Cutaneous manifestations of hepatitis C in the era of new antiviral agents

The association of chronic hepatitis C virus(HCV) infection with a wide spectrum of cutaneous manifestations has been widely reported in the literature, with varying strength of epidemiological association. Skin diseases which are certainly related with chronic HCV infection due to a strong epidemiological and pathogenetic association are mixed cryoglobulinemia, lichen planus and porphyria cutanea tarda. Chronic pruritus and necrolytic acral erythema are conditions that may share a possible association with HCV infection, while several immune-mediated inflammatory skin conditions, such as psoriasis, chronic urticaria and vitiligo, have been only anecdotally reported in the setting of chronic HCV infection. Traditional interferonbased treatment regimens for HCV infection are associated with substantial toxicity and a high-risk of immune-related adverse events, while the advent of new direct-acting antivirals with sustained virological response and improved tolerability will open the door for all-oral, interferon-free regimens. In the new era of these direct acting antivirals there will be hopefully a renewed interest in extra-hepatic manifestations of HCV infection. The aim of the present paper is to review the main cutaneous HCV-related disorders- mixed cryoglobulinemia, lichen planus, porphyria cutanea tarda and chronic pruritus- and to discuss the potential impact of new antiviral treatments on the course of these extrahepatic manifestations of chronic HCV infection.

Psoriasis:Biologic treatment and liver disease

Patients with moderate or severe psoriasis have a high prevalence of chronic liver disease. Chronic liver disease in these patients is related to metabolic syndrome, alcohol abuse or viral infections. Therefore,treatment of these patients is challenging. Classic systemic treatments may be contraindicated because of their immunosuppressive and hepatotoxic potential.First-line therapy in this setting is generally ultraviolet B phototherapy combined with topical treatment, but its feasibility and efficacy are sometimes limited. The therapeutic options are further restricted by concomitant psoriatic arthritis. Biologic treatments have shown to be effective in psoriasis and psoriatic arthritis, and they are largely devoid of liver toxicity. Anti-tumor necrosis factor-alpha(TNF-α) treatments have proven to be effective and safe in patients with chronic hepatitis C virus(HCV) infections and other non-infectious chronic liver disorders, including alcoholic and non-alcoholic liver diseases. However, in chronic hepatitis B virus(HBV), anti-TNF-α treatments carry a high risk of HBV reactivation. Anti-interleukin-12/23 treatments are also effective in patients with psoriasis, but data regarding their safety in chronic hepatitis infections are still limited. Safety reports in patients with psoriasis and chronic HCV infection are contradictory, and in chronic HBVevidence indicate a potential risk of viral reactivation. Moreover, concerns remain about the long-term safety of both TNF-α antagonists and ustekinumab. Non-viral liver diseases such as alcoholic and non-alcoholic liver diseases are more prevalent in patients with psoriasis than in the general population. TNF-α antagonists have also been prescribed in these patients. Although data are still scarce in this setting, results suggest a favorable profile in patients with psoriasis and non-alcoholic liver diseases. We review the literature regarding all these aspects.