Extrahepatic manifestations of chronic hepatitis B.

Several extrahepatic manifestations are associated with chronic HBV infection, many with significant morbidity and mortality. The cause of these extrahepatic manifestations is generally believed to be immune mediated. PAN is a rare, but serious, systemic complication of chronic HBV affecting the small- and medium-sized vessels. PAN is seen more frequently in North American and European patients and rarely in Asian patients. PAN ultimately involves multiple organ systems, some with devastating consequences, though the hepatic manifestations are often more mild. The optimal treatment of HBV-associated PAN is thought to include a combination of antiviral and immunosuppressive therapies. HBV-associated GN occurs mainly in children, predominantly males, in HBV endemic areas of the world, but is only occasionally reported in the United States. In children, GN is usually self-limited with only rare progression to renal failure. In adults, the natural disease course of GN may be more relentless, slowly progressing to renal failure. Immunosuppressive therapy in HBV-related GN is not recommended, but antiviral therapy with alpha-interferon has shown promise. The serum-sickness like "arthritis-dermatitis" prodrome is seen in approximately one third of patients acquiring HBV. The joint and skin manifestations are varied, but the syndrome spontaneously resolves at the onset of clinical hepatitis with few significant sequelae. Occasionally, arthritis following the acute prodromal infection may persist; however, joint destruction is rare. The association between HBV and mixed essential cryoglobulinemia remains controversial; but a triad of purpura, arthralgias, and weakness, which can progress to nephritis, pulmonary disease, and generalized vasculitis, has characterized the syndrome. Finally, skin manifestations of HBV infection typically present as palpable purpura. Though papular acrodermatitis of childhood has been reported to be caused by chronic HBV, this association remains controversial.