Successful treatment of activated occult hepatitis B in a non-responder chronic hepatitis C patient
© Emara and Radwan; licensee BioMed Central Ltd. 2011
Received: 15 September 2011
Accepted: 14 November 2011
Published: 14 November 2011
We reported a 23 years old male with chronic hepatitis C virus infection, discontinued from pegylated interferon/ribavirin combination therapy due to a lack of early virological response. He has developed activation of occult hepatitis B virus that was successfully treated by a one year of lamivudine therapy.
Keywordsoccult hepatitis B hepatitis C pegylated interferon lamivudine
Occult hepatitis B virus infection (OBI) is defined as the presence of hepatitis B virus (HBV) DNA, in serum and/or the liver tissue without detectable HBsAg with or without anti-HBc or anti-HBs outside the pre-seroconversion window period . In chronic hepatitis C virus (HCV) infection, the presence of OBI has been associated with liver enzymes flare , increased severity of liver disease towards advanced fibrosis and cirrhosis , poor response to standard interferon-alpha in many [3, 4], but not all  studies, and increased risk of hepatocellular carcinoma . Concerning response to interferon therapy in chronic HCV a previous study by the first author found OBI to be a statistically non significant cause of interferon non-response .
Laboratory characteristics of the patient
Week 12 after interferon
Six months after Lamivudine therapy
Twelve months after lamivudine therapy
Six months after lamivudine discontinuation
HCV RNA (IU/ml)
HBV DNA (IU/ml)
It is not recommended to screen for OBI in chronic HCV before initiation of antiviral therapy  and that is why we do not routinely perform HBV DNA examination or serological markers assay  before initiation of antiviral therapy for chronic HCV. So we had only a baseline HBsAg for this patient. On follow up all serological markers remained negative (HBsAg, HBeAg, anti-HBc, Anti-HBs), this may point for a primary occult infection in this patient rather than a false occult infection. In the former a low dose of HBV infection may occur and establish the lymphatic system and later may invade the liver , while in the later defective laboratory techniques may not detect an antigenically modified HBsAg .
There is a reciprocal inhibition of replication between both HBV and HCV, with dominance of HCV inhibitory effect on HBV replication by its core protein , therefore HBV may flare up when the HCV virus is treated , and this may explain the slightly high levels of HBV DNA (> 2000 IU/ml) in this patient. But what is not completely understood is that this patient is a non-responder to interferon therapy, however HBV flared and HCV RNA increased than the base line values. And also the decrease in HCV RNA levels noticed when HBV DNA was undetected. This may not favor the reciprocal inhibition of replication between HBV and HCV in this case.
Both younger age and lack of biochemical flare (no increase in serum transaminases) could point to an immune tolerance state of HBV infection in this patient.
There is no consensus about management of OBI when HBV DNA levels are low , while when HBV DNA level exceeds 2000 IU , treatment may be introduced. Relying on liver biopsy, evidence of fibrosis was detected (F2), although it is due to HCV rather than HBV infection, a decision to treat this patient with HBV viral load > 2000 IU was taken as the presence of this OBI may favor progression of this fibrosis towards cirrhosis. Our patient continued on lamiviudine therapy for 1 year during this year he had his HBV DNA examination twice and both were undetected. Due to financial constraints this patient discontinued lamivudine, 6 months after this we examined for HBV and HCV viral load, HBV DNA was still undetected and HCV RNA level was 7062 IU/ml.
In HBeAg negative chronic HBV infection treatment should be continued until HBsAg clearance. While in HBeAg positive cases a 6 months treatment period after HBeAg seroconversion is recommended before discontinuation of therapy . Our patient is negative for all HBV serological markers and hence no finite duration for therapy could be planned. HBV DNA clearance thus may be the therapeutic target in this patient. In our case a one year treatment with lamivudine seems to be successful to treat this seronegative OBI activation, with HBV DNA clearance is the primary end point.
Check the presence of OBI when HCV therapy fails may be justifiable. Lamivudine could successfully be used in the treatment of occult hepatitis B activation.
Written informed consent was obtained from the patient for publication of this Case Report and any accompanying data. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
List of abbreviations
Occult hepatitis B virus infection
hepatitis B virus
hepatitis C virus
The authors would thank Dr. Soha Elhawari for revising this work. She had no conflict of interest.
- Brechot C, Thiers V, Kremsdorf D, Nalpas B, Pol S, Paterlini-Brechot P: Persistent hepatitis B virus infection in subjects without hepatitis B surface antigen: clinically significant or purely "occult"? Hepatology 2001, 34: 194-203.View ArticlePubMedGoogle Scholar
- Kannangai R, Vivekanandan P, Netski D, Mehta S, Kirk G, Thomas D, Torbenson M: Liver enzyme flares and occult hepatitis B in persons with chronic hepatitis C infection. J Clinical Virol 2007, 39: 101-105. 10.1016/j.jcv.2007.03.006View ArticleGoogle Scholar
- Cacciola I, Pollicino T, Squadrito G, Cerenzia G, Orlando M, Raimondo G: Occult hepatitis B virus infection in patients with chronic hepatitis C liver disease. N Engl J Med 1999, 341: 22-6. 10.1056/NEJM199907013410104View ArticlePubMedGoogle Scholar
- Fukuda R, Ishimura N, Hamamoto S, Moritani M, Uchida Y, Ishihara S, Akagi S, Watanabe M, Kinoshita Y: Co-infection by serologically silent hepatitis B virus may contribute to poor interferon response in patients with chronic hepatitis C by down-regulation of type-I interferon receptor gene expression in the liver. J Med Virol 2001, 63: 220-227. 10.1002/1096-9071(200103)63:3<220::AID-JMV1004>3.0.CO;2-3View ArticlePubMedGoogle Scholar
- Nirei K, Kaneko M, Moriyama M, Arakawa Y: The clinical features of chronic hepatitis C are not affected by the coexistence of hepatitis B virus DNA in patients negative for hepatitis B surface antigen. Intervirology 2000, 43: 95-101. 10.1159/000025030View ArticlePubMedGoogle Scholar
- Sheu J, Huang G, Shih L: Hepatitis C and B viruses in hepatitis B surface antigen-negative hepatocellular carcinoma. Gastroenterology 1992, 103: 1322-1327.PubMedGoogle Scholar
- Emara MH, El-Gammal NE, Mohamed LA, Bahgat MM: Occult Hepatitis B Infection in Egyptian Chronic Hepatitis C Patients: Prevalence, Impact on Pegylated Interferon/Ribavirin Therapy. Virol J 2010, 7: 324. 10.1186/1743-422X-7-324PubMed CentralView ArticlePubMedGoogle Scholar
- Ferraro D, Bonura C, Giglio M, Di Stefano R, Almasio PL, Di Marco V: Occult HBV infection and suppression of HCV replication in the early phase of combination therapy for chronic hepatitis C. J Biol Regul Homeost Agents 2003, 17: 172-5.PubMedGoogle Scholar
- Michalak T, Pardoe I, Coffin C, Churchill N, Freake D, Smith P: Occult lifelong persistence of infectious hepadna virus and residual liver inflammation in woodchucks convalescent from acute viral hepatitis. Hepatology 1999, 29: 928-38. 10.1002/hep.510290329View ArticlePubMedGoogle Scholar
- Weber B: Diagnostic impact of the genetic variability of the hepatitis B virus surface antigen gene. J Med Virol 2006, 78: S59-S65. 10.1002/jmv.20610View ArticlePubMedGoogle Scholar
- Shih C, Lo S, Miyamura T, Chen S, Lee Y: Suppression of Hepatitis B Virus Expression and Replication by Hepatitis C Virus Core Protein in HuH-7 Cells. J Virol 1993, 67: 5823-5832.PubMed CentralPubMedGoogle Scholar
- European Association for the Study of the Liver: EASL Clinical Practice Guidelines: Management of chronic hepatitis B. J Hepatol 2009, 50: 227-242. 10.1016/j.jhep.2008.10.001View ArticleGoogle Scholar
- Raimondo G, Allain JP, Brunetto MR, Buendia MA, Chen DS, Colombo M, Craxì A, Donato F, Ferrari C, Gaeta GB, Gerlich WH, Levrero M, Locarnini S, Michalak T, Mondelli MU, Pawlotsky JM, Pollicino T, Prati D, Puoti M, Samuel D, Shouval D, Smedile A, Squadrito G, Trépo C, Villa E, Will H, Zanetti AR, Zoulim F: Statements from the Taormina expert meeting on occult hepatitis B virus infection. J Hepato 2008, 49: 625-657. 10.1016/j.jhep.2008.07.005View ArticleGoogle Scholar
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