Extrahepatic Manifestations of Hepatitis C Virus Infection

doi:10.1059/0003-4819-125-4-199608150-00017

Extrahepatic Manifestations of Hepatitis C Virus Infection

C. Ferri, MD;
L. La Civita, MD; and
A.L. Zignego, MD

University of Pisa, Pisa, Italy University of Florence, Florence, Italy

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TO THE EDITOR:

Gumber and Chopra [1] recently reviewed the extrahepatic manifestations of chronic hepatitis C virus (HCV) infection. They focused on the striking association between HCV and mixed cryoglobulinemia. This immune-complex-mediated systemic vasculitis is secondary to “benign” B-lymphocyte expansion.

The HCV infection of lymphocytes [2] represents the remote event that triggers chronic B-cell proliferation. The immune system alteration may promote various disorders (mixed cryoglobulinemia, autoimmune hepatitis, porphyria cutanea tarda, membranoproliferative glomerulonephritis, and lung fibrosis. These manifestations could be the result of a variable combination of genetic and environmental factors, HCV mutants [3], and other infectious agents.

Here, we point out the crucial role of lymphoproliferation in patients with HCV infection (Table 1). In a limited number of patients with mixed cryoglobulinemia, the “benign” B-cell proliferation can evolve to frank non-Hodgkin lymphoma [2]. The same phenomenon has been anecdotally reported in patients with chronic hepatitis C. We recently described a cohort of 14 patients with chronic hepatitis C complicated by B-cell non-Hodgkin lymphoma observed over a long follow-up period [4]. In a few of these patients, HCV RNA has been detected in bone marrow or lymph node biopsy specimens using one-tube, nested polymerase chain reaction [2, 4].

View this table:

Table 1. Systemic Disorders Related to HCV Infection*

Moreover, in a series of 50 patients with “idiopathic” B-cell non-Hodgkin lymphoma, we found a surprisingly high frequency of HCV infection [5]. In 32% of these patients, HCV RNA has been shown in both sera and peripheral lymphocytes. Hepatitis C virus is probably the trigger factor of a multistep pathologic process, as has been hypothesized for other virus-induced neoplasias in humans.

Throughout the world, chronic hepatitis C has become an increasingly diffuse disorder. The possible appearance of malignant lymphoproliferation during the natural course of HCV infection is an uncommon but severe complication that can affect overall prognosis.

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C. Ferri, MD

L. La Civita, MD

A.L. Zignego, MD