Occult Hepatitis C Virus Infection in Patients in Whom the Etiology of Persistently Abnormal Results of Liver‐Function Tests Is Unknown

TLDR

Patients with long‑standing abnormal liver‑function tests of unknown cause (ALF‑EU) remain undiagnosed after excluding known liver diseases. The authors examined liver biopsies from 100 ALF‑EU patients lacking anti‑HCV antibodies and serum HCV RNA, detecting intrahepatic HCV RNA by RT‑PCR and in situ hybridization in liver tissue and peripheral‑blood mononuclear cells. HCV RNA was found in 57 % of the biopsies, predominantly negative‑strand RNA of genotype 1b, with 70 % of these patients also harboring viral RNA in PBMCs, and occult infection correlated with increased necroinflammatory activity and fibrosis.

Abstract

BackgroundThere are patients in whom the etiology of long-standing abnormal results of liver-function tests is unknown (ALF-EU) after exclusion of all known causes of liver diseases. We analyzed the presence of hepatitis C virus (HCV) RNA in liver-biopsy specimens from 100 patients who were negative for anti-HCV antibodies and for serum HCV RNA and who had ALF-EU MethodsHCV RNA status was tested by reverse-transcription polymerase chain reaction (RT-PCR) and by in situ hybridization, in liver and peripheral-blood mononuclear cells (PBMCs) ResultsHCV RNA was detected in liver-biopsy specimens from 57 of 100 patients negative for anti-HCV antibodies and for serum HCV RNA (i.e., who had occult HCV infection). HCV RNA of negative polarity was found in the liver of 48 (84.2%) of these 57 patients with occult HCV infection. Nucleotide-sequence analysis confirmed the specificity of detection of HCV RNA and that patients were infected with the HCV 1b genotype. Of these 57 patients with intrahepatic HCV RNA, 40 (70%) had viral RNA in their PBMCs. With regard to liver histology, patients with occult HCV infection were more likely to have necroinflammatory activity (P=.017) and fibrosis (P=.022) than were patients without intrahepatic HCV RNA ConclusionPatients with ALF-EU may have intrahepatic HCV RNA in the absence of anti-HCV antibodies and of serum HCV RNA