An unusual case of cholelithiasis
Article Outline
Case history
In January 2006, during a complete medical examination, cholelithiasis and a slight dilatation of the portal vein (13–14
mm) were diagnosed by ultrasonography in a 43-year-old male patient. At that time, hematological and biochemical parameters were normal and the patient had no markers of hepatitis B virus (HBV surface antigen, antibody to HBV core and HBV-DNA) or hepatitis C virus (HCV: anti-HCV and HCV-RNA) infections and antibodies to Epstein–Barr virus and cytomegalovirus tested negative as well. The levels of liver enzymes (alanine aminotransferase, ALT, aspartate aminotransferase, AST, and gamma-glutamyl transpeptidase, GGTP) were within the normal range even with an upper limit of normality of 30IU/L for ALT1 (ALT: 15IU/L; AST: 19IU/L; GGTP: 32IU/L). All known causes of liver disease were excluded on the basis of laboratory and clinical data. No travel history to areas of endemic infections was referred. In 2008 although the patient had normal alpha1-antitrypsin levels (101mg/dl, normal range 93–224mg/dl) he was studied for mutations in the alpha1-antitrypsin gene due to familial antecedents and was diagnosed of being heterozigous for the PiS (Glu264Val) mutation. In April 2009, the patient suffered a biliary colic and was submitted to cholecystectomy by laparoscopy. Complete biochemical and hematological analysis were performed. Liver enzyme levels were normal (ALT: 17IU/L; AST: 19IU/L; GGTP: 19IU/L). The remaining biochemical and hematological parameters also showed values within the normal ranges. The patient tested negative to anti-HCV and HCV-RNA in serum. During cholecystectomy a liver biopsy was obtained for histological examination and for molecular analysis. Liver histology was completely normal without evidence of inflammation.
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Evidence-based opinion
The next step was to exclude the presence of very low viremia levels which may remain undetectable by conventional molecular techniques used to detect HBV-DNA and HCV-RNA. Thus, HBV-DNA tested negative whereas levels of HCV-RNA as low as 317genomecopies/ml were detected after concentration of viral particles by ultracentrifugation of 2ml of serum.2 Because of the identification of trace levels of HCV-RNA in serum then a piece of the liver biopsy which had been obtained for histological examination was subjected to detailed molecular analysis.
We tested for the presence of the genomic and antigenomic HCV-RNA in the liver biopsy by a strand specific real-time PCR3 and for HBV-DNA. While HBV-DNA in liver was negative, both genomic and antigenomic HCV-RNA were detected. Furthermore, by in situ hybridization4 it was determined that 0.5% of the hepatocytes were infected by HCV (Fig. 1). We concluded that this patient had an occult HCV infection in spite of having normal levels of liver enzymes and no evidences of liver damage.
Fig. 1.
HCV-RNA detection by in situ hybridization in the liver biopsy of the patient. The arrow shows the in situ hybridization signal in the cytoplasm of a hepatocyte.
Occult HCV infection was first described in patients with abnormal liver function tests of unknown etiology and this occult infection is characterized by the detection of HCV-RNA in liver in the absence of anti-HCV and serum HCV-RNA tested by conventional techniques4 although they may have low levels of circulating HCV virions only detectable after ultracentrifugation of serum samples.2
Occult HCV seems to induce a milder liver disease than “classical” chronic HCV infection, but occult HCV has been found in patients with liver cirrhosis or hepatocellular carcinoma.5, 6 In the present report it has been shown that people without evidences of liver disease and with normal levels of liver enzymes may well have an occult HCV infection, indicating that occult HCV infection may be associated with a wide spectrum of liver damage ranging from normal liver histology to cirrhosis. Our findings also suggest that prevalence of occult HCV infection may be higher than expected. As these patients have circulating HCV particles they may spread this infection within their family setting as it has been reported recently.7
Funding
None.
Competing interests
None declared.
Ethical approval
Not required.
References
- Update definitions of healthy ranges for serum alanine aminotransferase levels. Ann Intern Med. 2002;137:1–10
- Ultracentrifugation of serum samples allows detection of hepatitis C virus RNA in patients with occult hepatitis C. J Virol. 2007;81:7710–7715
- . Detection of hepatitis C virus (HCV) RNA in the liver of healthy anti-HCV antibody-positive, serum HCV-RNA negative patients with normal alanine aminotransferase levels. J Infect Dis. 2006;194:53–60
- Occult hepatitis C virus infection in patients in whom the etiology of persistently abnormal results of liver-function tests is unknown. J Infect Dis. 2004;189:7–14
- . Comparative study between occult hepatitis C virus infection and chronic hepatitis C. J Viral Hepat. 2007;14:36–40
- . HBV, HCV and TTV detection by in situ polymerase chain reaction could reveal occult infection in hepatocellular carcinoma: comparison with blood markers. J Clin Pathol. 2006;59:526–529
- . Hepatitis C virus infection in the family setting of patients with occult hepatitis C. J Med Virol. 2009;81:1198–1203
PII: S1386-6532(09)00434-X
doi:10.1016/j.jcv.2009.09.018
© 2009 Elsevier B.V. All rights reserved.
