Biliary Cirrhosis-autoimmune Hepatitis Overlap Syndrome Research Articles

Efficacy of ursodeoxycholic acid alone or combined with immunosuppressant in primary biliray cirrhosis-autoimmune hepatitis overlap syndrome

Objective To evaluate the efficacy of ursodeoxycholic acid (UDCA) alone or combined with immunosuppressant in primary biliary cirrhosis-autoimmune hepatitis overlap syndrome (PBC-AIH). Methods From January 2001 to December 2014, 41 patients with PBC-AIH were screened out from patients with autoimmune hepatitis (AIH) and retrospectively analyzed. According to their therapy, they were divided into UDCA alone group (n=20) and UDCA combined with immunosuppressant group (n=21). Before and after treatment, serum biochemical indicators, immune indicators and response rates of the two groups were compared. Rank sum test or t-test was performed for statistical analysis. Results After treatment for 12 months, the levels of globulin, alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and γ-glutamyl transferase (GGT) of UDCA alone group were all lower than those before treatment ((35.76±5.36) g/L vs (40.51±9.07) g/L, 32.5 U/L(12.0-149.9 U/L) vs 75.0 U/L(11.0-667.0 U/L), 34.0 U/L(8.0-77.9 U/L) vs 66.1 U/L(19.0-399.0 U/L), 134.0 U/L(63.0-389.7 U/L) vs 256.0 U/L(107.0-503.0 U/L), 78.0 U/L(12.0-444.0 U/L) vs 204.0 U/L(80.0-725.4 U/L)), and the differences were statistically significant (t=2.721, Z=-3.454, -3.421, -3.743 and -3.784; all P 0.05). Conclusions For PBC-AIH patients, in one year the remission of biochemical indicators is similar between UDCA alone and UDCA combined with immunosuppressant, however the level of IgG of UDCA combined with immunosuppressant group is lower than that of UDCA alone group. Key words: Hepatitis, autoimmune; Overlap syndrome; Ursodeoxycholic acid; Immunosuppressive agents; Efficacy

Combination therapy of ursodeoxycholic acid and budesonide for PBC-AIH overlap syndrome: a meta-analysis.

In this study, a meta-analysis of randomized controlled trials comparing ursodeoxycholic acid (UDCA) monotherapy with combination therapies utilizing UDCA and budesonide was performed. We found that combination therapy with UDCA and budesonide was more effective than UDCA monotherapy for primary biliary cirrhosis–autoimmune hepatitis overlap syndrome. Moreover, compared to prednisone, budesonide has fewer side effects.

A case of primary biliary cirrhosis-autoimmune hepatitis overlap syndrome with idiopathic thrombocytopenic purpura treated by partial splenic embolization

A case of primary biliary cirrhosis-autoimmune hepatitis overlap syndrome with idiopathic thrombocytopenic purpura treated by partial splenic embolization

Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome: simplified criteria may be effective in the diagnosis in Chinese patients.

To evaluate the Paris criteria, the revised diagnostic criteria and the simplified diagnostic scoring system in the diagnosis of primary biliary cirrhosis (PBC)-autoimmune hepatitis (AIH) overlap syndrome in Chinese patients. Medical records of the patients who were diagnosed with PBC at the Union Hospital and Tongji Hospital, Tongji Medical University, Huazhong University of Science and Technology (Wuhan, Hubei Province, China) from 2003 to 2012 were retrospectively reviewed. The overlap syndrome was diagnosed based on the Paris criteria, the revised criteria and the simplified criteria, respectively. Patients' clinical characteristics, laboratory examination results and histological findings were collected. The sensitivity and specificity of the three criteria for diagnosing PBC-AIH overlap syndrome were calculated. PBC-AIH overlap syndrome was diagnosed in 2, 13 and 10 patients with PBC based on the Paris, the revised and the simplified criteria, respectively. The sensitivity and specificity of the simplified criteria in diagnosing the overlap syndrome was 90.0% and 98.2%, which were the highest among the three criteria, followed by the revised criteria. The Paris criteria showed a high specificity (100%) but a relatively low sensitivity (20.0%). In addition, some patients who did not fulfil the Paris criteria still benefited from the immunosuppressive agents. For Chinese patients with the PBC-AIH overlap syndrome, the simplified criteria appear to be the most efficacious compared with the Paris criteria and the revised criteria. Further studies should be performed to confirm these observations with respect to long-term outcomes and therapeutic implications.

ステロイド剤が著効したPBC-AIHが疑われた1例

初診時の精査では原因の特定が困難な慢性肝炎が存在する．症例は71歳，女性．全身倦怠感，食思不振を主訴に来院した．B型，C肝炎ウィルスは陰性，自己抗体は陰性，IgGは1919 mg/dl，抗ミトコンドリア（M2）抗体陽性であった．総ビリルビン26.0 mg/dl，PT-INRは1.31であり重症化を示唆していたのでプレドニゾロン40 mg/dayにて治療を開始したところ速やかに肝機能は改善した．治療後の肝生検では小葉間胆管の破壊とけずりとり壊死がみられ，慢性肝炎（F1，A1）であった．今後自己免疫性肝炎（AIH），原発性胆汁性肝硬変（PBC），またはPBC-AIH overlap syndromeに推移する可能性があるcryptogenic chronic hepatitisと考えられた．

Analysis of clinical features and efficacy of 44 cases of primary biliray cirrhosis-autoimmune hepatitis overlap syndrome

Objective To analyze the long term efficacy and prognosis of ursodeoxycholic acid (UDCA) combined immunosuppressive therapy in primary biliary cirrhosis-autoimmune hepatitis overlap syndrome (PBC-AIH). Methods A total of 44 PBC-AIH cases were selected from 387 autoimmune liver diseases cases in The General Hospital of Tianjin Medical University from January 2001 to January 2011,and the medical data,treatments and efficacies were retrospective analyzed.Results The serum levels of alanine aminotransferase (ALT),aspartate aminotransferase (AST),alkaline phosphatase (ALP),γ glutamyl transpeptidase (GGT) and total bilirubin (TBil) increased in different degrees in 44 PBC-AIH patients.Globulin or immunoglobulin G(IgG) increased in 84.09％(37/44) patients,immunoglobulin M(IgM) increased in 38.63％ (17/44) patients.The positive rate of antinuclear anti-body (ANA), anti-mitochondrial antibody (AMA) and anti-smooth muscle antibodies (SMA) was 97.73％,90.91％ and 11.36％,respectively. Pathological features were interface hepatitis and different degrees of intrahepatic bile ducl injuries. After UDCA combined immunosuppressant treatment,the remission rate was 61.36 ％ (27/44),the incomplete response rate was 29.55％ (13/44) and the treatment failure rate was 9.09％ (4/44).Six cases with remission withdrawal medicine,and the recurrence rate was 5/6.By the end of follow-up,the levels of ALT,AST,ALP,GGT and TBil significantly decreased in PBC-AIH patients compared with those before treatment.ALP,GGT,ALT and AST levels significantly decreased in the first 6 months while ALP and GGT showed slight upward trend at the end of follow up. The disease progression rate was 25.33％ in PBC-AIH patients (13/44) during the follow-up,and the 10 year survival rate was 93.33％ (28/30).Conclusion UDCA combined immunosuppressive therapy in PBC AIH treatment can significantly improve patients' blood biochemical indexes,delay disease progression,improve survival rate,and the remission rate is also high.However the recurrence rate is high after withdrawal of medicine. Key words: Liver cirrhosis,biliary; Hepatitis,autoimmune; Mixed connective tissue disease; Ursodeoxycholic acid; Immunosuppressive agents; Prognosis

Patients With Autoimmune Hepatitis Who Have Antimitochondrial Antibodies Need Long-term Follow-up to Detect Late Development of Primary Biliary Cirrhosis

Patients with autoimmune hepatitis (AIH) who have antibodies against mitochondrial proteins (AMA positive) are believed to have an autoimmune syndrome that should be managed as AIH. Of patients with AMA-positive AIH, we report on 3 individuals to demonstrate how autoimmune liver disease can progress over time. Specific features of primary biliary cirrhosis (PBC) overlapped in time in these patients. Our observations indicate the importance of careful follow up of patients with AMA-positive AIH; health care professionals that treat such patients should therefore be aware of longitudinal clinical changes that might indicate development of PBC in this setting.

Prevalence of Primary Biliary Cirrhosis–Autoimmune Hepatitis Overlap Syndrome

The prevalence of and the most appropriate way to diagnose the primary biliary cirrhosis (PBC)-chronic autoimmune hepatitis (AIH) overlap syndrome are uncertain. We investigated the prevalence of PBC and AIH and their level of overlap at a tertiary referral center, along with clinical, biochemical, and serologic characteristics. We reviewed data from all patients with PBC (n = 609) and/or AIH (n = 15) examined at the Tufts Medical Center (Boston, MA) from January 1, 2000, to June 20, 2006. PBC was diagnosed based on 2 of the following 3 results: 6 months of positive results in tests for cholestatic liver enzymes, a positive result in a test for antimitochondrial antibodies, or a liver biopsy that indicated PBC. AIH was defined as an alanine aminotransferase level of 200 U/L or greater (≥ 5-fold above normal), a liver biopsy that indicated severe interface hepatitis, and levels of immunoglobulin G 2-fold or greater than that of normal. Only 6 patients with PBC (1%) met the Paris criteria for the overlap syndrome. If we included 9 patients with PBC who did not meet the Paris criteria, but had results from liver enzyme tests and liver biopsy analyses that indicated improvement after treatment with prednisone, the prevalence was 15 (2.8%). This is at the low end of previously reported prevalence values for overlap of PBC and AIH (2%-20%). The prevalence of the PBC-AIH overlap syndrome varies among medical centers. We propose that if the definition of PBC-AIH overlap syndrome be modified to include patients with unequivocal responses to prednisone despite not meeting the Paris criteria, this would improve treatment of patients.

Primary Biliary Cirrhosis-Autoimmune Hepatitis Overlap Syndrome Concomitant with Systemic Sclerosis, Immune Thrombocytopenic Purpura

A 58-year-old Japanese woman presented with chronic fluctuating liver dysfunction with purpura. Raynaud's phenomenon had been diagnosed 4 years previously. At the initial examination, skin biopsy showed limited cutaneous systemic sclerosis (SSc). Laboratory investigations revealed liver dysfunction. Anti-nuclear antibodies, anti-mitochondria M2 antibody, anti-thyroglobulin antibody, and platelet-associated IgG were positive. Primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH) were diagnosed serologically, clinically and histologically. Immune thrombocytopenic purpura (ITP) was diagnosed by bone marrow puncture, clinical and laboratory findings, and Helicobacter pylori IgG was positive. She was treated with prednisolone 30 mg/day, ursodeoxycholic acid 600 mg/day, and a 7-day course of lansoprazole plus amoxicillin and clarithromycin. Thrombocytes increased rapidly and transaminase improved at day 7. We report a rare case of PBC-AIH overlap syndrome with concurrent ITP and SSc which suggest the presence of shared genetic susceptibility factors in multiple autoimmune conditions including PBC, AIH, ITP and SSc.

Primary biliary cirrhosis–autoimmune hepatitis overlap syndrome: Complete biochemical and histological response to therapy with ursodesoxycholic acid

Primary biliary cirrhosis–autoimmune hepatitis overlap syndrome: Complete biochemical and histological response to therapy with ursodesoxycholic acid

Long term outcome and response to therapy of primary biliary cirrhosis—autoimmune hepatitis overlap syndrome

Whether primary biliary cirrhosis (PBC)-autoimmune hepatitis (AIH) overlap syndrome requires immunosuppressive therapy in addition to ursodeoxycholic acid (UDCA) is a controversial issue. Seventeen patients with simultaneous form of strictly defined overlap were followed for 7.5 years. First-line treatment was UDCA alone (UDCA) in 11 and combination of immunosuppressors and UDCA (UDCA + IS) in 6. Characteristics at presentation were not significantly different between the 2 groups. In the UDCA + IS group (f-up 7.3 years), biochemical response in terms of AIH features (ALT<2ULN and IgG < 16 g/L) was achieved in 4/6 and fibrosis did not progress. In the UDCA group, biochemical response was observed in three patients together with stable or decreased fibrosis (f-up 4.5 years) whereas the eight others were non-responders with increased fibrosis in four (f-up 1.6 years). Seven of these eight patients subsequently received combined therapy for 3 years. Biochemical response was obtained in 6/7 and no further increase of fibrosis was demonstrated. Overall, fibrosis progression in non-cirrhotic patients occurred more frequently under UDCA monotherapy (4/8) than under combined therapy (0/6) (P = 0.04). Combination of UDCA and immunosuppressors appears to be the best therapeutic option for strictly defined PBC-AIH overlap syndrome.

Clinico-pathology characteristics of primary biliary cirrhosis-autoimmune hepatitis overlap syndrome

原发性胆汁性肝硬化(primary biliary cirrhosis, PBC)和自身免疫性肝炎(autoimmune hepatitis, AIH)是两种常见的自身免疫性肝病,具有各自特有的临床表现,但近年来发现部分患者同时具有这两种疾病的特点,称之为"重叠综合征",本文对11例PBC/AIH重叠综合征患者的临床、生化及治疗反应进行分析研究。

Biochemical, histological parameters and response to UDCA treatment in primary biliary cirrhosis and primary biliary cirrhosis-autoimmune hepatitis overlap syndrome

Biochemical, histological parameters and response to UDCA treatment in primary biliary cirrhosis and primary biliary cirrhosis-autoimmune hepatitis overlap syndrome

Biochemical, histological parameters and response to UDCA treatment in primary biliary cirrhosis and primary biliary cirrhosis-autoimmune hepatitis overlap syndrome

Biochemical, histological parameters and response to UDCA treatment in primary biliary cirrhosis and primary biliary cirrhosis-autoimmune hepatitis overlap syndrome

Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome: clinical features and response to therapy.

The association of primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH) is thought to be rare, and its optimal treatment is unknown. Of 130 consecutive patients with a diagnosis of PBC, we identified 12 cases (9.2%) of overlap syndrome (10 females, 2 males; median age, 50 years) strictly defined by the presence of at least two of the three recognized biochemical, serological, and histological criteria of each disease. One patient had initially pure PBC and developed AIH characterized by a flare of alanine transaminase (ALT) (1,330 IU/L; N < 35), elevated immunoglobulin G (IgG) (42 g/L; N < 14.0), and presence of anti-smooth muscle antibodies (ASMA) after 20 months of ursodeoxycholic acid (UDCA) therapy. A complete clinical and biochemical remission was achieved under combination of corticosteroids and UDCA. Eleven patients had features of both diseases at presentation: high serum levels of alkaline phosphatase (AP) (median: 280 IU/L; N < 100), ALT (140 IU/L), and IgG (30.8 g/L), presence of mitochondrial antibodies (n = 9) or ASMA (n = 9), florid bile duct lesions (n = 8), and moderate or severe periportal or periseptal lymphocytic piecemeal necrosis (n = 11). UDCA (13-15 mg/kg/d) given alone in 5 patients induced a significant decrease in biochemical cholestasis but not in ALT levels, and liver fibrosis progressed in 3 patients. Corticosteroids given alone in 6 patients induced a significant decrease in ALT, IgG, and AP levels, but none had a biochemical normalization. The patients with persistently abnormal liver tests under either UDCA or corticosteroids received both UDCA and corticosteroids. A further marked biochemical improvement was observed, and all patients became asymptomatic. We conclude that, in patients with PBC: 1) overlap syndrome with AIH is not rare; 2) flares of AIH may occur either spontaneously or under UDCA; and 3) combination of UDCA and corticosteroids is required in most patients to obtain a complete biochemical response. Overlap syndrome may represent an important and unrecognized cause of resistance to UDCA in patients with PBC.