Hepatitis C virus as a systemic disease: reaching beyond the liver.

Kirat Gill,Richard Manch,Hasmik Ghazinian,Robert Gish

doi:10.1007/s12072-015-9684-3

Abstract

Chronic hepatitis C (CHC) is associated with multiple extrahepatic manifestations that may impact infected patients. The mechanisms through which these develop include those which are immunological, in which the chronic persistence of virus leads to the circulation of immune complexes (mixed cryoglobulinemia) and other autoimmune phenomena, and those which are virological and related to the extrahepatic tropism of the virus to other tissues. It is estimated that 40–74 % of patients with CHC may develop at least one extrahepatic manifestation during the course of the disease. Extrahepatic syndromes may represent the first signal of hepatitis C infection in some patients. CHC is associated with a four-fold increased risk of insulin resistance and type 2 diabetes mellitus; with cardiovascular disease in 17–37 % of patients; and with increased risk for cerebrovascular deaths, with a biological gradient of cerebrovascular mortality correlating with an increasing serum viral load. CHC is also associated with lymphoproliferative disorders, particularly non-Hodgkin B-cell lymphoma. The kidney is involved in 35–60 % of patients with CHC-associated mixed cryoglobulinemia. The prevalent type of glomerulonephritis associated with mixed cryoglobulinemia is membranoproliferative glomerulonephritis. In 30 % of cases, renal involvement begins with a nephritis syndrome and acute renal failure, while in 55 % there is only mild hematuria, microalbuminuria, proteinuria and renal insufficiency. CHC is also associated with cognitive impairment, especially in memory and concentration. Thus, extrahepatic CHC manifestations involve multiple organ systems outside the liver linked to a variety of comorbidities which may lead to significantly increased mortality from non-liver-related events.

Highlights

The hepatitis C virus (HCV) has significant and obvious hepatic implications
The mechanisms through which these develop include those which are immunological, in which the chronic persistence of virus leads to the circulation of immune complexes and other autoimmune phenomena, and those which are virological and related to the extrahepatic tropism of the virus to other tissues
Chronic hepatitis C (CHC) is associated with a four-fold increased risk of insulin resistance and type 2 diabetes mellitus; with cardiovascular disease in 17–37 % of patients; and with increased risk for cerebrovascular deaths, with a biological gradient of cerebrovascular mortality correlating with an increasing serum viral load

Summary

Introduction

The hepatitis C virus (HCV) has significant and obvious hepatic implications. too often, the extrahepatic, multi-organ ramifications of this virus are overlooked. In power of concentration and speed of working memory, that is unaccounted for by depression, fatigue, or a history of injection drug use has been reported in CHC patients [79] In their Taiwan-based study, Chiu et al found an increased incidence of dementia in those with CHC after adjustment for variables such as hepatic encephalopathy and alcohol-related disease [80]. Data are limited on the resolution of extrahepatic manifestations with the new direct acting antiviral medications, multiple studies over the course of the past few decades have shown marked improvement of EMs upon eradication of HCV after treatment with previous therapies, primarily combination therapy with peg-IFN and ribavirin. Viral eradication with sofosbuvir/ledipasvir has been associated with improvement in health-related quality of life and work productivity [87]

Conclusion

Findings

Compliance with ethical standards