Chronic hepatitis: Current dilemmas

Abstract

P roblems relating to chronic hepatitis continue to provide one of the most frequent reasons for hepatology consultation today. Physicians remain puzzled by nomenclature and classification. Often there is a problem in differentiating mild nonprogressive from serious progressive disease. There are no firm guidelines for the use of corticosteroid and immunosuppressive drugs, particularly in chronic hepatitis B. “Chronic hepatitis” implies an ongoing inflammatory process in the liver. It need not be a viral or other infectious process since there are examples of chronic active hepatitis with a toxic etiology. The hallmark of the inflammatory process is a four to fivefold, or more, elevation of serum transaminase levels. How long the disorder has to be observed before calling it chronic is unsettled. The Mayo Clinic controlled trial of treatment of chronic hepatitis required a minimum duration of disease of 10 weeks [l]. However, we have seen occasional instances of slow but complete recovery from acute viral hepatitis that took as long as 12 months. The diagnosis of chronic hepatitis may be uncertain, therefore, until the patient has been observed for a year or more. Of course, clinical and laboratory findings may be virtually diagnostic of chronic disease when the patient is first seen. However, acute hepatitis with submassive necrosis or with “impaired regeneration” [z] often results in a prolonged illness that may simulate chronic disease, both clinically and on liver biopsy. Yet such patients usually recover completely if they survive the acute illness. Nomenclature and classification of chronic hepatitis are muddled and will remain so until we understand the etiology and pathogenesis of all forms of the disease. The terms “chronic persistent hepatitis” and “chronic active hepatitis” are imperfect (“chronic persistent” is redundant and “chronic active” is a problem when the disease is quiescent] but are now fairly well accepted by all. They do not indicate etiology. It is likely, although unproved, that all instances of chronic persistent hepatitis represent continuing infection with B or non-A, non-B hepatitis viruses. The etiology of most chronic active hepatitis, however, remains unknown. Only a small fraction of cases in England, Australia and the United States have hepatitis B surface antigen (HBsAg) and a very small additional proportion can be assumed to have hepatitis B because of the finding of high-titer anti-HBc and absent anti-HBs. In some parts of the world, hepatitis B is more prevalent and there are other areas, such as Argentina, where idiopathic chronic active hepatitis appears to be rare [3]. An occasional patient with chronic active hepatitis has Wilson’s disease. Chronic active toxic hepatitis is infrequent except in countries in which oxyphenisatin is still sold. Very convincing cases have been described with prolonged use of nitofurantoin and a somewhat similar lesion with perihexaline maleate. Whether the use of other drugs that are capable of causing acute hepatic necrosis (methyldopa, diphenylhydantoin, isoniazid, acetaminophen, dantrolene) can also result in chronic hepatitis remains an intriguing question. In most if not all instances, the severity of the hepatic reaction from these drugs is great enough to preclude long-term use and chronic hepatic damage. There is no widely accepted label for the large proportion of cases of chronic active hepatitis of uncertain cause. The term “lupoid hepatitis,” coined by Mackay and colleagues, has lost favor and is not used at all by some [4]. Our liver group continues to use this designation for a relatively homogeneous group of patients, mostly women, with progressive liver disease, extrahepatic manifestations, abnormal immunologic test results and a uniformly excellent response to corticosteroid therapy. It is tempting to assume that other female patients with chronic active hepatitis, who may lack antinuclear antibody and the lupus erythematosus cell phenomenon but who do not have hepatitis B or a background of disease onset after blood transfusion, have this same “immunologic” type of liver disease, but probably it is best to label their disease “idiopathic chronic active hepatitis.” A problem of practical importance is differentiating between chronic persistent and chronic active forms of chronic hebatitis. This can be simple when clinical and/or laboratory data show serious disease. On the other hand, there are occasional patients with cirrhosis in whom the laboratory test abnormality is limited to elevated transaminase levels and in whom clinical ev-