Autoimmune Diseases ; drug therapy ; pathology ; Cholangitis ; drug therapy ; immunology ; pathology ; Cholangitis, Sclerosing ; drug therapy ; immunology ; pathology ; Hepatitis, Autoimmune ; drug therapy ; immunology ; pathology ; Humans ; Interferon-gamma ; therapeutic use ; Liver Cirrhosis, Biliary ; drug therapy ; immunology ; pathology ; Ursodeoxycholic Acid ; therapeutic use

Adult ; Aged ; Female ; Hepatitis, Autoimmune ; blood ; complications ; drug therapy ; pathology ; Humans ; Liver Cirrhosis, Biliary ; blood ; complications ; drug therapy ; pathology ; Male ; Middle Aged ; Retrospective Studies

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

Drugs, Chinese Herbal ; therapeutic use ; Female ; Hepatitis, Autoimmune ; complications ; drug therapy ; pathology ; Humans ; Liver ; pathology ; physiopathology ; Liver Cirrhosis, Biliary ; complications ; drug therapy ; pathology ; Liver Function Tests ; Middle Aged ; Syndrome

Immunosuppressive therapy can improve clinical, biochemical and histological features and considerably prolong survival in patients with autoimmune hepatitis. Although ethnicity may affect disease severity and presentation, the long-term outcome of immunosuppression in Korean populations is unknown. This study was aimed to assess the efficacy of immunosuppressive therapy and determine the prognosis of autoimmune hepatitis in Korean populations. We reviewed the medical records of 86 patients diagnosed as having autoimmune hepatitis at the Samsung Medical Center between 1994 and 2008. Seventy-two (83.7%) patients reached remission after a median treatment duration of 3.5 months (range 1 to 44 months). Attempts to withdraw medications were made in 24 cases after the median treatment duration of 36 months (median 6 to 125 months). Thirteen of 24 (54.1%) patients relapsed after treatment withdrawal. Of the 86 patients, 6 (7.2%) experienced disease progression and the overall 5-and 10-yr progression-free survival rates were 91.2% and 85.5%, respectively. In conclusion, immunosuppressive therapy for autoimmune hepatitis results in a favorable rate of remission and excellent progression-free survival, but the relapse rate after treatment withdrawal is high. This suggests that long-term immunosuppressive therapy may be particularly important for treatment of Korean patients.
Adolescent ; Adult ; Aged ; Azathioprine/therapeutic use ; Disease-Free Survival ; Drug Therapy, Combination ; Female ; Hepatitis, Autoimmune/*drug therapy/mortality/pathology ; Humans ; Immunosuppressive Agents/*therapeutic use ; Male ; Middle Aged ; Prednisolone/therapeutic use ; Prognosis ; Recurrence ; Republic of Korea ; Retrospective Studies ; Time Factors ; Treatment Outcome

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

Autoimmune hepatitis (AIH) is an immune-mediated chronic liver disease characterized by hepatocellular inflammation, necrosis, and fibrosis, which can progress to cirrhosis and fulminant hepatic failure. The standard treatment for AIH includes corticosteroids alone or in combination with azathioprine. Although most patients achieve remission using the standard regimen, some patients do not respond due to either drug intolerance or refractory disease; in such cases alternative immunosuppressive agents should be explored. The second-line therapies are cyclophilin inhibitors such as cyclosporine A or tacrolimus, and nowadays mycophenolate mofetil (MMF) is widely used if azathioprine-based therapies are not tolerated. Although these are recommended as an alternative to the first-line regimen, there is insufficient evidence for the efficacy of second-line therapies, with the evidence based mainly on expert opinion. Therefore, we report an AIH patient receiving the standard regimen in whom remission did not occur due to side effects to azathioprine, but was successfully treated with MMF in combination with corticosteroids as an alternative to the standard regimen.
Alanine Transaminase/analysis ; Alopecia/etiology ; Antibiotics, Antineoplastic/*therapeutic use ; Aspartate Aminotransferases/analysis ; Azathioprine/adverse effects ; Female ; Hepatitis, Autoimmune/*drug therapy/pathology ; Humans ; Liver/enzymology/pathology ; Middle Aged ; Mycophenolic Acid/*therapeutic use ; Pancytopenia/etiology ; Prednisolone/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

A 37-year-old male presented with fever and jaundice was diagnosed as hepatitis A complicated with progressive cholestasis and severe autoimmune hemolytic anemia. He was treated with high-dose prednisolone (1.5 mg/kg), and eventually recovered. His initial serum contained genotype IA hepatitis A virus (HAV), which was subsequently replaced by genotype IIIA HAV. Moreover, at the time of development of hemolytic anemia, he became positive for immunoglobulin M (IgM) anti-hepatitis E virus (HEV). We detected HAV antigens in the liver biopsy specimen, while we detected neither HEV antigen in the liver nor HEV RNA in his serum. This is the first report of hepatitis A coinfected with two different genotypes manifesting with autoimmune hemolytic anemia, prolonged cholestasis, and false-positive IgM anti-HEV.
Adult ; Anemia, Hemolytic, Autoimmune/*diagnosis/drug therapy/etiology ; Anti-Inflammatory Agents/therapeutic use ; Cholestasis/*diagnosis/drug therapy/pathology ; Coinfection/*diagnosis ; Genotype ; Hepatitis A/complications/*diagnosis/genetics ; Hepatitis E/complications/*diagnosis/genetics ; Humans ; Immunoglobulin M/blood ; Liver/pathology/virology ; Male ; Prednisolone/therapeutic use ; RNA, Viral/blood