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LETTER

Extrahepatic Manifestations of Hepatitis C Virus Infection

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

15 August 1996 | Volume 125 Issue 4 | Page 344

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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: [in this window] [in a new window]   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.

Author and Article Information

Top Author & Article Info References

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

References

Top Author & Article Info References

1. Gumber SC, Chopra S. Hepatitis C: a multifaceted disease. Review of extrahepatic manifestations. Ann Intern Med. 1995; 123:615-20.

2. Ferri C, Monti M, La Civita L, Longombardo G, Greco F, Pasero G, et al. Infection of peripheral blood mononuclear cells by hepatitis C virus in mixed cryoglobulinemia. Blood. 1993; 82:3701-4.

3. Zignego AL, Ferri C, Giannini C, Monti M, La Civita L, Careccia G, et al. Hepatitis C virus genotype analysis in patients with type II mixed cryoglobulinemia. Ann Intern Med. 1996; 124:31-4.

4. Ferri C, La Civita L, Monti M, Longombardo G, Greco F, Pascro G, et al. Can hepatitis C be complicated by malignant lymphoma? Lancet. 1995; 346:1226-7.

5. Ferri C, Caracciolo F, Zignego AL, La Civita L, Monti M, Longombardo G, et al. Hepatitis C virus infection in patients with non-Hodgkin's lymphoma. Br J Haematol. 1994; 88:392-4.

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