Liver Transplant Costs and Activity After United Network for Organ Sharing Allocation Policy Changes.

Importance: A new liver allocation policy was implemented by United Network for Organ Sharing (UNOS) in February 2020 with the stated intent of improving access to liver transplant (LT). There are growing concerns nationally regarding the implications this new system may have on LT costs, as well as access to a chance for LT, which have not been captured at a multicenter level.

Objective: To characterize LT volume and cost changes across the US and within specific center groups and demographics after the policy implementation.

Metabolic Impact of MKP-2 Upregulation in Obesity Promotes Insulin Resistance and Fatty Liver Disease.

The mechanisms connecting obesity with type 2 diabetes, insulin resistance, nonalcoholic fatty liver disease, and cardiovascular diseases remain incompletely understood. The function of MAPK phosphatase-2 (MKP-2), a type 1 dual-specific phosphatase (DUSP) in whole-body metabolism, and how this contributes to the development of diet-induced obesity, type 2 diabetes (T2D), and insulin resistance is largely unknown. We investigated the physiological contribution of MKP-2 in whole-body metabolism and whether MKP-2 is altered in obesity and human fatty liver disease using MKP-2 knockout mice models and human liver tissue derived from fatty liver disease patients.

Abundance of Phase 1 and 2 Drug-Metabolizing Enzymes in Alcoholic and Hepatitis C Cirrhotic Livers: A Quantitative Targeted Proteomics Study.

To predict the impact of liver cirrhosis on hepatic drug clearance using physiologically based pharmacokinetic (PBPK) modeling, we compared the protein abundance of various phase 1 and phase 2 drug-metabolizing enzymes (DMEs) in S9 fractions of alcoholic ( = 27) or hepatitis C (HCV, = 30) cirrhotic versus noncirrhotic (control) livers ( = 25). The S9 total protein content was significantly lower in alcoholic or HCV cirrhotic versus control livers (i.e.

Interpreting Outcomes in DCDD Liver Transplantation: First Report of the Multicenter IDOL Consortium.

Background: In the United States, 5% of adult liver transplant recipients receive a graft donation after circulatory determination of death (DCDD). Concerns for ischemic cholangiopathy (IC), a disease of diffuse intrahepatic stricturing limits broader DCDD use. Single-center reports demonstrate large variation in outcomes.

Microcystin-LR induced liver injury in mice and in primary human hepatocytes is caused by oncotic necrosis.

Microcystins are a group of toxins produced by freshwater cyanobacteria. Uptake of microcystin-leucine arginine (MC-LR) by organic anion transporting polypeptide 1B2 in hepatocytes results in inhibition of protein phosphatase 1A and 2A, and subsequent cell death. Studies performed in primary rat hepatocytes demonstrate prototypical apoptosis after MC-LR exposure; however, no study has directly tested whether apoptosis is critically involved in vivo in the mouse, or in human hepatocytes.

Transporter Expression in Liver Tissue from Subjects with Alcoholic or Hepatitis C Cirrhosis Quantified by Targeted Quantitative Proteomics.

Although data are available on the change of expression/activity of drug-metabolizing enzymes in liver cirrhosis patients, corresponding data on transporter protein expression are not available. Therefore, using quantitative targeted proteomics, we compared our previous data on noncirrhotic control livers (n = 36) with the protein expression of major hepatobiliary transporters, breast cancer resistance protein (BCRP), bile salt export pump (BSEP), multidrug and toxin extrusion protein 1 (MATE1), multidrug resistance-associated protein (MRP)2, MRP3, MRP4, sodium taurocholate-cotransporting polypeptide (NTCP), organic anion-transporting polypeptides (OATP)1B1, 1B3, 2B1, organic cation transporter 1 (OCT1), and P-glycoprotein (P-gp) in alcoholic (n = 27) and hepatitis C cirrhosis (n = 30) livers. Compared with control livers, the yield of membrane protein from alcoholic and hepatitis C cirrhosis livers was significantly reduced by 56 and 67%, respectively.

Increased hepatic receptor interacting protein kinase 3 expression due to impaired proteasomal functions contributes to alcohol-induced steatosis and liver injury.

Chronic alcohol exposure increased hepatic receptor-interacting protein kinase (RIP) 3 expression and necroptosis in the liver but its mechanisms are unclear. In the present study, we demonstrated that chronic alcohol feeding plus binge (Gao-binge) increased RIP3 but not RIP1 protein levels in mouse livers. RIP3 knockout mice had decreased serum alanine amino transferase activity and hepatic steatosis but had no effect on hepatic neutrophil infiltration compared with wild type mice after Gao-binge alcohol treatment.

Lack of Direct Cytotoxicity of Extracellular ATP against Hepatocytes: Role in the Mechanism of Acetaminophen Hepatotoxicity.

Background: Acetaminophen (APAP) hepatotoxicity is a major cause of acute liver failure in many countries. Mechanistic studies in mice and humans have implicated formation of a reactive metabolite, mitochondrial dysfunction and oxidant stress as critical events in the pathophysiology of APAP-induced liver cell death. It was recently suggested that ATP released from necrotic cells can directly cause cell death in mouse hepatocytes and in a hepatoma cell line (HepG2).

Mitochondrial protein adducts formation and mitochondrial dysfunction during N-acetyl-m-aminophenol (AMAP)-induced hepatotoxicity in primary human hepatocytes.

3'-Hydroxyacetanilide orN-acetyl-meta-aminophenol (AMAP) is generally regarded as a non-hepatotoxic analog of acetaminophen (APAP). Previous studies demonstrated the absence of toxicity after AMAP in mice, hamsters, primary mouse hepatocytes and several cell lines. In contrast, experiments with liver slices suggested that it may be toxic to human hepatocytes; however, the mechanism of toxicity is unclear.

Lack of direct cytotoxicity of extracellular ATP against hepatocytes: role in the mechanism of acetaminophen hepatotoxicity.

Background: Acetaminophen (APAP) hepatotoxicity is a major cause of acute liver failure in many countries. Mechanistic studies in mice and humans have implicated formation of a reactive metabolite, mitochondrial dysfunction and oxidant stress as critical events in the pathophysiology of APAP-induced liver cell death. It was recently suggested that ATP released from necrotic cells can directly cause cell death in mouse hepatocytes and in a hepatoma cell line (HepG2).

Bile acid-induced necrosis in primary human hepatocytes and in patients with obstructive cholestasis.

Accumulation of bile acids is a major mediator of cholestatic liver injury. Recent studies indicate bile acid composition between humans and rodents is dramatically different, as humans have a higher percent of glycine conjugated bile acids and increased chenodeoxycholate content, which increases the hydrophobicity index of bile acids. This increase may lead to direct toxicity that kills hepatocytes, and promotes inflammation.

Late-onset renal vein thrombosis: A case report and review of the literature.

Introduction: Renal vein thrombosis, a rare complication of renal transplantation, often causes graft loss. Diagnosis includes ultrasound with Doppler, and it is often treated with anticoagulation or mechanical thrombectomy. Success is improved with early diagnosis and institution of treatment.

Combined transmesenteric and transhepatic recanalization of chronic portal and mesenteric vein occlusion to treat bleeding duodenal varices.

Two patients presented with bleeding duodenal varices secondary to mesenteric and portal vein chronic occlusion. After a failed transhepatic recanalization, a combined transmesenteric and transhepatic approach was used to recanalize the chronic portal and mesenteric venous obstruction. The occluded segment was treated with transmesenteric stent placement in one patient and stent placement and coil embolization of varices in the second patient.

Mechanisms of acetaminophen-induced cell death in primary human hepatocytes.

Unlabelled: Acetaminophen (APAP) overdose is the most prevalent cause of drug-induced liver injury in western countries. Numerous studies have been conducted to investigate the mechanisms of injury after APAP overdose in various animal models; however, the importance of these mechanisms for humans remains unclear. Here we investigated APAP hepatotoxicity using freshly isolated primary human hepatocytes (PHH) from either donor livers or liver resections.

Donor risk index predicts graft failure reliably but not post-transplant infections.

Background: The Donor Risk Index (DRI) is used to predict graft survival following liver transplantation, but has not been used to predict post-operative infections in graft recipients. We hypothesized that lower-quality grafts would result in more frequent infectious complications.

Methods: Using a prospectively collected infection data set, we matched liver transplant recipients (and the respective allograft DRI scores) with their specific post-transplant infectious complications.

Self expandable metal stents for anastomotic stricture following liver transplant.

Background: Endoscopic treatment for biliary strictures with plastic stent placement has been used widely. The use of covered self-expandable metal stents (CSEMS) has been reported in anastomotic strictures post liver transplant. The aim of this study was to evaluate the efficacy of different CSEMS in these subjects.

Impact of stem cell marker expression on recurrence of TACE-treated hepatocellular carcinoma post liver transplantation.

Background: Liver transplantation is the most effective therapy for cirrhosis-associated hepatocellular carcinoma (HCC) but its utility is limited by post-transplant tumor recurrence. Use of the Milan, size-based criteria, has reduced recurrence rate to less than 10% but many patients remain ineligible. Reduction of tumor size with local therapies has been used to "downstage" patients to allow them to qualify for transplantation, but the optimal criteria to predict tumor recurrence in these latter patients has not been established.

Quantifying increased hepatic arterial flow with test balloon occlusion of the splenic artery in liver transplant recipients with suspected splenic steal syndrome: quantitative digitally subtracted angiography correlation with arterial Doppler parameters.

Purpose: The purpose of this study is to quantify hepatic arterial flow (HAF) in liver transplants with splenic steal syndrome (SSS) pre- and post-test balloon occlusion of the splenic artery utilizing Doppler ultrasound (DUS) and quantitative digitally subtracted angiography (Q-DSA).

Methods: A total of 193 liver transplants were evaluated retrospectively. Hepatic arterial velocity (HAV) and HAF were calculated utilizing DUS and Q-DSA (i-flow prototype, Siemens) pre- and post-splenic artery balloon occlusion.

Elderly recipients of hepatitis C positive renal allografts can quickly develop liver disease.

Our institution explored using allografts from donors with Hepatitis C virus (HCV) for elderly renal transplantation (RT). Thirteen HCV- elderly recipients were transplanted with HCV+ allografts (eD+/R-) between January 2003 and April 2009. Ninety HCV- elderly recipients of HCV- allografts (eD-/R-), eight HCV+ recipients of HCV+ allografts (D+/R+) and thirteen HCV+ recipients of HCV- allografts (D-/R+) were also transplanted.

Evolution of β-Cell Replacement Therapy in Diabetes Mellitus: Islet Cell Transplantation.

Diabetes mellitus remains one of the leading causes of morbidity and mortality worldwide. According to the Centers for Disease Control and Prevention, approximately 23.6 million people in the United States are affected.

Endovascular therapy for hepatic artery stenosis and thrombosis following liver transplantation.

Purpose: To evaluate the effectiveness of endovascular management of steno-oclusive disease in liver transplants.

Methods: Retrospective review of liver transplant recipients with hepatic artery stenosis (HAS) or thrombosis (HAT) was performed. The HAS group was treated with balloon angioplasty with selective stent placement.

Evolution of β-Cell Replacement Therapy in Diabetes Mellitus: Pancreas Transplantation.

Diabetes mellitus remains one of the leading causes of morbidity and mortality worldwide. According to the Centers for Disease Control and Prevention, approximately 23.6 million people in the United States are affected.

Liver transplantation for T3 lesions has higher waiting list mortality but similar survival compared to T1 and T2 lesions.

Background: Restrictive staging criteria for liver transplant (LT) patients with HCC in the U.S. have resulted in favorable long-term recurrence-free survival, but these criteria exclude a subgroup of patients who, despite tumor size beyond T2 stage, demonstrate an acceptable outcome.

Liver allografts from hepatitis C positive donors can offer good outcomes in hepatitis C positive recipients: a US National Transplant Registry analysis.

Organ donors are screened for the hepatitis C antibody (anti-HCV) and those with positive tests can be used under extended criteria donation. However, there is still a question of long-term organ viability. The aim of this study was to assess the long-term outcomes of anti-HCV positive (HCV+) liver grafts.