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

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.

Body Composition Changes in Patients with Chronic Hepatitis C

“…Chronic hepatitis C (CHC) represents a systemic disease with multiple extrahepatic complications [1][2][3]. The prevalence of the chronic infection with hepatitis C virus (HCV) in Europe was reported to be between 0.4 -3.5% in the general population [4].…”

Extrahepaticus manifesztációk idült hepatitis C-vírus-fertőzöttekben

“…Az I. típusban, amely az esetek 10-15%-át jelenti, monoklonális IgM jelenik meg. Általában a lymphoproliferativ betegségeket jellemzi (myeloma multiplex, Waldenström-féle macroglobulinaemia, krónikus lymphocytás leukaemia, non-Hodgkinlymphoma, nehézlánc-betegség) [13].…”

“…típus a leggyakoribb, az esetek 50-60%-a, poliklonális IgG és monoklonális IgM megjelenésével. Jellegzetes HCV-fertőzésre, de más idült gyulladásokban, autoimmun folyamatokban is megjelenhetnek (sziszté-más lupus erythematodes, rheumatoid arthritis) [8,13].…”

“…típusú cryoglobulinaemia kevert IgM típusú poliklonális immunkomplexekkel. Autoimmun folyamatokat, fertőzéseket, szövetszéteséssel járó kórképeket jelezhet [13].…”

“…Az immunkomplexek lerakódása a glomerularis kapillári-sokban és a mesangiumban hozza létre a I. típusú membranoproliferativ glomerulonephritist (MPGN), amely a leggyakoribb HCV-asszociált veseérintettség [12,13,20].…”