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Langerhans cell histiocytosis (LCH) is a malignant disease of the histiocytes involving various organ systems. The spectrum of liver involvement in LCH ranges from mild transaminitis to end-stage liver disease. The hallmark of hepatic LCH is secondary sclerosing cholangitis, which manifests due to a progressive destruction of the biliary tree by malignant histiocytes. Chemotherapy remains the mainstay of treatment for active LCH. Early recognition, diagnosis and a systematic approach to the management of LCH can ameliorate the disease process. Nonetheless, the liver involvement in these patients may progress despite the LCH being in remission. Liver transplantation (LT) remains central in the management of such patients. Various facets of the management of LCH, especially those with liver involvement remain unclear. Furthermore, aspects of LT in LCH with regards to the indication, timing and post-LT management, including immunosuppression and adjuvant therapy, remain undefined. This review summarises the current evidence and discusses the practical aspects of the role of LT in the management of LCH.

Steatohepatitis and diarrhea are well-known complications in children undergoing liver transplantation (LT) for progressive familial intrahepatic cholestasis (PFIC) type 1. Despite medical management with bile acid binders, the condition is progressive and can be associated with allograft loss. We report the case of a seven-year-old boy who underwent LT at the age of 2 years for PFIC type 1. Over the next five years, he developed refractory diarrhea, emaciation, worsening liver function, and steatohepatitis. Aiming to interrupt the enterohepatic circulation, at the age of 7 years, he underwent a total internal biliary diversion. The patient's postprocedure period was uneventful. His diarrhea settled and the transaminases normalized his follow-up liver biopsy after a year showed a complete resolution of steatohepatitis. At 18 months' follow-up, he has gained weight and remains asymptomatic. In this report, we show post-LT complications especially allograft injury related to the pathology of PFIC-1 can be safely and effectively managed by performing a total internal biliary diversion.

Standardization of immunomodulation protocols has enabled ABO-incompatible liver transplants with outcomes similar to those of ABO-compatible liver transplants. Patients with the A2 blood group are unique because they have a diminished expression of the A antigen. Despite rare immune complications, this phenomenon of diminished expression has led to treatment of type A2 donors according to the regimen for type O blood group donors in ABO-incompatible liver transplants. Additionally, the requirement for pretransplant recipient immunomodulation is consi dered minimal when considering these donors. The transplant of a type A2 donor kidney to a type B recipient is well recognized; however, for liver donation the A2-to-B transplant is rare. Here, we present a case of 48-year-old male patient with blood group type B who underwent ABO-incompatible liver transplant of a right lobe liver graft from a type A2 donor. Postoperatively, despite adequate immunosuppression and initiation of thera - peutic plasma exchange, the patient developed severe and refractory antibody-mediated rejection that ultimately abated with a splenectomy. This report highlights the low but tangible risk of antibody-mediated rejection in ABO-incompatible liver transp lants from type A2 donors and emphasizes the importance of serial monitoring of anti-A isohemag glutinin titers and posttransplant splenectomy to ensure that liver grafts with antibody-mediated rejection can be rescued.

Langerhans cell histiocytosis (LCH) is a rare but important cause of end-stage liver disease in children. Conventional chemotherapeutic agents that are otherwise the standard-of-care in LCH may be counterproductive in patients with hepatic decompensation. Furthermore, the precise role of liver transplantation (LT) in the management of LCH remains unclear.Review of a prospectively collected database (January 2014 to December 2020) of children with liver disease was performed. All clinical details of patients with LCH managed at our center were collected and data analyzed. Based on the outcomes, a management algorithm was proposed.Of the eight (five male) patients referred to our unit, six (75%) underwent LT (four and two for compensated and decompensated cirrhosis, respectively). Median age at diagnosis of LCH was 25 (range: 9-48) months. Two patients, who had previously completed LCH-specific chemotherapy, underwent upfront LT for compensated cirrhosis. Other two patients with compensated cirrhosis showed evidence of active disease. They underwent LT following completion of chemotherapy. Two children with decompensated cirrhosis also had evidence of active disease and were started on modified chemotherapy Both of them had progression of liver disease while on chemotherapy. Hence, an urgent LT was performed which was followed by completion of chemotherapy in these patients. On a median follow-up of 30.5 (10.5-50) months, all post-LT patients were alive with stable graft function and showed no disease recurrence.We demonstrate that an algorithmic approach, along with newer chemotherapeutic agents, results in excellent outcomes in LCH patients with liver involvement. Larger multicentric studies on this rare disease are, however, needed to validate our findings.

Congenital bile acid synthesis defect type 3 is a rare metabolic liver disease with only eight patients reported in literature. We describe clinical, pathological and molecular features for a ninth patient. A 4-month-old infant presented to us with conjugated hyperbilirubinemia. His liver biopsy revealed giant cell change, steatosis, and activity with diffuse fibrosis. Immunostaining with bile salt export pump showed preserved canalicular pattern and γ-glutamyl transferase 1 staining showed unusual complete membranous pattern. Genetic workup revealed homozygous single base pair duplication in exon 3 of the CYP7B1 gene. He succumbed to liver disease at 7 months of age.

Objective : Spectrum of hepatic presentation in Langerhans cell histiocytosis (LCH) varies from asymptomatic hepatomegaly to secondary sclerosing cholangitis leading to cirrhosis with or without decompensation. Conventional chemotherapy may be counterproductive in a patient with LCH and hepatic decompensation. We analysed the outcomes of our patients with hepatic presentation of LCH, including their post liver transplant (LT) follow up. Methods: A retrospective analysis was performed on patients with hepatic presentation of LCH referred to our unit. Their clinical profile, chemotherapy protocol, details of LT and survival were analysed. A management algorithm based on the outcomes was proposed. Results: Five of 8 patients were male. Median age of diagnosis was 25(9-48) months. 8(100%) patients had portal hypertension with 4(50%) having decompensated cirrhosis. 6 (75%) patients underwent LT of which 2 had acute decompensation and 4 had sclerosing cholangitis with portal hypertension. Of the two remaining patients, 1 did not tolerate chemotherapy and succumbed, whereas 1 patient after first cycle of chemotherapy was lost to follow up. As their liver disease was worsening during chemotherapy (after 8 & 20 weeks of chemotherapy), two patients underwent urgent LT followed by continuation of chemotherapy. After median follow-up of 30.5 (10.5-50) months, all patients were alive with stable graft function and no disease recurrence. Conclusion: As shown in our series, an algorithmic approach to patient and treatment selection for LCH patients with liver involvement combined with newer chemotherapeutic agents and an optimized immunosuppression can result in excellent outcomes for a hitherto unfamiliar disease.

Cholestatic jaundice in new born and infants results from biliary obstruction or hepatocellular dysfunction. Biliary atresia (BA) and Idiopathic neonatal hepatitis comprises the major aetiology. Cholestasis due to toxins is rare in infants. Indian childhood cirrhosis (ICC) and ICC like diseases have been described in infants. Herein, authors are describing a case of infantile cholestasis presenting at 4 months of age who was diagnosed to have copper related hepatotoxicosis on liver biopsy. Copper tumblers were used for preparation of formula milk that likely was the source of exogenous copper and the child improved well after removing the source of exogenous copper.