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)

The Kings College group was the first to describe a clinical syndrome similar to autoimmune hepatitis in children and young adults transplanted for non-immune mediated liver diseases. They coined the term "de novo autoimmune hepatitis". Several other liver transplant centres confirmed this observation. Even though the condition is uncommon, patients with de novo AIH are now seen in most of the major transplant centres. The disease is usually characterized by features of acute hepatitis in otherwise stable transplant recipients. The most characteristic laboratory hallmark is a marked hypergammaglobulinaemia. Autoantibodies are common, mostly ANA. We described also a case of LKM1-positivity in a patients transplanted for Wilson's disease, however this patients did not develop clinical or histological features of AIH. Development of SLA/LP-autoantibodies is also not described. Therefore, serologically de novo AIH appears to correspond to type 1 AIH. Like classical AIH patients respond promptly to treatment with increased doses of prednisolone and azathioprine, while the calcineurin inhibitors cyclosporine or tacrolimus areof very limited value - which is not surprising, as almost all patients develop de novo AIH while receiving these drugs. Despite the good response to treatment, most patients remain a clinical challenge as complete stable remissions are uncommon and flares, relapses and chronic disease activity can often occur. Pathogenetically this syndrome is intriguing. It is not clear, if the immune response is directed against allo-antigens, neo-antigens in the liver, or self-antigens, possibly shared by donor and host cells. It is very likely that the inflammatory milieu due to alloreactive cells in the transplanted organ contribute to the disease process. Either leading to aberrant antigen presentation, or providing co-stimulatory signals leading to the breaking of self-tolerance. The development of this disease in the presence of treatment with calcineurin inhibitors supports the view held by most specialists in autoimmune hepatitis that these drugs, even though effective in acute disease, are not helpful in the long-term management of autoimmune liver diseases.
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PMID:De novo autoimmune hepatitis after liver transplantation. 1793 Dec 3

Diagnosis of Autoimmune Hepatitis (AIH) often represents a clinical challenge. The clinical spectrum of disease is quite heterogeneous. AIH can affect patients of all age groups, both sexes, and any race and region. The course may range from subclinical and very mild to acute attacks of hepatitis up to fulminant hepatic failure. Other patients present very late with the picture of cryptogenic cirrhosis. Laboratory features may also differ. Autoantibodies vary, and some patients do not display any autoantibodies at the time of clinical presentation. SLA/LP-autoantibodies are the only antibodies specific for the diagnosis of AIH, but they are only present in about 20% of cases. The most common feature in all patients with AIH is an elevation of IgG levels, usually a selective or highly preferential elevation of IgG in comparison to IgA and IgM. However, in some patients the relative increase in IgG levels may be within the normal limits, because the normal range is quite wide. The diagnosis of AIH should not be made without a liver biopsy showing inflammatory hepatitis. Histology mayshow typical features such as enrichment of plasma cells and piecemeal necroses, but distinction from other inflammatory liver disease including allergic drug reactions may be difficult. The International Autoimmune Hepatitis Group has tried to define diagnostic criteria on the basis of consensus discussions. These were revised in 1999 in the light of some clinical studies. However, the criteria are complicated, and not useful in everyday practise. In addition, the criteria were only designed as a scientific tool in order to create comparable groups in publication from different centres. Therefore, the International Autoimmune Hepatitis Group has re-approached the problem with the aim of defining simplified criteria for everyday use. With the help of various specialised centres in the world we evaluated a number of hypothetical criteria, and found out, that four criteria with two categories are sufficient to either make or exclude the diagnosis of AIH with positive and negative predictive values well over 90%: 1 point2 points1. IgG>16 g/l>18 g/l2. ANA, SMA>1 : 40>1 : 80 or SLA/LP+3. Histologycompatible withtypical for AIH4. Viral markersnegativeA value of 6 or more points makes the diagnosis of AIH very likely, a value of 7 or 8 points demonstrates definite AIH. The simplified criteria should help in the diagnosis of AIH in patients with liver disease, and they seem to be valid world-wide. Prospective data are needed to validate these criteria further.
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PMID:Diagnostic criteria for autoimmune hepatitis. 1793 Dec 12

Since first being described in 1998, de novo autoimmune hepatitis (AIH) after liver transplantation has been reported in several cases suffering from non-autoimmune liver diseases and primary biliary cirrhosis (PBC). Glutathione S-transferase (GST) T1 genotype mismatches between donor and recipient have also been suggested to constitute a risk factor for de novo AIH. Here, we report a 33-yr-old woman who presented complaining of marked fatigue and jaundice four yr after living-donor liver transplantation for PBC. On examination, transaminase levels were highly elevated and ANA and antimitochondrial antibody M2 were positive. Histological findings showed zonal necrosis with lymphoplasmacytic infiltration closely resembling AIH. She had pretreatment AIH score of 16 and 19 points after relapse of de novo AIH. Two color fluorescence in situ hybridization with X and Y chromosome-specific probes clearly revealed that the hepatocytes were of donor origin and lymphocytes were of patient origin. The GSTT1 genotype of the patient and the donor were the same null type, suggesting that mechanisms other than GSTT1 mismatches may exist in de novo AIH development. In conclusion, recipient immune cells attacked the allogeneic transplanted liver of the patient via de novo AIH, although the exact participation of autoimmune mechanisms is unclear.
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PMID:De novo autoimmune hepatitis following living-donor liver transplantation for primary biliary cirrhosis. 1819 May 52

A 15-year-old girl was admitted in April 2004 owing to fatigue and loss of appetite. Her paediatrician had found elevated serum levels for alkaline phosphatase. The endoscopic retrograde cholangiography documented typical signs of primary sclerosing cholangitis with involvement of the small and large ducts. The liver biopsy revealed extensive septal and portal fibrosis. No evidence of inflammatory bowel disease was present. She was started on ursodeoxycholic acid therapy and improved clinically. After 22 months she presented again with rising transaminase levels up to 600 U/l. The second liver biopsy was strongly suggestive for autoimmune hepatitis besides the already known features of primary sclerosing cholangitis. Elevated levels of IgG, and elevated titres for ANA and antismooth muscle antibodies (ASMA) were also found. The duct irregularities seen on re-endoscopic retrograde cholangiography were slightly regredient as compared with the first investigation. We added prednisolone and azathioprine to the ursodeoxycholic acid and the transaminase levels dropped together with clinical improvement.
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PMID:Autoimmune hepatitis 2 years after the diagnosis of primary sclerosing cholangitis: an unusual overlap syndrome in a 17-year-old adolescent. 1830 6

Overlap of autoimmune hepatitis and systemic lupus erythematosus (SLE) is a comparatively rare condition. Although both autoimmune hepatitis and SLE can share common autoimmune features such as polyarthralgia, hypergammaglobulinemia and positive ANA, it has been considered as two different entities. We report a case of anti-LKM1 positive autoimmune hepatitis who developed SLE two years later. The presence of interface hepatitis with lymphoplasma cell infiltrates and rosette formation points to the autoimmune hepatitis rather than SLE hepatitis. Autoimmune hepatitis is infrequently accompanied by SLE, therefore, it could be recommended to investigate for SLE in patients with autoimmune hepatitis.
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PMID:[A case of anti-LKM 1 positive autoimmune hepatitis accompanied by systemic lupus erythematosus]. 1845 93

Liver disorders with a likely autoimmune pathogenesis in childhood include autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC), and de novo AIH after liver transplantation. AIH is divided into two subtypes according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1) or liver kidney microsomal antibody (LKM1, type 2). There is a female predominance in both. LKM1 positive patients tend to present more acutely, at a younger age, and commonly have partial IgA deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment, and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC. The clinical, biochemical, immunological, and histological presentation of ASC is often indistinguishable from that of AIH type 1. In both, there are high IgG, non-organ specific autoantibodies, and interface hepatitis. Diagnosis is made by cholangiography. Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates, times to normalization of biochemical parameters, and decreased inflammatory activity on follow up liver biopsies. However, the cholangiopathy can progress. There may be evolution from AIH to ASC over the years, despite treatment. De novo AIH after liver transplantation affects patients not transplanted for autoimmune disorders and is strikingly reminiscent of classical AIH, including elevated titres of serum antibodies, hypergammaglobulinaemia, and histological findings of interface hepatitis, bridging fibrosis, and collapse. Like classical AIH, it responds to treatment with prednisolone and azathioprine. De novo AIH post liver transplantation may derive from interference by calcineurin inhibitors with the intrathymic physiological mechanisms of T-cell maturation and selection. Whether this condition is a distinct entity or a form of atypical rejection in individuals susceptible to the development of autoimmune phenomena is unclear. Whatever its etiology, the recognition of this potentially life-threatening syndrome is important since its management differs from that of standard anti-rejection therapy.
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PMID:Autoimmune paediatric liver disease. 1852 33

Nephrogenic systemic fibrosis (NSF) is a rare disorder in patients with chronic kidney disease characterized by an increased tissue deposition of collagen. Its pathogenesis remains unclear. Prior studies indirectly suggested a possible impact of chronic inflammation and accelerated atherosclerosis--a common feature in kidney diseased patients--whereas recent data focused almost exclusively on gadolinium (Gd)-based MR contrast agents. Usually NSF develops a maximum of 2-3 months after Gd. Longer intervals have not yet been described. Therefore, we present the first case with an extraordinary long time course in terms of chronic inflammation. A 52-year-old Caucasian woman with end-stage renal disease was admitted to our hospital with progressive muscle weakness and skin induration resulting in growing immobility. Her past medical history revealed a secondary HPT, multiple vascular complications, a seronegative rheumatoid arthritis, and a pituitary gland adenoma. The latter conditions led to multiple MR examinations with Gd-based contrast agents, the last one more than 4 years ago. Numerous laboratory tests were performed including ESR, CRP, intact parathyroid hormone (iPTH), serum ferritin, cyclic-citrullinated peptide antibodies (CCP), ANA, ANCA, immunoelectrophoresis, and serology for hepatitis as well as human immunodeficiency virus. Eventually a skin biopsy of her left thigh was obtained. The laboratory investigation showed persistently elevated levels of CRP, ESR, serum ferritin, and iPTH, whereas all other parameters were inconspicuous. The hisology displayed typical signs of nephrogenic systemic fibrosis. NSF can occur at any time after Gd exposure in the long term. Gd is a necessary, but not the sole cause of NSF. Certain other cofactors such as chronic inflammation and accelerated atherosclerosis seem to be involved.
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PMID:Chronic inflammation and accelerated atherosclerosis as important cofactors in nephrogenic systemic fibrosis following intravenous gadolinium exposure. 1855 Dec 45

Chronic hepatitis C virus (HCV) infection is a worldwide public health problem with a global prevalence of 2-3%. It is believed that about 170 million people are currently infected (about 3% of the world's population), and a further 3-4 million are infected each year. HCV is the main reason for liver transplantation in the developed world, and the main cause of liver-related morbidity and mortality in a number of countries, including Italy. It is not only a frequent cause of chronic liver diseases such as hepatitis, cirrhosis and hepatocellular carcinoma, but is also involved in the pathogenesis of various autoimmune and rheumatic disorders (arthritis, vasculitis, sicca syndrome, porphyria cutanea tarda, lichen planus, nephropathies, thyroid diseases, and lung fibrosis), as well as in the development of B-cell lymphoproliferative diseases. Furthermore, patients suffering from C hepatitis tend to produce rheumatoid factor, cryoglobulins and a large series of autoantibodies (ANA, anti-SSA/SSB, SAM, ATG, aCL). The use of glucocorticoids or immuno-suppressant agents in HCV infected individuals, which are needed to treat autoimmune and rheumatic disorders, leads to a risk of worsening the clinical outcome of HCV. Under these conditions, the viral infection often needs to be treated with antiviral agents, mainly pegylated interferon combined with ribavirin. However, cyclosporine A seems to be safe and effective in patients with autoimmune disease (AD) and concomitant chronic HCV infection as is documented by the reduction in viremia and transaminases, particularly in patients with high baseline levels. Finally, HCV is the main trigger of mixed cryoglobulinemia. An attempt at viral eradication is therefore indicated in most patients, and is particularly effective in the case of mild or moderate manifestations. In severe cases, rituximab is an apparently safe and effective alternative to conventional immunosuppression and, specifically, it controls B-cell proliferation.
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PMID:HCV infection: pathogenesis, clinical manifestations and therapy. 1857 Jul 53

Liver involvement in systemic lupus erythematosus (SLE) is infrequent. The coexistence of SLE and autoimmune hepatitis is rare (1.3-1.7%). We report a case of a 27 year old female with no history of systemic illnesses or alcohol abuse that presented with acute hepatitis with jaundice, abdominal pain, and increased liver function tests. Viral markers were negative. ANA was strongly positive. Patient was suspected to have SLE but no definite diagnosis made. She remained asymptomatic for 9 years but then she had recurrence of hepatitis. She also presented with malar rash, arthritis, and proteinuria. At that time a liver biopsy showed autoimmune hepatitis. Other tests which confirmed SLE included a positive antidsDNA, positive antismith antibody and decreased complement levels. She was started on prednisone 40 mg with mild improvement of symptoms and transaminase values, but when azathioprine 100 mg was added a marked improvement in liver function tests was observed. After a year in azathioprine she remained with SLE in remission. To our knowledge this is the third reported case and the first in the Western Hemisphere of jaundice as the initial presentation of SLE.
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PMID:Systemic lupus erythematosus presenting as acute iceric hepatitis: a case report. 1922 19

We present a case of toxic hepatitis related to infliximab treatment in a 38-year-old woman with rheumatoid arthritis (RA). The patient had previously been treated with different disease-modifying drugs (DMARDs) alone or in combination but had never revealed signs of liver dysfunction. Due to high disease activity, treatment with infliximab (3 mg/kg i.v.) was initiated in combination with methotrexate (MTX) (25 mg/week) and folic acid (5 mg/week). The patient stopped MTX and folic acid on her own initiative after 3 weeks due to improvement of joint symptoms. After seven infusions, progressive elevations of the transaminases up to five times the upper normal limit were noted and treatment with infliximab was terminated. Serological tests for viral and autoimmune hepatitis and for ANA and anti-dsDNA were all negative. Specific infliximab antibodies could not be detected. Ultrasound of the liver was normal. Liver biopsy showed late signs of acute toxic hepatitis without MTX-related fibrosis. This is one the first cases that convincingly demonstrates that infliximab treatment may cause toxic hepatitis. Moreover, the case suggests a lack of hepatic cross-toxicity between infliximab and etanercept as the patient continued with etanercept without new episodes of liver dysfunction.
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PMID:Toxic hepatitis induced by infliximab in a patient with rheumatoid arthritis with no relapse after switching to etanercept. 1937 Mar 7


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