Clinical Science
 

Extrahepatic manifestations of chronic hepatitis C

Patrice Cacoub 1 *, Thierry Poynard 1, Pascale Ghillani 1, Frederic Charlotte 1, Martine Olivi 2, Jean Charles Piette 1, Pierre Opolon 1, for the MULTIVIRC GROUP 1

1Hôpital La Pitié-Salpêtrière, Paris, France 2Pharmacy University, Paris, France

^*Correspondence to Patrice Cacoub, Department of Internal Medicine, Hôpital La Pitié-Salpêtrière, 83 Boulevard de l'Hôpital, 75651 Cedex 13 Paris, France

 

Abstract

Objective

To assess the prevalence of clinical and biologic extrahepatic manifestations of hepatitis C virus (HCV) infection and to identify associations between clinical and biologic manifestations.

Methods

To analyze the natural history of extrahepatic manifestations of HCV infection, we reviewed only the data recorded prospectively during the first visit of 1,614 patients with chronic HCV infection, coming from a single monocenter cohort. Exclusion criteria were positivity for hepatitis B surface antigen or human immunodeficiency virus. The prevalence of dermatologic, rheumatologic, neurologic, and nephrologic manifestations; diabetes; arterial hypertension; autoantibodies; and cryoglobulins were assessed. Then, using multivariate analysis, we identified demographic, biochemical, immunologic, virologic, and liver histologic factors associated with the presence of extrahepatic manifestations.

Results

At least 1 clinical extrahepatic manifestation was observed in each of 1,202 patients (74%). Five manifestations had a prevalence >10%: arthralgia (23%), paresthesia (17%), myalgia (15%), pruritus (15%), and sicca syndrome (11%). Four biologic abnormalities had a prevalence >5%: cryoglobulins (40%), antinuclear antibodies (10%), low thyroxine level (10%), and anti-smooth muscle antibodies (7%). Only vasculitis, arterial hypertension, purpura, lichen planus, arthralgia, and low thyroxine level were associated with cryoglobulin positivity. By univariate and multivariate analyses, the most frequent risk factors for the presence of clinical and biologic extrahepatic manifestations were age, female sex, and extensive liver fibrosis.

Conclusion

Extrahepatic clinical manifestations are frequently observed in HCV patients and involve primarily the joints, muscles, and skin. The most frequent immunologic abnormalities include mixed cryoglobulins, antinuclear antibodies, and anti-smooth muscle antibodies. The most frequent risk factors for the presence of clinical and biologic extrahepatic manifestations are advanced age, female sex, and extensive liver fibrosis.

Received: 2 February 1999; Accepted: 25 May 1999

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Specific Extrahepatic Disorders Tied To Hepatitis C In Large Study

A DGReview of
Hepatology

12/06/2002
By Anne MacLennan

There is a significant link between hepatitis C virus (HCV) infection and several skin, renal and haematologic disorders, a massive study in the United States has found.

Of specific concern are porphyria cutanea tarda (PCT), lichen planus, vitiligo, cryoglobulinemia, membranoproliferative glomerulonephritis (GN) and non-Hodgkin's lymphoma (NHL).

Patients with any of these conditions should be tested for HCV infection, urge these researchers from The Houston Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas.

In this hospital-based study, Dr H B El-Serag and colleagues examined the cases of 34,204 HCV-infected patients hospitalized between 1992 and 1999 and 136,816 randomly chosen controls without HCV and matched with cases by year of admission.

Although HCV has been associated before with several extrahepatic conditions, until this one, most studies have involved small numbers of patients and lacked a control group.

These authors used the computerized databases of the US Department of Veterans Affairs.

Both in- and outpatient files were searched for several disorders: skin (PCT, vitiligo and lichen planus), renal (membranous GN and membranoproliferative GN), haematologic (cryoglobulin, Hodgkin's and NHL), endocrine (diabetes, thyroiditis) and rheumatologic (Sjogren's syndrome).

In analysing the link between HCV and these disorders, the researchers controlled for age, gender, ethnicity and period of military service.

Overall, the HCV-infected patients as compared with controls were younger (45 years versus 57 years), more frequently non-white (39.6 percent vs 26.3 percent) and more frequently male (98.1 percent vs 97.0 percent).

A significantly greater proportion of patients than controls had PCT, vitiligo, lichen planus and cryoglobulinemia, and there was also a greater prevalence among patients of membranoproliferative GN but not of membranous GN.

Although there was no significant difference between the two groups in prevalence of thyroiditis, Sjogren's syndrome or Hodgkin's or NHL, NHL became significant after the researchers took age into account.

Diabetes was found to be more prevalent in controls than in cases, but there was no significant link after age was considered.
Hepatology 2002 Dec;36(6):1439-45.