Outcomes of Liver Transplantation in Patients With Preexisting Coronary Artery Disease.

BACKGROUND: Advances in surgical and medical technology over the years has made liver transplantation possible for older and higher risk patients. Despite rigorous preoperative cardiac testing, cardiovascular events remain a major cause of death after orthotopic liver transplantation (OLT). However, there are little data on the outcomes of OLT in patients with preexisting coronary artery disease (CAD). This study aimed to compare all-cause and cardiovascular mortality of patients with and without history of CAD undergoing OLT. METHODS: Six hundred ninety-three adult patients with cirrhosis underwent liver transplantation between July 2013 and December 2018 (female n = 243, male n = 450; median age 59). RESULTS: During the study period of 5 y (median follow-up, 24.1 mo), 92 of 693 patients (13.3%) died. All-cause mortality in the CAD group was significantly higher than in the non-CAD group (26.7% versus 9.6%; P <0.01). Cardiovascular events accounted for 52.5% of deaths (n = 21) in patients with CAD compared with 36.5% (n = 19) in non-CAD patients. At 6 mo, patients with combined nonalcoholic steatohepatitis (NASH)/CAD had significantly worse survival than those with CAD or NASH alone ( P <0.01). After 6 mo, patients with CAD alone had similar survival to those with combined NASH/CAD. CONCLUSIONS: Patients with preexisting CAD before liver transplantation are at higher risk of death from any cause, specifically cardiovascular-related death. This risk increases with coexisting NASH. The presence of NASH and CAD at the time of liver transplant should prompt the initiation of aggressive risk factor modification for patients with CAD.

Mesenchymal stem cells: A novel treatment option for primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is a progressive liver disease for which there is no effective therapy. Hepatocytes and cholangiocytes from a PSC patient were cocultured with mesenchymal stem cells (MSCs) to assess in vitro change. A single patient with progressive PSC was treated with 150 million MSCs via direct injection into the common bile duct. Coculture of MSCs with cholangiocytes and hepatocytes showed in vitro improvement. Local delivery of MSCs into a single patient with progressive PSC was safe. Radiographic and endoscopic evaluation showed stable distribution of multifocal structuring in the early postoperative period. MSCs may be effective for the treatment of PSC.

Analysis of Native Kidney Function Recovery With Renal Scintigraphy Following Simultaneous Liver-Kidney Transplantation.

BACKGROUND: Patients undergoing simultaneous liver-kidney transplantation (SLK) have impaired native kidney function. The relative contribution of allograft versus native function after SLK is unknown. We sought to characterize the return of native kidney function following SLK. METHODS: Following SLK, patients underwent technetium-99 m-mercaptoacetyltriglycine renal scintigraphy following serum creatinine nadir. Kidney contributions to estimated glomerular filtration rate (eGFR) were determined. Patients with native kidney function at serum creatinine nadir contributing eGFR ≥30 versus <30 mL/min/1.73 m 2 were compared, and multiple linear regression analysis for native eGFR improvement was performed. RESULTS: Thirty-one patients were included in this analysis. Average native kidney contribution to overall kidney function following SLK was 51.1% corresponding to native kidney eGFR of 44.5 mL/min/1.73 m 2 and native kidney function eGFR improvement of 30.3 mL/min/1.73 m 2 ( P < 0.001). Twenty-six of 31 patients had native kidney contribution of eGFR ≥30 mL/min/1.73 m 2 . Hepatorenal syndrome as the sole primary etiology of kidney dysfunction was 100% specific for native kidney eGFR >30 mL/min/1.73 m 2 and predicted native eGFR improvement ( P = 0.03). CONCLUSIONS: Substantial improvement in native kidney function follows SLK, and hepatorenal syndrome as the sole primary etiology of kidney dysfunction is predictive of improvement. Whether such patients are suitable for liver transplant followed by surveillance with option for subsequent kidney transplants requires investigation.

Hepatocellular carcinoma and solid pseudopapillary neoplasm of the pancreas complicating familial adenomatous polyposis: two cases and review of the literature.

Familial adenomatous polyposis (FAP) is characterized by colorectal polyposis and extracolonic tumors. Adenocarcinoma of the pancreas and hepatocellular carcinoma are rare in FAP. In this case series, we describe a mother and daughter with FAP who developed a hepatocellular carcinoma and solid pseudopapillary neoplasm of the pancreas, respectively.

Liver Transplant Outcomes in Patients With Postcapillary Pulmonary Hypertension.

Postcapillary pulmonary hypertension (PH) can be seen in cirrhosis. Research and treatment goals exist for patients with portopulmonary hypertension but not for postcapillary PH. The aim of this study was to investigate outcomes after liver transplant (LT) for patients with postcapillary PH. Methods: This was a retrospective cohort study of 1173 patients who underwent LT at our center between 2010 and 2020. Using a propensity score matched analysis followed by multivariable Cox modeling on matched patients, we compared post-LT survival between patients with and without postcapillary PH. We also compared several post-LT outcomes between patient with different types of PH. Results: Sixty-eight patients had PH, and 50 had postcapillary PH. The median age was 59 y and the sample was 54% male. There was no significant difference in mortality between patients with postcapillary PH and patients without PH (hazard ratio, 1.72; 95% confidence interval, 0.90-3.31; P = 0.10). There was no significant difference in survival between patients with any type of PH and those without PH. There was no significance difference in post-LT survival, acute kidney injury, or pulmonary edema between patients with different types of PH. Patients with postcapillary PH who survived had a higher cardiac output than those who died (11 L/min in patients who lived, as compared with 8 L/min in patients who died; P = 0.03). Conclusions: Postcapillary PH does not appear to convey a negative impact on post-LT survival. A higher cardiac output may be protective against mortality in patients with postcapillary PH.

Narrative review of portal vein thrombosis in cirrhosis: pathophysiology, diagnosis, and management from an interventional radiology perspective.

Objective: This paper examines the incidence, clinical presentation, and pathophysiology of portal vein thrombosis (PVT) in cirrhosis. Additionally, we have reviewed the literature regarding the current status of medical and interventional radiology management of PVT and have proposed a novel algorithm for the management given different clinical scenarios. Lastly two representative cases displaying endovascular treatment options are provided. Background: Portal vein thrombus in the setting of cirrhosis is an increasingly recognized clinical issue with debate on its pathophysiology, natural course, and optimal treatment. Approximately one-third of patients are asymptomatic, and detection of the thrombus is an incidental finding on imaging performed for other reasons. In 30% to 50% of patients, PVT resolves spontaneously. However, there is increased post-transplant mortality in patients with completely occlusive PVT, therefore effective early revascularization strategies are needed for patients with complete PVT who are expected to undergo liver transplant. Additionally, no consensus has been reached regarding PVT treatment in terms of timing and type of interventions as well as type and duration of anticoagulation. Methods: Computerized literature search as well as discussion with experts in the field. Conclusions: Management of PVT is complex, as many variables affect which treatments can be used. Anticoagulation appears to be the optimal first-line treatment in patients with acute PVT but without bleeding varices or mesenteric ischemia. Minimally invasive treatments include various methods of mechanical thrombectomy, chemical thrombolysis, and transjugular intrahepatic portosystemic shunt (TIPS) placement with or without variceal embolization. Definitive recommendations are difficult due to lack of high quality data and continued research is needed to evaluate the efficacy of different anticoagulants as well as the timing and use of various minimally invasive therapies in specific circumstances.

Recipient and Donor Outcomes After Living-Donor Liver Transplant for Unresectable Colorectal Liver Metastases.

Importance: Colorectal cancer is a leading cause of cancer-related death, and nearly 70% of patients with this cancer have unresectable colorectal cancer liver metastases (CRLMs). Compared with chemotherapy, liver transplant has been reported to improve survival in patients with CRLMs, but in North America, liver allograft shortages make the use of deceased-donor allografts for this indication problematic. Objective: To examine survival outcomes of living-donor liver transplant (LDLT) for unresectable, liver-confined CRLMs. Design, Setting, and Participants: This prospective cohort study included patients at 3 North American liver transplant centers with established LDLT programs, 2 in the US and 1 in Canada. Patients with liver-confined, unresectable CRLMs who had demonstrated sustained disease control on oncologic therapy met the inclusion criteria for LDLT. Patients included in this study underwent an LDLT between July 2017 and October 2020 and were followed up until May 1, 2021. Exposures: Living-donor liver transplant. Main Outcomes and Measures: Perioperative morbidity and mortality of treated patients and donors, assessed by univariate statistics, and 1.5-year Kaplan-Meier estimates of recurrence-free and overall survival for transplant recipients. Results: Of 91 evaluated patients, 10 (11%) underwent LDLT (6 [60%] male; median age, 45 years [range, 35-58 years]). Among the 10 living donors, 7 (70%) were male, and the median age was 40.5 years (range, 27-50 years). Kaplan-Meier estimates for recurrence-free and overall survival at 1.5 years after LDLT were 62% and 100%, respectively. Perioperative morbidity for both donors and recipients was consistent with established standards (Clavien-Dindo complications among recipients: 3 [10%] had none, 3 [30%] had grade II, and 4 [40%] had grade III; donors: 5 [50%] had none, 4 [40%] had grade I, and 1 had grade III). Conclusions and Relevance: This study's findings of recurrence-free and overall survival rates suggest that select patients with unresectable, liver-confined CRLMs may benefit from total hepatectomy and LDLT.

Cardiac considerations in liver transplantation.

Cardiovascular events have a major impact on overall outcomes after liver transplantation. Today's transplant patients are older than those in the past and therefore are more likely to have coexisting cardiac comorbidities. In addition, pathophysiologic effects of advanced liver disease on the circulatory system pose challenges in perioperative management. This review discusses important preoperative, intraoperative, and postoperative cardiac considerations in patients undergoing liver transplant.

Pazopanib for severe bleeding and transfusion-dependent anemia in hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is a rare angiogenic disorder causing chronic gastrointestinal bleeding, epistaxis, and severe anemia. Pazopanib is an oral multi-kinase angiogenesis inhibitor with promise to treat bleeding in HHT. We analyzed outcomes of HHT patients with the most severe bleeding causing RBC transfusion dependence treated on a predefined institutional pazopanib treatment pathway (with data collected retrospectively). The primary endpoint was achievement of transfusion independence. Secondary endpoints included hemoglobin, epistaxis severity score, RBC transfusion and iron infusion requirements, number of local hemostatic procedures, ferritin and transferrin saturation, compared using paired and repeated measures mean tests. Thirteen transfusion-dependent HHT patients received pazopanib [median (range) dose 150 (25-300) mg daily)] for a median of 22 months. All patients achieved transfusion independence. Compared with pretreatment, pazopanib increased mean hemoglobin by 4.8 (95% CI, 3.6-5.9) g/dL (7.8 vs. 12.7 g/dL, P < 0.0001) and decreased mean epistaxis severity score by 4.77 (3.11-6.44) points (7.20 vs. 2.43 points, P < 0.0001) after 12 months of treatment. Compared with 3 months of pretreatment, RBC transfusions decreased by 93% (median of 16.0 vs. 0.0 units, P < 0.0001) and elemental iron infusion decreased by 92% (median of 4500 vs. 0 mg, P = 0.005) during the first 3 months of treatment; improvements were maintained over time. Pazopanib was well-tolerated: hypertension, lymphocytopenia, and fatigue were the most common TEAEs. In conclusion, pazopanib was safe and effective to manage severe bleeding in HHT, liberating all patients from transfusion dependence and normalizing hematologic parameters at doses lower than used to treat malignancies. These findings require confirmation in a randomized trial.

The spectrum of histopathological findings after SVR to DAA for recurrent HCV infection in liver transplant recipients.

Sustained virological response (SVR) to the treatment of recurrent HCV in liver transplant recipients has excellent clinical outcomes; however, little is known about the effects on allograft histology. The study aimed to assess the histology of the allograft liver. In this single-center, retrospective cohort study, patients with recurrent hepatitis C (HCV) in allograft liver who were cured with antiviral therapy between 2010 and 2016 were identified. Biopsies were reviewed by two liver pathologists blinded to the treatment and SVR status. Paired analysis was performed to compare pre- and post-treatment histological features. Of the 62 patients analyzed, 22 patients received PEGylated interferon/ribavirin (IFN) therapy, while 40 patients received direct-acting antiviral agents (DAA). The mean age was 57 years, 24% were female, and 79% were Caucasian. RNA in situ hybridization testing for HCV and HEV was negative in all the tested patients. Significant reduction in the inflammatory grade of post-treatment biopsy specimens was noted in all subjects (n = 57; p < 0.001) and in the IFN group (n = 21; p = 0.001) but not in the DAA group (p = 0.093). Of all subjects, 21% had worsening stage, 31% had improvement, and 48% had no change in stage. Of the treatment groups, 27% in the IFN and 17% in the DAA groups had worsening stage; however, the results were not statistically significant in all subjects or by treatment modality. Persistent inflammatory infiltrates and fibrosis was noted in allograft tissue of patients cured with DAA. Significant improvement in grade was noted in the IFN group, without a significant change in stage.