Hepatitis B Core Antibody Positivity Research Articles

HBcAb Positivity as a Risk Factor for Missing HIV RNA Undetectability after the 3TC+DTG Switch.

Hepatitis B Core antibody (HBcAb) positivity is the surrogate marker of hepatitis B occult infection. This condition is not a contraindication for switching to two-drug (2DR) antiretroviral therapy; however, the removal of tenofovir may contribute to poor control of HBV replication. A multicentre retrospective cohort study investigated the impact of HBcAb positivity on HIV control in patients switching to a 2DR with Lamivudine and Dolutegravir (3TC-DTG). In this study, a comparison analysis was conducted between HBcAb-positive and -negative PLWH regarding HIV-RNA suppression, considering: (1): Target Not Detected (TND) < 20 cp/mL; (2) Target Detected (TD) < 20 cp/mL; and (3) Detectable > 20 cp/mL and <50 cp/mL and >50 copies/mL. A total of 267 patients on 2DR with 3TC-DTG were included. In comparison to HBcAb-negative, HBcAb-positive patients were older (45 years [35-54]) and had a lower CD4+ nadir (248 vs. 349 cells/mmc, p = 0.007). No difference in the maintenance of virological suppression was present in the two groups of patients before the switch. Although no patient had an HIV-RNA > 20 cp/mL after the switch, significantly fewer HBcAb-positive compared with -negative subjects resulted in TND at 12, 24, and 36 months after the switch: 52 (69.3%) versus 164 (85.4%), p = 0.004, 50 [72.5%] versus 143 [89.9%], p = 0.001, and 30 [66.7%] versus 90 [92.8%], p = 0.001, respectively. HBcAb positivity is associated with an increased risk of suboptimal HIV suppression during the 36 months after 3TC/DTG simplification. This finding reinforces the relevance of the OBI condition in PLWH and raises the issue of careful virological monitoring of such cases.

HBcAb positivity increases the risk of postoperative complications after extended hemihepatectomy for hilar cholangiocarcinoma.

Hepatitis B core antibody (HBcAb) positivity is considered a prior hepatitis B virus (HBV) infection. However, little is known about the effect of HBcAb positivity on surgical safety for hilar cholangiocarcinoma (hCCA). The present study aims to investigate the role of HBcAb positivity on postoperative complications of hCCA. A retrospective analysis was performed on the status of HBcAb positivity, liver fibrosis, perioperative surgical complications, and long-term outcomes of hCCA patients with Hepatitis B surface antigen (HBsAg) negativity who underwent surgical treatment in Tongji Hospital from April 2012 to September 2019. HBcAb positivity with negative HBsAg occurs in 137 hCCA patients (63.1%). A total of 99 hCCA patients with negative HBsAg underwent extended hemihepatectomy, of whom 69 (69.7%) and 30 (30.3%) were HBcAb-positive and HBcAb-negative, respectively. Significant fibrosis was detected in 63.8% of the patients with HBcAb-positive, which was markedly higher than those with HBcAb-negative (36.7%) (p=0.016). The postoperative complications and 90-day mortality rates were 37.4% (37/99) and 8.1% (8/99), respectively. The incidence of postoperative complications in HBcAb-positive patients (44.9%) was significantly higher than that in HBcAb-negative patients (20.0%) (p=0.018). All the patients who died within 30-day after surgery were HBcAb-positive. Multivariate analysis showed that the independent risk factors for complications were HBcAb positivity, preoperative cholangitis, portal occlusion >15 min, and significant fibrosis. There were no significant differences in recurrence-free survival (RFS) and overall survival (OS) between HBcAb-positive and HBcAb-negative patients (p=0.642 and p=0.400, respectively). HBcAb positivity is a common phenomenon in hCCA patients from China, a country with highly prevalent HBcAb positivity. The status of HBcAb-positive markedly increases the incidence of postoperative complications after extended hemihepatectomy for hCCA patients.

Surveillance of Liver Function in Uveitis with or without Chronic HBV Infection

Introduction: Immunosuppressive therapy for uveitis may cause liver damage. Methods: To investigate incidence of liver damage during uveitis treatment, we compared serological Hepatitis B core antibody (HBcAb) status with risk of liver dysfunction in all participants (n = 992), in anterior uveitis (AU) (n = 489), and combined of intermediate, posterior, or panuveitis (IPPU) patients (n = 503). The primary endpoint was incidence of elevated serum alanine aminotransferase level above 2-fold upper limits of normal within 6 months. Results: The incidence rate of primary endpoint for HBcAb-negative and HBcAb-positive patients was 65 and 212 per 1,000 person years, respectively. The absolute rate difference was 147 (95% confidence interval [CI], 80–213) per 1,000 person years. HBcAb positivity was associated with a higher risk for primary endpoint in all participants (adjusted hazard ratio [aHR], 3.53; 95% CI, 1.79–6.99; p value = 2.8 × 10⁻⁴) and in IPPU (aHR, 3.80; 95% CI, 1.61–9.01; p value = 0.002). No significant association with primary endpoint was observed for HBcAb positivity in AU (aHR, 3.21; 95% CI, 0.94–10.95; p value = 0.063). AU was mainly treated with topical eye drops (74.0%), whereas IPPU cases received systemic therapy including prednisone (94.0%), cyclosporine (80.9%), or other additionally combined immunomodulatory agents (14.9%). Conclusion: Noninfectious uveitis cases with HBcAb positivity have an increased risk of liver damage. This association was predominantly driven by IPPU but was not significant in AU, suggesting that the association is mediated by systemic therapy.

Hepatitis B Virus Screening and Real Life Data in Patients with Solid Tumor Receiving Chemotherapy.

Reactivation of the hepatitis B virus (HBV) either during or after chemotherapy may cause serious and sometimes fatal hepatitis. All patients undergoing chemotherapy should therefore be screened in terms of HBV before chemotherapy. The purpose of this research was to identify HBV screening rates in patients with solid cancer undergoing parenteral chemotherapy and to determine the outcomes of patients undergoing HBV screening. Data for patients undergoing parenteral chemotherapy for solid cancer from January 1, 2012 to December 30, 2018 were retrieved from our electronic health record patient files in this retrospective study. Screening was defined as hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (HBcAb) tests carried out within six months prior the first chemotherapy session. Four thousand fifty-eight (63%) of the 6440 patients who underwent parenteral chemotherapy were screened for HBsAg and/or HBcAb. The proportions of patients screened for HBsAg and HBcAb improved from 38.8% (2012) to 76.3% (2018), and from 0.2% (2012) to 43% (2018), respectively (P<0.001). The HBsAg and HBcAb positivity rates were 2.9% and 36.5%, respectively. Antiviral prophylaxis was started in 11.8% of HBsAg-negative/HBcAb-positive patients and 40.5% of HBsAg-positive patients. HBV reactivation did not occur in patients receiving antiviral prophylaxis, but was identified in 7.2% of HBsAg-positive patients and 0.6% of HBsAg-negative/HBcAb-positive patients without antiviral prophylaxis. Although HBV screening rates before chemotherapy are increasing among solid cancer patients, the rate of initiation of antiviral prophylaxis is still low. It is therefore important to raise awareness regarding HBV reactivation during/after chemotherapy.

Epidemiological Correlations Between Head and Neck Cancer and Hepatitis B Core Antibody Positivity.

Hepatitis B core (HBc) antibody positivity indicates a history of hepatitis B virus (HBV) infection and latent infection. We conducted a retrospective case-control study of 512 and 495 head and neck cancer (HNC) and non-HNC patients treated at the Okayama University Hospital, Head and Neck Cancer Center from 2008-2017. Demographic data and risk factors that might affect HNC diagnosis were analyzed to assess their effects. Cancer diagnosis was found to correlate with HBc antibody positivity [odds ratio (OR)=1.50, 95% confidence interval (CI)=1.09-2.08], smoking (OR=3.03, 95%CI=2.16-4.25), and a previous history of cancer (OR=4.12, 95%CI=2.79-6.09). The HBs antigen positivity rate in both groups was very close to that observed in the general Japanese population. The HBc antibody positivity rate was very high only in the HNC group. HBc antibody positivity and HNC are epidemiologically correlated.

Hepatitis B Seropositivity is Associated with Increased Cardiac Allograft Vasculopathy after Heart Transplantation

Viral triggers have been implicated in the pathogenesis of cardiac allograft vasculopathy (CAV), the Achilles heel of heart transplantation (HT). Cytomegalovirus is associated with impaired coronary endothelial function, and in pediatric HT patients a variety of viruses, particularly adenovirus, are associated with graft dysfunction or loss. Hepatitis B virus (HBV) is associated with vasculitis and vascular processes in non-HT patients. We thus investigated the association between HBV seropositivity and CAV after HT. The 173 HT patients assessed for HBV serology from 1997 to 2017 were divided into hepatitis B core antibody (HBcAb) positive (n=29) and HBcAb negative (n=144) groups. Primary outcomes were CAV and the combined end-point of CAV or cardiovascular mortality. Baseline patient and donor clinical and demographic data for the 2 groups were similar. Kaplan-Meier analysis showed that 20-year freedom from CAV was significantly higher in the HBcAb-negative vs HBcAb-positive group (80 vs 50%, log-rank p=0.003, Figure 1A). Similarly, 20-year freedom from CAV or cardiovascular mortality was higher for the HBcAb-negative group (75 vs 45%, log-rank p=0.018). Consistently, multivariable analysis showed HBcAb positivity to be independently associated with a significant ∼3-fold increased risk of CAV (95% CI 1.38-5.01, p=0.003, Figure 1B), and a 2-fold increased risk of CAV or cardiovascular mortality (95% CI 1.11-3.90, p=0.021). Hepatitis B seropositivity is independently associated with an increased risk of CAV in HT recipients. Future studies are needed to examine the effect of anti-viral therapies.

Characterization of Occult Hepatitis B Infection Among Injecting Drug Users in Tehran, Iran.

BackgroundHepatitis B virus (HBV) infection is a major health problem worldwide.ObjectivesThe aim of this study was to investigate the frequency of occult hepatitis B infection (OBI) and its associated risk factors, together with the molecular characterization of the virus in injecting drug users of Tehran.Patients and MethodsThe study consisted of 229 injecting drug users. Serum samples were collected and tested for the presence of hepatitis B core antibody (HBcAb) and hepatitis B surface antigen (HBsAg) by an enzyme-linked immunosorbent assay (ELISA). HBV B virus DNA was extracted from the serum samples, and a fragment of the S gene was amplified using the nested polymerase chain reaction. The genotype, subgenotypes, subtype, and S gene mutation of HBV were determined by direct sequencing. A phylogenetic tree was constructed using the neighbor-joining method.ResultsSixty-four (28%) participants were HBcAb positive, 59 cases were HBcAb positive and HBsAg negative, and 5 cases were HBsAg positive. Hepatitis B DNA was found in three HBsAg-positive cases. Thirteen of 59 (22%) individuals were hepatitis B DNA positive. The phylogenetic tree of hepatitis B DNA showed the existence of genotype D. The only significant correlation was between sharing a syringe and OBI.ConclusionsIn comparison with the rate of HBcAb positivity reported in other Iranian studies, the rate was higher in the present study. There were a few variations, genotypes, and subtypes among the infected injecting drug users. Further investigations are needed to unravel the molecular characterization of OBI.

Positive HBcAb is associated with higher risk of early recurrence and poorer survival after curative resection of HBV-related HCC.

Previous studies predicted the prognosis of hepatocellular carcinoma (HCC) mainly based on tumour-related factors, whereas the impacts of hepatitis B virus (HBV)-related factors are usually ignored. The objective of this exploratory study was to investigate the prognostic role of hepatitis B core antibody (HBcAb) on post-operative survival and recurrence of HCC. A retrospective analysis of 3388 HBsAg positive (HBV-related) HCC patients treated by curative resection was performed. Multivariate analysis of independent prognostic factors was performed by Cox proportional hazards regression model. HBcAb positivity was an independent prognostic factor for recurrence-free survival (RFS) of HBV-related patients (P < 0.001, HR: 1.723, 95% CI: 1.278-2.324), and the 1-, 3-, 5-year RFS rates for HBcAb-negative patients were significantly better than those of HBcAb-positive patients (92.5%, 72.1% and 65.9% vs 77.9%, 58.6% and 46.9%, P < 0.001). HBcAb-positive HCC was much bigger (P = 0.006), more often involved with vascular invasion (P = 0.001), elevated AFP (P = 0.001) and ALT (P = 0.046) levels, but less often involved with capsule formation (P = 0.034). Besides vascular invasion, tumour size, interferon-α treatment, AFP and GGT level, HBcAb positivity was an independent prognostic factor for early intrahepatic recurrence of HBV-related patients (P = 0.025, HR: 1.766, 95% CI: 1.073-2.907) and the majority of HBcAb-positive recurrence were early recurrence while most of HBcAb-negative recurrence were late recurrence (P = 0.004). Positive HBcAb may represent a more invasive phenotype of HBV-related HCC, and is associated with a higher risk of early intrahepatic recurrence and poorer RFS of HBV-related patients after curative resection.

Clinical and Virologic Courses of Hepatitis B Surface Antigen-Negative and Hepatitis B Core or Hepatitis B Surface Antibody-Positive Renal Transplant Recipients

Recent findings suggest that reactivation of hepatitis B (HB) virus (HBV) in renal transplantation recipients with a past HBV infection is an important cause of morbidity and mortality. In the present study, we reviewed the clinical and virologic courses of past HBV infections in recipients following renal transplantation. We retrospectively analyzed pretransplant HB surface antigen (HBsAg), HB core antibody (HBcAb), HB surface antibody (HBsAb), and HBV deoxyribonucleic acid (DNA) levels in 147 patients who underwent renal transplantation at our institution between September 2000 and November 2011. Thirty-four (23.1%) of the patients were diagnosed with a past HBV infection. The mean age of patients with a past HBV infection was significantly older than that of those without (48.4 vs 41.1 years, P = .002), while the duration of hemodialysis (HD) was significantly longer (138 vs 79.5 months, P = .027) and ratio of cadaveric transplantation procedures was higher (41.2% vs 21.2%, P = .035). During the follow-up period after renal transplantation, HBsAg was negative, HBV DNA was undetectable, and serum alanine aminotransferase level was normal in all patients. There were no statistically differences for graft and patient survival, and serum creatinine level between patients with and without a past HBV infection. Our results indicate that a past HBV infection is significantly associated with older age, longer duration of HD, and cadaveric transplantation. However, no HBV reactivation occurred in our previously infected patients, and the presence of HBcAb or HBsAb positivity did not influence graft or patient survival or renal function following renal transplantation.

Outcomes of Liver Transplantation in Simultaneously Hepatitis B Surface Antigen and Hepatitis C Virus RNA Positive Recipients: The Deleterious Effect of Donor Hepatitis B Core Antibody Positivity

BackgroundRecent data from Italian studies have shown excellent results of liver transplantation (LT) in hepatitis B virus (HBV)–infected patients with grafts from hepatitis B core antibody (HBcAb)—positive donors, whereas such grafts in hepatitis C virus (HCV)–infected recipients have displayed poorer outcomes. We investigated the results of LT with HBcAb-positive grafts in patients with ongoing HBV and HCV coinfections. MethodsFrom August 1999 to December 2009, we performed 27 adult primary LTs from deceased heart-beating donors into recipients showing hepatitis B surface antigen (HBsAg)- and HCV-RNA-positivity simultaneously: 12 patients received a graft from an HBsAg-negative HBcAb-positive donor (core+D group) and 15 from an HBcAb-negative donor (core−D group). Immunosuppression included a calcineurin inhibitor, antimetabolite and steroids which were suspended at 6 months. Anti-HBV prophylaxis was always perfomed with anti-HBs immunoglobulins and nucleos(t)idic analogues. ResultsThe groups were similar regarding variables of donor, recipient, donor-recipient match, LT procedure, and acute rejection treatment. Median follow-up for surviving grafts was 67 months (range, 16–141). Among all patients, HCV-RNA remained positive after LT. The prevalence of histologically proven recurrent HCV hepatitis was similar in the 2 groups: 83% core+D vs 73% core−D. No recurrent HBV hepatitis occurred during the follow-up. Graft survival at 5 years was significantly lower in the core+D group (core+D 48% vs core−D 87%; P = .018), in which a significantly higher prevalence of graft loss was caused by HCV recurrence (core+D 5/12, 42% vs core−D 1/15, 7%; P = .03). All of the 5 core+D patients who lost their grafts due to HCV recurrence did not receive anti-HCV therapy (4 owing to an aggressive disease and 1 because of patient refusal). ConclusionsOutcomes of LT in patients with ongoing HBV and HCV coinfection are adversely affected by donor HBcAb positivity, an effect that is mainly mediated by the dismal course of HCV recurrence after LT.

Risk of de novo hepatitis in liver recipients from hepatitis‐B core antibody‐positive grafts – a systematic analysis

SkagenMany transplant programs utilize liver grafts from hepatitis-B core antibody (HBcAb)-positive and hepatitis-B surface antigen (HBsAg)-negative donors. However, there is risk for de novo hepatitis B (DNH) in recipients of these grafts. We reviewed 26 studies reporting the rates of DNH in recipients receiving HBcAb-positive liver grafts. Four hundred and sixty-two donor-recipient pairs were included to evaluate the risk of DNH stratified by the recipient's immune status to hepatitis B and type of prophylactic therapy given, if any. The rate of DNH was highest (58%) in the stratum of hepatitis-B (HBV) naïve recipients who did not receive prophylaxis. In HBV naïve recipients, prophylactic therapy (lamivudine and/or hepatitis-B immunoglobulin - HBIG) reduced DNH to 11% (odds ratio [OR] = 11.1, 95% CI 4.98-25, p < 0.0001 for DNH without prophylaxis). Recipients with hepatitis-B surface antibody (HBsAb) positivity had DNH rates of 18% without prophylaxis and 0% with prophylaxis (OR = 9.2, 95% CI 1.1-83.3, p = 0.039). Recipients with both HBsAb and HBcAb positivity had DNH rates of 4% without prophylaxis and 3% with prophylaxis (p = 1.00), while recipients with HBcAb positivity alone had DNH rates of 14% without prophylaxis and 3% with prophylaxis (p = 0.21). There was no significant difference between the types of HBV prophylaxis received whether lamivudine, HBIG or both. However, in the subgroup who received HBIG alone, rates of DNH were higher after cessation of HBIG prophylaxis compared to DNH rates with indefinite HBIG (p = 0.0002). In summary, the risk of DNH is highest for HBV naïve liver recipients from HBcAb-positive donors. Recipients who are HBV naïve as well as those recipients with isolated HBsAb positivity derive significant benefit from HBV prophylaxis after transplantation with a HBcAb-positive graft. The ideal prophylactic regimen for prevention of DNH is unclear, but based on our analysis of the literature, antivirals alone may suffice. More data are needed with the newer antivirals for hepatitis B.

Liver Match, a prospective observational cohort study on liver transplantation in Italy: Study design and current practice of donor–recipient matching

Background The Liver Match is an observational cohort study that prospectively enrolled liver transplantations performed at 20 out of 21 Italian Transplant Centres between June 2007 and May 2009. Aim of the study is to investigate the impact of donor/recipient matching on outcomes. In this report we describe the study methodology and provide a cross-sectional description of donor and recipient characteristics and of graft allocation. Methods Adult primary transplants performed with deceased heart-beating donors were included. Relevant information on donors and recipients, organ procurement and allocation were prospectively entered in an ad hoc database within the National Transplant Centre web-based Network. Data were blindly analysed by an independent Biostatistical Board. Results The study enrolled 1530 donor/recipient matches. Median donor age was 56 years. Female donors ( n = 681, median 58, range 12–92 years) were older than males ( n = 849, median 53, range 2–97 years, p < 0.0001). Donors older than 60 years were 42.2%, including 4.2% octogenarians. Brain death was due to non-traumatic causes in 1126 (73.6%) cases. Half of the donor population was overweight, 10.1% was obese and 7.6% diabetic. Hepatitis B core antibody (HBcAb) was present in 245 (16.0%) donors. The median Donor Risk Index (DRI) was 1.57 (>1.7 in 35.8%). The median cold ischaemia time was 7.3 h (≥10 in 10.6%). Median age of recipients was 54 years, and 77.7% were males. Hepatocellular carcinoma (HCC) was the most frequent indication overall (44.4%), being a coindication in roughly 1/3 of cases, followed by viral cirrhosis without HCC (28.2%) and alcoholic cirrhosis without HCC (10.2%). Hepatitis C virus infection (with or without HCC) was the most frequent etiologic factor (45.9% of the whole population and 71.4% of viral-related cirrhosis), yet hepatitis B virus infection accounted for 28.6% of viral-related cirrhosis, and HBcAb positivity was found in 49.7% of recipients. The median Model for End Stage Liver Disease (MELD) at transplant was 12 in patients with HCC and 18 in those without. Multivariate analysis showed a slight but significant inverse association between DRI and MELD at transplant. Conclusions The deceased donor population in Italy has a high-risk profile compared to other countries, mainly due to older donor age. Almost half of the grafts are transplanted in recipients with HCC. Higher risk donors tend to be preferentially allocated to recipients with HCC, who are usually less ill and older. No other relevant allocation strategy is currently adopted at national level.

The nephrologist in the HAART era

The nephrologist in the HAART era

Significance of prior hepatitis B virus infection in the development of hepatocellular carcinoma in patients with chronic hepatitis C.

To clarify the clinical significance of prior hepatitis B virus (HBV) infection in the development of C-viral hepatocellular carcinoma (HCC), we conducted two studies: (1) Two hundred thirty-four patients with C-viral HCC and 320 patients with C-viral chronic liver disease without HCC admitted to our hospital between 1990 and 1994 were analyzed for the association of hepatitis B core antibody (HBcAb) positivity with HCC by multivariate logistic regression analysis, and this revealed HBcAb positivity as an independent risk factor for development of HCC adjusted for age and sex. (2) Four hundred fifty-nine patients with biopsy-proven hepatitis C virus-related chronic liver disease between 1986 and 1998 were enrolled in the cohort study and followed for the development of HCC. During an average follow-up of 6.6 +/- 3.3 years, HCC developed in 63 patients, 37 of 160 patients positive for HBcAb and 26 of 299 patients negative for HBcAb. Multivariate Cox proportional regression analysis showed that the incidence of HCC increased by age, advanced stage of liver fibrosis, mean alanine aminotransferase value of more than 80 IU/liter, and positivity of HBcAb. Sustained virological responders after interferon therapy revealed a reduced risk for HCC development. In conclusion, prior HBV infection was shown to be one of the independent risk factors for development of HCC in C-viral chronic liver disease.