Complex Abdominal Wall Reconstruction with Biologic Mesh for Ventral/Umbilical Hernias in Patients with Cirrhosis: Technique and Outcomes.

INTRODUCTION: Patients with cirrhosis undergoing non-liver transplant surgery have a higher risk or adverse events than those without cirrhosis. The main objectives of this study were to describe characteristics, outcomes, and outcome predictors of cirrhotic patients undergoing complex abdominal wall reconstruction (CAWR) with biologic mesh. MATERIALS AND METHODS: This study had retrospective and prospective components, including all cirrhotic patients at our center with CAWR for ventral/umbilical hernia repair with biologic mesh between December 2016 and November 2021. RESULTS: We studied 37 patients with cirrhosis. Their mean age was 57.2 years, and 64.9% were male. The median body mass index (BMI) was 28.1kg/m2. Ascites was present in 83.3% of patients. The other most common comorbidities were alcohol abuse (67.6%), hypertension (37.8%), and diabetes (24.3%). All complications in aggregate occurred in 11 patients (29.7%). Six patients (16.2%) underwent reoperation. Surgical site infections (SSIs) occurred in five patients (13.5%). Four deaths occurred within 90 days (11.2% cumulative mortality). By 120 days, there were five deaths (14.2% mortality, but none due to the operation). Seven predictor variables achieved an area under the receiver operating characteristic curve (AUROC) for SSI of 0.963, and two predictors yielded an AUROC of 0.825 for 120-day mortality. CONCLUSIONS: Our results suggest that CAWR for ventral/umbilical hernias among cirrhotic patients is feasible given a dedicated CAWR team in collaboration with transplant surgeons and a transplant hepatologist. The rates of adverse outcomes were low or at the midpoint of the range of the study-specific estimates.

Trends and outcomes of liver transplantation among older recipients in the United States.

BACKGROUND: The average age of recipients and donors of liver transplantation (LT) is increasing. Although there has been a change in the indications for LT over the years, data regarding the trends and outcomes of LT in the older population is limited. AIM: To assess the clinical characteristics, age-related trends, and outcomes of LT among the older population in the United States. METHODS: We analyzed data from the United Network for Organ Sharing database between 1987-2019. The sample was split into younger group (18-64 years old) and older group (≥ 65 years old). RESULTS: Between 1987-2019, 155758 LT were performed in the United States. During this period there was a rise in median age of the recipients and percentage of LT recipients who were older than 65 years increased (P < 0.05) with the highest incidence of LT among older population seen in 2019 (1920, 23%). Common primary etiologies of liver disease leading to LT in older patients when compared to the younger group, were non-alcoholic steatohepatitis (16.4% vs 5.9%), hepatocellular carcinoma (14.9% vs 6.9%), acute liver failure (2.5% vs 5.2%), hepatitis C cirrhosis (HCV) (19.2 % vs 25.6%) and acute alcoholic hepatitis (0.13% vs 0.35%). In older recipient group female sex and Asian race were higher, while model for end-stage liver disease (MELD) score and rates of preoperative mechanical ventilation were lower (P < 0.01). Median age of donor, female sex, body mass index (BMI), donor HCV positive status, and donor risk index (DRI) were significantly higher in older group (P < 0.01). In univariable analysis, there was no difference in post-transplant length of hospitalization, one-year, three-year and five-year graft survivals between the two groups. In multivariable Cox-Hazard regression analysis, older group had an increased risk of graft failure during the five-year post-transplant period (hazard ratio: 1.27, P < 0.001). Other risk factors for graft failure among recipients were male sex, African American race, re-transplantation, presence of diabetes, mechanical ventilation at the time of LT, higher MELD score, presence of portal vein thrombosis, HCV positive status, and higher DRI. CONCLUSION: While there is a higher risk of graft failure in older recipient population, age alone should not be a contraindication for LT. Careful selection of donors and recipients along with optimal management of risk factors during the postoperative period are necessary to maximize the transplant outcomes in this population.

Fatal acute respiratory distress syndrome caused by blastomycosis after recent orthotopic liver transplantation in a non-endemic area.

In blastomycosis, immunosuppression such as that following solid organ transplantation appears to be a risk factor for the development of overwhelming lung infection fulfilling criteria for the acute respiratory distress syndrome. Our transplant center, located outside traditional endemic areas for Blastomyces spp, experienced a case of fatal acute respiratory distress syndrome secondary to blastomycosis pneumonia in a recipient of recent orthotopic liver transplantation. The patient expired despite support with veno-venous extracorporeal membrane oxygenation.

Improving Liver Transplant Outcomes for Hepatitis C Virus Hepatocellular Carcinoma in the Direct-Acting Antiviral Therapy Era.

BACKGROUND: Direct-acting antiviral (DAA) therapy has transformed the outcomes of liver transplant (LT) with hepatitis C virus (HCV). This study aimed to analyze the effects of DAA treatment for HCV-associated hepatocellular carcinoma (HCC) in LT. METHODS: We included patients confirmed with HCC on explant, analyzed data from United Network for Organ Sharing, and defined the pre-DAA era (2012-2013) and DAA era (2014-2016). RESULTS: HCV-associated HCC cases totaled 4778 (62%) during the study period. In the DAA era, the median recipient age was older and the median days on the waiting list were longer. For the donor, median age, body mass index, and the rate of HCV significantly increased in the DAA era. In pathology, the median largest tumor size was significantly higher; however, the rate of completed tumor necrosis was significant higher in the DAA era. The 3-year graft/patient survival had significantly improved in the DAA era. In multivariable analysis, the DAA era (hazard ratio, 0.79; 95% confidence interval, 0.68-0.91) had significantly affected the 3-year graft survival. CONCLUSIONS: DAA has a significant beneficial effect on LT. In the DAA era, graft survival for HCV-associated HCC has been significantly improving.

Inferior Liver Transplant Outcomes during early COVID-19 pandemic in United States.

Background: : Since its declaration as a global pandemic on March11th 2020, COVID-19 has had a significant effect on solid-organ transplantation. The aim of this study was to analyze the impact of COVID-19 on Liver transplantation (LT) in United States. Methods: : We retrospectively analyzed the United Network for Organ Sharing database regarding characteristics of donors, adult-LT recipients, and transplant outcomes during early-COVID period (March 11- September 11, 2020) and compared them to pre-COVID period (March 11 - September 11, 2019). Results: : Overall, 4% fewer LTs were performed during early-COVID period (4107 vs 4277). Compared to pre-COVID period, transplants performed in early-COVID period were associated with: increase in alcoholic liver disease as most common primary diagnosis (1315 vs 1187, P< 0.01), higher MELD score in the recipients (25 vs 23, P<0.01), lower time on wait-list (52 vs 84 days, P<0.01), higher need for hemodialysis at transplant (9.4 vs 11.1%, P=0.012), longer distance from recipient hospital (131 vs 64 miles, P<0.01) and higher donor risk index (1.65 vs 1.55, P<0.01). Early-COVID period saw increase in rejection episodes before discharge (4.6 vs 3.4%, P=0.023) and lower 90-day graft/patient survival (90.2 vs 95.1 %, P<0.01; 92.2 vs 96.5 %, P<0.01). In multivariable cox-regression analysis, early-COVID period was the independent risk factor for graft failure at 90-days post-transplant (Hazard Ratio 1.77, P<0.01). Conclusions: : During early-COVID period in United States, overall LT decreased, alcoholic liver disease was primary diagnosis for LT, rate of rejection episodes before discharge was higher and 90-days post-transplant graft survival was lower.

Successful Management of COVID-19 Infection in 2 Early Post-Liver Transplant Recipients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has affected all facets of life and continues to cripple nations. COVID-19 has taken the lives of more than 2.1 million people worldwide, with a global mortality rate of 2.2%. Current COVID-19 treatment options include supportive respiratory care, parenteral corticosteroids, and remdesivir. Although COVID-19 is associated with increased risk of morbidity and mortality in patients with comorbidities, the vulnerability, clinical course, optimal management, and prognosis of COVID-19 infection in patients with organ transplants has not been well described in the literature. The treatment of COVID-19 differs based on the organ(s) transplanted. Preliminary data suggested that liver transplant patients with COVID-19 did not have higher mortality rates than untransplanted COVID-19 patients. Table 1 depicts a compiled list of current published data on COVID-19 liver transplant patients. Most of these studies included both recent and old liver transplant patients. No distinction was made for early liver transplant patients who contract COVID-19 within their posttransplant hospitalization course. This potential differentiation needs to be further explored. Here, we report 2 patients who underwent liver transplantation who acquired COVID-19 during their posttransplant recovery period in the hospital. CASE DESCRIPTIONS: Two patients who underwent liver transplant and contracted COVID-19 in the early posttransplant period and were treated with hydroxychloroquine, methylprednisolone, tocilizumab, and convalescent plasma. This article includes a description of their hospital course, including treatment and recovery. CONCLUSION: The management of post-liver transplant patients with COVID-19 infection is complicated. Strict exposure precaution practice after organ transplantation is highly recommended. Widespread vaccination will help with prevention, but there will continue to be patients who contract COVID-19. Therefore, continued research into appropriate treatments is still relevant and critical. A temporary dose reduction of immunosuppression and continued administration of low-dose methylprednisolone, remdesivir, monoclonal antibodies, and convalescent plasma might be helpful in the management and recovery of severe COVID-19 pneumonia in post-liver transplant patients. Future studies and experiences from posttransplant patients are warranted to better delineate the clinical features and optimal management of COVID-19 infection in liver transplant recipients.

Successful liver transplantation in a patient recovered from COVID-19.

Transplantation in potential candidates who have recently recovered from COVID-19 is a challenge with uncertainties regarding the diagnosis, multi-organ systemic involvement, prolonged viral shedding in immunocompromised patients, and optimal immunosuppression. A 42 year male with alcoholic hepatitis underwent a successful deceased donor liver transplantation 71 days after the initial diagnosis of COVID-19. At the time of transplant, he was SARS-CoV-2 PCR negative for 24 days and had a MELD score of 33. His post-operative course was complicated by acute rejection which responded to intense immune-suppression using T-cell depletion and steroids. He was discharged with normal end-organ function and no evidence of any active infection including COVID-19. Prospective organ transplant recipients who have recovered from COVID-19 can be considered for transplantation after careful pre-transplant evaluation, donor selection, and individualized risk-benefit analysis.

Seasonal Impacts on the Incidence of Esophageal Variceal Hemorrhage: A Nationwide Analysis across a Decade.

BACKGROUND/AIMS: Seasonal variation has previously been reported in relation to the incidence of non-variceal upper gastrointestinal bleeding; however, the impact of seasonal variation on variceal bleeding is not known. METHODS: We conducted a cross-sectional study using the Nationwide Inpatient Sample database from 2005 to 2014. International Classification of Diseases, Clinical Modification- 9th Revision codes were used to identify patients hospitalized with a primary or secondary diagnosis of esophageal variceal hemorrhage. The data were analyzed based on the month of hospitalization. Our primary aim was to assess seasonal variations in variceal bleeding-related hospitalizations. The secondary aims were to assess the impact of seasonal variation on outcomes in variceal bleeding including in-hospital mortality and healthcare resource utilization. RESULTS: A total of 348,958 patients hospitalized with esophageal variceal bleeding were included. The highest number of hospitalizations was reported in December (99.3/day) and the lowest was reported in June (90.8/day). In-hospital mortality was highest in January (11.5%) and lowest in June (9.8%). There was no significant difference in hospital length of stay or total hospitalization costs across all months in all years combined. CONCLUSION: There appears to be a seasonal variation in the incidence and mortality of variceal hemorrhage in the United States. December was the month with the highest number of daily hospitalizations while the nadir occurred in June.

Heart Transplantation for Hepatitis C Virus Non-Viremic Recipients From Hepatitis C Virus Viremic Donors.

Multiple strategies have been implemented to increase the donor pool to avoid transplant wait-list mortality. The approval of highly effective direct-acting antiviral regimens for the treatment of hepatitis C virus (HCV) has enabled expansion of the donor pool by allowing the transplantation of organs from HCV-viremic donors to HCV-negative recipients. Multiple centers have recently published data on outcomes of heart transplantation from HCV-viremic heart donors to HCV-negative recipients, with acceptable posttransplant outcomes. However, areas of uncertainty remain, particularly in the long-term risks of intentional HCV transmission, as well as the possibility that sustained virologic response may not be achieved. In this article, we review the literature illustrating both the risks and benefits of transplantation of organs from HCV-viremic donors to HCV-negative recipients. We also present the data collected at our institution regarding this special patient population.

Diagnosis, Treatment, and Management of Orthotopic Liver Transplant Candidates With Portopulmonary Hypertension.

Portopulmonary hypertension (POPH) is seen in 5-8% of orthotopic liver transplantation (OLT) candidates and has significant implications for clinical outcomes. POPH is characterized by vasoconstriction and remodeling of the pulmonary vasculature. It is exacerbated by the hyperdynamic circulation that is common in advanced liver disease. Screening all OLT candidates with transthoracic echocardiography to assess pulmonary pressures and right ventricular function is crucial, as clinical symptoms alone are not reliable. Any significant right ventricular dysfunction or dilatation along with an elevation in estimated pulmonary pressures usually triggers further investigation with right heart catheterization. The mainstays of therapy of POPH are vasodilators that are used in pulmonary arterial hypertension. They include monotherapy or combination therapy with prostanoids, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors/guanylate cyclase stimulator. Limited evidence from smaller studies and case series suggests that a timely diagnosis of POPH and the early initiation of treatment improve patient outcomes, whether or not OLT is ultimately undertaken. Given the historically high perioperative mortality rate of more than 35%, POPH remains a contraindication to OLT unless it is treated and responsive to vasodilator therapy. We review the current literature and International Liver Transplant Society practice guidelines (2016) for the latest in understanding POPH, its pathogenesis, diagnosis, modern pharmacological treatment, indications, and contraindications for OLT, as well as perioperative management.

Impact of Cardiovascular Risk Factors on Long-Term Mortality After Liver Transplantation.

Immunosuppression with calcineurin inhibitors has contributed to an increased prevalence of hypertension, diabetes, and hypercholesterolemia in patients receiving liver transplantation. This study evaluated the prevalence of cardiovascular risk factors, their management, and long-term mortality after liver transplantation. Medical records were reviewed in 333 adult patients who underwent orthotopic liver transplantation. Data were collected on medical diagnoses before and after transplantation, medication use, and on long-term mortality. The 333 patients in the study included 223 men and 110 women, mean age 59 ± 10 years. The mean follow-up was 50 ± 28 months. After transplantation, there was a high prevalence of hypertension (67%), hypercholesterolemia (46%), diabetes mellitus (42%), and chronic kidney disease (45%). Out of 333 patients in the study, 96 patients (29%) died during follow-up. Stepwise logistic regression was performed to identify the risk factors that might influence long-term mortality outcomes. Based on pretransplant characteristics, positive independent risk factors that increased mortality were age at transplant and hepatitis C. After transplantation, positive predictive factors were diabetes mellitus and cancer. A negative predictive risk factor for mortality was hypercholesterolemia. Analysis of medication after transplantation showed that positive predictive factors were the use of insulin, steroids, and antibiotics. Negative predictors for mortality were tacrolimus and mycophenolate. Our data suggest that diabetes mellitus and hepatitis C play an important role in worsening posttransplant mortality.

The management of eosinophilic gastroenteritis.

Eosinophilic gastroenteritis (EG) is a rare disorder characterized by eosinophilic infiltration of the gastrointestinal tract. No medication at present is approved by the Food and drug administration of United States for the treatment of EG. The rarity of the disease limits our experience with the different management options. It also limits the ability to conduct randomized controlled trials that could clearly delineate the efficacy of new therapeutic agents. This review assesses the various management options that have been tried on patients with EG.

Timing of hepatic artery reperfusion and biliary strictures in liver transplantation.

During orthotopic liver transplantation (OLT), biliary tract perfusion occurs with hepatic artery reperfusion (HARP), commonly performed after the portal vein reperfusion (PVRP). We examined whether the average time interval between PVRP and HARP impacted on postoperative biliary strictures occurrence. Patients undergoing OLT from 2007 to 2009 were included if they were ≥18 years old, had survived 3 months postoperatively, and had data for PVRP and HARP. Patients receiving allografts from DCD donors were excluded. Patients were followed for 6 months post-OLT. Seventy-five patients met the study inclusion criteria. Of these, 10 patients had a biliary stricture. There was no statistical difference between those with and without biliary stricture in age, gender, etiology, MELD score, graft survival, and time interval between PVRP and HARP. Ninety percent of patients with biliary stricture had a PVRP-HARP time interval >30 minutes, as opposed to 77% of patients without biliary stricture. However, this was not statistically significant. The cold ischemia time was significantly different between the two groups. Time interval for HARP after PVRP did not appear to affect the development of biliary strictures. However, 30 minutes may be suggested as a critical time after which there is an increase in biliary stricture occurrence.

Can we direct organ allocation based on predicted outcome? Hepatocellular carcinoma outside of UCSF criteria or retransplant?

BACKGROUND: In this study, we ask between patients with graft failure listed for retransplant and patients with hepatocellular carcinoma (HCC) outside of UCSF criteria, who has the greater survival benefit with transplantation? METHODS: This is a retrospective analysis, of liver transplant (LT) patients, done between February 2002 and December 2009 at our center. Patients were included in the "extended HCC" group if their tumor was pathologically beyond UCSF criteria at LT and in the "redo" group if they underwent LT for graft failure occurring more than 3 months after the initial LT. Extended criteria donors (ECDs) were defined as donors above 70 years old, DCD, serology positive for HCV, and split grafts. RESULTS: There were 25 redos and 37 extended HCC patients. Use of ECDs or high donor risk index organs was associated with poor outcome in both groups (P = 0.005). Overall, the extended HCC population had a much better survival than redos, both at 1 and 3 years. CONCLUSION: These two very different but high risk patient populations have very different survival rates. At a time where regulatory agencies demand more and more with regards to transplant outcomes, we think the transplant community has to reflect on whether allocation justice and fair access to transplant are respected if we start allocating organs based on outcomes.

Stereotactic body radiation therapy in hepatocellular carcinoma and cirrhosis: evaluation of radiological and pathological response.

BACKGROUND: Loco-regional therapies for cirrhotic patients with hepatocellular carcinoma (HCC) who are awaiting liver transplantation (OLT) attempt to prevent tumor progression. However, there is limited data regarding the efficacy of stereotactic body radiation therapy (SBRT) as loco-regional treatment. METHODS: From 2006 to 2009, 27 HCC patients (AJCC I, II) listed for OLT underwent SBRT. Thirty-nine lesions were treated and 27 assessed radiologically. Seventeen patients had OLT, liver explants were analyzed and 22 lesions underwent pathological evaluation. RESULTS: In a cumulative analysis of all imaging, 30% had complete response, 7% had partial response, 56% were stable, and 7% had progression of disease. Of the 22 pathologically evaluated lesions, 37% were responders: 14% with complete response, 23% with partial response, and 63% with no response. Side effects from SBRT were recorded in three patients, which included nausea in two and liver decompensation in one. CONCLUSION: SBRT achieves total or partial radiological response in 37% of patients and total or partial pathological response in 37% of patients with early HCC in the setting of cirrhosis. SBRT may be a safe and effective alternative for local tumor control in patients with HCC and cirrhosis awaiting OLT.

Liver transplantation for hepatocellular carcinoma: defining the impact of using extended criteria liver allografts.

BACKGROUND: This series compares outcomes of patients with hepatocellular carcinoma (HCC) listed for orthotopic liver transplantation (OLT) within and outside Milan criteria, and determines the impact of extended criteria liver allografts (ECD). METHODS: Records of patients listed for liver transplantation at a single center from 1998 to 2007 were reviewed retrospectively. RESULTS: Ninety-seven HCC patients were listed for OLT, 77 underwent transplantation; 47 received ECDs and 30 standard organs. ECDs were more frequently allocated to outside Milan recipients. Wait time for OLT was shorter for outside Milan patients (4 vs. 7 months P=0.04) but hazard rate of dropout was higher (26%, 46%, and 73% at 6,12, and 24 months compared with 2%, 14%, and 60% P<0.01). Tumor size more than 3 cm (P=0.02) and model for end-stage liver disease score at listing more than 11 (P=0.04) were independent predictors of dropout. Hazard rate of OLT was similar within and outside Milan (61%, 80%, and 90% at 6, 12, and 24 months vs. 60%, 70%, and 86% P=0.38). Post-OLT survival at 1 year and 4 years were 88% and 63% within Milan compared with 79% and 62% among Milan out recipients (P=0.95). No significant post-OLT survival predictor was found. CONCLUSION: The use of ECD organs provided patients with HCCs outside Milan criteria access to liver transplant at a rate comparable to patients within Milan and model for end-stage liver disease HCC priority. Similar patient survival post-OLT can be achieved using standard or ECD organs. The higher risk of drop out in patients outside Milan, and even within Milan, with tumors more than 3 cm justifies the use of ECD organs for timely transplantation.

Surgical dilemma: liver resection or liver transplantation for hepatocellular carcinoma and cirrhosis. Intention-to-treat analysis in patients within and outwith Milan criteria.

BACKGROUND: The optimal role of surgery in the management of hepatocellular carcinoma (HCC) is in continuous evolution. OBJECTIVE: The objective of this study was to analyse survival rates after liver resection (LR) and orthotopic liver transplantation (OLT) for HCC within and outwith Milan criteria in an intention-to-treat analysis. METHODS: During 1997-2007, 179 patients with cirrhosis and HCC either underwent LR (n= 60) or were listed for OLT (n= 119). Patients with incidental HCC after OLT, preoperative macrovascular invasion before LR, non-cirrhosis and Child-Pugh class C cirrhosis prior to OLT were eliminated, leaving 51 patients primarily treated with LR and 106 patients listed for primary OLT (84 of whom were transplanted) to be included in this analysis. A total of 66 patients fell outwith Milan criteria (26 LR, 40 OLT) and 91 continued to meet Milan criteria (25 LR, 66 OLT). RESULTS: The median length of follow-up was 26 months. The mean waiting time for OLT was 7 months. During that time, 21 patients were removed from the waiting list as a result of tumour progression. Probabilities of dropout were 2% and 13% at 6 and 12 months, respectively, for patients within Milan criteria, and 34% and 57% at 6 and 12 months, respectively, for patients outwith Milan criteria (P < 0.01). Tumour size >3 cm was found to be the independent factor associated with dropout (hazard ratio [HR] 6.0). Postoperative survival was slightly higher after OLT, but this was not statistically significant (64% for OLT vs. 57% for LR). Overall survival from time of listing for OLT or LR did not differ between the two groups (P= 0.9); for patients within Milan criteria, 1- and 4-year survival rates after LR were 88% and 61%, respectively, compared with 92% and 62%, respectively, after OLT (P= 0.54). For patients outwith Milan criteria, 1- and 4-year survival rates after LR were 69% and 54%, respectively, compared with 65% and 40%, respectively, after OLT (P= 0.42). Tumour size >3 cm was again found to be an independent factor for poor outcome (HR 2.4) in the intention-to-treat analysis. CONCLUSIONS: Survival rates for patients with HCC are similar in LR and OLT. Liver resection can potentially decrease the dropout rate and serve as a bridge for future salvage LT, particularly in patients with tumours >3 cm.