Maha Boktour

Hepatocellular carcinoma: a review

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is a leading cause of cancer-related death worldwide. In the United States, HCC is the ninth leading cause of cancer deaths. Despite advances in prevention techniques, screening, and new technologies in both diagnosis and treatment, incidence and mortality continue to rise. Cirrhosis remains the most important risk factor for the development of HCC regardless of etiology. Hepatitis B and C are independent risk factors for the development of cirrhosis. Alcohol consumption remains an important additional risk factor in the United States as alcohol abuse is five times higher than hepatitis C. Diagnosis is confirmed without pathologic confirmation. Screening includes both radiologic tests, such as ultrasound, computerized tomography, and magnetic resonance imaging, and serological markers such as α-fetoprotein at 6-month intervals. Multiple treatment modalities exist; however, only orthotopic liver transplantation (OLT) or surgical resection is curative. OLT is available for patients who meet or are downstaged into the Milan or University of San Francisco criteria. Additional treatment modalities include transarterial chemoembolization, radiofrequency ablation, microwave ablation, percutaneous ethanol injection, cryoablation, radiation therapy, systemic chemotherapy, and molecularly targeted therapies. Selection of a treatment modality is based on tumor size, location, extrahepatic spread, and underlying liver function. HCC is an aggressive cancer that occurs in the setting of cirrhosis and commonly presents in advanced stages. HCC can be prevented if there are appropriate measures taken, including hepatitis B virus vaccination, universal screening of blood products, use of safe injection practices, treatment and education of alcoholics and intravenous drug users, and initiation of antiviral therapy. Continued improvement in both surgical and nonsurgical approaches has demonstrated significant benefits in overall survival. While OLT remains the only curative surgical procedure, the shortage of available organs precludes this therapy for many patients with HCC.

Combined lung and liver transplantation: Analysis of a single-center experience

Patients with end‐stage lung disease complicated by cirrhosis are not expected to survive lung transplantation alone. Such patients are potential candidates for combined lung‐liver transplantation (CLLT), however few reports document the indications and outcomes after CLLT. This is a review of a large single‐center CLLT series. Eight consecutive CLLT performed during 2009‐2012 were retrospectively reviewed. One patient received a third simultaneous heart transplant. Mean age was 42.5u2009±u200911.5 years. Pulmonary indications included cystic fibrosis (CF) (nu2009=u20093), idiopathic pulmonary fibrosis (nu2009=u20092), α1‐antitrypsin deficiency (AATD) (nu2009=u20091) and pulmonary hypertension (nu2009=u20092). Liver indications were CF (nu2009=u20093), hepatitis C (nu2009=u20092), AATD (nu2009=u20091), cryptogenic (nu2009=u20091), and cardiac/congestive (nu2009=u20091). Urgency was reflected by median lung allocation score (LAS) of 41 (36.0‐89.0) and median predicted FEV1 of 25.7%. Median donor age was 25 (20‐58) years with median cold ischemia times of 147 minutes and 6.1 hours for lung and liver, respectively. Overall patient survival at 30 days, 90 days and 1 year was 87.5%, 75.0% and 71.4% respectively. One patient had evidence of acute lung rejection, and no patients had liver allograft rejection. Early postoperative mortalities (90 days) were caused by sepsis in 2 recipients who exhibited the highest LAS of 69.9 and 89.0. The remaining recipients had a median LAS of 39.5 and 100% survival at 1‐year. Median length of stay was 25 days (7‐181). Complications requiring operative intervention included bile duct ischemia (nu2009=u20091) and bile leak (nu2009=u20091), ischemia of the bronchial anastomosis (nu2009=u20091), and necrotizing pancreatitis with duodenal perforation (nu2009=u20091). This series reflects a large single‐center CLLT experience. Sepsis is the most common cause of death. The procedure should be considered for candidates with LASu2009<u200950. Liver Transpl 20:46–53, 2014.

Combined lung and liver transplantation

Patients with end‐stage lung disease complicated by cirrhosis are not expected to survive lung transplantation alone. Such patients are potential candidates for combined lung‐liver transplantation (CLLT), however few reports document the indications and outcomes after CLLT. This is a review of a large single‐center CLLT series. Eight consecutive CLLT performed during 2009‐2012 were retrospectively reviewed. One patient received a third simultaneous heart transplant. Mean age was 42.5u2009±u200911.5 years. Pulmonary indications included cystic fibrosis (CF) (nu2009=u20093), idiopathic pulmonary fibrosis (nu2009=u20092), α1‐antitrypsin deficiency (AATD) (nu2009=u20091) and pulmonary hypertension (nu2009=u20092). Liver indications were CF (nu2009=u20093), hepatitis C (nu2009=u20092), AATD (nu2009=u20091), cryptogenic (nu2009=u20091), and cardiac/congestive (nu2009=u20091). Urgency was reflected by median lung allocation score (LAS) of 41 (36.0‐89.0) and median predicted FEV1 of 25.7%. Median donor age was 25 (20‐58) years with median cold ischemia times of 147 minutes and 6.1 hours for lung and liver, respectively. Overall patient survival at 30 days, 90 days and 1 year was 87.5%, 75.0% and 71.4% respectively. One patient had evidence of acute lung rejection, and no patients had liver allograft rejection. Early postoperative mortalities (90 days) were caused by sepsis in 2 recipients who exhibited the highest LAS of 69.9 and 89.0. The remaining recipients had a median LAS of 39.5 and 100% survival at 1‐year. Median length of stay was 25 days (7‐181). Complications requiring operative intervention included bile duct ischemia (nu2009=u20091) and bile leak (nu2009=u20091), ischemia of the bronchial anastomosis (nu2009=u20091), and necrotizing pancreatitis with duodenal perforation (nu2009=u20091). This series reflects a large single‐center CLLT experience. Sepsis is the most common cause of death. The procedure should be considered for candidates with LASu2009<u200950. Liver Transpl 20:46–53, 2014.

Pre-transplant utilization of sorafenib is not associated with increased complications after liver transplantation

Hepatocellular carcinoma (HCC) is increasing in incidence, resulting in approximately 35% of orthotopic liver transplantation (OLT) performed each year. Sorafenib (SOR) is a multi‐kinase inhibitor that is approved for the treatment of unresectable HCC. Concerns have been raised regarding the safety of SOR in patients undergoing major surgery. We retrospectively reviewed 79 consecutive patients with HCC receiving OLT. Patient data were compared for those who received SOR pre‐OLT with those who did not. SOR was continued until time of transplant. During this time period, 15 patients received SOR pre‐OLT and 64 did not. The two groups were similar with regards to demographic and clinical data. SOR patients were more likely to have larger tumors, more tumor nodules, and be outside of Milan criteria. The rate of recurrence of HCC was not different between the groups (13% in SOR group, 11% in no‐SOR group). Surgical complications were not increased in patients receiving SOR prior to OLT. Survival rate was also similar between the two groups (median follow‐up 19.7 months). In this small cohort of patients, use of SOR prior to liver transplantation does not confer an increased risk of surgical complications, even when continued until the day of surgery.

Conventional TACE and drug-eluting bead TACE as locoregional therapy before orthotopic liver transplantation: comparison of explant pathologic response.

Background Hepatocellular carcinoma (HCC) is responsible for significant morbidity and mortality worldwide. Despite its increasing incidence, significant progress has been made in the clinical management of HCC. Transarterial chemoembolization (cTACE) has been shown to improve survival in patients with unresectable HCC; it has also been successfully used as bridging therapy before orthotopic liver transplantation (OLT) in efforts to delay tumor growth or to downstage HCC. TACE with drug-eluting beads (DEB-TACE), a novel drug delivery system that produces a slow and sustained release of chemotherapeutic agent, has recently been shown to have similar efficacy to conventional TACE (cTACE); it also exhibits fewer adverse effects resulting from reduced systemic drug concentrations. To date, the pathologic response rate to cTACE compared with DEB-TACE in patients undergoing OLT has not been well described. Methods A total of 111 consecutive patients with HCC who underwent cTACE (n=76) or DEB-TACE (n=35) before OLT at a single center between January 2005 and December 2010 were evaluated. Results Complete necrosis was achieved in 50.9% and 57.1% of cTACE and DEB-TACE patients, respectively; at least 50% necrosis was evident in approximately three fourths of patients in both groups. Rates of necrosis and tumor recurrence did not differ between groups. Dropout from the transplant list was equal in both groups. Conclusions Either modality is an acceptable treatment to achieve tumor control for patients awaiting OLT and can be expected to result in excellent necrosis rates in the majority of patients.

Efficacy and cost‐effectiveness of voriconazole prophylaxis for prevention of invasive aspergillosis in high‐risk liver transplant recipients

Aspergillus infection remains a significant and deadly complication after liver transplantation (LT). We sought to determine whether the antifungal prophylactic use of voriconazole reduces the incidence of invasive aspergillosis (IA) in high‐risk LT recipients without prohibitively increasing cost. During the study era (April 2008 to April 2014), 339 deceased donor LTs were performed. Of those patients, 174 high‐risk recipients were administered antifungal prophylaxis with voriconazole. The median biological Model for End‐Stage Liver Disease score at the time of LT was 33 (range, 18‐49) with 56% requiring continuous renal replacement therapy and 50% requiring ventilatory support immediately before transplantation. Diagnosis of IA was stratified as proven, probable, or possible according to previously published definitions. No IA was documented in patients receiving voriconazole prophylaxis. At 90 days after LT, the institutional cost of prophylaxis was

The Impact of Share 35 Policy on Patient Survival in Patients Undergoing Liver Transplantation With Gender- and Race-Mismatched Donors: An Analysis of the United Network for Organ Sharing Registry

5324 or 5.6% of the predicted cost associated with post‐LT aspergillosis. There was no documentation of resistant strains isolated from any recipient who received voriconazole. In conclusion, these data suggest that voriconazole prophylaxis is safe, clinically effective, and cost‐effective in high‐risk LT recipients. Liver Transpl 22:163–170, 2016.

Su1483 AST Platelet Ratio (APRI Scores) Correlates With Hepatoportal Pressure Measurements

Introduction: The United Network for Organ Sharing (UNOS) instituted the Share 35 policy in June 2013 in order to reduce death on liver transplant waitlist. The effect of this policy on patient survival among patients with gender- and race-mismatched donors has not been examined. Research Question: To assess the impact of Share 35 policy on posttransplantation patient survival among patients with end-stage liver disease (ESLD) transplanted with gender- and race-mismatched donors. Design: A total of 16 467 adult patients with ESLD who underwent liver transplantation between 2012 and 2015 were identified from UNOS. An overall Cox proportional hazards model adjusting for demographic, clinical, and geographic factors and separate models with a dummy variable of pre- and post-Share 35 periods as well as its interaction with other factors were performed to model the effect of gender and race mismatch on posttransplantation patient survival and to compare the patient survival differences between the first 18 months of Share 35 policy to an equivalent time period before. Results: Comparison of the pre- and post-Share 35 periods did not show significant changes in the numbers of gender- and race-mismatched transplants, or the risk of death for gender-mismatched recipients. However, black recipients with Hispanic donors (hazard ratio: 0.51, 95% confidence interval, 0.29-0.90) had significantly increased patient survival after Share 35 policy took effect. Conclusion: The Share 35 policy had a moderate impact on posttransplantation patient survival among recipients with racially mismatched donors according to the first 18-month experience. Future research is recommended to explore long-term transplantation.

Post-Transplant Length of Stay and Discharge Disposition Is Impacted By Pre-Transplant Location But Not Transplant Survival

Background and aims: The presence of fibrosis on liver biopsy is a prognostic tool for management of liver disease. AST/PLT ratio index (APRI) has been shown to be a useful tool to non-invasively predict fibrosis. Hepatoportal pressure gradient (HPPG) measurements have been used as an instrument to predict complications from cirrhosis. To the best of our knowledge, there has been no prior study comparing HPPG measurements to APRI scores. We aimed to elucidate the relationship between APRI scores and HPPG measurements. Methods: We retrospectively reviewed liver biopsy results of patients (n = 125) between 2009 and 2011. Patients who had no coinciding liver function tests within one week of liver biopsy (n=25) and those without coinciding measurements of hepatic venous pressures (n =58) were also excluded. A total of 67 patients were analyzed. The AST platelet ratio (APRI) were obtained and compared to HPPG =10 (n=13) mmHg. Results: Median age was 60 (range 30-80) and 38 (59%) were male. Hepatitis C was present in 35 (52%) of patients, 13 of whom had undergone liver transplantation with recurrence of hepatitis C. Table 1 shows the etiology of liver diagnoses. Mean APRI score was 0.52 + 0.51 in patients who had HPPG =10, p =0.04. Pearsons correlation between APRI score and HPPG measurement was 0.27, p = 0.03. Conclusions: AST/platelet ratio index (APRI) has been shown to be an important noninvasive diagnostic marker for fibrosis. There is a significant relationship between APRI scores and the severity of hepatoportal pressures. Etiology of liver disease diagnoses in our patients