mycophenolic-acid and Cholangitis--Sclerosing

Autoimmune liver disease (ALD) is a chronic liver disease caused by immune dysfunction in the body. However, no causative or curative medical treatment with proven efficacy exists to cure ALDs, and liver transplantation (LT) remains the only effective treatment available. However, the problem of recurrence of ALDs (rALDs) still remains after LT, which seriously affects the survival rate of the patients. Therefore, clinicians need to be aware of the risk factors affecting rALDs after LT. Therefore, this meta-analysis aims to define the risk factors for rALDs, which include the recurrence of primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune hepatitis.. A systematic search in Pubmed, Embase, Cochrane library and Web of Science databases was performed from 1980 to 2019. The inclusion criteria were risk factors for developing rALDs after LT. However, case series, case reports, reviews, meta-analysis and studies only including human immunodeficiency virus cases, children, and pregnant patients were excluded.. The electronic database search yielded 1728 results. Sixty-three retrospective cohort studies met the inclusion criteria and 13 were included in the meta-analysis. The final cohort included 5077 patients, and among them, 21.96% developed rALDs. Colectomy before LT, HR 0.59 (95% confidence interval [CI]: 0.37-0.96), cholangiocarcinoma, HR 3.42 (95% CI: 1.88-6.21), multiple episodes of acute cellular rejection, HR 2.07 (95% CI: 1.27-3.37), model for end-stage liver disease score, HR 1.05 (95% CI: 1.02-1.08), use of mycophenolate mofetil, HR 1.46 (95% CI: 1.00-2.12) and the use of cyclosporin A, HR 0.69 (95% CI: 0.49-0.97) were associated with the risk of rprimary sclerosing cholangitis. In addition, the use of tacrolimus, HR 1.73 (95% CI: 1.00-2.99) and cyclosporin A, HR 0.59 (95% CI: 0.39-0.88) were associated with the risk of rALD.. Multiple risk factors for rALDs were identified, such as colectomy before LT, cholangiocacinoma, multiple episodes of acute cellular rejection, model for end-stage liver disease score, and especially the use of mycophenolate mofetil, cyclosporin A and tacrolimus.

Topics: Adult; Calcineurin Inhibitors; Cholangiocarcinoma; Cholangitis, Sclerosing; Colectomy; Cyclosporine; End Stage Liver Disease; Enzyme Inhibitors; Female; Graft Rejection; Hepatitis, Autoimmune; Humans; Liver Cirrhosis, Biliary; Liver Diseases; Liver Transplantation; Male; Middle Aged; Mycophenolic Acid; Recurrence; Retrospective Studies; Risk Factors; Survival Rate; Tacrolimus

Therapies for treatment of patients with primary sclerosing cholangitis (PSC) include administration of ursodeoxycholic acid (UDCA) alone, or combination with metronidazole (MTZ) or mycophenolate mofetil (MMF), respectively. However, the optimum regimen still remains inconclusive. We aimed to compare interventions in terms of patient mortality or liver transplantation (MOLT), progression of liver histological stage (POLHS), serum bilirubin, alkaline phosphatase (ALP) levels and adverse events (AE).. We searched PubMed, Embase and the Cochrane Library for randomized controlled trials until 31, Jan 2015. We estimated hazard ratios (HRs), odds ratios (ORs) and mean difference (MD) between treatments on clinical outcomes. Sensitivity analyses based on the dose of UDCA, quality of trials or treatment duration were also performed.. Ten RCTs were included. Compared with UDCA plus MTZ, UDCA (HR 0.28, 95%CI 0.01-3.41), UDCA plus MMF (HR 0.08, 95%CI 0.00-4.18), or OBS (HR 0.28, 95%CI 0.01-3.98) all provided an increased risk of MOLT. UDCA provided a significant reduction in bilirubin and ALP levels compared with OBS (MD -13.92, P < 0.001; MD -484.34, P < 0.001; respectively). With respect to POLHS, although differing not significantly, UDCA plus MTZ had a tendency to improve LHS more than UDCA (OR 1.33), UDCA plus MMF (OR 3.24) or OBS (OR 1.08). Additionally, UDCA plus MTZ (MD -544.66, P < 0.001) showed a significant reduction in ALP levels compared with OBS, but appeared to be associated with more AEs compared with UDCA (OR 5.09), UDCA plus MMF (OR 4.80) or OBS (OR 7.21).. MTZ plus UDCA was the most effective therapy in survival rates and liver histological progression.

Topics: Adult; Aged; Alkaline Phosphatase; Bilirubin; Cholagogues and Choleretics; Cholangitis, Sclerosing; Disease Progression; Humans; Liver; Liver Transplantation; Metronidazole; Middle Aged; Mycophenolic Acid; Odds Ratio; Proportional Hazards Models; Randomized Controlled Trials as Topic; Research Design; Severity of Illness Index; Treatment Outcome; Ursodeoxycholic Acid; Young Adult

Inflammatory Bowel Disease (IBD) is thought to be the result of an overly aggressive immune response to ubiquitous antigens. Immuno -modulation and -suppression is therefore currently the treatment of choice. It was long anticipated that the course of pre-existing IBD should improve after orthotopic liver transplantation (OLT) due to increased immunosuppression. We report the case of a patient who developed acute fulminant colitis despite triple immunosuppression and mesalazine and review the relevant literature.

Topics: Cholangitis, Sclerosing; Colectomy; Colitis, Ulcerative; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Liver Transplantation; Mesalamine; Middle Aged; Mycophenolic Acid; Prednisone; Recurrence; Tacrolimus

Autoimmune hepatitis is a chronic liver disease of unknown aetiology characterized by interface hepatitis, hypergammaglobulinaemia and circulating autoantibodies. In the last decade a number of advancements have been made in the field of clinical and basic research: the simplified diagnostic criteria, the complete response defined as normalization of transaminase levels, the molecular identification of the antigenic targets of anti-liver cytosol antibody type 1 and anti-soluble liver antigen, the detection of anti-actin antibodies, the description of de novo autoimmune hepatitis after liver transplantation for non-autoimmune liver diseases, the characterization of autoimmune hepatitis with overlapping features of primary biliary cirrhosis or primary sclerosing cholangitis, the preliminary experience with novel treatment strategies based on cyclosporine, mycophenolate mofetil and budesonide, the role played by "impaired" regulatory T cells and the development of novel animal models of autoimmune hepatitis.

Topics: Animals; Autoantibodies; Autoantigens; Biomarkers; Budesonide; Cholangitis, Sclerosing; Cyclosporine; Glucocorticoids; Hepatitis, Autoimmune; Humans; Hypergammaglobulinemia; Immunity, Cellular; Immunoglobulin G; Immunosuppressive Agents; Liver Cirrhosis, Biliary; Liver Transplantation; Mice; Mycophenolic Acid; Rats; Transaminases

Autoimmune Hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and overlap syndromes of these three disease entities are regarded as autoimmune liver diseases. These conditions are important differential diagnoses of elevated liver function tests as about 10 % of liver transplantations in Europe and North America are for these indications. The diagnosis is often difficult but can be facilitated by sequential measurement of relevant autoantibodies, exclusion of other liver disease, ultrasound, ERCP and liver histology. In AIH immunosuppressive therapy has been shown to prevent or stop the development of cirrhosis and improve the prognosis of the patients decisively. In other autoimmune liver diseases this evidence is missing making individual therapeutic decisions necessary. Ursodesoxycholic acid (UDCA) seems to slow disease progression in particular in early stages of PBC.

Topics: Adult; Autoantibodies; Autoimmune Diseases; Azathioprine; Biopsy; Child; Cholagogues and Choleretics; Cholangiopancreatography, Endoscopic Retrograde; Cholangitis, Sclerosing; Diagnosis, Differential; Enzyme-Linked Immunosorbent Assay; Female; Hepatitis, Autoimmune; Humans; Immunoassay; Immunosuppression Therapy; Immunosuppressive Agents; Liver; Liver Cirrhosis, Biliary; Liver Diseases; Liver Function Tests; Liver Transplantation; Male; Middle Aged; Mycophenolic Acid; Prognosis; Ultrasonography; Ursodeoxycholic Acid

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown etiology. Despite advances in understanding the pathophysiology underlying this disorder, no effective medical therapy has been identified for halting disease progression. The aim of this investigation was to determine the safety and estimated efficacy of mycophenolate mofetil (MMF) for the treatment of PSC. Thirty patients with PSC received MMF 1 g daily to a maximum of 3 g daily for 1 yr. Liver tests were determined at 3-month intervals with the Mayo risk score calculated at baseline and at the end of therapy. Twenty-three (77%) patients completed 1 yr of therapy. Significant but clinically marginal improvement in serum alkaline phosphatase level after 1 yr of therapy was observed (1135 +/- 581 U/L vs 912 +/- 463 U/L, p= 0.02). No other significant changes in liver biochemistries or Mayo risk score was observed. Seven patients (23%) discontinued MMF due to adverse events possibly related to therapy. Adverse reactions resolved spontaneously or with dose reduction in 10 (33%) patients. One patient developed pancreatitis, bacterial cholangitis, and sepsis during the eighth month of MMF therapy. No patient developed cytopenia on therapy. In conclusion, MMF does not appear to have clinically important benefits for PSC despite being tolerated by most patients. The results of this pilot study do not support further study of MMF as a single agent in the treatment of PSC.

Topics: Adult; Aged; Alkaline Phosphatase; Anti-Inflammatory Agents, Non-Steroidal; Aspartate Aminotransferases; Bilirubin; Cholangitis, Sclerosing; Humans; Immunosuppressive Agents; Liver; Middle Aged; Mycophenolic Acid; Pilot Projects

Ursodeoxycholic acid has been ineffective in the treatment of primary sclerosing cholangitis. Because the pathogenesis of primary sclerosing cholangitis is related to immune destruction of bile duct epithelium, several immune suppressive agents have been evaluated. Mycophenolate mofetil is a potent immunosuppressant that is now widely used in organ transplantation.. In this pilot study to determine if mycophenolate mofetil when combined with ursodeoxycholic acid could prevent evidence of clinical progression and improve the biochemical, histological and/or cholangiographic features of primary sclerosing cholangitis compared with patients treated with ursodeoxycholic acid alone.. Twenty-five patients with well-defined primary sclerosing cholangitis were randomized to ursodeoxycholic acid (13-15 mg/kg/day) with or without mycophenolate mofetil (1000 mg b.d.). Cholangiography and liver biopsy were performed at study entry and after 2 years of treatment. Symptoms, clinical features of liver disease and biochemical tests were monitored at 3-month intervals.. The mean age 44 years, 58% male, 84% Caucasian and 64% had ulcerative colitis. After 2 years, there were no differences in laboratory values, histological stage or cholangiograms between patients treated with ursodeoxycholic acid alone and those treated with mycophenolate mofetil + ursodeoxycholic acid.. Mycophenolate mofetil combined with ursodeoxycholic acid does not appear to provide additional benefit compared with standard doses of ursodeoxycholic acid alone in the treatment of primary sclerosing cholangitis.

Topics: Adult; Biopsy; Cholagogues and Choleretics; Cholangitis, Sclerosing; Female; Humans; Immunosuppressive Agents; Liver; Male; Mycophenolic Acid; Pilot Projects; Prospective Studies; Ursodeoxycholic Acid

Cyclosporine (CSA) is an alternative treatment for autoimmune hepatitis (AIH), however, its unknown long-term safety and efficacy have limited its use.. Examine the long-term outcome of children and young adults with AIH treated with CSA for at least 4 years.. Twenty patients were included in this retrospective study: 15 with classical AIH and 5 with autoimmune hepatitis/autoimmune sclerosing cholangitis overlap syndrome (ASC). CSA was administered as first (12 patients) or second-line (8 patients) treatment, alone or in combination with azathioprine or mycophenolate mofetil and/or prednisone.. CSA determined initial clinical and biochemical remission in all patients. At the end of follow-up (median 8.6; range 4-20.4 years), all patients are alive with their native liver; 15 in complete remission (75%), 2 with incomplete response to treatment and 3 listed for liver transplant. Side effects were mild and transitory after dose tapering or, in 1 case, after CSA withdrawal. Hypertrichosis and moderate gingival hyperplasia were the most frequent. Two patients presented mild transient glomerular filtration rate (GFR) reduction. Median GFR at the beginning and end of treatment was not statistically different for all patients.. CSA was effective and safe in the long-term treatment of our cohort of patients with AIH, tailoring the treatment remains key-points during CSA administration.

Topics: Adolescent; Azathioprine; Child; Child, Preschool; Cholangitis, Sclerosing; Cyclosporine; Drug Therapy, Combination; Female; Follow-Up Studies; Hepatitis, Autoimmune; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Mycophenolic Acid; Prednisone; Remission Induction; Retrospective Studies; Syndrome; Time Factors; Treatment Outcome

Autoimmune hepatitis (AIH) is an immune-mediated liver disease, which requires long-term immunosuppression. Ten to fifteen percent of patients experience insufficient/intolerance response to standard therapy. Although alternate immunosuppression has been applied, there is little long-term data reported on safety, efficacy, steroid-dose reduction and disease evolution in patients with difficult AIH who were on Tacrolimus therapy.. Clinical, biochemical, immunological profiles, treatment response and side effects of 17 AIH patients treated with Tacrolimus between 2003 and 2014 were analyzed from two tertiary referral liver centers.. Tacrolimus was started on 16/17 (94%) patients due to insufficient response to standard therapy. The median duration of treatment was 24 months and patients were followed up for median of 60 months. Tacrolimus dosage was 2 mg/day (median). During first year of therapy, there was a significant improvement in immunoglobulin G and Aspartate transaminase level. 9/17 (52%) compliant and definite AIH patients remained on Tacrolimus at end of follow-up and prednisolone dose reduction was achieved from 10 to 5 mg. All patients are alive and one patient underwent liver transplantation. 4/17 (24%) patients developed overlap with primary sclerosing cholangitis over follow-up period. No significant side effects were observed with Tacrolimus therapy.. Tacrolimus could be used in compliant patients with difficult to treat AIH in experienced centers. Its use is safe and can improve liver biochemistry, IgG and reduce steroid requirement. However, due to the lack of immunomodulatory effect, unmet need for effective immune-regulatory therapies still remain for AIH patients.

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents; Aspartate Aminotransferases; Azathioprine; Cholangitis, Sclerosing; Cyclosporine; Female; Follow-Up Studies; Hepatitis, Autoimmune; Humans; Immunoglobulin G; Immunosuppressive Agents; Male; Mercaptopurine; Middle Aged; Mycophenolic Acid; Prednisolone; Retreatment; Tacrolimus; Time Factors; Treatment Outcome; Young Adult

Topics: Cholangitis, Sclerosing; Humans; Immunosuppressive Agents; Mycophenolic Acid; Research Design

Topics: Adult; Cholangitis, Sclerosing; Humans; Immunosuppressive Agents; Liver Function Tests; Male; Mycophenolic Acid

Topics: Cholangitis, Sclerosing; Humans; Immunosuppressive Agents; Liver Cirrhosis, Biliary; Mycophenolic Acid