Michael A. Heneghan

Background: Autoimmune hepatitis (AIH) is an important indication for liver transplantation (LT), but recurrence affects over 30% of recipients, threatening long-term survival. Current strategies to prevent recurrence and progressive graft fibrosis remain suboptimal, with limited evidence to guide selection of immunosuppressive regimens. We aimed to develop a dynamic, individualized, artificial intelligence–powered model for post-transplant recurrent AIH. Methods: We conducted a multicenter, retrospective cohort study of 706 patients who underwent LT for AIH between January 1987 and June 2020 at 33 centers in North America, South America, Europe, and Asia. We trained 4 predictive machine learning models—Logistic Regression, Random Forest, XGBoost, and Gradient Boost—to predict recurrent AIH (rAIH) using 62 clinical and laboratory variables, including demographic, biochemical features, and immunosuppressive drugs up to 1-year post-transplant. Feature importance was assessed using SHapley Additive exPlanations (SHAP) to enable interpretability at both individual and population levels. Results: AIH recurred in 16.5% of patients after LT. SHAP analysis identified younger age at LT, higher necroinflammatory activity in the explanted liver, and elevated MELD score at LT as key predictors of rAIH in the overall population. Tacrolimus-based therapy was associated with a lower risk of recurrence, while cyclosporine use conferred a higher risk. The addition of long-term prednisone to a regimen of tacrolimus and mycophenolate mofetil did not provide additional protective effect against rAIH. Conclusions: Our AI-powered clinical decision model provides personalized prediction of post-transplant rAIH. While it offers insight into modifiable and non-modifiable predictors, prospective validation is required before informing immunosuppressive decisions.

Pregnancy is accompanied by complex physiological adaptations that influence hepatic metabolism, bile transport, coagulation, and immune tolerance, which may precipitate the development of pregnancy-specific liver disorders. Gestational liver disease comprises a distinct group of conditions such as hyperemesis gravidarum (HG), intrahepatic cholestasis of pregnancy (ICP), acute fatty liver of pregnancy (AFLP), and the spectrum of preeclampsia that includes hepatic involvement and Hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. Although heterogeneous in presentation and pathophysiology, these disorders share the potential for significant maternal and fetal morbidity and mortality. Early recognition and hepatology-guided interpretation of abnormal liver biochemistry during pregnancy are critical to differentiate gestational liver disease from underlying chronic liver disease and to identify conditions that require urgent intervention. Management of gestational liver disease requires coordinated, multidisciplinary care focused on maternal stabilization, appropriate disease-specific therapy, and carefully timed delivery according to both maternal and fetal risk. Treatment strategies range from supportive and nutritional management for HG, biochemical and symptom control with ursodeoxycholic acid for ICP, and urgent delivery and intensive supportive care for AFLP to delivery with antihypertensive and anticonvulsant therapy for hypertensive disorders and HELLP syndrome. Although each condition poses unique diagnostic and therapeutic challenges, complications associated with gestational liver disease in pregnancy may be reduced through proactive management and multidisciplinary involvement. This review summarizes current evidence on the pathophysiology, diagnostic evaluation, management strategies, and pregnancy outcomes associated with pregnancy-specific liver disorders. Cite this article as: Frolkis A, Ergenc I, Heneghan MA. Liver conditions specific to pregnancy: optimizing management and outcomes. Turk J Gastroenterol. Published online April 8, 2026. doi: 10.5152/tjg.2026.26024.

Introduction Primary biliary cholangitis (PBC) is a rare chronic cholestatic disease that despite current therapy has significant ongoing unmet needs, including risks of cirrhosis and life-impairing symptoms. The current treatment approach is a step-up model, wherein first-line therapy, ursodeoxycholic acid (UDCA), is given for a minimum of 12 months before the addition of second-line therapy is considered for non-responding patients. This ‘waiting to fail’ approach, focused on the needs of low-risk patients, allows, we postulate, a key process of biliary epithelial cell (BEC) senescence to become established, driving accelerated bile duct loss and aggressive disease. Preclinical mouse modelling has shown that early use of the farnesoid X receptor agonist obeticholic acid (OCA), currently only used as second-line therapy following UDCA failure, reverses BEC senescence, changing the clinical course of disease. Here, we describe the design of the Optimising Primary thErapy in pRimAry biliary cholangitis (OPERA) trial. The aim of OPERA is to explore a new paradigm for disease-modifying treatment of PBC: risk-informed early treatment stratification, with patients at increased risk offered UDCA and OCA combination with the goal of complete biochemical remission. Methods and analysis OPERA is a multicentre, randomised, double-blind, placebo-controlled trial of OCA in combination with UDCA, as first-line treatment for high-risk PBC. This is a multicentre trial in England, which will be undertaken in specialist clinics in secondary/tertiary referral centres (or as per local set up). These centres will be specialists in the area of PBC management and will manage patients from across their local region. OPERA will recruit and randomise 106 adults, within 6 months of PBC diagnosis, who are at an enhanced risk of non-response to standard first-line therapy, between either: (1) UDCA and OCA or (2) UDCA and matched placebo in a 1:1 ratio. The primary efficacy outcome measure is the percentage of participants showing normalisation of serum alkaline phosphatase and total bilirubin values at 26 weeks (disease remission). Ethics and dissemination Favourable ethical opinion was received from London – Riverside Research Ethics Committee (reference: 22/LO/0878). Potential participants will be fully informed of their rights and the benefits and harms of the trial by the research team before giving informed consent to participate in the trial. Results will be disseminated in peer-reviewed publications, at national and international conferences, in peer-reviewed journals and to participants and the public (using lay language). Trial registration number ISRCTN17176388.

Preexisting liver disease, particularly the presence of cirrhosis and portal hypertension (PHT), presents a significant challenge during gestation, necessitating close collaboration between obstetric and hepatology/gastroenterology teams. Women with underlying liver conditions face an increased likelihood of adverse maternal and fetal outcomes. Proactive identification and management of the potential risks associated with pregnancy in this patient group is therefore crucial. While the desire to start a family is deeply personal, each pregnancy carries unique risks requiring careful consideration. Although no single recommendation can comprehensively address all forms of liver disease, pregnancy in women with underlying hepatic conditions can be both safe and achievable when managed througha multidisciplinary team approach, involving the mother and her partner from the preconception stage through to the postpartum period. This review summarizes the current evidence regarding the risks and management strategies for pregnancy complicated by preexisting liver disease, including cirrhosis and PHT, steatotic liver disease, viral hepatitis, autoimmune liver disease, and liver transplant recipients. Cite this article as: I E, A F, MA H. Preexisting liver disease and pregnancy: optimizing care to optimize outcomes. Turk J Gastroenterol. Published online January 2, 2026. doi: 10.5152/tjg.2026.25753.

Autoimmune hepatitis (AIH) may present with a diverse spectrum of clinical manifestations and disease stages. It is a life-threatening condition that, if undiagnosed or inadequately treated, can progress to liver failure, cirrhosis and decompensation. The primary goals of treatment are to prevent both acute and chronic liver failure while preserving quality of life. Various obstacles to achieving these goals contribute to difficult-to-treat AIH. One of the most significant advancements has been the shift towards personalised treatment, particularly through the fine-tuning of thiopurine therapy using metabolite monitoring and combination with low-dose allopurinol when necessary. Mycophenolate mofetil (MMF) has solidified its role as a leading second-line option in thiopurine intolerant patients. A controversial head-to-head randomised controlled trial comparing MMF with azathioprine as a first-line treatment has further advanced MMF’s position as a therapeutic option. MMF may now be considered a valid first-line option in carefully selected cases. Tacrolimus remains the preferred third-line agent, with the most extensive clinical experience supporting its long-term use. Among biological therapies, infliximab and rituximab have taken a leading role in the management of refractory AIH. These therapies are poised to play an increasingly significant role in both induction and maintenance treatment in the future. In this review, we summarise the therapeutic strategies for difficult-to-treat AIH, from thiopurine optimisation to the emerging role of biologic therapies.

Objective Patients with autoimmune hepatitis (AIH) receive variable corticosteroid and thiopurine regimens. Our aim was to undertake a cohort study to determine whether earlier introduction of azathioprine allowed reduction in cumulative corticosteroid burden. We also determined temporal trends in treatment choices and outcomes. Method 226 adults with AIH treated from 1970 to 2020 at Kings College Hospital were divided into two groups: patients who received azathioprine therapy within 8 weeks of initiation of corticosteroid therapy (early group, n=106) and patients who had received azathioprine more than 8 weeks after corticosteroid initiation (late group, n=120). Results Cumulative exposure to corticosteroid was not significantly different between each group. 80% of patients achieved normalisation of aspartate aminotransferase within 6 months of corticosteroid induction compared with 64.5% in the late group (p=0.013). When evaluated by decade, the cumulative corticosteroid exposure and dose declined over time (pConclusion Earlier introduction of azathioprine after corticosteroid therapy resulted in a higher rate of transaminase normalisation at 6 months but did not significantly reduce the cumulative prednisolone exposure over 5 years. Temporal effects in the management of AIH are evident, whereby earlier introduction of thiopurines in recent decades facilitated more rapid reduction in corticosteroid dose while achieving a higher rate of biochemical response.

Purpose of review: This review highlights the management, maternal and fetal outcomes, and the critical role of prepregnancy counseling for women with portal hypertension (PHT), a topic of growing clinical relevance as pregnancies in women with PHT have increased over the last two decades. Recent findings: Pregnancy exacerbates PHT due to physiological changes that increase blood flow and vascular resistance, raising the risk of life-threatening complications like variceal bleeding. The distinction between noncirrhotic (NCPH) and cirrhotic portal hypertension (CPH) is essential, as maternal risks vary significantly. Summary: Optimal care for women with PHT requires preconception counseling to assess risks, adjust medications, and plan necessary investigations such as variceal and splenic artery aneurysm screening and, if necessary, plan additional interventions. A multidisciplinary team – including hepatologists, obstetricians, anesthetists, and radiologists – is crucial for personalized management, addressing both the mode of delivery and peripartum care. While PHT complicates pregnancy, favorable outcomes are achievable with proactive planning and close follow-up during pregnancy.