Factors associated with isolated anti‐hepatitis B core antibody in HIV‐positive patients: impact of compromised immunity

Summary. In regions that are hyperendemic for chronic hepatitis B virus (HBV) infection, prevalence of and risk factors associated with isolated anti‐hepatitis B core antibody (anti‐HBc) in HIV‐positive patients are less well described. HIV‐positive patients who were tested for hepatitis B surface antigen (HBsAg), anti‐hepatitis B surface antibody (anti‐HBs) and anti‐HBc at designated hospitals for HIV care in Taiwan were included for analysis. HBV DNA was detected by real‐time polymerase chain reaction in patients with and without isolated anti‐HBc. Of 2351 HIV‐positive patients, 450 (19.1%) were HBsAg positive, 411 (17.5%) were anti‐HBc positive alone and 963 (41.0%) for both anti‐HBs and anti‐HBc. Compared with patients who were positive for both anti‐HBs and anti‐HBc, patients with isolated anti‐HBc were older, less likely to have anti‐hepatitis C virus antibody (anti‐HCV), had lower CD4 lymphocyte counts and higher plasma HIV RNA loads. Older age (adjusted odds ratio, 1.029; 95% confidence interval, 1.015–1.043) and CD4 <100 cells/μL (adjusted odds ratio, 1.524; 95% confidence interval, 1.025–2.265) were independently associated with isolated anti‐HBc by logistic regression, while presence of anti‐HCV and injecting drug use were not. HBV DNA was detectable in 8.3% of 277 patients with isolated anti‐HBc and 14.3% of 56 patients with both anti‐HBs and anti‐HBc (P = 0.160). In a country hyperendemic for HBV infection, HIV‐positive patients at older age and with CD4 <100 cells/μL were more likely to have isolated anti‐HBc, suggesting that compromised immunity plays a role in the presence of this marker.     

Significant background rates of HBV and HCV infections in patients and risks of blood transfusion from donors with low anti-HBc titres or high anti-HBc titres with high anti-HBs titres in Japan: a prospective, individual NAT study of transfusion-transmitted HBV, HCV and HIV infections

Background The Japanese Red Cross (JRC) conducted a prospective study to evaluate the frequency of transfusion‐transmitted HBV, HCV and HIV infections to assess the risk of transfusion of blood components routinely supplied to hospitals. Study Design and Methods Post‐transfusion specimens from patients at eight medical institutes were examined for evidence of infection with HBV (2139 cases), HCV (2091) and HIV (2040) using individual nucleic acid amplification testing (NAT). If these specimens were reactive, pre‐transfusion specimens were also examined for the virus concerned by individual NAT. In the event that the pre‐transfusion specimen was non‐reactive, then all repository specimens from implicated donors were tested for the viruses by individual donation NAT. In addition, a further study was carried out to evaluate the risk of transfusion of components from donors with low anti‐HBc titres or high anti‐HBc with high anti‐HBs titres. Results Transfusion‐transmitted HCV and HIV infections were not observed. One case of post‐transfusion HBV infection was identified (rate, 0·0004675; 95% CI for the risk of transmission, 1 in 451–41 841). The background rates of HBV, HCV and HIV infections in patients prior to transfusion were 3·4% (72/2139), 7·2% (150/2091) and 0% (0/2040), respectively. Sixty‐four anti‐HBc‐ and/or anti‐HBs‐reactive blood components were transfused to 52 patients non‐reactive for anti‐HBc or anti‐HBs before and after transfusion (rate, 0; 95% CI for the risk of transmission, <1 in 22). Conclusion This study demonstrated that the current criteria employed by JRC have a low risk, but the background rates of HBV and HCV infections in Japanese patients are significant.     

Prevalence and virological features of occult hepatitis B virus infection in female sex workers who work uncontrolled in Turkey

Background: There is little information about the prevalence of occult hepatitis B virus infection (OHBVI). We have investigated the prevalence and virological features of OHBVI among female sex workers (FSWs) in Istanbul. Methods: Hepatitis B surface antigen (HBsAg) was tested in FSWs who work uncontrolled and were admitted to Venereal Diseases Hospital. HBV DNA and anti‐HBs were investigated in all the HBsAg‐negative cases. Hepatitis B envelope (HBe) antigen, anti‐HBe, anti‐hepatitis B core (HBc) antigen, HBV genotype, S gene and precore (PC)/basic core promoter (BCP) mutations were determined in HBV DNA‐positive sera. Results: Two hundred and eighty‐six volunteers were enrolled and 32.5% (n=93) of them had anti‐HBs positivity. HBV DNA (range 30–209 copy/ml) was positive in 11 anti‐HBs‐negative and two anti‐HBs‐positive cases. The prevalence of OHBVI was 4.5% (13/286). Anti‐HBc was positive in 77% (10/13) of those with OHBVI and anti‐HBe positivity was 53.8% (7/13). Only genotype D was present in all occult HBV‐infected cases. One PC (G1896A) and one BCP (T1762/A1764) mutation was found, but S gene mutation was not detected in any of the samples. Conclusion: In this population, OHBVI may have a negligible role in the horizontal transmission because of a very low viral load, and PC and core promoter mutations are very rare.     

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.     

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.     

Prevalence of occult hepatitis B & C in HIV patients infected through sexual transmission.

BACKGROUND: Prevalence of Hepatitis B virus (HBV) and Hepatitis C virus (HCV) markers including active and occult infection has not been described in diverse cohorts among HIV-infected patients in India. Earlier studies have explained the role of HBV/HCV co-infection in cohorts of injection drug users (IDUs) but the sexual co-transmission of HBV/ HCV is not completely understood. OBJECTIVE: The objective of this study was to assess the prevalence of occult HBV & HCV infection in HIV positive sexually acquired transmission risk group. MATERIALS AND METHODS: 58 sexually acquired HIV positive patients were taken up for the study of occult HBV/HCV co-infection. Data on demographics, sexual behaviour, sexually transmitted diseases (STD), medical history, laboratory tests viz., serum ALT and CD4 count were recorded. HBV serology included HBsAg, anti HBs, IgG anti HBc and HBV DNA (PCR). HCV serology included anti HCV & HCV RNA (RT-PCR). RESULTS: Occult HBV infection (HBV DNA) was observed in 12.2% (7/58 with HBsAg -ve and IgG anti HBc +ve subjects) while an overall prevalence of HBV DNA was 13.7% (12% occult & 1.7% in HBsAg+ve patients). Out of 58 HIV positive patients 29.3% demonstrated reactivity for any marker of past or current HBV infection. (HBsAg 1.7%, anti HBs 10.3% anti HBc IgG 17.2%). 4/58 (6.8%) revealed anti HCV positivity along with HCV RNA positivity by RT-PCR while 6/58 (10.3%) individuals revealed an occult HCV infection (anti HCV negative). The overall HCV RNA prevalence was 17.2%. 2 out of 58 (3.4%) individuals were positive for occult infection of both HBV DNA & HCV RNA (Triple infection HIV/HBV/ HCV). The HBV/HCV co-infected group (n = 18) showed a significantly high ALT (114.3 + 12.3 U/I) & low CD4 count (202.5 + 33.7 cells/mm3). The percent prevalence of HBV/ HCV co-infection was higher in the illiterate group, in men less than 30 years of age, and in those who were married and exhibited polygamous activity. CONCLUSIONS: The study demonstrated that in HIV infected patients testing only serological viral markers like HBsAg, antiHBcIgG & anti HCV, fails to identify the true prevalence of co-infection with HBV & HCV. Qualitative PCR for HBV DNA & HCV RNA detects co-infection in patients who are negative for serological markers. Also, in subjects who had only a sexual risk factor for parenterally transmitted infections, HIV may enhance the sexual transmission of HBV and HCV.     

A seroepidemiological survey of the effect of hepatitis B vaccine and hepatitis B and C virus infections among elementary school students in Siem Reap province,Cambodia

Aim

This study aimed to survey the prevalence and incidence of hepatitis B (HBV) and hepatitis C virus (HCV) infection among elementary school students in Siem Reap province, Cambodia and to evaluate the effects of a national infant HBV vaccination program introduced in 2001.

Methods

Students in 3rd grade during the 2011, 2012, and 2013 academic years were enrolled in this study; at the time of the second examination, in the 2014–2015 academic year, the students were in 5th or 6th grade. The incidence and prevalence rates of HBV and HCV infection were estimated and full HBV sequences were analyzed.

Results

Among 248 students (107 male and 141 female) born between 1999 and 2005, five students were HBV surface antigen (HBs‐Ag) positive (2.02%), and all of them were infected with genotype C. Among them, subgenotype C1 was found in four students and, unexpectedly, complete genetic sequence identity of subgenotype C1 was found in two students from different families. The anti‐HBV core (HBc) and anti‐HBs prevalence rates were 10.89% and 16.13%, respectively. Twenty‐five students were positive for anti‐HBs and negative for both HBsAg and anti‐HBc (10.08%; estimated serological vaccination rate); this rate increased significantly with the birth year (P = 0.0229). Prevalence of anti‐HCV was 2.82%, and HCV RNA was not detected. The estimated incidence of HBV and HCV infection were both 0/1000 person‐years (PY) (95% confidence interval, 0–20.61/1000 PY and 0–14.50/1000 PY, respectively).

Conclusion

Hepatitis B virus full‐genome sequencing and serological analysis revealed the possibility of horizontal transmission of HBV among Cambodian schoolchildren. However, the anti‐HBc positivity rate decreased along with increasing age and estimated serological vaccination rates.     

Evaluating the risk of hepatitis B reactivation in patients with haematological malignancies: is the serum hepatitis B virus profile reliable?

Background/Aim: Patients with an occult hepatitis B virus (HBV) infection undergoing deep immunosuppression are potentially at risk of HBV reactivation. In order to assess whether a polymerase chain reaction (PCR) assay for HBV DNA in serum could be used to predict the reactivation of an occult HBV infection, we performed a retrospective study in a cohort of Sicilian patients with oncohaematological diseases. Methods: We studied by a highly sensitive ad hoc nested PCR for serum HBV DNA 75 HBsAg‐negative oncohaematological patients requiring chemotherapy. Results: Thirty‐three patients (44%) were HBV seronegative (anti‐HBc and anti‐HBs negative) and 42 patients (56%) were HBV seropositive (anti‐HBc and/or anti‐HBs positive). Baseline serum HBV DNA was positive in nine out of 33 HBV‐seronegative patients and in nine out of 42 HBV‐seropositive patients (27.3 vs. 21.4%; P=NS). HBsAg seroconversion was observed in five out of 33 seronegative vs. six out of 42 seropositive patients (15 vs. 14%, P=0.9), and in five out of 18 HBV DNA‐positive vs. six out of 57 HBV DNA‐negative patients (27.7 vs. 10.6%P=0.11). Hepatitis C virus infection was found in 18 patients (24.3%), although with no correlation to HBV serological status, presence of serum HBV DNA or frequency of HBsAg seroconversion. Conclusions: In oncohaematological patients undergoing chemotherapy, highly sensitive serum HBV DNA testing at baseline has a 28% predictive ability to forecast HBsAg seroconversion in HBV DNA‐positive patients, and a 90% ability to forecast persistent HBsAg negativity in HBV DNA‐negative patients, a better performance than serological tests.     

Occult Hepatitis B Virus Infection in Japanese Chronic Hemodialysis Patients

We investigated the prevalence of occult hepatitis B virus (HBV) infection in Japanese chronic hemodialysis patients. Hemodialysis patients (n = 1041) were screened for occult HBV. The presence of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody, and hepatitis B core antibody (anti‐HBc) was determined by various chemiluminescent immunoassays. HBV‐DNA was quantified in patients positive for anti‐HBc using quantitative real‐time polymerase chain reaction. Among the 1041 patients, six (0.6%) were HBsAg‐positive and 218 (20.9%) were anti‐HBc‐positive. All HBsAg‐positive patients also tested positive for the presence of HBV DNA. Of 212 HBsAg‐negative and anti‐HBc‐positive patients, three were positive for HBV DNA. Our study showed that the prevalence of occult HBV infection in chronic hemodialysis patients from eastern Japan was 0.3%.     

Incidence of hepatitis B virus infection in young Chinese blood donors born after mandatory implementation of neonatal hepatitis B vaccination nationwide

This study was carried out to determine the incidence of hepatitis B virus (HBV) infection in the young generation born after mandatory implementation of hepatitis B vaccination since 1992. Repeat blood donors born between 1992 and 1997 were enrolled, who gave blood at least twice during the past 3 years. Donors were tested for HBV infection markers of HBsAg, anti‐HBc, anti‐HBs and viral DNA by immunoassays (EIAs) and nucleic acid tests (NAT). A total of 14 937 pre‐donation screening qualified young repeat donors aged 18‐23 years were tested with 9 (0.06%) being HBsAg by EIA and 10 (1:1494) HBV DNA positive by Ultrio NAT (10.4 IU/mL), respectively. HBV DNA was further detected in 1:192 (9/1732) anti‐HBc+ repeat donors with Ultrio Plus NAT (3.4 IU/mL). Most cases were identified as occult HBV infection (OBI). Of 14 937 repeat donors, 20.9% were anti‐HBc+ positive, while approximately 50% of 12 024 repeat donors were anti‐HBs negative or had levels <100 IU/L. HBsAg+ or OBI strains were classified as wild type of genotype B or genotype C. Incident HBV infection in repeat donors was approximately 1:18.5 person‐years (1.1%/year) but significantly less frequent in donors with confirmed HBV vaccination (2.4%‐3.3%) than those unsure of vaccination status (10.5%; P = .0023). Hepatitis B virus vaccination appears largely protective of HBV infection, but incidence of infections increases in young adults with mostly undetectable or low anti‐HBs or occasionally high anti‐HBs. A boost of hepatitis B vaccine for adolescents prior to age 18 years may reduce HBV infection, and implementation of more sensitive NAT in blood donation screening may improve HBV safety in blood transfusion.     

Persistent and transient hepatitis B virus (HBV) infections in children born to HBV‐infected mothers despite active and passive vaccination

Summary. Combined passive and active immunization for newborns very effectively prevents perinatal hepatitis B virus (HBV) infections. In the Netherlands, babies born to hepatitis B surface antigen (HBsAg)‐positive women receive passive immunization with hepatitis B and at least three active HBsAg vaccinations. Serological testing for the presence of HBV markers was offered for all infants born to HBsAg‐positive mothers between January 2003 and July 2007, after completion of their vaccination schedule. About 75% of the infants (n = 1743) completed their HB‐vaccination schedule and participated in the serologic evaluation. Twelve of them (0.7%) were found to be HBV infected. Furthermore, we identified three older children with high levels of anti‐HBc, anti‐HBs and anti‐HBe, while they were HBsAg and HBV DNA negative. This serologic profile is evidence for a resolved HBV infection. In the group of older children (1.5–5 years of age, n = 728), about half of the HBV‐infected children (3 of 7) had already cleared their infection at the time of sampling. For a proper evaluation of the efficacy of a new intervention programme to prevent vertical HBV transmission, it is also important to analyse the HBV markers in serum collected when the children are older than 1.5 years. In a programmatic setting, all children born to HBV‐infected mothers should be tested not only for the level of anti‐HBs but also for the absence of HBsAg, because 2 of the 12 HBV‐infected children (17%) had a high level of anti‐HBs.     

Low risk of hepatitis B reactivation in patients with severe COVID‐19 who receive immunosuppressive therapy

A significant proportion of patients infected with SARS‐CoV‐2 develop severe respiratory symptoms due to an excessive immune response. Treatment of this condition may include immunosuppressive therapies, such as IL‐6 receptor antagonists and corticosteroids, which pose a risk for patients with active or past hepatitis B virus (HBV) infection. In this prospective cohort study, we analysed the risk of HBV reactivation in patients with severe COVID‐19 and resolved HBV infection undergoing immunosuppressive therapy. From 15th March to 30th April 2020, 600 patients with severe COVID‐19 were admitted to our hospital and treated with immune modulators. Data regarding HBV infection were available in 484, of whom 69 (14%) were HBsAg negative/anti‐HBc positive. For these patients, HBV reactivation prophylaxis with entecavir was strongly recommended. Complete follow‐up was available in 61 patients: 72% were male, median age was 67 years, and anti‐HBs was >10 IU/mL in 72%. The immunosuppressive drug most used was tocilizumab (72%). Despite HBV prophylaxis recommendation, 38 (62%) patients received entecavir and 23 (38%) did not. Baseline features of both groups were similar. At follow‐up, we found no cases of HBsAg seroreversion and only 2 (3%) patients (no prophylaxis group) had detectable serum HBV‐DNA (<15 IU/mL). Both were anti‐HBs negative and had normal aminotransferase levels. Our data show that the risk of HBV reactivation in patients with severe COVID‐19 and resolved HBV infection undergoing immunosuppressive treatment is low. However, if a systematic follow‐up after hospital discharge is unfeasible in patients without anti‐HBs, a short course of antiviral prophylaxis may be a safe option.     

Previous hepatitis B virus infection is associated with worse disease stage and occult hepatitis B virus infection has low prevalence and pathogenicity in hepatitis C virus‐positive patients

Abstract: Background: Anti‐hepatitis C virus (anti‐HCV) patients with chronic liver disease (CLD) frequently show markers of previous hepatitis B virus (HBV) infection. Moreover, they may carry occult HBV infection. These features might influence clinical and biochemical features as well as stage of disease. Aim: To assess the prevalence and clinical associations of previous (positivity for anti‐HBs and/or anti‐HBc antibodies) and occult HBV infection (positivity for HBV‐DNA by nested‐PCR) in the serum of anti‐HCV‐positive, HCV‐RNA‐positive, HBsAg‐negative patients with various degrees of CLD seen at a tertiary referral centre. Patients: A total of 119 patients fulfilled the inclusion criteria (84 chronic hepatitis and 35 liver cirrhosis). Results: Forty‐eight patients (40.3%) showed markers of previous HBV infection. This feature was more frequent (P = 0.02) among cirrhotics (57%) as compared to chronic hepatitis patients (33%). Chronic hepatitis patients positive for markers of previous HBV infection had worse histology as compared to negative ones (grading: 6.4 ± 2.7 versus 4.6 ± 3.0, P = 0.004; staging: 1.6 ± 1.2 versus 1.0 ± 1.0, P = 0.01). Eight patients were positive for HBV‐DNA in serum (6.7%). No difference in the presence of occult HBV infection was seen between various degrees of liver disease (7.1% of chronic hepatitis, 5.7% of cirrhosis) and among patients who were positive (10.4%) or negative (4.2%) for markers of previous HBV infection. No significant biochemical, virological, or histological difference was observed between age, age at infection, duration of infection, marker patterns of previous HBV infection‐matched HBV‐DNA‐positive and negative chronic hepatitis patients. Conclusions: Our findings suggest that previous HBV infection among anti‐HCV patients is associated with worse disease stage. In these patients, the prevalence of occult HBV infection is low and there is no difference in distribution among patients with or without markers of previous HBV infection. Furthermore, it does not seem to be associated with disease stage. Lastly, at least among patients with chronic hepatitis, it does not seem to affect the severity of disease.     

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.     

Low levels of awareness, vaccine coverage, and the need for boosters among health care workers in tertiary care hospitals in India

Background and Aim: The risk of acquiring hepatitis B virus (HBV) infection through exposure to blood or its products is highest amongst health care workers (HCWs). Despite potential risks, a proportion of HCWs never get vaccinated. India is second to China in the numbers of people with chronic HBV. This study aimed to investigate the vaccination practices and the prevalence of HBV infection in HCWs in India. Methods: A total of 2162 HCWs were screened for the presence of serological markers of HBV and hepatitis C virus (HCV). Occult HBV infection was tested by detection of HBV‐DNA for surface and core regions by nested polymerase chain reaction in HBsAg‐negative and IgG anti‐hepatitis core antigen–positive subjects. Results: Only 1198 (55.4%) of the 2162 HCWs screened had been vaccinated; and 964 (44.6%) were not vaccination‐status conscious; of these HCWs, 600 (27.7%) had never been vaccinated and 364 (16.4%) were unaware of their vaccination status. Protective (> 10 IU/mL) anti‐hepatitis B surface (anti‐HBs) antigen titers were seen in only 61.7%. The anti‐HBs titers were found to be lower with the passage of time; the median anti‐HBs titers in subjects who were vaccinated > 10 years ago were significantly lower than those who had been vaccinated < 5 years ago (P < 0.001). One percent of HCWs were HBsAg‐positive, and 24.7% of 700 HCWs screened had past exposure (IgG‐anti‐HBc‐positive). Occult HBV was detected in 5% of 120 positive subjects with past exposure; all had anti‐HBs titers > 10 IU/mL. Conclusions: Even today, 28% HCWs in India are unvaccinated and 17% are unaware of their vaccination status. This data suggests that use of hepatitis B immune globulin be mandatory in needle‐pricked HCWs in India, and that implementation of awareness strategies is urgent. Since the anti‐HBs titers decline in a fair proportion, there is justification for giving a booster dose of vaccine 10 years after primary vaccination to HCWs in India.     

T‐ and B‐cell responses and previous exposure to hepatitis B virus in ‘anti‐HBc alone’ patients

A serologic response to hepatitis B virus (HBV) defined as ‘anti‐HBc alone’ is commonly observed, but its significance remains unclear. This study aimed to define the relationship between ‘anti‐HBc alone’ serostatus and HBV infection, including HBV‐specific T‐ and B‐cell memory responses. We enrolled 31 ‘anti‐HBc alone’ patients. Total HBV DNA and cccDNA were tested by nested polymerase chain reaction (PCR) analysis in liver samples from 22 ‘anti‐HBc alone’ patients vs controls (chronic or resolved HBV infection), followed by HBsAg/HBcAg immunohistochemical (IHC) staining. IFN‐γ secretion by HBV‐specific T cells was compared in individuals who were ‘anti‐HBc alone’ (n = 27), resolved HBV (n = 21), chronic HBV (n = 24) and 12 healthy controls using enzyme‐linked immunospot (ELISpot) assays. An HBsAg‐IgG B‐cell ELISpot assay was performed in ‘anti‐HBc alone’ patients before and after one dose of recombinant HBsAg vaccine. The majority (23/31, 74.2%) of the ‘anti‐HBc alone’ individuals were co‐infected with HCV. Infrequent intrahepatic total HBV DNA (2/22, 9.1%) and cccDNA (1/22, 4.5%) were detected in biopsies; HBsAg and HBcAg IHC staining was negative. HBV‐specific T‐cell responses were similar between ‘anti‐HBc alone’ individuals and HBV resolvers. Circulating HBV‐memory B‐cell responses were detected in all ‘anti‐HBc alone’ individuals, consistent with an HBsAg‐specific memory pool. After one HBV vaccine dose, increased anti‐HBs antibody levels were observed, accompanied by an expansion of HBsAg‐specific memory B cells (P = 0.0226). ‘Anti‐HBc alone’ individuals showed HBV‐specific T‐cell and memory B‐cell responses typical of previous viral exposure and protective memory, suggesting a resolved infection.     

Prevalence of hepatitis B virus infection in non‐Hodgkin lymphoma: a systematic review and meta‐analysis

Background and aim: A recent meta‐analysis has demonstrated an association between hepatitis C virus and non‐Hodgkin lymphoma (NHL). There is also evidence on the association between hepatitis B virus (HBV) and NHL. The aim of this study was to evaluate this evidence using a meta‐analytic approach. Methods: We searched the MEDLINE database from 1962 to 2008 for case–control studies that have reported the association of HBV with NHL. We calculated the odds ratio (OR) and 95% confidence intervals (CI) to assess the prevalence of HBV infection and pooled the results using three different statistical models. Results: Our search yielded 12 studies with 11 studies (3262 NHL patients, 1 523 205 controls) evaluating HBV infection in NHL and one study (3888 HBV‐infected individuals, 205 203 controls) that had investigated for NHL in HBV infection. The OR of detecting HBV infection in NHL when compared with the control population was 2.56 (95% CI, 2.24–2.92) by the fixed effects model; 2.61 (95% CI, 2.29–2.98) by the exact method and 2.67 (95% CI, 2.04–3.49) by the random effects model suggesting a high prevalence of HBV carrier state in lymphoma. There was evidence of statistical heterogeneity which disappeared after exclusion of retrospective studies on sensitivity analysis. Conclusions: The results of this study suggest a possible causal relation between HBV infection and NHL which needs to be confirmed by experimental and epidemiological studies. In countries where prevalence of HBV infection is 1% or more, it may be prudent to screen patients with NHL for occult HBV infection.     

Hepatitis C virus among non‐injecting cocaine users (NICUs) in South America: can injectors be a bridge?

Aim To investigate the factors associated with hepatitis C virus (HCV) infection among non‐injecting cocaine users (NICUs) and to compare practices associated with HCV and HIV infection. Design An intercountry cross‐sectional study. Setting Buenos Aires and Montevideo metropolitan areas. Participants A total of 871 NICUs. Measurements NICUs were interviewed and their blood was drawn and used for HCV, HIV, HBV surface antigen (HbsAg), HB‐anticore and Venereal Disease Research Laboratory (VRDL) antibody assays. Bivariate and multivariate logistic regression analyses included comparisons of HCV and HIV mono‐infected participants with HCV–HIV seronegatives. Findings Prevalence rates were 8.8 [95% confidence interval (CI): 6.9–10.8) for HCV and 7.9 (95% CI: 6.1–9.7) for HIV. HCV‐infected NICUs were twice as likely as HCV–HIV seronegatives to have shared straws for cocaine snorting or sniffing, even when adjusted for other variables. HCV prevalence rates ranged from 3.6% among NICUs who denied sharing straws and having had an injection drug user (IDU) or an HIV‐positive sexual partner to 12.6% among participants who reported ever having shared straws or having had either an IDU‐ or HIV‐positive sexual partner (χ²_trend = 6.56, P = 0.01). Conclusions Non‐injecting cocaine users from South America are vulnerable to multiple infections and HCV infection appears to occur through the sharing of straws. HCV infection is associated with intimate relationships with IDUs or HIV‐seropositive partners, supporting the hypothesis that HCV risk may be due primarily to risk‐taking behaviour associated with drugs in this population.     

HBV reactivation in patients with HCV/HBV cirrhosis on treatment with direct‐acting antivirals

Anecdotal reports suggest that patients with chronic hepatitis C virus (HCV) hepatitis and overt or occult hepatitis B virus (HBV) coinfection may reactivate HBV when HCV is suppressed or cleared by direct‐acting antivirals (DAAs). We assessed the prevalence of overt or previous HBV coinfection and the risk of HBV reactivation in patients with HCV cirrhosis treated with DAAs. This was a retrospective cohort of 104 consecutive patients with HCV cirrhosis treated with DAAs. Serum HCV‐RNA and HBV‐DNA were tested at weeks 4, 8 and 12 of DAAs therapy and at week 12 of follow‐up. At the start of DAAs, eight patients (7.7%) were HBsAg positive/HBeAg negative with undetectable HBV‐DNA and low levels of quantitative HBsAg (four on nucleos(t)ide analogues [NUCs] and four inactive carriers), 37 patients (35.6%) had markers of previous HBV infection (25 anti‐HBc positive, 12 anti‐HBc/anti‐HBs positive) and 59 (56.7%) had no evidence of HBV infection. Sixty‐seven patients (64.4%) were HCV‐RNA negative at week 4 and 98 (94.2%) achieved sustained virological response. All four HBsAg‐positive patients treated with NUCs remained HBV‐DNA negative, but three of four untreated patients showed an increase in HBV‐DNA of 2‐3 log without a biochemical flare and achieved HBV‐DNA suppression when given NUCs. During or after DAAs, by conventional assay, HBV‐DNA remained not detectable in all 37 anti‐HBc‐positive patients but in three of them (8.1%) HBV‐DNA became detectable with a highly sensitive PCR. HBV reactivation is likely to occur in untreated HBV/HCV‐coinfected cirrhotic patients when they undergo HCV treatment with DAAs. Pre‐emptive therapy with NUCs should be considered in this setting. Anti‐HBc‐positive patients rarely reactivate HBV without clinical or virological outcomes.