Child ; Female ; Hepatitis, Autoimmune ; diagnosis ; drug therapy ; Humans ; Male

Chemical and Drug Induced Liver Injury ; diagnosis ; therapy ; Diagnosis, Differential ; Hepatitis, Autoimmune ; diagnosis ; therapy ; Humans

OBJECTIVEIn order to provide a reliable basis for the diagnosis and treatment of autoimmune hepatitis (AIH) and its overlap syndrome, we investigated the clinical, immunological characteristics of and the therapeutic methods for AIH and AIH-primary biliary cirrhosis (PBC) overlap syndrome.

METHODSOne hundred seven patients (77 with AIH and 30 with AIH-PBC overlap syndrome) were enrolled in the study. Their clinical manifestations, serum liver function tests (LFTs) findings, serum immunoglobulins, liver histopathological changes and their responsiveness to the therapies were investigated.

RESULTSThe age distribution of AIH patients showed a single peak during their fifties and their main clinical manifestations were malaise, abdominal distension, anorexia and jaundice. Serum gamma globulin and IgG were significantly higher than their normal levels. 74% of the patients were positive for anti-nuclear antibody (ANA), 32% of the patients were positive for anti-smooth muscle antibody (AMA), and over 50% of the patients suffered from concurrent extrahepatic autoimmune diseases. The main histological changes in the liver biopsies were interface hepatitis (65%), lobular hepatitis and rosette formation of liver cells. Bridging necrosis was observed in severe AIH cases. In the AIH-PBC overlap syndrome patients, the levels of serum ALT, AST, GGT, ALP and incidences of ANA and AMA/AMA-M2 were all significantly higher than those of the AIH group. After treating AIH patients with prednisolone and azathioprine (Aza), complete response was seen in 42 cases (70%), sustained response was seen in 26 cases (43%). Sixteen cases had relapses after the withdrawal of the treatment or prednisolone dosage was reduced lower than 10 mg/d. The cases having normal serum ALT, AST, gamma-globulin and IgG levels after treatment were still responding to the reduced prednisolone dosage of 5-10 mg/d without azathioprine added. After combination with ursodeoxycholic acid (UDCA) treatment, the liver function tests (AST, ALT, TBil) of AIH-PBC overlap syndrome patients also significantly improved compared to those before the treatment (P<0.01).

CONCLUSIONAIH and AIH-PBC overlap syndrome are not rare in our clinics. Their diagnoses should be based on the clinical presentations, biochemical and immunological indices and liver histological changes. In AIH cases, once their AST, ALT, gamma-globulin and IgG levels return to normal, the prednisolone dosage can be maintained at 5-10 mg/d and Aza can even be withdrawn. Good improvement for patients with AIH-PBC overlap syndrome can be obtained with UDCA and immunosuppression treatment.

Female ; Hepatitis, Autoimmune ; diagnosis ; drug therapy ; Humans ; Liver Cirrhosis, Biliary ; diagnosis ; drug therapy ; Male ; Middle Aged ; Prognosis ; Syndrome

OBJECTIVETo investigate the clinical features of autoimmune hepatitis (AIH) in children so as to improve the awareness of the disease.

METHODThe medical records of 12 children who were clinically diagnosed as AIH between 2004 and 2008 were reviewed. The scoring system of the International Autoimmune Hepatitis Group (IAIHG) for diagnosis of AIH was used to confirm the diagnoses. Clinical manifestations, laboratory examinations, liver pathology results and prognosis were retrospectively analyzed.

RESULTEleven patients were diagnosed as AIH by the scoring system and 10 of them were type I, one had not been typed. The average time from onset to diagnosis was (7.5 ± 7.4) months. Seven patients (63.6%) had acute onset, among them 2 cases progressed to subacute severe hepatitis, 3 (27.3%) had deliquescence onset and 1 (9.1%)was complicated with hepatic cirrhosis. Levels of serum globulin and IgG were tested and were higher in 10 cases (90.9%) with average (39.4 ± 7.4) g/L and (31 ± 12) g/L respectively. Antinuclear antibodies (ANA) were measured positive in 10 cases, and 1 was anti-smooth muscle antibody (SMA) positive. Liver-kidney microsomal antibody (LKM-1) and anti-mitochondrial antibody (AMA) were detected in none of them. The liver pathology of 11 cases could be divided into acute and chronic hepatitis in 5 and 6 cases, respectively. Severe submassive liver necrosis and severe fibrosis were identified in 3 cases respectively. Lymphocytes infiltration, interfaces hepatitis and rosette-like annulation of hepatocytes were found in 81.8%, 36.4%, and 18.2% of cases on liver pathology. Eleven patients were followed up with therapy of single glucocorticoids or glucocorticoids combined with immunosuppressive agents. The disease of 2 cases deteriorated and 3 cases died. One case was still under therapy, 1 case was stabilized and 4 cases had recurrence.

CONCLUSIONThe children with AIH had diverse symptoms, signs, onsets and laboratory test results. The liver pathological changes were less typical. Rate of misdiagnosis was high in early stage. Prognosis was poor in most cases even though properly treated. Therefore close attention needs to be paid to children with AIH.

Adolescent ; Antibodies, Antinuclear ; blood ; Child ; Child, Preschool ; Diagnostic Errors ; Female ; Hepatitis, Autoimmune ; diagnosis ; drug therapy ; immunology ; pathology ; Humans ; Immunoglobulin G ; blood ; Liver Cirrhosis ; pathology ; Male ; Retrospective Studies

Autoimmune hepatitis (AIH) has been reported in association with Sjogren's syndrome (SS). Drug-induced AIH has been rarely reported. A rare case of the co-development of AIH and SS in a 53-year-old woman after the consumption of herbal medicines is described. After admission, the patient complained of dryness in her mouth, and she was subsequently diagnosed with SS, which had not been detected previously. The patient's bilirubin and aminotransferase levels initially decreased following conservative management; however, they later began to progressively increase. A diagnosis of AIH was made based on the scoring system proposed by the International Autoimmune Hepatitis Group. The patient was administered a combination of prednisolone and azathioprine, and the results of follow-up liver-function tests were found to be within the normal range. This is an unusual case of AIH and SS triggered simultaneously by the administration of herbal medicines.
Alanine Transaminase/blood ; Aspartate Aminotransferases/blood ; Azathioprine/therapeutic use ; Bilirubin/blood ; Female ; Hepatitis, Autoimmune/complications/*diagnosis/drug therapy ; *Herbal Medicine ; Humans ; Liver/pathology ; Liver Function Tests ; Middle Aged ; Prednisolone/therapeutic use ; Sjogren's Syndrome/complications/*diagnosis/drug therapy

BACKGROUND/AIMS: Overlap syndrome of autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) (AIH-PBC overlap syndrome) is a rare disease that has not been clearly characterized in Korean patients. This study investigated the clinical features of AIH-PBC overlap syndrome compared with those of AIH and PBC alone. METHODS: This retrospective cohort study included 158 consecutive patients who were diagnosed as AIH (n=61), PBC (n=81), or AIH-PBC overlap syndrome (n=9) based on the Paris and the International Autoimmune Hepatitis Group (IAIHG) criteria from 2001 to 2011 in Korea. We compared the clinical features of these three groups retrospectively, including their biochemical characteristics, treatments, responses, and clinical outcomes. RESULTS: The AIH-PBC overlap syndrome patients exhibited biochemical characteristics of both AIH and PBC, and showed a similar response to ursodeoxycholic acid (UDCA) monotherapy as for the PBC patients. However, the response of AIH-PBC overlap syndrome patients to UDCA and steroid combination therapy was worse than the response of AIH patients to steroid-based therapy (P=0.024). Liver cirrhosis developed more rapidly in AIH-PBC overlap syndrome patients than in AIH patients group (P=0.013), but there was no difference between AIH-PBC overlap syndrome patients and PBC patients. The rates of developing hepatic decompensation did not differ significantly between the groups. CONCLUSIONS: The AIH-PBC overlap syndrome patients exhibited a worse response to UDCA and steroid combination therapy and a faster cirrhotic progression compared with AIH patients.
Adult ; Aged ; Cohort Studies ; Drug Therapy, Combination ; Female ; Hepatitis, Autoimmune/complications/*diagnosis ; Humans ; Liver/metabolism/pathology ; Liver Cirrhosis, Biliary/complications/*diagnosis/drug therapy ; Male ; Middle Aged ; Republic of Korea ; Retrospective Studies ; Steroids/therapeutic use ; Treatment Outcome ; Ursodeoxycholic Acid/therapeutic use

OBJECTIVETo realize the clinical features of autoimmune hepatitis-primary biliary cirrhosis (AIH+PBC) overlap syndrome.

METHODSWe analyzed and compared the biochemistry, autoimmune antibodies, and liver biopsy results of 129 autoimmune hepatic disease cases retrospectively, using the international criteria to see which could be diagnosed as AIH/PBC overlap syndrome.

RESULTSOur 35 AIH+PBC overlap syndrome patients were mainly women, with a sex ratio of 1 female: 10 male, and a median age of 50.79+/-11.27 (20 to 70 years old). They had AIH characteristics such as flare of ALT, AST and elevated immunoglobulin G (IgG), gamma-immunoglobulin. There were also antinuclear antibodies (74.3%); moderate or severe periportal or periseptal lymphocytic infiltration, piecemeal necrosis, and florid bile duct lesions, high serum levels of ALP, presence of mitochondrial antibodies (68.6%) and M2 antibodies (45.7%), and features of PBC.

CONCLUSIONSAIH+PBC overlap syndrome is not rare. It should be diagnosed in time and to find effective treatments for it.

Adult ; Autoantibodies ; blood ; Cholagogues and Choleretics ; therapeutic use ; Female ; Hepatitis, Autoimmune ; complications ; diagnosis ; drug therapy ; Humans ; Immunoglobulin G ; blood ; Liver Cirrhosis, Biliary ; complications ; diagnosis ; drug therapy ; Male ; Middle Aged ; Retrospective Studies ; Ursodeoxycholic Acid ; therapeutic use

Autoimmune hepatitis is characterized by autoantibodies, hypergammaglobulinemia, and interface hepatitis on histological examination. The features lack diagnostic specificity, and other diseases that may resemble autoimmune hepatitis must be excluded. The clinical presentation may be acute, acute severe (fulminant), or asymptomatic; conventional autoantibodies may be absent; centrilobular necrosis and bile duct changes may be present; and the disease may occur after liver transplantation or with features that suggest overlapping disorders. The diagnostic criteria have been codified, and diagnostic scoring systems can support clinical judgment. Nonstandard autoantibodies, including antibodies to actin, α-actinin, soluble liver antigen, perinuclear antineutrophil antigen, asialoglycoprotein receptor, and liver cytosol type 1, are tools that can support the diagnosis, especially in patients with atypical features. Prednisone or prednisolone in combination with azathioprine is the preferred treatment, and strategies using these medications in various doses can ameliorate treatment failure, incomplete response, drug intolerance, and relapse after drug withdrawal. Budesonide, mycophenolate mofetil, and calcineurin inhibitors can be considered in selected patients as frontline or salvage therapies. Molecular (recombinant proteins and monoclonal antibodies), cellular (adoptive transfer and antigenic manipulation), and pharmacological (antioxidants, antifibrotics, and antiapoptotic agents) interventions constitute future directions in management. The evolving knowledge of the pathogenic pathways and the advances in technology promise new management algorithms.
Anti-Inflammatory Agents/*therapeutic use ; Autoantibodies/*blood ; Azathioprine/therapeutic use ; Biomarkers/blood ; Diagnosis, Differential ; Drug Therapy, Combination ; Hepatitis, Autoimmune/*diagnosis/*drug therapy ; Humans ; Immunosuppressive Agents/*therapeutic use ; Prednisolone/therapeutic use ; Prednisone/therapeutic use

Systemic sclerosis (SSc) is a chronic systemic disease that affects the skin, lungs, heart, gastrointestinal tract, kidneys, and musculoskeletal system. Although up to 90% of patients with scleroderma have been estimated to have gastrointestinal involvement, liver disease has been reported only rarely. A 51-year-old woman was hospitalized due to esophageal variceal bleeding. Her serum was positive for anti-nuclear antibody and anti-centromere antibody. Sclerodactyly was noted on both hands, and she had recently developed Raynaud's syndrome. Punch biopsy of the hand showed hyperkeratosis, regular acanthosis, and increased basal pigmentation in the epidermis, and thick pale collagenous bundles in the dermis. Liver biopsy showed chronic active hepatitis with bridging fibrosis. Consequently, she was diagnosed with liver cirrhosis due to autoimmune hepatitis (AIH) combined with SSc. AIH had subsided after administration of prednisolone at 40 mg per day. She received 5-10 mg/day of prednisolone as an outpatient, and her condition has remained stable. Patients with either AIH or SSc should be monitored for further development of concurrent autoimmune diseases. The early diagnosis of AIH combined with SSc will be helpful in achieving optimal management.
Anti-Inflammatory Agents/therapeutic use ; Antibodies, Antinuclear/blood ; Esophageal and Gastric Varices ; Female ; Gastrointestinal Hemorrhage ; Hepatitis, Autoimmune/complications/*diagnosis/drug therapy ; Humans ; Liver Cirrhosis/*diagnosis/etiology/pathology ; Middle Aged ; Prednisolone/therapeutic use ; Raynaud Disease/diagnosis ; Scleroderma, Systemic/complications/*diagnosis ; Skin/pathology

Autoimmune hepatitis (AIH) is an unresolving, predominantly periportal hepatitis that is usually displays hypergammaglobulinemia, and tissue autoantibodies, and this malady is responsive to immunosuppressive therapy. Our understanding about this clinical entity has been greatly expanded since the first description by Waldenstrom 50 years ago. The codified diagnostic criteria of AIH prepared by International Autoimmune Hepatitis Group are still valid, but new attempts are being made to overcome the shortcomings of this scoring system. Immunosuppressive therapies using prednisone and azathioprine are currently the mainstay for the treatment of AIH, but there are still many practical questions to be solved.
Adolescent ; Adult ; Aged ; Autoantibodies ; Azathioprine/administration & dosage/*therapeutic use ; Child ; Child, Preschool ; Drug Therapy, Combination ; Female ; Hepatitis, Autoimmune/*diagnosis/*drug therapy/etiology ; Humans ; Immunosuppressive Agents/administration & dosage/*therapeutic use ; Male ; Middle Aged ; Prednisone/administration & dosage/*therapeutic use