Idiopathic Chronic Active Hepatitis Research Articles

The relationship between hepatic copper content and morphologic changes in the liver of West Highland White Terriers.

Liver tissue from 17 West Highland White Terriers (WHWTs) with cirrhosis, subacute bridging necrosis, hepatitis, or massive necrosis were examined for the presence, composition, and distribution of inflammatory foci. Copper analysis was performed on the specimens. The foci of inflammation and necrosis composed a significant part of the lesion in 15 of the samples. The foci were of two types. One, characteristic of idiopathic chronic active hepatitis, consisted of one or two apoptotic hepatocytes attended by lymphocytes and plasma cells. These foci were found primarily in the vicinity of the portal tracts, not associated with centrolobular copper-laden hepatocytes. The other type of focus was characteristic of copper toxicosis. These foci were larger and composed of debris-filled macrophages, lymphocytes, plasma cells, and scattered neutrophils, and on occasion apoptotic hepatocytes were found at the periphery. These foci were always found around the central vein among the copper-laden hepatocytes. Such foci were found only in dogs with copper concentration > 2,000 parts/million on a dry weight basis. These morphologic studies show that clinical liver disease in WHWTs is caused by more than one etiologic agent. Among 17 WHWTs with clinical liver disease, two had copper toxicosis, five had idiopathic chronic active hepatitis, and 10 had hepatic disease of undetermined type.

Acute cellular rejection of liver allografts is increased in frequency in patients with autoimmune idiopathic chronic active hepatitis (AICAH): [formula omitted] UCLA School of Medicine, Los Angeles, CA

Acute cellular rejection of liver allografts is increased in frequency in patients with autoimmune idiopathic chronic active hepatitis (AICAH): [formula omitted] UCLA School of Medicine, Los Angeles, CA

Geographical variation in prevalence of hepatitis B virus DNA in HBsAg negative patients.

AIMS--To study the geographical variation of the prevalence of hepatitis B virus (HBV) DNA in hepatitis B surface antigen (HBsAg) negative subjects. METHODS--A nested polymerase chain reaction (PCR) assay was used to amplify the core region of HBV. The assay was able to detect 10 molecules of a full length HBV plasmid. RESULTS--When applied to HBsAg negative paraffin wax embedded liver samples from Italy, Hong Kong, and the United Kingdom, a geographical variation in the prevalence of HBV-DNA positivity was noted. Two of 18 (11%) of Italian samples and 2/29 (6.9%) of Hong Kong samples were positive for HBV-DNA while none of the 70 cases from the United Kingdom was positive by nested PCR. Contamination by plasmid DNA was excluded using a novel method based on heteroduplex formation. One HBV-DNA positive case had idiopathic chronic active hepatitis, but the diagnoses in the other three HBV-DNA positive cases did not suggest any aetiological connection between HBV-DNA positivity and liver pathology. CONCLUSIONS--HBV-DNA could be detected in the liver tissues of a proportion of HBsAg negative subjects. The prevalence of such cases is related to the endemic rate of a geographical region. The use of HBV PCR on paraffin wax embedded tissues will be valuable for future studies on the molecular epidemiology of HBV.

Auto‐immune features in patients with idiopathic chronic active hepatitis who are seronegative for conventional auto‐antibodies

In patients with chronic active hepatitis (CAH), the absence of the conventional serum auto-antibodies (antinuclear, smooth muscle and liver-kidney microsomal) is often taken as evidence against an auto-immune aetiology and as indicative that the disease is unlikely to respond to immunosuppressive therapy. We report 12 British patients (11 female) who presented with histologically florid CAH (11 with cirrhosis or fibrosis and seven with ascites) but without significant titres of these antibodies or any other demonstrable aetiological feature (cryptogenic CAH), who have been followed up for a median of 5.25 years (range: 0.75-16 years). Ten had hypergammaglobulinaemia and/or specific elevations of serum IgG concentrations at presentation and five of 10 patients tested were found to have the HLA allotypes B8 and DR3. Remission was initially induced with prednisolone with or without azathioprine in all patients. Six patients subsequently relapsed on one or more occasions, either spontaneously while on maintenance therapy or during attempts to withdraw corticosteroids, and required increases or reintroduction of immunosuppressive therapy to regain disease control. Retrospective analysis of pretreatment samples from 11 of the patients revealed that all had been seropositive at presentation for auto-antibodies against the liver membrane lipoprotein preparation known as liver-specific membrane lipoprotein (LSP) and/or against the hepatic asialoglycoprotein receptor (ASGP-R), titres of which subsequently fluctuated in direct relation to response to treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Idiopathic Chronic Active Hepatitis in Iceland

ABSTRACT. An epidemiological study of idiopathic chronic active hepatitis in Iceland during 1970‐79 is described. Patients were identified by examining all request forms for surgical specimens (117 141) sent to the Department of Pathology in that period. The diagnosis was established by a review of clinical records and liver biopsies. The patients were interviewed if clinical or serological information was lacking. Although 33.9% of all deaths in Iceland were autopsied during this period, no previously undiagnosed case of idiopathic chronic active hepatitis was found among the deceased. Eighteen new cases were found, 17 females and one male. The mean age at the time of diagnosis established by liver biopsy was 53 years (range 3–79). The most common symptoms were fatigue and/or malaise (89%) and jaundice (61%) and the prevalence of immunological markers was high. The average annual incidence was 0.83/100000 and the prevalence 8/100000. Because of the ethnic origin of Icelanders, these figures might possibly apply to Norway and the British Isles.

Chronic hepatitis: Current dilemmas

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-

Wilson's disease: Diagnostic difficulties in the patient with chronic hepatitis and hypoceruloplasminemia

Wilson's disease presents as a classical hereditary syndrome of clinical and biochemical abnormalities. Life-long treatment with copper-chelating agents may dramatically alter the subsequent course and outcome. Hence, considerable attention has been drawn to early recognition and treatment. Since the presentation of Wilson's disease may simulate chronic active hepatitis of unknown etiology, it has been emphasized that the diagnosis of the genetic disorder should be suspected and excluded in this clinical setting. In this report we describe the difficulties encountered in the evaluation of a patient with non-Wilsonian chronic active hepatitis and low serum ceruloplasmin levels. This case illustrates that the distinction between the Wilson's disease homozygote and the hypoceruloplasminemic patient with idiopathic chronic active hepatitis may be difficult to establish and requires a critical evaluation of data to avoid diagnostic pitfalls.

Immunological Abnormalities Associated with liver Disease: Cause or Effect?

Immunological abnormalities are demonstrable in patients with various types of liver damage. These may be (a) non-specific and unrelated to pathogenesis, e.g. auto-antibodies such as anti-nuclear factor; (b) specifically directed against liver antigens but not pathogenetic, e.g. cell mediated immune (CMI) reactions to liver antigen as seen in experimental carbon tetrachloride poisoning; (c) of such a nature as to modify the pathology produced by hepatotoxic agents, e.g. hepatitis B virus or alcohol; (d) primarily responsible for hepatic pathology, e.g. in idiopathic chronic active hepatitis. The latter two possibilities remain unproven although there is growing evidence that immune responses do play some role in the pathogenesis of acute and chronic hepatitis B and possibly also in the pathogenesis of alcoholic liver disease. It seems much less likely that primary abnormalities of the immune systems are responsible for any type of liver disease. In summary, therefore, the available evidence suggests that immune reactions could develop as a consequence of liver damage and only in certain circumstances do these reactions play a role in the development and continuation of hepatic pathology.