Occult hepatitis C virus infection in Iranian patients with cryptogenic liver disease

The diagnosis of cryptogenic liver disease is made when after extensive evaluations, recognizable etiologies of chronic liver disease are excluded. In this study, the presence of hepatitis C virus (HCV) RNA was tested in peripheral blood mononuclear cells (PBMCs) taken from Iranian patients who although were found negative for plasma HCV RNA and anti‐HCV antibodies, suffered from chronic liver disease of unknown etiology. From September 2007 to March 2010, 69 patients from Tehran with chronic liver disease of unknown etiology who were referred to our center were enrolled in the present study. PBMCs were isolated from 10 mL peripheral blood specimens. HCV‐RNA status was tested in plasma and PBMCs samples by reverse‐transcription polymerase chain reaction (RT‐PCR). HCV‐RNA was detected in HCV‐positive PBMCs specimens by RT‐PCR method. HCV genotypes were subsequently analyzed in HCV‐positive samples using restriction fragment length polymorphism (RFLP) assay; then HCV genotypes were confirmed by sequencing of 5′ non‐coding fragments after cloning PCR products into pJET1.2/blunt cloning vector. HCV‐RNA was detected in PBMCs specimens belonging to 7 (10%) out of 69 patients. Genotyping of the HCV‐RNA isolated from PBMCs showed that 3 (43%) patients with occult HCV infection had genotype 1b, 2 (29%) had genotype 1a, and another 2 (29%) had genotype 3a. The results of this study suggest that patients with chronic liver disease of unknown etiology may have occult HCV infection in the absence of anti‐HCV antibodies and plasma HCV‐RNA. It has been suggested that in the absence of liver biopsy specimens, analysis of PBMC sample for HCV‐RNA would be informative. J. Med. Virol. 83:989–995, 2011. © 2011 Wiley‐Liss, Inc.