Mukul Vij

Objective: To determine whether liver transplantation (LT) confers durable oncologic benefit in combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and to identify predictors of recurrence that may guide transplant candidacy. Background: cHCC-CCA is a rare primary liver malignancy with aggressive biological behavior. LT has traditionally been contraindicated due to concerns regarding recurrence. We evaluated long-term outcomes of LT versus liver resection (LR) and compared LT outcomes for cHCC-CCA with those for hepatocellular carcinoma (HCC). Methods: Patients with cHCC-CCA who underwent LT or LR between 2010 and 2024 were identified from a prospective database. Survival outcomes, recurrence patterns, and risk factors for recurrence were analyzed. Outcomes of LT for cHCC-CCA were additionally compared with HCC. Results: A total of 79 patients underwent LT (diagnosed on explant) and 32 underwent LR for cHCC-CCA. 5-year overall survival (OS) and recurrence-free survival (RFS) were superior following LT compared with LR (OS: 89.9% vs. 65.6%, P =0.007; RFS: 84.8% vs. 53.1%, P =0.001). This benefit was maintained for tumors within UCSF criteria [overall survival (88.7% LT vs. 65.6% LR, log rank P 0.014) and RFS (89.8% LT vs. 51.6% LR, P P =0.721). Within the LT cohort, macrovascular invasion (HR 25.01, P =0.003) and poor tumor differentiation (HR 7.29, P =0.004) independently predicted recurrence. Conclusion: In carefully selected patients, cHCC-CCA within UCSF criteria can achieve transplant outcomes comparable to HCC. Macrovascular invasion and poor tumor differentiation are major predictors of recurrence and may inform candidate selection for LT.

Introduction: Familial hypertriglyceridemia (FHTG) is a rare but important cause of recurrent acute pancreatitis (RAP) in children. Liver transplantation (LT) may be the only definitive metabolic cure for this condition, although such an approach has not been reported previously. Method: In the current report, we describe a 8‐year‐old girl suffering from RAP secondary to FHTG for whom an LT led to complete resolution of her metabolic defect. Case Description: An 8‐year‐old girl with FHTG had severe RAP since the age of 6 years. Her serum triglyceride (TG) levels ranged between 2000 and 5439 mg/dL during the episodes of acute pancreatitis severe enough to cause hospitalisations. Acute episodes were managed with insulin–dextrose infusion and therapeutic plasma exchange. She was maintained on hypolipidemic agents along with a fat‐restricted diet, despite which the TG levels continued to remain elevated, triggering further attacks of pancreatitis. In due course, she developed progressive wasting and stunting. After multidisciplinary evaluation and based on a strong scientific rationale, a living donor liver transplant (LDLT) was offered with a left lateral segment from her father. Post‐transplant, the child had an uneventful recovery, without any medical or surgical complications, and her serum TG levels normalized within 6 weeks. At 11 months follow‐up, her TG levels are 75 mg/dL, and she is free of any further episodes of pancreatitis. Conclusion: This is the first report of a successful cure of FHTG via LDLT, highlighting its potential as a definitive therapeutic option for selected pediatric patients with severe, refractory HTG.

Background: Biliary atresia (BA), a fibroinflammatory disease of the extra‐ and intra‐hepatic bile ducts, is associated with hypoplasia±sclerosis of the portal vein (PV) due to obliterative portal venopathy (OPV). It renders the native PV not suitable for reconstruction during living donor liver transplantation (LDLT). We aimed to predict preoperatively who would require portal vein replacement during LDLT. Methods: A retrospective review of children who underwent LDLT for BA from January 2019 to June 2024 was performed. Patient demographics, operative characteristics, and post‐LDLT outcomes were analyzed. Preoperative factors predictive of the need to replace PV were identified, and a predictive model was developed. Results: In the study period, 152 children who underwent LDLT for BA were included. Median (IQR) age and weight were 9 (7–12) months and 6.9 (5.9–8) kg, respectively. Primary LDLT was performed in 54 children, while 98 underwent LDLT after Kasai portoenterostomy (KP). Branch patch anastomosis was the most common type of PV reconstruction. Replacement of the native PV was required in 42 recipients, including 22 branch patch anastomoses, which were converted to vein conduit reconstruction due to thrombosis. There was no significant difference in the need for PV replacement in patients with and without prior KP. Preoperative body mass index (BMI) and mid‐portal vein (mPVA) area were independently predictive of the usability of native PV. Conclusions: In children who underwent LDLT for BA, OPV caused significant PV narrowing, necessitating its replacement. Its etiology remains unknown and is not related to KP. The model, which incorporates BMI and mPVA, predicts the usability of native PV for anastomosis.

Progressive familial intrahepatic cholestasis (PFIC) comprises a heterogeneous group of rare, autosomal recessive liver disorders characterised by defective bile formation and secretion, leading to progressive cholestasis, pruritus, growth impairment, and early onset liver failure. Advances in molecular genetics have identified distinct causative pathogenic variants involving key hepatocellular transporters of bile salts, and phospholipids, giving rise to multiple PFIC subtypes. Early recognition is crucial, as timely medical management and surgical interventions may delay disease progression, while liver transplantation remains the definitive therapy for advanced cases. Through this comprehensive review, we seek to strengthen pathologists understanding of the disease by outlining its morphomolecular and immunohistochemical features, together with the subtleties and diagnostic hallmarks critical for accurate diagnosis.

Background and aims: To validate the applicability of the new histological criteria for autoimmune hepatitis (AIH) proposed by the International AIH Pathology Group (IAIH‐PG) among Chinese patients with AIH and drug‐induced liver injury (DILI). Methods: The gold standard for diagnosis relied on clinical response: discontinuing treatment without relapse supported DILI, while relapse or ongoing immunosuppressive treatment confirmed AIH. This two‐centre retrospective cohort study included inpatients with DILI or AIH from January 2002 to March 2023. Cases that underwent liver biopsy were selected according to inclusion and exclusion criteria. The diagnostic performance of the criteria was assessed by an area under the receiver operating characteristic curve (AUROC). Results: Out of 69 patients: AIH (41, 59%) and DILI (28, 41%). The accuracy, sensitivity and specificity of the new histological criteria for likely and possible AIH were 70%, 98% and 29%, respectively, with an AUROC of 0.8236 [95% confidence interval (CI): 0.7533–0.8938]. For likely AIH, the accuracy, sensitivity and specificity were 73%, 61% and 89%, respectively, with an AUROC of 0.9177 [95% CI: 0.8757–0.9596]. Moreover, for possible AIH, significant differences were found in serum alanine aminotransferase levels [178.4 (87.0, 435.0) versus 536.5 (206.9, 930.4) U/L] and antinuclear antibody (ANA) ≥1:160 [10 (67%) versus 1 (6%)], as well as in lobular lymphoplasmacytic infiltrate [15 (100%) versus 12 (71%)] and more than mild inflammation [13 (87%)versus 6 (35%)] between AIH and DILI (all P values were <0.05). Conclusion: The new histological criteria exhibit good diagnostic efficacy in distinguishing AIH from DILI in China, with high AUROC. Key discriminators include low aminotransferase, ANA ≥1:160, lobular lymphoplasmacytic infiltrate and more than mild inflammation, which may further improve diagnostic accuracy for AIH.