Graft verus host disease (GVHD) following Liver transplantation is rare life threatening complication with very high mortality rate around 85%. Due to increased recognition of this condition management approach is rapidly evolving due to newer diagnostic methods and drugs. Etiology, risk factors, pathogenesis, preventive strategies, management approach and newer drugs are discussed. We present our experience of 2 cases from a large cohort of 1052 Liver transplant operations over a decade.

Hereditary tyrosinemia type 1 (HT1) is an autosomal recessive disorder caused by a defect in fumarylacetoacetate hydroxylase (FAH) encoded by the FAH gene. Patients with HT1 disorder present with increased blood tyrosine, succinyl acetoacetate, and succinyl acetone levels, and develop clinical manifestations including liver failure, kidney tubular dysfunction, growth failure, rickets, pseudo-porphyric crises, and hepatocellular carcinoma. We encountered two siblings with HT1. Among the siblings, the elder brother developed acute liver failure with coagulopathy at the age of 2 months and was rescued by liver transplantation (LT) following combination therapy with continuous hemodiafiltration and plasma exchange. The younger sister was followed up from the prenatal period for signs of HT1 due to prior history of the condition in her sibling. She was initially considered a carrier of HT1 owing to the lack of overt signs of the disease and negative urine screening for succinyl acetone (SA). She was eventually diagnosed with HT1 because of liver disorder at 9 months of age, associated with a positive urine SA result. Her disease state was controlled by treatment with nitisinone (NTBC). DNA analysis of both siblings identified heterozygous status for a previously reported FAH pathogenic allele (c.782C > T) and a novel likely pathogenic variant (c.688C.G). The siblings have stable lives with no developmental delay or impaired growth. NTBC treatment is effective in preventing the progression of liver and kidney diseases. However, even in cases treated without LT, clinicians should follow up the clinical outcomes over long term, as patients may require LT when developing complications, such as hepatocellular carcinoma.

OBJECTIVE: The evidence suggests that most vulnerable subjects to COVID-19 infection suffer from patients with comorbidities or immunosuppression, including liver transplant recipients. Liver graft dysfunction may be a rare complication. Some patients complain about the post-COVID-19 syndrome. The aim of this study was to assess medium- and short-term outcomes in liver transplant patients.
METHODS: A retrospective case series was performed at a tertiary referral center. We screened 845 patients who had liver transplant (LT) in our center. All consecutive LT patients with COVID-19 during the Spanish outbreak from March 2020 to April 2021 were included. Demographics, pre-existing comorbidities, clinical and radiological data of COVID-19 infection, complications, and liver graft function were assessed at diagnosis and 3-month follow-up.
RESULTS: Overall, 20 LT patients were diagnosed with confirmed COVID-19. We included 16 patients that met the inclusion criteria, 8 nonhospitalized (50%) and 8 (50%) hospitalized patients were analyzed. The median follow-up was 5.33 months (IQR 3.06-8.26). One patient died during the follow-up. All patients presented some grade of respiratory or functional symptoms. Dyspnea and fatigue were the most prevalent symptoms during the 3-month follow-up. No liver graft dysfunction were reported despite of partial immunosuppression withdrawal in four patients (25%). One patient had cardiovascular complications.
CONCLUSIONS: Our results suggest the presence of post-COVID-19 syndrome with mild residual physical and psychological dysfunction in this subgroup of patients at 3 months after COVID-19. However, no cases of loss or liver graft dysfunction were reported.

BACKGROUND: Due to the complexity of the surgical procedure portal vein thrombosis (PVT) has long been considered an absolute contraindication to liver transplantation (LT). The presence of a large splenorenal shunt (SRS) could make portal anastomosis a valid option.
METHODS: We report the case of a 37-year-old female patient with Grade III PVT and a large SRS, who underwent orthotopic LT. Liver was implanted using a 1992-Belghiti piggyback technique and portal anastomosis was performed using the large spleno-renal shunt. We observed good graft reperfusion and postoperative Doppler ultrasound showed normal portal vein flow. She was discharged on postoperative day 7, with an excellent graft function. At six months follow-up, patient is alive with normal hepatic vascularization.
CONCLUSIONS: Due to paucity of reports, there is currently no consensus on the indication to LT and/or surgical technique. In the present case, once the transplant benefit was evaluated, the Grade III PVT was not considered a contraindication to LT.
CONCLUSIONS: The presence of a Grade III PVT associated with a large SRS should not be considered a contraindication for LT, and the use of the shunt vein should be considered a feasible option to perform portal anastomosis.

A 45 year old female with a body mass index (BMI) of 24 underwent successful liver transplantation (LT) for alcoholic cirrhosis using a donor liver from an obese woman with microvesicular steatosis (80%) and minimal macrovesicular steatosis (5-10%) on liver biopsy. Ascites and hepatosplenomegaly developed soon after LT with progressive increase of serum alkaline phosphatase to 1340 IU/L while aspartate aminotransferase (AST), and alanine transaminase (ALT), and total bilirubin remained normal. Imaging showed marked hepatomegaly, extensive fatty infiltration of the liver, and compression of the hepatic veins with narrowing of the intrahepatic inferior vena cava (IVC). Liver biopsy on post-operative day 39 revealed 90-100% macrovesicular steatosis, steatohepatitis, and portal fibrosis. A hepatic venogram showed a 10 cm segment of intrahepatic IVC stenosis that was stented, improving portal venous pressure measurements. However, portal hypertension requiring diuretic therapy and multiple paracenteses remained. By 3 months after LT, her liver had grown to 22 cm, transaminases increased 2-4 times the upper limit of normal with a 2:1 AST to ALT ratio. Liver biopsy at post-LT day 82 showed no change in steatosis and steatohepatitis despite corticosteroid withdrawal and interval periportal and perisinusoidal fibrosis. 12 weeks after LT, the patient was found to have low apolipoprotein B (65 mg/dL), high-density lipoprotein (HDL) (<10 mg/dL), low-density lipoproteins (LDL) (9 mg/dL), and total cholesterol (<50 mg/dL) levels. Therapy was started for NASH with high dose (800 IU daily) vitamin E and pioglitazone 15 mg daily, and she received topical vegetable oil and oral essential fatty acid supplements. Liver enzymes normalized after 3 months and her lipid profile improved markedly (HDL 27 mg/dL, total cholesterol 128 mg/dL), with progressive decrease in liver size and resolution of ascites after 5 months of therapy. At 2 years post-LT, the liver enzymes remain normal and lipids have normalized.