Viral Outcome in Patients with Occult HBV Infection or HCV-Ab Positivity Treated for Lymphoma

ABSTRACT HBV and HCV reactivation has been widely reported in patients undergoing immunosuppressive therapy for oncohaematological diseases. We aimed to evaluate the HBV and HCV reactivation events in patients with non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HL) underwent cytotoxic chemotherapy containing or not rituximab. This is a retrospective observational study, including all patients with NHL and HL attending an Italian tertiary referral hospital, the University of Naples "Federico II". A total of 322 patients were enrolled. We evaluated serum HBV and HCV markers. A total of 47 (38%) patients with occult HBV infection were enrolled. Seven/47 were treated with therapeutic cytotoxic schedule containing rituximab. Of them, 6/7 received prophylaxis with lamivudine. HBV reactivation was observed in two patients treated with rituximab. A reactivation was observed in the only patient (HBcAb+/HBsAb+) not receiving lamivudine prophylaxis, and the other one was observed in 1 patient with isolated HBcAb positivity during lamivudine prophylaxis. Moreover, 8 patients with HCV-Ab positivity were enrolled. No viral reactivation was observed in these patients. In conclusion, patients with occult HBV infection receiving chemotherapy containing rituximab for lymphoma without antiviral prophylaxis are at risk of viral reactivation. On the contrary, there is no risk of reactivation in patients undergoing rituximab-free schedule. Our findings suggest that there is also very low risk of HCV reactivation. This preliminary report underlines the concept that HBV reactivation is strongly related to the type of immunosuppressive therapy administered and that antiviral prophylaxis needs to be tailored.

Occult HBV among Anti-HBc Alone: Mutation Analysis of an HBV Surface Gene and Pre-S Gene

PURPOSE: The aim of this study is to investigate the molecular characteristics of occult hepatitis B virus (HBV) infection in ‘anti-HBc alone’ subjects. MATERIALS AND METHODS: Twenty-four patients with ‘anti-HBc alone’ and 20 control patients diagnosed with HBV were analyzed regarding S and pre-S gene mutations. All specimens were analyzed for HBs Ag, anti-HBc, and anti-HBs. For specimens with an anti-HBc alone, quantitative analysis of HBV DNA, as well as sequencing and mutation analysis of S and pre-S genes, were performed. RESULTS: A total 24 were analyzed for the S gene, and 14 were analyzed for the pre-S gene through sequencing. A total of 20 control patients were analyzed for S and pre-S gene simultaneously. Nineteen point mutations of the major hydrophilic region were found in six of 24 patients. Among them, three mutations, S114T, P127S/T, M133T, were detected in common. Only one mutation was found in five subjects of the control group; this mutation was not found in the occult HBV infection group, however. Pre-S mutations were detected in 10 patients, and mutations of site aa58–aa100 were detected in 9 patients. A mutation on D114E was simultaneously detected. Although five mutations from the control group were found at the same location (aa58–aa100), no mutations of occult HBV infection were detected. CONCLUSION: The prevalence of occult HBV infection is not low among ‘anti-HBc alone’ subjects. Variable mutations in the S gene and pre-S gene were associated with the occurrence of occult HBV infection. Further larger scale studies are required to determine the significance of newly detected mutations.

Detection of occult HBV infection and probably window period infection among single NAT reactive blood donors / 国际检验医学杂志

Objective To analyze hepatitis B virus(HBV) infection stage in single nucleic acid test(NAT)reactive blood donors.Methods Blood donor samples were screened routinely for HBV DNA by using transcription-mediated amplification(TMA) NAT and quantitative polymerase chain reaction(PCR).Then serum markers of HBV were also detected.The HBV infection stage was analyzed.Results Among the 225 single NAT reactive samples,78(34.67%) were identified to be reactive for HBV DNA by TMA NAT discrimination test and/or PCR test,of which 63(82.89%) were occult HBV infection(OBI),13(17.11%) were probably window period infection(pWP),and 2 cases could not be classified for infection stage.Among the OBI samples,49 samples(77.78%) were with HBV DNA concentration less than 20 IU/mL,whereas,there were only 4 samples(30.77%) in pWP samples.The 225 samples were classified into three groups according to the S/CO of NAT, including 1-<6 group,6-<10 group and 10-17 group, the confirmed HBV DNA positive rates of which were 13.11%,13.64% and 47.18%,and the positive rate of 10-17 group was higher than 1-<6 group and 6-<10 group(P<0.05).In all 63 OBI samples,there were 8(12.70%),3(4.76%) and 52(82.54%) samples were classified into S/CO 1-<6,6-<10 and 10-17,respectively.All of the 13 pWP samples were with NAT S/CO of 10-17.Conclusion Part of single NAT reactive blood donors could be with HBV infection,of which OBI might be popular than pWP, with very low concentration of HBV DNA.Deferral of single NAT reactive blood donors could reduce transfusion-transmitted HBV infection.

Recurrence of occult hepatitis B virus infection in a recipient of a liver transplant for HCV-related cirrhosis: full length genome, mutations analysis and literature review.

The outcome of liver transplant recipients in HCV chronic carriers with Anti-HBc only concerning occult HBV infection is unknown. We report here the case of a patient who underwent liver transplantation (LT) for cirrhosis post chronic hepatitis C who received an allograft from a donor with no marker of hepatitis B infection. After LT, HBV DNA was detected in the serum in the absence of HBsAg while HCV RNA remained negative. To determine the origin of this occult HBV infection, we retrospectively examined stored serum and liver tissue, pre and post-transplantation, for HBV DNA by PCR. A stored liver biopsy of the donor before transplantation was also tested. HBV DNA was detected in the pre-transplant liver but not in the donor liver. HBV viral load quantified by real time PCR after LT ranged from about 102 to 5x103 HBV DNA copies/mg of liver, while in sera, concentrations ranged from 102 to 3x103 HBV DNA copies/ml. All PCR products in the S gene from liver and sera were sequenced. Analysis of sequences showed the presence of an HBV strain genotype D. The nucleotide homology between the patient‟s HBV strains before and after LT was 96 % across the analyzed regions. Full length HBV genomes were amplified from the sera using Rolling Circle Amplification and then sequenced. Analysis of sequences confirmed the genotype D, but did not show obvious mutations that could contribute to HBsAg seronegativity and low HBV viral replication. Factors leading to occult HBV infection are still unclear, but it is well establish that occult HBV infection is frequent in HCV patients. This underlines the role of extra hepatic sites for HBV replication, potentially lymphocytes acting as “reservoirs”.

Significance of anti-HBc screening of blood donors & its association with occult hepatitis B virus infection: Implications for blood transfusion.

Background & objective: Expansions of blood donor screening and improved laboratory detection of viral markers have remarkably reduced the risk for infection with transfusion-transmitted viruses. This study was aimed to evaluate the presence of anti-HBc and to determine the presence or absence of HBV DNA in the serum samples from HBsAg negative, anti-HBc positive blood donors in a tertiary care hospital blood bank from Delhi. Methods: A total of 2175 HBsAg negative, first time volunteer blood donors were included in the study from blood bank, Lok Nayak Hospital, New Delhi. The blood specimens from all these subjects were evaluated for anti-HBV-core antigen (anti-HBc) serology, anti-HBV-surface antigen (anti-HBs) titres and HBeAg. The presence of HBV DNA was evaluated by testing, through polymerase chain reaction (PCR) techniques. Results: Of the 2175 HBsAg negative voluntary blood donors, 413 (19.8%) were tested to be positive for anti-HBc alone. Of these, 153 (group-I) were anti-HBs negative whereas group-II comprises a total of 260 anti-HBs positive cases i.e. 89 out of 413 had anti-HBs titres of 10-99 IU/l and the remaining 171 had anti-HBs titres of 100-500 IU/l. HBV DNA was detected in 7.5 per cent anti-HBc positive samples irrespective of anti-HBs status. Interpretation & conclusions: Our results showed that 18.9 per cent of our donor population was anti-HBc reactive, and hence inclusion of anti-HBc testing will lead to a high discard rate. The presence of HBV DNA in fairly high percentage of anti-HBc positive samples highlighted the need for a stringent and better screening system to prevent occult HBV infection.

Occult hepatitis B virus infection in immunocompromised patients

Occult hepatitis B infection is characterized by hepatitis B virus (HBV) DNA in the serum in the absence of hepatitis B surface antigen (HBsAg). We assessed occult HBV infection prevalence in two groups of immunocompromised patients (maintenance hemodialysis patients and HIV-positive patients) presenting HBsAg-negative and anti-HBc positive serological patterns, co-infected or not by HCV. Thirty-four hemodialysis anti-HIV negative patients, 159 HIV-positive patients and 150 blood donors who were anti-HBc positive (control group) were selected. HBV-DNA was detected by nested-PCR. Occult hepatitis B infection was not observed in the hemodialysis patients group but was found in 5 percent of the HIV-patients and in 4 percent of the blood donors. Immunosuppression in HIV positive patients was not a determining factor for occult HBV infection. In addition, no significant relationship between HBV-DNA and HCV co-infection in the HIV-positive patient group was found. A lack of significant associations was also observed between positivity for HBV-DNA and CD4 count, viral load and previous lamivudine treatment in these HIV-positive patients.

The significance of anti-HBc and occult hepatitis B virus infection in the occurrence of hepatocellular carcinoma in patients with HBsAg and anti-HCV negative alcoholic cirrhosis / 대한간학회지

BACKGROUND/AIMS: Alcohol and the hepatitis B virus (HBV) exert synergistic effects in hepatocelluar carcinogenesis. We aimed to elucidate the clinical significance of the antibody to hepatitis B core antigen (anti-HBc) and occult HBV infection on the development of hepatocellular carcinoma (HCC) in patients with alcoholic liver cirrhosis (LC). METHODS: Patients with alcoholic LC alone (n=193) or combined with HCC (n=36), who did not have HBsAg or antibody to hepatitis C virus were enrolled. Clinical data and laboratory data including anti-HBc were investigated at enrollment. The polymerase chain reaction was applied to HBV DNA using sera of patients with HCC or LC after age and sex matching. RESULTS: Patients with HCC were older (60+/-11 years vs. 53+/-10 years, mean+/-SD, P<0.001), more likely to be male (100% vs. 89%, P=0.03), and had a higher positive rate of anti-HBc (91.2% vs. 77.3%, P=0.067), and a higher alcohol intake (739+/-448 kg vs. 603+/-409 kg, P=0.076) than those with LC. Age was the only significant risk factor for HCC revealed by multiple logistic regression analysis (odds ratio, 1.056; P=0.003). The positive rate of anti-HBc and alcohol intake did not differ in age- and sex-matched subjects between the LC (n=32) and HCC (n=31) groups. However, the detection rate of serum HBV DNA was higher in the HCC group (48.4%) than in the LC group (0%, P<0.001). CONCLUSIONS: Anti-HBc positivity is not a risk factor for HCC. However, occult HBV infection may be a risk factor for HCC in patients with alcoholic LC.

NAT testing for HBV,HCV,HIV on donors' samples negative by ELISA tests / 中国输血杂志

Objective To perform NAT testing on samples negative for HBsAg, anti-HCV and anti-HIV by ELISA, and to learn how many infected blood samples could be missed by ELISA tests.Methods Pooling the donor samples by STAR2000 sampling processor and extracting nucleic acid automatically, HBV DNA, HCV RNA and HIV-1 RNA were amplified and detected by Roche COBAS AmpliScreen TM HBV、HCV V2.0 和HIV-1 V1.5 systems. Samples of 8 donors with negative HBsAg but positive HBV DNA were tested by COBAS HBV MONITOR TM for quantitative determinations. HBsAg confirmation tests were done every 2 weeks by ABBOTT Murex HBsAg V3.Results A total of 16320 ELISA negative donor samples were tested and 8 samples were HBV DNA positive. The missing rate was 0.49‰. No HCV RNA and HIV-1 RNA were detected. Those 8 donor samples, negative for HBsAg but positive for HBV DNA,were all positive for HBcAb by ABBOTT,and 3 of them were positive for HbeAb Low serum HBV DNA loads, in the range of 102~103 copies/ml, were found in the 8 donor samples. HBsAg confirmations were performed and one donor became HBsAg positive after 18 weeks.Conclusion The results show that there is 0.49‰ missing rate of HBV with HBsAg screening by ELISA. HBcAb screening or NAT may be warranted in blood donor screening to limit HBV transmission through blood transfusion.The reason for missing HBV positive samples by ELISA could be occult HBV infection.