Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sixty-five patients with histologically proven chronic active hepatitis of unknown cause but associated with the antiliver/kidney microsome antibody type 1, confirmed by immunofluorescence and immunoprecipitation, were selected as forming a special entity. This disease was found to be rare with a prevalence of 5/1,000,000. The female to male ratio was 8:1. The condition occurred at all ages but was most common between the ages of 2 and 14 years. In 22 of the 65 cases, the hepatitis was associated with an autoimmune disease, most commonly insulin-dependent diabetes, autoimmune thyroid disease and vitiligo. The same autoimmune diseases were present in first-degree relatives from seven families. In 36 cases, the onset of disease resembled acute viral hepatitis. Serum biochemical tests showed marked elevation in aminotransaminases and hypergammaglobulinemia. Paradoxically, serum and salivary IgA levels were often normal or low. Histologic findings were multifocal hepatic necrosis with bridging in the acute stage, and aggressive hepatitis with mononuclear cell infiltration or macronodular cirrhosis in the late stages. Serologically, apart from the presence of antiliver/kidney microsome antibody type 1, the disease was characterized by the absence of antiactin, antimitochondria and antinucleus antibodies; however, organ-specific autoantibodies were often present. The clinical course was usually severe: six patients in the acute stage presented with fulminant hepatitis, and all, except two, other patients progressed to cirrhosis. Prolonged treatment with corticosteroids and immunosuppressants was usually effective in rendering the cirrhosis inactive. The cumulative survival rate was 51% at 14 years. We propose to call this entity "anti-LKM1 chronic active hepatitis" or "autoimmune hepatitis type II" to differentiate it from classical "lupoid hepatitis" or autoimmune hepatitis type I.
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PMID:Chronic active hepatitis associated with antiliver/kidney microsome antibody type 1: a second type of "autoimmune" hepatitis. 367 93

We retrospectively studied 94 children with urticaria longer than six weeks in duration. The disease was equally distributed among the sexes and the following age subgroups (0-3.9 years, 4.0-7.9 years, 8.0-11.9 years and 12.0-15.9 years). A cause of the urticaria was identified or suspected in 15 of the patients. These included eight patients with cold urticaria, two with infection (hepatitis, sinusitis), two with food allergy, one patient with juvenile rheumatoid arthritis, one with arthralgia associated with a positive ANA and one with a low level of total hemolytic complement (CH50). Follow-up of a year of more on 52 patients revealed a median duration of urticarial symptoms of 16.0 months, with 58% of children becoming symptom free for six months or more, whereas the remaining 42% continued to have recurrent symptoms but without the development of an underlying serious illness. Results of the present study indicate that the etiology of chronic urticaria in childhood remains mostly undetermined but that the prognosis is generally favorable. However, one must consider an underlying infection or autoimmune disease as a potential etiology.
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PMID:Chronic urticaria in childhood: natural course and etiology. 688 5

Of the two major types of chronic active hepatitis, that associated with autoimmunity, CAH-Type A, has been the more extensively studied and is better recognised. On the other hand, the type associated with the HBV carrier state, CAH-Type B, is the more prevalent, particularly so in South East Asia, and the time is ripe for the immunology of this type to be clarified. Whilst most encounters between host and HBV will result in an acute hepatitis with lasting immunity, a non-sterilizing outcome with a persisting carrier state may ensue. The reasons for persistent infection with HBV are still not elucidated, but may include: (i) incorporation of viral DNA into the host genome, (ii) a carrier state in which there is full T cell tolerance to the virus and its surface antigen, or (iii) an unstable tolerance marked by a persisting damaging immune response to viral antigens expressed on the liver cell membrane, with associated CAH. Whether an autoimmune-type CAH can be included as one possible outcome of HBV infection is uncertain; whilst the association of an HB viral antigen with a liver cell membrane component is one theoretical way by which an autoimmune response could be generated, most cases of autoimmune hepatitis, at least in Caucasian areas, show no evidence of current or past infection with HBV or indeed with any other virus. Thus, pending further knowledge, CAH-Type A must be regarded as a primary autoimmune disease of the liver, and CAH-type B as resulting from an ineffective host response to a chronic virus infection of the liver.
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PMID:Immunology of chronic hepatitis. 696 27

Nonalcohol-induced fatty liver is widely believed to be a benign condition with little or no risk of disease progression. There have been occasional reports of progression to cirrhosis but none in the absence of preexisting fibrosis on the index biopsy specimen even when co-existing hepatitis was present (steatohepatitis). From our histological database (1978 to 1985), we identified 161 patients with fatty liver seen at our institution and traced the case notes of 156. One hundred five patients were initially excluded as having an alcohol-induced cause, and the remaining 51 either were seen in the clinic (37) or had died, in which cases copies of their death certificates were obtained (14). A further 7 patients were excluded after clinic attendance gave evidence of alcohol excess and another 4 after review of their initial biopsy showed the presence of fibrosis or steatohepatitis. The apparent cause of the steatosis in the 40 included patients with strictly nonalcohol-induced pure fatty liver was obesity in 12, diabetes in 4 (1 obese patient), and cachexia associated with extrahepatic malignancy in 6. Four of the remaining 19 had serological evidence of an autoimmune disorder, but none of these had any clinical or histological features of autoimmune liver disease. Nine patients had evidence of hyperlipidemia, 3 of whom were also obese. At a median follow-up of 11 years (7 to 16), 12 of 26 living patients had abnormal results of liver blood tests and had repeat liver biopsies performed. None had progressed to steatohepatitis or cirrhosis; 1 obese patient had developed mild fibrosis 9.8 years after her index biopsy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The natural history of nonalcoholic fatty liver: a follow-up study. 748 79

Molecular mimicry has been characterized as the presence of common epitopes, either linear or conformational, shared by host and microbial determinants. Such cross-reactivity may lead to an autoimmune disease. On the other hand molecular mimicry between certain viral proteins and host determinant may protect invading virus to be eliminated by immune system and may promote persistence. In this mini-review I discuss the molecular mimicry of S peplomer protein of mouse hepatitis virus, strain JHM (MHV-JHM) to the host Fc gamma receptor (Fc gamma R). MHV-JHM induces in rodents acute encephalomyelitis and surviving animals develop demyelinating disease with concomitant persistent infection. We have demonstrated that rabbit IgG, but not is F(ab')2 fragments, monoclonal rat and mouse IgG and the rat 2.4G2 anti-Fc gamma R mab immunoprecipitated natural and recombinant S peplomer protein of several strains of MHV. Furthermore, MHV-JHM infected cells formed rosettes with anti-sheep red blood cell (SRBC) - antibody coated SRBC. The 2.4G2 anti-Fc gamma R mab are able to neutralize several strains of MHV, presumably by binding to S peplomer protein. Therefore, the Fc binding site of S is present on the surface of MHV-infected cells. This molecular mimicry between S peplomer protein of MHV-JHM and Fc gamma R has been extended to other members of Coronaviridae, namely bovine coronavirus and transmissible gastroenteritis virus but not to infectious bronchitis virus. The molecular mimicry of viral antigens to Fc receptors has been described also for members of Herpesviridae, namely Herpes simplex, cytomegalovirus and Varicella zoster.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Molecular mimicry between Fc receptors and viral antigens. 750 51

Since their initial description in 1957, the interferons (IFNs) have been increasingly used to treat a wide array of diseases. Acute adverse effects, i.e. 'flu-like' syndromes, hypo- or hypertension, tachycardia, headache, myalgias and gastrointestinal disorders, occur within the first hour or day after starting treatment. They are seldom treatment-limiting and are easily manageable. Sub-acute and chronic effects develop after several days, usually within 2 and 4 weeks of therapy. The most typical is neurological toxicity, including fatigue/asthenia, and behavioural and cognitive changes. Such symptoms may seriously impair quality of life and result in treatment discontinuation. Seizures have seldom been described. Other infrequent central nervous system adverse effects include vertigo, cramp and oculomotor nerve paralysis. Distal paraesthesias and peripheral neuropathy have been reported. IFN-associated autoimmunity is quite rare but a matter of concern. Biological or clinical manifestations usually require several months to become apparent. Autoantibodies have been shown to develop in most patients but have been inconsistently associated with clinical symptoms of systemic lupus erythematosus, rheumatoid-like arthritis and thyroiditis. Both hypo- and hyperthyroidism have been described but are usually reversible. Other infrequent autoimmune reactions include diabetes, pemphigus and worsening of multiple sclerosis. Although several patients present with a pre-existing autoimmune disorder, no predisposing factor has been clearly established. While hypotension and tachycardia are the most frequent acute cardiovascular complications, a few additional cases of cardiac arrhythmias and myocardial ischaemia have been reported after a short course or several weeks of treatment. These latter complications do not appear to be dose-dependent or age-related. Isolated cases of congestive heart failure have also been described. Mild proteinuria has been observed in 15 to 25% of patients, but acute renal toxicity is uncommon. A transient rise in serum aminotransferase levels is frequently noted during the first stage of therapy, especially in patients receiving the highest dosages. Direct hepatotoxicity is extremely rare. Autoimmune hepatitis, which is ill-diagnosed as chronic viral hepatitis, and de novo induction of autoimmune hepatitis, account for the majority of liver diseases. Haematotoxicity is relatively common but mild to moderate, and develops gradually during the first weeks of treatment. Neutropenia is the most common haematological toxicity, but is usually not dose-limiting and resolves rapidly upon drug discontinuation. Myelosuppression, autoimmune and immune allergic haemolytic anaemias and thrombocytopenias have seldom been described. Cutaneous adverse effects comprised nonspecific erythema and hair loss and, less frequently, vasculitis, local ulcerations at the site of injection and exacerbation of psoriasis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical toxicity of the interferons. 751 63

The occurrence of thyroid abnormalities and the appearance of organ- and non-organ-specific autoantibodies during long-term recombinant interferon alpha-2a (IFN-alpha) therapy were studied in 86 and 51 consecutive outpatients with hepatitis C and B virus-related chronic active hepatitis (CAH-HCV and CAH-HBV), respectively. Most patients had longstanding community-acquired hepatitis. At baseline, 9.3% of CAH-HCV and 3.9% of CAH-HBV patients showed clinical and/or biochemical signs of thyroid dysfunction. The remaining patients were euthyroid, although anti-thyroid autoantibodies were found in 33/78 (42.3%) of CAH-HCV and in 5/49 (10.2%) of CAH-HBV patients. During IFN-alpha treatment, increased anti-thyroid autoantibody levels were seen in 40% of CAH-HCV initially negative patients, while they became detectable in no more than 10% of CAH-HBV patients. Interferon-alpha-induced hypo- or hyperthyroidism was recorded in 12 of 35 CAH-HCV patients treated for 12 months (34.3%). Only one CAH-HBV patient developed hyperthyroidism. High titers of anti-nuclear autoantibodies (ANA) were recorded at enrollment in 5/36 (13.8%) of CAH-HCV and in 3/16 (18.7%) of CAH-HBV patients. Only one CAH-HCV patient displayed anti-parietal cell antibodies (PCA). After IFN-alpha treatment, ANA were found in 10/28 (35.7%) and PCA in 2/28 (7.1%) of CAH-HCV patients, while an additional CAH-HBV patient developed PCA, but not ANA. However, no signs of systemic autoimmune disease were recorded.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Autoimmunity and thyroid function in patients with chronic active hepatitis treated with recombinant interferon alpha-2a. 774 99

Primary biliary cirrhosis (PBC) is an autoimmune disease of the liver with unknown etiology. Autoreactive T lymphocytes that infiltrate the liver may play a major role in the bile duct damage that accompanies the disease. We hypothesized that cytokines produced by T lymphocytes and other cells are central to the disease process. Therefore, we used reverse transcription-polymerase chain reaction (PCR) and Southern hybridization to identify cytokine message directly from liver tissue of 11 patients with PBC and 5 patients with autoimmune hepatitis (AI-CAH). Messenger RNA (mRNA) for interleukin (IL)-2, IL-5, IL-6, interferon gamma (IFN-gamma), and transforming growth factor beta (TGF-beta) were detected in the majority of the specimens from patients with PBC. The presence of IL-5 was associated with PBC (P < .001, PBC vs. AI-CAH). Because IL-5 is a potent eosinophil differentiation factor, we looked for evidence of activated eosinophils within the infiltrate. We observed the deposition of the primary cytotoxic granule protein of eosinophils, major basic protein (MBP), within the portal region of livers from patients with PBC. Moreover, we detected message for a cytotoxic T-lymphocyte (CTL) granzyme in 87.5% of these livers indicating that mature CTL are present. Thus, we present evidence for two effector pathways that may contribute to the tissue damage observed in PBC and have identified message for cytokines that may regulate these pathways.
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PMID:Cytokine patterns and cytotoxic mediators in primary biliary cirrhosis. 780 43

To elucidate the role played by interferon-alpha (IFN alpha) in the pathogenesis of autoimmune endocrine disease, we determined the autoantibody status, thyroid function test results, hemoglobin-A1c levels, and clinical symptoms of 58 patients who received IFN alpha for treatment of chronic active type C hepatitis. Each patient was treated for 6 months with a total dose of 391 +/- 140 x 10(6) U (mean +/- SD). Thyroid microsomal and/or thyroglobulin antibodies newly appeared or were increased in titer in 6 patients, 2 of whom developed hypothyroidism during IFN alpha therapy. Neither islet cell antibodies nor insulin-dependent diabetes mellitus developed during IFN alpha therapy, although hemoglobin-A1c levels were increased in 2 patients. One patient became positive for antimitochondrial antibodies, and another patient with preexisting antimitochondrial antibodies also manifested deterioration in liver function test results. Parietal cell antibodies and smooth muscle cell antibodies were the most frequent newly developed antibodies in 7 patients. Adrenal medullary cell antibodies and nuclear antibodies newly developed in 2 and 1 patients, respectively. At least 1 of 8 autoantibodies newly appeared in 19 patients (32.8%) and hypothyroidism developed in 2 patients (3.4%) during IFN alpha therapy. On the other hand, in 19 age- and sex-matched patients who did not receive IFN alpha, no autoantibody appeared, and no autoimmune disease developed during a follow-up period of 3 months. These findings suggest that IFN alpha acts as an immunomodulatory agent, inducing autoantibody production and the development of autoimmune disease in susceptible patients. Special attention should be paid to the development of hypothyroidism during IFN alpha therapy.
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PMID:Autoimmune endocrine disease induced by recombinant interferon-alpha therapy for chronic active type C hepatitis. 788 51

Although the growth in liver transplantations (LTX) recorded by the Pitt-UNOS Liver Transplant Registry since October 1987 continues, the rate of increase has been declining in recent years. Among children, the number of procedures reached a peak in 1990 and declined each year thereafter. The number of centers performing LTX continued to increase. However, in 1992, compared with previous years, the greatest proportion of centers had a decreased volume of procedures, and the fewest number of new centers were opened. Upon examining characteristics of pediatric recipients from 1987 through 1992, no significant trends were noted for sex, race, age, or nationality. The distribution of functional status in 1992 was similar to that prior to 1991. Compared with recipients in the other 2 time periods, recipients in 1991 were more likely to be in the best functional status and least likely to be in the ICU. The most common indication for LTX in children was biliary atresia, though the proportion of recipients with this primary liver disease decreased significantly over the study period. Significant increases were noted in the proportions of pediatric recipients with autoimmune disease (though this remains a relatively uncommon indication) and fulminant liver failure. There have been trends in many of the characteristics examined for adult recipients. The proportion of male recipients grew significantly between 1987 and 1992. Decreasing proportions of White recipients and increases among Hispanics and Asians were found. The mean and median ages of adult recipients peaked in 1990, with a slight decrease in 1992 reflecting a slight rise in the proportion of the youngest age group and a slight decline for the oldest age group. Adult recipients had better functional status in 1991 than earlier recipients, and the distribution in 1992 was very similar to that in 1991. The trend in the proportion of recipients with positive CMV serology followed very closely the pattern in age distribution, peaking in 1991 and dropping slightly in 1992. The proportions of multiorgan recipients were similar in all 3 time periods. However, in 1992, contrasting with previous years, most multiorgan procedures involved only a kidney. Alcoholic cirrhosis continued to be the most common reason for LTX, though the combination of non-A, non-B hepatitis and hepatitis C accounted for only 20 fewer recipients. The proportions of recipients with hepatitis B and malignancies (the indications with the poorest survival) declined significantly. The cumulative probability of patient (retransplantation-free) survival 5 years after initial transplantation was 0.7 (0.58) for pediatric recipients.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Trends in liver transplantation in the United States. 791 52


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