Saro Khemichian

Combined liver-kidney transplantation is preferable to liver transplant alone for cirrhotic patients with renal failure.

Background The role of combined liver-kidney transplantation (CLKT) for cirrhotic patients with renal failure (RF) is controversial. Since the model for end-stage liver disease era, there has been a rise in the number of CLKT. Using the Organ Procurement Transplant Network/United Network for Organ Sharing database, this study was undertaken to compare outcomes of cirrhotic patients with RF who received either liver transplant alone (LTA) or CLKT between 2002 and 2008. Methods Analysis was limited to cirrhotic patients 18 years old or older, with serum creatinine level 2.5 mg/dL or higher at the time of orthotopic liver transplantation (OLT) or who received dialysis at least twice during the week before OLT. Patients who received CLKT were categorized based on the cause of their underlying RF. Results Overall liver allograft and patient survival rates of LTA patients were significantly lower compared with CLKT patients (P<0.001). CLKT patients with hepatorenal syndrome showed significantly higher patient and liver allograft survival rates. Liver allograft survival was superior among CLKT patients irrespective of whether they received dialysis. Prevalence of posttransplantation RF was higher for LTA patients at 6 months and 3 years of follow-up (P<0.001). LTA was a significant risk factor both for graft loss and mortality. Recipient hepatitis C virus seropositivity, donor age, donor cause of death, and life support at the time of OLT were also risk factors for graft loss and death. Conclusions Cirrhotic patients with RF, in particular with hepatorenal syndrome, CLKT is preferable to LTA because it improves liver allograft and patient survival.

Randomized trial of 1-week versus 2-week intervals for endoscopic ligation in the treatment of patients with esophageal variceal bleeding.

The appropriate interval between ligation sessions for treatment of esophageal variceal bleeding is uncertain. The optimal interval would provide variceal eradication as rapidly as possible to lessen early rebleeding while minimizing ligation‐induced adverse events. We randomly assigned patients hospitalized with acute esophageal variceal bleeding who had successful ligation at presentation to repeat ligation at 1‐week or 2‐week intervals. Beta‐blocker therapy was also prescribed. Ligation was performed at the assigned interval until varices were eradicated and then at 3 and 9 months after eradication. The primary endpoint was the proportion of patients with variceal eradication at 4 weeks. Four‐week variceal eradication occurred more often in the 1‐week than in the 2‐week group: 37/45 (82%) versus 23/45 (51%); difference = 31%, 95% confidence interval 12%‐48%. Eradication occurred more rapidly in the 1‐week group (18.1 versus 30.8 days, difference = −12.7 days, 95% confidence interval −20.0 to −5.4 days). The mean number of endoscopies to achieve eradication or to the last endoscopy in those not achieving eradication was comparable in the 1‐week and 2‐week groups (2.3 versus 2.1), with the mean number of postponed ligation sessions 0.3 versus 0.1 (difference = 0.2, 95% confidence interval −0.02 to 0.4). Rebleeding at 4 weeks (4% versus 4%) and 8 weeks (11% versus 9%), dysphagia/odynophagia/chest pain (9% versus 2%), strictures (0% versus 0%), and mortality (7% versus 7%) were similar with 1‐week and 2‐week intervals. Conclusion: One‐week ligation intervals led to more rapid eradication than 2‐week intervals without an increase in complications or number of endoscopies and without a reduction in rebleeding or other clinical outcomes; the decision regarding ligation intervals may be individualized based on patient and physician preferences and local logistics and resources. (Hepatology 2016;64:549‐555)

Sofosbuvir and Simeprevir Therapy for Recurrent Hepatitis C Infection After Liver Transplantation.

Introduction Antiviral therapy for recurrent hepatitis C in liver transplant recipients has been associated with low efficacy, poor tolerability, and drug-drug interactions. Recent approval of various hepatitis C direct-acting antivirals has resulted in improvement of these parameters. We evaluated the efficacy and safety of 12 week all-oral interferon- and ribavirin-free therapy with sofosbuvir and simeprevir. Methods Thirty-two genotype 1 liver transplant recipients with recurrent hepatitis C infection were retrospectively analyzed. All patients received 12 weeks of sofosbuvir 400 mg and simeprevir 150 mg orally daily. The primary endpoint was sustained virologic response 12 weeks after treatment. Results Sustained virologic response 12 weeks after treatment was achieved in 30 of 32 (94%; 95% confidence interval, 79-99%) patients. All patients enjoyed on-treatment virological response. Both patients who relapsed were cirrhotic, previously treated with Q80K polymorphism. Significant improvements in alkaline phosphatase, albumin, alanine aminotransferase levels, and platelets were seen at 12-week post therapy. Treatment was well tolerated. No grade 3 or 4 adverse events were noted. Headache and fatigue were the most common complaints. Conclusion Combination of sofosbuvir and simeprevir for 12 weeks resulted in 94% sustained virological response-12 rates in patients with hepatitis C genotype 1 and was well tolerated.

Pulmonary vein leiomyosarcoma

A 54-year-old man presented with a 1-day history of left upper extremity weakness and numbness. Physical examination showed decreased breath sounds in the right lung field and a cold left upper extremity with absent distal pulses. The patient’s chest radiograph showed a large opacity in the right upper lobe and a computed tomography scan confirmed a large right upper lobe lung mass, causing compression of the rightmain bronchus and neartotal occlusion of the right pulmonary artery (Fig. 1a). The patient underwent emergent angiography, which showed occlusion of the left axillary artery and reconstitution of flow was established. A transthoracic (Fig. 1b) and a subsequent transoesophageal echocardiogram showed a left atrial multilobular mass arising from the right pulmonary vein and prolapsing through the mitral valve in diastole. Right extrapleural pneumonectomy and resection of the left atrial cuff (including the mitral valve) was carried out (Fig. 1c). Pathological examination of the specimen showed a 19 11 8.5 cm poorly differentiated, highgrade leiomyosarcoma. The tumour showed areas of

Daclatasvir and sofosbuvir treatment of decompensated liver disease or post‐liver transplant hepatitis C virus recurrence in patients with advanced liver disease/cirrhosis in a real‐world cohort

We report the findings of an early access program providing treatment for chronic hepatitis C virus infection (any genotype) with daclatasvir and sofosbuvir with/without ribavirin to patients with Child‐Pugh class C cirrhosis or prior liver transplant recipients with recurrent hepatitis C virus infection and advanced fibrosis/cirrhosis. Patients had <12‐month life expectancies per the local investigator. Patients received daclatasvir 60 mg and sofosbuvir 400 mg once daily, with/without ribavirin, for 24 weeks. Sustained virologic response (SVR) at posttreatment week 12 (SVR12) was measured. Assessments adhered to local standards. One patient (prior Child‐Pugh class C who improved to class B) enrolled by exemption was included in the overall data but not the class C cohort efficacy/safety data. Of the 77 treated patients, including 62 liver transplant recipients (genotype 1, n = 43, 69%; genotype 3, n = 16, 26%) and 14 patients with Child‐Pugh class C cirrhosis (genotype 1, n = 4, 29%; genotype 3, n = 10, 71%), 63 (82%) completed treatment. SVR12 rates by modified intention‐to‐treat analysis (excluding nonvirologic failures lost to follow‐up and withdrawal [consent/no reason]) in the overall, liver transplant, and Child‐Pugh class C cohorts were 84% (n = 64/76), 90% (n = 56/62), and 62% (n = 8/13), respectively. Rates increased to 96% (n = 64/67), 97% (n = 56/58), and 89% (n = 8/9), respectively, in patients with available virologic data (including early discontinuations); 22/23 patients with genotype 3 (96%) achieved SVR12. Single cases of virologic nonresponse and relapse (both in liver transplant recipients with genotype 1) and viral breakthrough (Child‐Pugh class C; genotype 3) occurred. Six patients died, 10 had adverse events leading to discontinuation, and 30 experienced serious adverse events. Conclusion: Daclatasvir plus sofosbuvir, with/without ribavirin, provided high SVR12 rates and was generally well tolerated in patients with life‐threatening disease and high unmet needs. (Hepatology Communications 2018;2:354‐363)

Comparison of Demographic and Clinical Characteristics of Hispanic and Asian Chronic Hepatitis B Patients in Southern California.

Objectives: There are few data regarding the clinical and serologic features of chronic hepatitis B (CHB) infection among Hispanics in the United States. The aims of this study were to compare and contrast clinical characteristics of Hispanic and Asian CHB patients. Methods: Demographic, clinical, and laboratory data were collected from Hispanic and Asian CHB patients seen between January 2013 and May 2014 at Los Angeles County Hepatitis Clinic. Results: A total of 55 Hispanic and 342 Asian CHB patients were identified. Almost all were foreign-born. Compared with Asians, Hispanics were more likely to report heterosexual transmission (P<0.0001) and blood transfusion history (P<0.0001) as risk factors. Overall, 31% of Hispanics had HBV>2000 IU/mL compared with 54% of Asians (P=0.004). Significantly more Asian HBeAg-negative/anti-HBe-positive CHB patients had high HBV DNA levels (>2000 IU/mL) with elevated ALT compared with Hispanic patients (P=0.04). Compared with Asians, Hispanic CHB patients were more likely to have elevated ALT and low HBV DNA levels (P=0.001). Among CHB patients who received antiviral therapy, response was comparable among Hispanics and Asians. There were no Hispanic CHB patients who experienced spontaneous reactivation or developed hepatocellular carcinoma. Conclusions: There were important differences in the clinical, demographic, and serologic characteristics between Hispanic and Asian CHB. Response rate to antiviral therapy was comparable. Further studies of Hispanic CHB patients in the United States are warranted.