen in two (15.3%) subjects with D2 genotype, while T143M mutation was seen in three (23.07%) subjects with A1genotype. At aa125, three (23.07%) subjects with D5 genotype had methionine instead of threonine. There were wild type sequences in five (38.4%) subjects, one each of D1, G genotypes (20%) and four A1 (80%) genotypes. None of the subjects had G145R mutation.
Conclusions:  Occult HBV infection may be common in household contacts of chronic HBV infected patients. Equal prevalence of A&D sub-genotypes was present in occult HBV subjects and in chronic HBV patients. Mutations of the S-gene are genotype specific in both occult as well as chronic HBV infection.     

High levels of serum hepatitis B virus DNA in patients with 'anti-HBc alone': role of HBsAg mutants

It remains unclear how the detection of hepatitis B core antibody (anti-HBc) in the absence of hepatitis B surface antigen (HBsAg) and antibody (anti-HBs) should be interpreted and whether all patients with this pattern need to be tested for hepatitis B virus (HBV)-DNA. This study aimed at reassessing the significance of 'anti-HBc alone' in unselected sera referred to the clinical laboratory and determining whether significant HBV viraemia can be found in this setting. Of the 6431 patients tested for HBsAg, total anti-HBc and anti-HBs in a Paris hospital over a 1-year period, 362 (5.6%) had 'anti-HBc alone' (24.8% of anti-HBc-positive patients). Only 11 of the 362 sera (3.0%) were found to be false positive. One patient was in the resolving phase of acute hepatitis B. HBV-DNA was detected in 10 of 362 (2.8%) patients, using a commercial standardized assay (threshold: 350 IU/mL). Viral loads exceeded 10(4) copies/mL in 6 of 10 patients. Mutations in the HBsAg immunodominant region were identified in seven of the viraemic patients. HBsAg was detected in only two cases when retested by one of the latest, multivalent assays. Neither human immunodeficiency virus nor hepatitis C virus serostatus distinguished between patients with and without HBV-DNA. In conclusion, 'anti-HBc alone' should be considered a risk marker for a so-called 'false occult' HBV infection with significant viraemia. Indeed, results in this hospital population indicate that a small proportion of patients with 'anti-HBc alone' have high viral loads, revealing the occurrence of infection with HBV mutants that escape detection even by multivalent HBsAg assays.     

Cryoglobulinemic glomerulonephritis with underlying occult HBV infection and Waldenström macroglobulinemia: A case report

Introduction:Occult hepatitis B virus (HBV) infection, defined as negative hepatitis B surface antigen (HBsAg) but detectable HBV DNA in serum and liver tissue, has very rarely been described in cryoglobulinemia (CG) patients. This case report sheds light on the possible link between occult HBV infection and CG.Patient concerns:A 76-year-old man presented with rapidly deteriorating renal function within 1 year.Diagnosis:Cryoglobulinemic glomerulonephritis was diagnosed through renal biopsy. Initially, the patient tested negative for HBsAg, but a low HBV viral load was later discovered, indicating an occult HBV infection. Further studies also revealed Waldenström macroglobulinemia (WM).Interventions:We treated the patient as WM using plasma exchange and rituximab-based immunosuppressive therapy.Outcomes:After 1 cycle of immunosuppressive treatment, there was no improvement of renal function. Shortly after, treatment was discontinued due to an episode of life-threatening pneumonia. Hemodialysis was ultimately required.Conclusion:Future studies are needed to explore the link between occult HBV infection and CG, to investigate the mediating role of lymphomagenesis, and to examine the effectiveness of anti-HBV drugs in treating the group of CG patients with occult HBV infection. We encourage clinicians to incorporate HBV viral load testing into the evaluation panel for CG patients especially in HBV-endemic areas, and to test HBV viral load for essential CG patients in whom CG cannot be attributed to any primary disease.     

A novel stop codon mutation within the hepatitis B surface gene is detected in the liver but not in the peripheral blood mononuclear cells of HIV‐infected individuals with occult HBV infection

Summary. To characterize occult HBV infection (OHB) in different compartments of HIV+ individuals. This retrospective study involved 38 consecutive HIV+ patients; 24 HBsAg negative (HBV?) and 14 HBsAg positive (HBV+). OHB was assessed in serum samples, liver tissue (LT) and peripheral blood mononuclear cells (PBMC) by genomic amplification of the partial S, X and precore/core regions. HBV genomic analysis was inferred by direct sequencing of PCR products. The intracellular HBV‐DNA was measured by a quantitative real‐time PCR. HBV+ patients were used as a control for HBV replication and genomic profile. In HBV? patients, HBV‐DNA was undetectable in all serum samples, while it was found positive in 7/24 (29%) LT in which genotype D prevailed (57%). HBV‐DNA was found in 6/7 (86%) PBMC of occult‐positive and none of occult‐negative LT. Significantly lower HBV‐DNA load was present in both compartments in OHB+ with respect to the HBV+ group (LT: P = 0.002; PBMC: P = 0.026). In the occult‐positive cases, HBV replication was significantly higher in LT than in PBMC (P = 0.028). A hyper‐mutated S gene in PBMC and a nucleotide mutation at position C695 in LT that produces a translational stop codon at amino acid 181 of the HBs gene characterized OHB. In this group of HIV+ persons, OHB is frequent and exhibits lower replication levels than chronic HBV in the different compartments examined. HBV‐DNA detection in PBMC may offer a useful tool to identify OHB in serum‐negative cases. The novel HBs gene stop codon found in LT could be responsible for reduced production leading to undetectability of HBsAg.     

High risk of hepatitis B‐virus reactivation after hematopoietic cell transplantation in hepatitis B core antibody‐positive patients

We investigated the serological changes in hepatitis B virus (HBV)‐related markers in 55 and 26 hepatitis B surface antigen (HBsAg)‐negative patients undergoing allogeneic and autologous stem cell transplantation, respectively, over the past 4 yr. Five of the 17 allogeneic and one of the five autologous patients with pretransplant anti‐hepatitis B core antigen antibodies (anti‐HBc) were HBsAg‐positive after transplantation, whereas none of the patients negative for anti‐HBc were HBsAg‐positive in both groups. All patients who became HBsAg‐positive received steroid‐containing immunosuppressive therapy for chronic graft versus host disease (GVHD) or myeloma. Four of the six patients developed flare of HBV hepatitis, and two patients did not. One patient developed fulminant hepatitis treated with lamivudine and plasma exchange. Other five patients received entecavir from the detection of HBsAg. Although HBV‐DNA levels became below the limit of detection in all patients, HBsAg positivity remained in three patients after 6 months of treatment. We concluded that anti‐HBc positivity is a risk factor for reactivation of HBV after both autologous and allogeneic transplantation, and HBV‐related markers should be monitored regularly in these patients. We also stress the efficacy of pre‐emptive use of antiviral agents in controlling HBV replication and limiting hepatic injury due to reactivation of HBV in these patients.     

HBV/HDV co‐infection in the Western Brazilian Amazonia: an intriguing mutation among HDV genotype 3 carriers

HDV infection still remains a serious public health problem in Amazonia. There are few data regarding the biomolecular aspects of HBV/HDV co‐infection in this region. We studied 92 patients HBsAg⁺/anti‐HDV IgG⁺ followed at the Hepatitis Referral Centers of Porto Velho (RO), Rio Branco and Cruzeiro do Sul (AC), Brazil, from March 2006 to March 2007 for whom the HDV and/or the HBV genotype could be determined. The HDV genotype could be determined in 90 patients, while the HBV genotypes could be positively determined in 74. HBV subgenotype F2 is the most prevalent (40.2%), followed by the subgenotypes A1 (15.2%) and D3 (8.7%), while 16.4% were other subgenotypes or genotypes, 4.3% were discordant and 15.2% were unamplifiable. Surprisingly, HDV genotype 3 (HDV‐3) was found in all of the HBV/HDV‐infected patients that could be genotyped for HDV, confirming that HDV‐3 can associate with non‐F HBV genotypes. However, a HDV‐3 mutant was found in 29.3% of patients and was more frequently associated with non‐F HBV genotypes (P < 0.001) than were nonmutant strains, suggesting that the mutation may facilitate association of HDV‐3 with non‐F HBV genotypes.     

Clearance of HBV DNA in immunized children born to HBsAg‐positive mothers,years after being diagnosed with occult HBV infection

In a previous study, we observed immunoprophylaxis failure due to occult hepatitis B virus (HBV) infection (OBI) despite the presence of adequate levels of anti‐HBs in 21 (28%) of 75 children born to HBsAg‐positive mothers. The aim of the study was to explore the maintenance of this cryptic condition in this population. Of 21 OBI‐positive children, 17 were enrolled. HBV serological profiles were determined by enzyme‐linked immunosorbent assay. Highly sensitive real‐time and standard PCR followed by direct sequencing were applied in positive cases. The mean age (±SD) of studied patients was 6.57 ± 2.75 years. All children still were negative for HBsAg. All but one (94%) were negative for HBV DNA. Only two children were positive for anti‐HBc. The results of the most recent anti‐HBs titration showed that 4 (23.5%) and 13 (76.5%) had low (<10 IU/mL) and adequate (>10 IU/mL) levels of anti‐HBs, respectively. The only still OBI‐positive patient had an HBV DNA level of 50 copy/mL, carried the G145R mutation when tested in 2009 and again in 2013 in the ‘a’ determinant region of the surface protein. Further follow‐up showed that after 18 months, he was negative for HBV DNA. In high‐risk children, the initial HBV DNA positivity early in the life (vertical infection) does not necessarily indicate a prolonged persistence of HBV DNA (occult infection). Adequate levels of anti‐HBs after vaccine and hepatitis B immune globulin immunoprophylaxis following birth could eventually clear the virus as time goes by. Periodic monitoring of these children at certain time intervals is highly recommended.     

Meta‐analysis of the association between anti‐HBc seropositivity and a poor prognosis of chronic HCV infection

Aim: The impact of serological HBsAg? and anti‐HBc+ on the prognosis of chronic hepatitis C virus (HCV) infection is unknown. We conducted a systematic review to analyze whether anti‐HBc positivity imposes any effect on the course of HCV‐related chronic liver disease. Methods: We retrieved references from online databases that included PubMed and EMBASE. Data were gathered with regard to demographic information, disease progression and prognosis, and the results of serological tests. The development of hepatocellular carcinoma (HCC) was the endpoint of follow‐up of all cohort studies. Results: Eighteen references were included in this study, of which four were cohort studies. Twelve studies were retrospective, observational and non‐interventional studies. According to our meta‐analysis, the rate of serological HBsAg? and anti‐HBc+ was higher among HCC patients compared with non‐HCC patients (odds ratio [OR], 1.55; 95% CI, 1.22–1.98). HCV patients that were anti‐HBc+ had a greater chance of developing HCC than their anti‐HBc? counterparts (OR, 2.15; 95% CI, 1.34–3.47). Conclusions: The serological status of HBsAg? and anti‐HBc+ appears to be correlated with a poor prognosis for chronic HCV infection. Though the general quality of these references was low, and multiple confounding factors existed, the likelihood of a poorer outcome of HCV patients that are positive for anti‐HBc should be considered by their physicians.     

Genomic variability associated with the presence of occult hepatitis B virus in HIV co‐infected individuals

Summary. Occult hepatitis B virus (O‐HBV) infection is characterized by the presence of HBV DNA without detectable hepatitis B surface antigen (HBV DNA+/HBsAg?) in the serum. Although O‐HBV is more prevalent during HBV/HIV co‐infection, analysis of HBV mutations in co‐infected patients is limited. In this preliminary study, HBV PreSurface (PreS) and surface (S) regions were amplified from 33 HIV‐positive patient serum samples – 27 chronic HBV (C‐HBV) and six O‐HBV infections. HBV genotype was determined by phylogenetic analysis, while quasispecies diversity was quantified for the PreS, S and overlapping polymerase regions. C‐HBV infections harboured genotypes A, D and G, compared to A, E, G and one mixed A/G infection for O‐HBV. Interestingly, nonsynonymous–synonymous mutation values indicated positive immune selection in three regions for O‐HBV vs one for C‐HBV. Sequence analysis further identified new O‐HBV mutations, in addition to several previously reported mutations within the HBsAg antigenic determinant. Several of these O‐HBV mutations likely contribute to the lack of detectable HBsAg in O‐HBV infection by interfering with detection in serologic assays, altering antigen secretion and/or decreasing replicative fitness.     

Prevalence and burden of HBV co‐infection among people living with HIV: A global systematic review and meta‐analysis

Globally, in 2017 35 million people were living with HIV (PLHIV) and 257 million had chronic HBV infection (HBsAg positive). The extent of HIV‐HBsAg co‐infection is unknown. We undertook a systematic review to estimate the global burden of HBsAg co‐infection in PLHIV. We searched MEDLINE, Embase and other databases for published studies (2002‐2018) measuring prevalence of HBsAg among PLHIV. The review was registered with PROSPERO (#CRD42019123388). Populations were categorized by HIV‐exposure category. The global burden of co‐infection was estimated by applying regional co‐infection prevalence estimates to UNAIDS estimates of PLHIV. We conducted a meta‐analysis to estimate the odds of HBsAg among PLHIV compared to HIV‐negative individuals. We identified 506 estimates (475 studies) of HIV‐HBsAg co‐infection prevalence from 80/195 (41.0%) countries. Globally, the prevalence of HIV‐HBsAg co‐infection is 7.6% (IQR 5.6%‐12.1%) in PLHIV, or 2.7 million HIV‐HBsAg co‐infections (IQR 2.0‐4.2). The greatest burden (69% of cases; 1.9 million) is in sub‐Saharan Africa. Globally, there was little difference in prevalence of HIV‐HBsAg co‐infection by population group (approximately 6%‐7%), but it was slightly higher among people who inject drugs (11.8% IQR 6.0%‐16.9%). Odds of HBsAg infection were 1.4 times higher among PLHIV compared to HIV‐negative individuals. There is therefore, a high global burden of HIV‐HBsAg co‐infection, especially in sub‐Saharan Africa. Key prevention strategies include infant HBV vaccination, including a timely birth‐dose. Findings also highlight the importance of targeting PLHIV, especially high‐risk groups for testing, catch‐up HBV vaccination and other preventative interventions. The global scale‐up of antiretroviral therapy (ART) for PLHIV using a tenofovir‐based ART regimen provides an opportunity to simultaneously treat those with HBV co‐infection, and in pregnant women to also reduce mother‐to‐child transmission of HBV alongside HIV.     

Detection and identification of occult HBV in blood donors in Taiwan using a commercial,multiplex, multi‐dye nucleic acid amplification technology screening test

Platelet components became routinely available to many institutions in the late 1960s and since then utilization has steadily increased. Platelets are produced by three principal methods and their manufacturing process is regulated by multiple agencies. As the field of platelet transfusion has evolved, a broad array of strategies to improve platelet safety has developed. This review will explore the evolution of modern platelet component therapy, highlight the various risks associated with platelet transfusion and describe risk reduction strategies that have been implemented to improve platelet transfusion safety. In closing, the reader will be briefly introduced to select investigational platelet and platelet‐mimetic products that have the potential to enhance platelet transfusion safety in the near future.