Persistently abnormal liver function tests: Marker of occult hepatitis C?

January 02, 2004

Patients with persistently abnormal liver function tests but no serologic evidence of liver disease may nevertheless have hepatitis C virus (HCV) infection, according to a study published in the January 1 issue of The Journal of Infectious Diseases, available online now.

Such occult (meaning hidden or concealed) infection is not supposed to occur--the conventional wisdom is that the virus leaves markers in serum or plasma, including specific antibodies and viral RNA, which have been the serologic cornerstones for diagnosing and monitoring HCV-infected patients. Although occult HCV infection generally appears to be mild, some patients have shown evidence of serious chronic liver injury. In addition, occult infection raises the possibility of disease spread via blood donations, hemodialysis and other procedures. Fortunately, the study also suggests a minimally invasive approach to detect occult infection.

The study, reported by a group headed by Vicente Carreño, MD, in Madrid, Spain, involved 100 patients with abnormally high levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) or gamma glutamyl transpeptidase (GGTP) for at least 12 months in whom all causes of liver disease, including HCV infection, had ostensibly been excluded. All three liver enzymes were elevated in eight patients, two of the enzymes in 48 and one enzyme in 44. For comparison, 30 patients with liver damage known to be of non-viral origin were also studied.

The investigators relied on two assays to demonstrate the presence or absence of HCV infection. First, using reverse transcription-polymerase chain reaction (RT-PCR) with primers from one region of the HCV genome, they detected the virus's RNA in liver biopsies from 57 (57%) of the patients with abnormal liver enzymes of unknown etiology, compared to none of the biopsies from control patients. When primers from another region of the genome were used in the RT-PCR assay, HCV RNA was found in liver biopsies from 40 (70%) of the 57 patients. The second method used was in situ hybridization, which demonstrated positive-strand HCV RNA in liver biopsies from the same 57 patients, but in none of those from the controls, and negative-strand HCV RNA in 48 (84%). The investigators noted that the latter finding suggested viral replication, which involves synthesis of a negative RNA intermediary.

The RT-PCR assay also detected HCV RNA in peripheral-blood mononuclear cells from 40 (70%) of the 57 patients with occult infection. The clinical implication of this finding, the investigators noted, is that a high percentage of patients with occult HCV infection may be more easily and more safely identified by obtaining and testing blood cells rather than liver cells.

In an accompanying editorial, Hervé Lerat, MD, and F. Blaine Hollinger, MD, of Baylor College of Medicine, Houston, commented that the distribution of hepatic enzyme elevations in the study population implied that clinicians should use both ALT and GGT to identify patients who may qualify for peripheral-blood mononuclear cell testing for occult HCV infection. They cautioned, however, that many issues about such infections remain to be resolved, including the central issue of whether the detected viral genomic material is infectious.
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Founded in 1904, The Journal of Infectious Diseases (JID) is the premier publication in the Western Hemisphere for original research on the pathogenesis, diagnosis and treatment of infectious diseases; on the microbes that cause them; and on disorders of host immune mechanisms. Articles in JID include research results from microbiology, immunology, epidemiology and related disciplines. JID is published under the auspices of the Infectious Diseases Society of America (IDSA), based in Alexandria, Va., a professional society representing more than 7,000 physicians and scientists who specialize in infectious diseases.

Note: Interviews with Drs. Carreño and Hollinger can be arranged by contacting Diana Olson at dolson@idsociety.org or 703-299-0201.

Infectious Diseases Society of America

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