Diagnosis and clinical impact of occult hepatitis B infection in patients with biopsy proven chronic hepatitis C: A multicenter study

Sagnelli, Evangelista; Imparato, Michele; Coppola, Nicola; Pisapia, R.; Sagnelli, Caterina; Messina, Vito; Piai, G.; Stanzione, Maria; Bruno, M.; Giovanni, Moggio; Caprio, Nunzio; Pasquale, Giuseppe; Camillo, Del Vecchio Blanco

doi:10.1002/jmv.21239

Cited by 59 publications

(16 citation statements)

References 46 publications

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“…Therefore, PBMC may be an alternative source to liver biopsy for detection of an occult HBV infection. This result also was comparable to Sagnelli et al study who showed that nearly a half of HCV patients with detectable HBV-DNA in PBMCs had negative results in plasma (23 vs. 12 cases) (23). Presence of occult HBV has been reported in association with the presence of markers of HBV exposure (anti-HBc ± anti-HBs).…”

Section: Discussionsupporting

confidence: 87%

“…But we found no correlation between the presence of anti-HBc and prevalence of HBV-DNA in HBsAg-negative and HCV positive patients, this was compatible with some studies (3, 24). However, other studies showed higher prevalence of occult HBV among individuals seropositive for anti-HBc and/or anti-HBs, especially those with the presence of anti-HBc alone, compared with patients who had not positive results for anti-HBc and anti-HBs (1, 17, 23). The clinical significance of occult HBV is still not understood and the overall trend in the literature shows inconsistent results.…”

Section: Discussionmentioning

confidence: 83%

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Prevalence of Occult Hepatitis B Virus in Plasma and Peripheral Blood Mononuclear Cell Compartments of Patients WithChronic Hepatitis C Infection in Tehran-Iran

et al. 2013

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BackgroundOccult hepatitis B virus (HBV) infection (OBI) is frequently reported in patients with chronic hepatitis C virus (HCV) infection. An association between OBI and more liver damage, cirrhosis, hepatocellular carcinoma, and reduced response to interferon therapy in patients with HCV infection is suggested.ObjectivesThe aim of this study was to determine the prevalence of occult HBV, and evaluate its clinical influence on patients with chronic HCV.Patients and MethodsA cohort study including50 patients with positive results for HCV, and negative results for HBsAg tests was performed. The patients were divided into two groups: one group had positive results for both HCV and occult HBV tests (n = 18), and the other had positive results for HCV, but negative findings for occult HBV (n = 32). All were treated with PEG-IFN alpha-2a and Ribavirin. Presence of HCV RNA was followed in these patients.ResultsHBV-DNA was detected using nested-PCR in 20% of plasma and 32.6% of peripheral blood mononuclear cell (PBMC) compartments. No significant differences were observed between patients with and without occult HBV for sex, age, duration of HCV infection, histological markers, presence of anti-HBc, HCV viral load, and HCV genotype. The response rate was significantly higher in patients with positive results for HBV-DNA test compared to those with negative findings (100% vs. 71.9 %, P < 0.05).ConclusionsIn conclusion, occult HBV was found in 36% of patients with negative results for HBsAg, but positive results for HCV. Detection of HBV-DNA in both PBMCs and plasma together in comparison with plasma alone provided more true identification of OBI.The SVR rate was significantly higher in coinfected patients than mono-infected ones.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 83%

Prevalence of Occult Hepatitis B Virus in Plasma and Peripheral Blood Mononuclear Cell Compartments of Patients WithChronic Hepatitis C Infection in Tehran-Iran

et al. 2013

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“…However, patients with “isolated” anti-HBc were found to have a significantly higher risk of HCC than the anti-HBs/anti-HBc-positive, most probably because these subjects showed more frequently an occult HBV infection in the liver. In fact, in our previous observation HBV DNA can be detected in plasma, peripheral blood mononuclear cells, or liver tissue of 80% of patients with “isolated” anti-HBc and of 60% of the anti-HBs/anti-HBc-positive, [14] suggesting a prolonged exposure to occult HBV replication that may favor the onset of HCC. However, it may also be hypothesized that circulating anti-HBs may prevent the risk of HCC, most probably by controlling HBV replication, as already suggested.…”

Section: Discussionmentioning

confidence: 99%

“…[13] Reactivation of occult HBV infection has been more frequently observed in patients showing anti-HBc as the only HBV marker (“isolated” anti-HBc). [14] …”

Section: Introductionmentioning

confidence: 99%

“…The presence of anti-HBc in HBsAg-negative subjects, a serological condition suggesting a resolved HBV infection, has been used by several authors as a surrogate marker of occult HBV infection in several case–control and cohort studies that investigated the association between serum HBsAg negativity/anti-HBc positivity and the onset of HCC, [7,8,11,14] but the results are inconsistent. A meta-analysis was conducted on 10 observational studies in 2010, [15] but the question of whether and to what extent HBsAg-negative patients with chronic liver disease and anti-HBc positivity are at higher risk of HCC is still open.…”

Section: Introductionmentioning

confidence: 99%

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Association between anti-HBc positivity and hepatocellular carcinoma in HBsAg-negative subjects with chronic liver disease

Coppola¹,

Onorato²,

Sagnelli³

et al. 2016

Medicine

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A meta-analysis was performed to ascertain to what extent hepatitis B surface antigen (HBsAg)-negative/anti-hepatitis B core (anti-HBc)-positive subjects with chronic liver disease are at a higher risk of developing hepatocellular carcinoma (HCC) than the anti-HBc-negative.All studies included had to fulfill the following characteristics and inclusion criteria: they investigated the relationship between HBsAg-negative/anti-HBc-positive serology and the occurrence of HCC, whether a case–control or cohort study, they provided relative risk (RR) or odds ratios (ORs) and 95% confidence intervals (CIs), were available as a full text written in English, and were published and indexed up to April 2015.Twenty-six original studies met the inclusion criteria, allowing a meta-analysis on 44,553 patients. The risk of HCC among the 9986 anti-HBc-positive subjects was 67% higher than in the 34,567 anti-HBc-negative (95% CI = 1.44–1.95, P < 0.0001). The results were similar when groups of patients with a different stage of liver disease (patients with chronic liver disease, patients with cirrhosis), with different ethnicity (Asian and non-Asian) and etiology (HCV and non-HCV) were considered. The risk of HCC was significantly higher in the 651 anti-HBs/anti-HBc-positive patients (RR = 1.36; 95% CI = 1.17–1.58, P = 0.03) and in the 595 anti-HBs-negative/anti-HBc-positive subjects (RR = 2.15; 95% CI = 1.58–2.92, P < 0.0001) than in the 1242 anti-HBs/anti-HBc negative. However, the RR from 8 studies indicated that the risk of HCC was 35% lower among the anti-HBs/anti-HBc-positive subjects compared to the anti-HBs-negative/anti-HBc-positive (RR = 0.65; 95% CI = 0.52–0.8, P < 0.0001).This meta-analysis shows that in HBsAg-negative subjects with chronic liver disease, anti-HBc positivity is strongly associated with the presence of HCC, an association observed in all subgroups according to the stage of the disease, etiology, and ethnicity.

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Prevalence and impact of occult hepatitis B infection in chronic hepatitis C patients treated with pegylated interferon and ribavirin

Levast

Larrat

Thélu

et al. 2010

Journal of Medical Virology

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The prevalence of occult hepatitis B, defined by absence of HBsAg and HBV DNA, ranges widely in patients with hepatitis C. This may influence the treatment of hepatitis C and the severity of liver disease. Sensitive and specific real-time PCR techniques are available commercially and can detect more reliably low HBV DNA levels. The aim of this study was to determine the prevalence of occult hepatitis B virus infection using the COBAS Taqman assay (Roche Diagnostics, Meylan, France) in the serum and liver of HBsAg negative patients with chronic hepatitis C and to evaluate its clinical consequences on liver pathology and its impact on the response to treatment with peg-IFNalpha and Ribavirin. HBV DNA detection was assessed retrospectively on 140 sera and 113 liver biopsies of HCV positive/HBsAg negative patients before treatment. A 4.4% (5/113) prevalence of occult hepatitis B was recorded in liver samples and in none of the sera. Anti-HBc was not detected in one, three of whom were sustained virological responders to treatment, one was relapsed responder and one was non-responder. Furthermore, in this cohort composed of 12% anti-HBs negative/anti-HBc positive and 20% anti-HBs positive/anti-HBc positive patients, anti-HBc was not associated with pre-therapeutic viral load, ALT serum levels, and histological activity or fibrosis. Using a commercial real-time PCR assay, we observed a low prevalence of occult B hepatitis. This, just as anti-HBC status, had no clinical impact in a large cohort of hepatitis C patients. It therefore does not appear useful to screen for occult hepatitis B in these patients with this test before beginning HCV treatment.

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Diagnosis and clinical impact of occult hepatitis B infection in patients with biopsy proven chronic hepatitis C: A multicenter study

Cited by 59 publications

References 46 publications

Prevalence of Occult Hepatitis B Virus in Plasma and Peripheral Blood Mononuclear Cell Compartments of Patients WithChronic Hepatitis C Infection in Tehran-Iran

Prevalence of Occult Hepatitis B Virus in Plasma and Peripheral Blood Mononuclear Cell Compartments of Patients WithChronic Hepatitis C Infection in Tehran-Iran

Association between anti-HBc positivity and hepatocellular carcinoma in HBsAg-negative subjects with chronic liver disease

Prevalence and impact of occult hepatitis B infection in chronic hepatitis C patients treated with pegylated interferon and ribavirin

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