Rescue liver re-transplantation after graft loss due to severe rejection in the setting of pre-transplant nivolumab therapy.

Immune checkpoint inhibitors (ICI) have been used to treat hepatocellular carcinoma (HCC) since 2017. The safety of ICIs in the setting of solid organ transplantation remains controversial. When used in the post-transplant setting, ICIs have been associated with high allograft rejection rates, but there are few published reports on the use of ICIs prior to transplant. We present the first reported case of rescue liver re-transplantation after loss of the first allograft due to severe acute rejection with extensive hepatic necrosis in the setting of pre-transplant ICI therapy with the PD-1 inhibitor nivolumab. It is likely that the durable immune response triggered by nivolumab contributes to graft rejection, therefore extreme caution should be taken when using ICIs before transplant until further investigation has been conducted on their safety in the pre-transplant setting.

Drug-Induced Liver Injury Associated with the Use of Everolimus in a Liver Transplant Patient.

Drug-induced liver injury (DILI) has not been previously reported as a complication of treatment with everolimus. A 56-year-old Caucasian male liver transplant recipient developed DILI after receiving everolimus. Elevations in transaminase levels occurred within a week of starting everolimus and an upward trend in the transaminase levels continued with supporting histopathologic changes confirmed by liver biopsy. Within one week of drug discontinuation, his liver enzymes normalized to baseline. This report includes a brief review of the pharmacokinetic properties of everolimus, a review of the relevant literature, and an analysis using the RUCAM and Naranjo algorithms.

Concomitant hepatic encephalopathy and refractory ascites: successful treatment with staged embolization of two large portosystemic shunts and transjugular intrahepatic portosystemic shunt placement.

A patient with cirrhosis, refractory ascites, and two large competitive portosystemic shunts presented with uncontrollable acute exacerbation of chronic hepatic encephalopathy (HE). A staged procedure was performed by first performing embolization of a large mesogonadal shunt to treat the HE. Three months later, a transjugular intrahepatic portosystemic shunt (TIPS) was created to address the ascites. A large paraumbilical vein shunt was embolized at TIPS placement to minimize the risk of recurrent HE. At 9-month follow-up, the ascites was well controlled with medical management with little or no HE.

Choosing the location for non-image guided abdominal paracentesis.

OBJECTIVES: The optimal location for paracentesis has not been studied scientifically. The evolving obesity epidemic has changed the physique of many patients with cirrhosis and ascites such that needles inserted into the abdominal wall may not reach fluid. We aimed to determine the location for paracentesis that would have the thinnest abdominal wall and the deepest amount of fluid. METHODS: Ultrasound measurements of abdominal wall thickness and depth of ascites were recorded in two locations, the infraumbilical midline (ML) and the left lower quadrant (LLQ), in 52 patients with cirrhosis and ascites admitted to a single inpatient liver unit. RESULTS: The abdominal wall was significantly thinner (1.8 vs. 2.4 cm; P<0.001) and the depth of ascites greater (2.86 vs. 2.29 cm; P=0.017) in the LLQ as compared with the infraumbilical ML position. In the left lateral oblique position, the difference in the depth of ascites was more pronounced when comparing the LLQ with the infraumbilical ML (4.57 vs. 2.78 cm; P<0.0001). CONCLUSIONS: The LLQ is preferable to the ML infraumbilical location for performing paracentesis.

Abnormal hepatic methionine and glutathione metabolism in patients with alcoholic hepatitis.

BACKGROUND: Abnormal methionine metabolism occurs in animals fed ethanol and in end-stage cirrhotic patients. Expected consequences of these abnormalities include reduced hepatic S-adenosylmethionine and glutathione (GSH) levels, impaired transmethylation, and reduced homocysteine catabolism, resulting in the often-observed hyperhomocystinemia in cirrhotic patients. These parameters have not been examined simultaneously in patients with less advanced alcoholic liver disease. METHODS: Six patients hospitalized for alcoholic hepatitis were studied. Plasma was analyzed for homocysteine, methionine, and GSH levels. Liver biopsies diagnosed acute alcoholic hepatitis and underlying fibrosis. Liver specimens were processed for messenger RNA (mRNA) levels and various metabolites and were compared with those of six normal controls. RESULTS: Three patients had cirrhosis, and three had only portal fibrosis. Plasma levels of homocysteine and methionine were increased in two of the three patients with cirrhosis but not in the patients with fibrosis. All patients had markedly lower plasma GSH levels (mean +/- SD: 0.27 +/- 0.19 microM, which is at least 10-fold lower than the normal range). Hepatic S-adenosylmethionine levels were reduced by 50%, whereas methionine, GSH, and cysteine levels were reduced by 70-80%. The mRNA levels of most enzymes involved in methionine metabolism and GSH synthesis were decreased, whereas albumin expression was unchanged. Despite the well known induction of cytochrome P450 2E1 in chronic alcoholics, its mRNA levels were nearly 70% lower in these patients. CONCLUSIONS: In alcoholic hepatitis, abnormal hepatic gene expression in methionine and GSH metabolism occurs and often contributes to decreased hepatic methionine, S-adenosylmethionine, cysteine, and GSH levels. It may be important to replenish these thiols in patients hospitalized with alcoholic hepatitis.