Management of Autoimmune Liver Diseases after Liver Transplantation

Autoimmune liver diseases are characterized by immune-mediated inflammation and eventual destruction of the hepatocytes and the biliary epithelial cells. They can progress to irreversible liver damage requiring liver transplantation. The post-liver transplant goals of treatment include improving the recipient’s survival, preventing liver graft-failure, and decreasing the recurrence of the disease. The keystone in post-liver transplant management for autoimmune liver diseases relies on identifying which would be the most appropriate immunosuppressive maintenance therapy. The combination of a steroid and a calcineurin inhibitor is the current immunosuppressive regimen of choice for autoimmune hepatitis. A gradual withdrawal of glucocorticoids is also recommended. On the other hand, ursodeoxycholic acid should be initiated soon after liver transplant to prevent recurrence and improve graft and patient survival in primary biliary cholangitis recipients. Unlike the previously mentioned autoimmune diseases, there are not immunosuppressive or disease-modifying agents available for patients with primary sclerosing cholangitis. However, colectomy and annual colonoscopy are key components during the post-liver transplant period

Unveiling the culprit: Exploring malignant thrombotic superior vena cava obstruction

Key Clinical Message This case image describes the complex proposed etiologies of a case of superior vena cava syndrome. Hence, different diagnostic and therapeutic modalities are needed in a multidisciplinary team approach

Management of Autoimmune Liver Diseases after Liver Transplantation

Autoimmune liver diseases are characterized by immune-mediated inflammation and eventual destruction of the hepatocytes and the biliary epithelial cells. They can progress to irreversible liver damage requiring liver transplantation. The post-liver transplant goals of treatment include improving the recipient’s survival, preventing liver graft-failure, and decreasing the recurrence of the disease. The keystone in post-liver transplant management for autoimmune liver diseases relies on identifying which would be the most appropriate immunosuppressive maintenance therapy. The combination of a steroid and a calcineurin inhibitor is the current immunosuppressive regimen of choice for autoimmune hepatitis. A gradual withdrawal of glucocorticoids is also recommended. On the other hand, ursodeoxycholic acid should be initiated soon after liver transplant to prevent recurrence and improve graft and patient survival in primary biliary cholangitis recipients. Unlike the previously mentioned autoimmune diseases, there are not immunosuppressive or disease-modifying agents available for patients with primary sclerosing cholangitis. However, colectomy and annual colonoscopy are key components during the post-liver transplant period.</jats:p

Pharmacological Therapy of Pruritus in Primary Biliary Cholangitis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Goals: We aim to summarize the current management of pruritus in primary biliary cholangitis (PBC) by evaluating the efficacy and safety of pharmacological therapies. Background: Pruritus is a common symptom of PBC, and evidence regarding the most effective antipruritic agents available is lacking. New pharmacotherapy for PBC has shown promising antipruritic effects. Study: We performed a systematic literature review and meta-analysis including all available double-blind, randomized, placebo-controlled clinical trials that evaluated the efficacy of pharmacotherapy for the symptomatic management of pruritus in PBC. Pruritus was assessed as either a change from baseline or a postintervention score. Results: We included 33 studies and 20 medications. Using the visual analog scale, cholestyramine did not significantly improve pruritus compared with placebo [standardized mean differences (SMD): -0.94, 95% CI: -2.05 to 0.17], whereas rifampin and nalfurafine hydrochloride both significantly improved pruritus (SMD: -3.29, 95% CI: -5.78 to -0.80; n=23 and SMD: -0.58, 95% CI: -1.04 to -0.12). In addition, Bezafibrate and linerixibat significantly improved pruritus (SMD: -1.05, 95% CI: -1.41 to -0.68; n=110 and SMD: -0.31, 95% CI: -0.62 to -0.04, respectively). This effect was also present within the subgroup analysis by pruritus scale, where both bezafibrate and linerixibat significantly improved pruritus compared with placebo (SMD: -1.09, 95% CI: -1.54 to -0.65; P<0.001; visual analog scale; as postintervention score and SMD: -0.31, 95% CI: -0.62 to -0.01; P=0.04; numeric rating scale; as a change from baseline score, respectively). Conclusions: Bezafibrate and Linerixibat are potential second-line antipruritic medications for PBC, particularly those with moderate to severe pruritus

Pharmacological Therapy of Pruritus in Primary Biliary Cholangitis A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Medina-Morales E, Bernal RB, Gerger H, et al. Pharmacological Therapy of Pruritus in Primary Biliary Cholangitis A Systematic Review and Meta-Analysis of Randomized Clinical Trials. Journal of Clinical Gastroenterology . 2023;57(2):143-152.Goals: We aim to summarize the current management of pruritus in primary biliary cholangitis (PBC) by evaluating the efficacy and safety of pharmacological therapies. Background: Pruritus is a common symptom of PBC, and evidence regarding the most effective antipruritic agents available is lacking. New pharmacotherapy for PBC has shown promising antipruritic effects. Study: We performed a systematic literature review and meta-analysis including all available double-blind, randomized, placebo-controlled clinical trials that evaluated the efficacy of pharmacotherapy for the symptomatic management of pruritus in PBC. Pruritus was assessed as either a change from baseline or a postintervention score. Results: We included 33 studies and 20 medications. Using the visual analog scale, cholestyramine did not significantly improve pruritus compared with placebo [standardized mean differences (SMD): −0.94, 95% CI: −2.05 to 0.17], whereas rifampin and nalfurafine hydrochloride both significantly improved pruritus (SMD: −3.29, 95% CI: −5.78 to −0.80; n=23 and SMD: −0.58, 95% CI: −1.04 to −0.12). In addition, Bezafibrate and linerixibat significantly improved pruritus (SMD: −1.05, 95% CI: −1.41 to −0.68; n=110 and SMD: −0.31, 95% CI: −0.62 to −0.04, respectively). This effect was also present within the subgroup analysis by pruritus scale, where both bezafibrate and linerixibat significantly improved pruritus compared with placebo (SMD: −1.09, 95% CI: −1.54 to −0.65; P<0.001; visual analog scale; as postintervention score and SMD: −0.31, 95% CI: −0.62 to −0.01; P=0.04; numeric rating scale; as a change from baseline score, respectively). Conclusions: Bezafibrate and Linerixibat are potential second-line antipruritic medications for PBC, particularly those with moderate to severe pruritus. Primary biliary cholangitis (PBC) is a chronic, immune-mediated liver disease characterized by destruction of intrahepatic bile ducts, and is associated with numerous extrahepatic complications.1 Approximately 60% to 70% of patients diagnosed with PBC experience pruritus at some point during their disease course, and nearly 35% have refractory pruritus.2 Pruritus can lead to sleep deprivation, fatigue, and emotional disturbances including depression and suicidal ideation, all of which leads to lower health-related quality of life (HRQoL).3 Successful symptomatic treatment of pruritus can improve patients’ quality of life, and is an essential component of the overall management of PBC. Treatment options for pruritus in patients with PBC are limited. Ursodeoxycholic acid (UDCA) has been shown to favorably alter the natural history of PBC, but its effect on pruritus has not been proven.4 To achieve improved control of pruritus in patients with cholestasis, the American Association for the Study of Liver Disease (AASLD) and the European Association for the Study of the Liver (EASL) recommend a step-wise pharmacological approach. Cholestyramine is considered/first-line therapy for pruritus. Rifampin, naltrexone, and sertraline are all recommended as potential second-line options.4,5 However, these medications lack adequate efficacy for the treatment of pruritus, and have unfavorable side effect profiles, which have prompted additional studies exploring novel treatment options. Novel medications have expanded the potential treatment options for the management of symptomatic pruritus in PBC. Ileal bile acid transport (IBAT) inhibitors and peroxisome proliferator-activated receptor agonists have both shown promising results in recent studies.6–9 Other novel therapeutics have also been studied. We performed a systematic review and meta-analysis of all randomized-controlled trials (RCTs) studying antipruritic medications used in PBC patients

The External Validation of GLOBE and UK-PBC Risk Scores for Predicting Ursodeoxycholic Acid Treatment Response in a Large U.S. Cohort of Primary Biliary Cholangitis Patients

Background: The cornerstone treatment for primary biliary cholangitis (PBC) is ursodeoxycholic acid (UDCA), but many patients exhibit an incomplete response, leading to disease progression. Risk prediction models like the GLOBE and UK-PBC scores hold promise for patient stratification and management. We aimed to independently assess the predictive accuracy of these risk scores for UDCA response in a prospective U.S. cohort. Methods: We conducted a prospective cohort study at a U.S. liver center, monitoring UDCA-treated PBC patients over a one-year follow-up. We evaluated the predictive efficacy of the GLOBE and UK-PBC scores for UDCA treatment response, comparing them to the Paris II criteria. Efficacy was assessed using univariate and multivariate analyses, followed by prognostic performance evaluation via receiver operating characteristic (ROC) curve analysis. Results: We evaluated 136 PBC patients undergoing UDCA therapy. Based on the Paris II criteria, patients were categorized into UDCA full-response and non-response groups. The GLOBE score identified a non-responder rate of 18% (p = 0.205), compared to 20% (p = 0.014) with the Paris II criteria. Multivariate analysis, adjusted for age and biochemical markers, showed that both the GLOBE and UK-PBC scores were strongly associated with treatment response (p &lt; 0.001). The area under the ROC curve was 0.87 (95% CI 0.83&minus;0.95) for the GLOBE score and 0.94 (95% CI 0.86&minus;0.99) for the UK-PBC risk score. Conclusions: Our study demonstrates that GLOBE and UK-PBC scores effectively predict UDCA treatment response in PBC patients. The early identification of patients at risk of an incomplete response could improve treatment strategies and identify patients who may need second-line therapies