tacrolimus and Cholangiocarcinoma

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

Cholangiocarcinoma has historically represented a major contraindication to liver transplantation at many centers because of its high recurrence rate and low disease-free survival rate, even after radical surgery. Novel neoadjuvant therapy protocols combined with demolitive surgery and liver transplantation seem to achieve successful results in terms of overall and disease-free survivals. Surgery frequently seems to be unsatisfactory only for patients also suffering from chronic cirrhosis or end-stage liver disease. We have reported a case of hilar cholangiocarcinoma occurring in a case of primary sclerosing cholangitis treated with neoadjuvant radiochemotherapy and endoscopic brachytherapy, followed by liver transplantation combined with pancreatoduodenectomy, who has survived free of disease for >8 years.

Topics: Antimetabolites, Antineoplastic; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Brachytherapy; Chemotherapy, Adjuvant; Cholangiocarcinoma; Cholangitis, Sclerosing; Disease-Free Survival; Female; Fluorouracil; Hepatectomy; Humans; Immunosuppressive Agents; Liver Transplantation; Middle Aged; Neoadjuvant Therapy; Pancreaticoduodenectomy; Radiotherapy, Adjuvant; Tacrolimus; Time Factors; Treatment Outcome