Occult hepatitis B virus infection (OBI) characterized by the absence of detectable HBsAg in the presence of HBV DNA in the serum and/or liver tissue remains a potential risk of transmission and diseases progression among different population groups. It could be associated with asymptomatic case up to chronic liver disease (CLD) and hepatocellular carcinoma (HCC). The objective of this study was to assess the magnitude and characteristics of OBI among patients with CLD of unidentified cause in Addis Ababa, Ethiopia. The study was conducted at the gastroenterology & hepatology referral clinic of three government and two private hospitals in Addis Ababa. Known CLD patients as evidenced by clinical and imaging criteria and/or with HBV surface antigen (HBsAg) negative results using rapid test kit were included. ELISA serological test to anti-HBc Ab, anti HBsAg Ab, and HBsAg were determined using BIORAD kits [ https://www.bio-rad.com ]. HBV-DNA was amplified, and viral loads were determined by quantitative real-time PCR using Abbott m2000rt platform following the manufacturer's instructions. Data analysis was done using SPSS version 20.A total of 48 CLD patients with no identified cause for their liver disease were identified during the study period. All the patients had evidence of CLD by clinical and imaging criteria and nine were excluded. Three (7.69%) of the 39 patients tested positive for HBsAg test done by ELISA making the negative predictive value of the rapid test kits 92.3% compared to ELISA. The remaining 36 patients had serology test for HBV and 16 (44.4%) had positive anti-HBV core antibody. Two (5.56%) of the 36 patients with HBV viral load determination had detectable HBV DNA suggesting presence of an occult hepatitis B infection. Occult hepatitis B infection is found to be an aetiology among CLD patients labelled as having no identified cause by the current standard of care using rapid HBsAg kits in a subset of patients in Ethiopia. This study signifies the high rate of OBI and past evidence of HBV infection among CLD patients and thus nucleic acid testing and/or anti-HBc shall be integrated to the routine health care system to minimize HBV infection risk of transmission and to enhance patient care.

The aim of the present study was to determine the presence of HCV RNA in the liver biopsies of patients with abnormal liver tests but without detectable serum HCV RNA and anti-HCV antibodies in sera. Liver biopsies and whole blood of total 31 patients who were negative for anti-HCV antibodies with elevated liver function tests were received at Division of Molecular Diagnostics, University of the Punjab Pakistan from January 2002 to June 2009 for the detection of HCV RNA. HCV RNA status of the subjects was tested by reverse-transcription PCR and quantified using SmartCycler II real-time PCR. HCV genotyping was carried out in HCV RNA positive samples using molecular genotyping method. HCV RNA was found in liver-biopsy specimens from 23 (74.2%) of the total 31 patients negative for anti-HCV antibodies and undetectable serum HCV RNA. HCV RNA of both negative and positive polarity was found in the livers of 8 (25.8%) patients. Genotyping analysis showed that 65% patients were infected with HCV 3a, 17% with 3b, 13% with 1a and 4% patients were found with untypable genotype. In a multivariate logistic regression model, patients having previous history surgeries, male sex and age above 30 years were significantly associated with the presence of occult HCV infection (p<0.05). In conclusion, patients with elevated liver enzymes and negative HCV antibodies and negative serum RNA may have occult HCV infection and its chance increases with previous history of surgeries, in male sex and above 30 years of age.

Occult hepatitis C infection is regarded as a new entity that should be considered when diagnosing patients with a liver disease of unknown origin. Using an ultrasensitive real-time PCR assay, we demonstrated that occult hepatitis C virus (HCV) infection cannot be found in peripheral blood mononuclear cells of patients with cryptogenic liver diseases, HCV--associated systemic vasculitis, or connective tissue diseases. The significance of such occult infection must be elucidated.

Occult hepatitis C virus (HCV) infection is a new recently characterized entity. This occult infection can be present in two different clinical situations: in anti-HCV negative, serum HCV-RNA negative patients with abnormal liver function tests and in anti-HCV positive subjects with normal values of liver enzymes and without serum HCV-RNA. This review describes recent studies of occult HCV infection in both kinds of patients.

The prevalence of antibody to hepatitis C virus (HCV) was studied in 207 patients with chronic liver disease of unknown etiology, in relation to clinical, epidemiological and histological features. Serum antibody to C-100 epitope of HCV was detected by ELISA in 82.6% of patients, with a significant difference compared with a group of patients with primary biliary cirrhosis (10%). The presence of anti-HCV antibody in serum did not correlate with age, sex, histological diagnosis, and activity and duration of the disease, nor with serum anti-HBc, used as a marker of exposure to hepatitis B virus infection. These results strongly support the view that most cases that were previously defined as cryptogenic forms of chronic liver disease are in fact related to HCV infection. There was a correlation between serum anti-HCV antibody and history of risk for parenteral exposure or of acute hepatitis. This correlation was particularly evident for transmission by parenteral route, suggesting that HCV infection may be transmitted often by this route (36.8% among anti-HCV antibody-positive patients and 11.1% among anti-HCV-negative patients). Liver disease in patients without risk factors for parenteral transmission and with lower prevalence of anti-HCV antibody may be caused by other as yet unidentified non-A, non-B (non-C) agents or may be of nonviral origin.

A randomized, controlled trial was undertaken to evaluate the response to recombinant interferon alfa-2a in patients with hepatitis B surface antigen negative chronic active hepatitis of unknown aetiology (community-acquired non-A, non-B hepatitis). Thirty patients were treated with thrice weekly interferon in a dose of 6 million units for 1 month, followed by 3 million units for 3 months and 1 million units maintenance therapy for 8 months. Patients who relapsed were returned to the previously effective dose. A control group of 30 patients received no treatment and were followed up for 12 months. Overall, 21/30 (70%) of treated patients had a complete response, with normalization of serum aminotransferase levels, and a further three (10%) had a partial response (a decrease to less than 50% of baseline levels). No significant changes were observed in the control patients. Five (24%) of the 21 complete responders relapsed during months 2-4 and 8/21 (38%) relapsed during maintenance therapy. Three (23%) of these 13 patients had a return to normal serum aminotransferase levels when the dose was increased and 7/13 (54%) demonstrated a significant decrease. In a retrospective analysis of patients' sera for antibody to hepatitis C virus, 23/26 patients testing positive were treatment responders compared to 1/4 antibody negative patients. Our results suggest that interferon alfa-2a is an effective treatment for community-acquired non-A, non-B hepatitis, but reactivation during treatment occurred in 62% of patients. We recommend use of a higher dose of interferon for at least 1 year with long-term follow up in order to exclude early or late reactivation after treatment withdrawal.