Safety and Effectiveness Using 8 Weeks of Glecaprevir/Pibrentasvir in HCV-Infected Treatment-Naïve Patients with Compensated Cirrhosis: The CREST Study.

INTRODUCTION: In clinical trials with hepatitis C virus-infected treatment-naïve (TN) patients with compensated cirrhosis (CC), glecaprevir/pibrentasvir (G/P), a fixed-dose, once-daily, pangenotypic regimen, has demonstrated sustained virologic response at posttreatment Week 12 (SVR12) > 95%. We evaluated the real-world safety and effectiveness of 8-week G/P therapy in TN patients with CC, including certain subgroups of interest. METHODS: The CREST study is a real-world, noninterventional, multicenter study retrospectively assessing data from Canada, Germany, Israel, Italy, and Spain. The full analysis set (FAS) designated all patients in the study; the modified analysis set (MAS) excluded patients who discontinued G/P for nonvirologic failure or who had missing SVR12 data. The primary endpoint was SVR12; safety endpoints were also assessed. RESULTS: A total of 386 patients were included in the FAS, 375 patients completed the study, and 325 patients were included in the MAS; 51 patients had missing SVR12 data. Overall, in the MAS and FAS, SVR12 was achieved in 99.1% and 84.2% of patients, respectively. In subgroups of interest, the percentage of patients achieving SVR12 in the MAS (and FAS) was: genotype (GT)3: 97.5% (80.6%); FibroScan® ≥ 12.5 kPa: 98.9% (89.3%); platelet count < 100 × 109/l: 100% (88.2%); both platelets < 150 × 109/l and FibroScan® > 20 kPa: 100% (88.9%); aspartate aminotransferase-to-platelet ratio index > 1.09: 98.7% (83.1%); fibrosis-4 index > 3.25: 98.6% (84.0%); albumin < 3 g/dl: 100% (91.7%); people who use drugs: 97.7% (84.3%); psychiatric disorders: 96.6% (84.8%); and human immunodeficiency virus coinfection: 100% (95.0%). Overall, 26.9% (104/386) of patients experienced an adverse event, none of which were classed as serious. CONCLUSION: In this real-world cohort, 8 weeks of G/P therapy was well tolerated in TN patients with CC. SVR12 rates were similar to clinical trials, supporting 8-week treatment in TN patients with CC, including those with signs of advanced liver disease and GT3 infection.

Intrahepatic cholestasis of pregnancy - prevalence and ethnic distribution in northern Israel.

OBJECTIVES: Intrahepatic cholestasis of pregnancy (ICP) is charachterized by pruritis and elevated serum bile acids (BA) and is associated with adverse obstetrical outcomes. ICP etiology is poorly understood and its incidence varies with ethnicity and geographical distribution. OBJECTIVES: Explore the prevalence and characteristics of ICP in the different Northern Israeli ethnic groups and compare maternal and perinatal outcomes according to disease severity. MATERIAL AND METHODS: Single-center retrospective study. Women who were diagnosed with ICP based on clinical presentation and elevated fasting BA (≥ 10 µmol/L) were included. Disease incidence, maternal and neonatal complications were explored according to ethnic subgroups analysis and obstetrical complications were examined according to disease severity. RESULTS: The incidence of ICP in the study population was 0.58%. Higher ICP incidence was found in our cohort compared with other reports arising from Central Israel (p < 0.001). The Christian patients had a higher incidence of ICP (1.1%) and preeclampsia (23.1%). A higher rate of neonatal intensive care unit (NICU) admissions was found in the Arab Muslim and Christian groups compared with the Jewish and Druze groups (p = 0.007). A higher rate of preeclampsia was found in the severe (BA ≥ 40 µmol/L) ICP group (p < 0.001). Patients in the severe ICP group had earlier gestational age at delivery (37 versus 38.14 weeks, p < 0.001). Birth weight was significantly lower in the severe ICP group (p = 0.018). CONCLUSIONS: The incidence of ICP at our institution was 0.58%, which is higher compared with previous reported Israeli incidence. Higher ICP and preeclampsia incidence were found among Arab Christian patients.

JAK2 mutation: an aid in the diagnosis of occult myeloproliferative neoplasms in patients with major intraabdominal vein thrombosis and normal blood counts.

BACKGROUND: Janus kinase-2 (JAK2) is mutated in a high proportion of patients with polycythemia vera and in a smaller number with essential thrombocythemia and primary myelofibrosis. Mutated JAK2 is an important diagnostic marker for myeloproliferative neoplasm (MPN) and may also play a major role in the pathogenesis of MPN. OBJECTIVES: To evaluate the prevalence of mutated JAK2 (JAK2-V617F) among patients with major intraabdominal vein thrombosis who had normal blood counts at diagnosis of the initial event. METHODS: The medical records of patients who presented with a major intraabdominal venous thrombosis and normal peripheral blood counts were obtained. JAK2-V617F mutation status was determined by real-time polymerase chain reaction. RESULTS: Twenty-two patients were available for this analysis and 9 (41%) were found to have JAK2-V617F. Patients with positive JAK2-V617F were younger and had more frequent clinical splenomegaly than those with wild-type JAK2. CONCLUSIONS: A high proportion of patients presenting with "idiopathic" major intraabdominal vein thrombosis and normal blood counts carry JAK2-V617F. We recommend searching for the mutation in this clinical setting to detect patients with occult MPN.

Vascular and biliary abnormalities mimicking cholangiocarcinoma in patients with cavernous transformation of the portal vein: role of color Doppler sonography.

OBJECTIVE: The purpose of this study was to describe and evaluate the sonographic and color Doppler features of tumorlike biliary and venous changes in patients with cavernous transformation of the portal vein (CTPV). METHODS: The sonographic studies of 24 patients with CTPV were reviewed. Sonographic evaluation of the biliary system included measurement of intrahepatic and extrahepatic biliary duct caliber changes and common bile duct (CBD) wall thickening and character. Color Doppler features of the portoportal collateral circulation at various locations (intrahepatic, periportal, gallbladder, pancreatic, and gastric regions) were carefully evaluated. RESULTS: Biliary abnormalities were detected in 13 (54%) of 24 patients with CTPV. All 13 patients (100%) had intrahepatic biliary dilatation; 11 patients (85%) had CBD abnormalities: diffuse CBD wall thickening causing diffuse narrowing of the true lumen in 7 (54%) and CBD dilatation proximal to the focal area of narrowing due to pericholedochal compressing venous collaterals in 4 (30%). A tumorlike solid mass appeared on the gray scale images of 2 patients (8%): 1 at the porta hepatis and the other at the pancreatic head level. Color Doppler imaging evaluation showed venous-type flow, suggesting a bulk of varicosities. CONCLUSIONS: Portoportal collaterals in patients with CTPV may alter the biliary and venous systems, causing biliary wall thickening, stenosis, intrahepatic and extrahepatic dilatation, and pseudotumors. Detailed sonographic and color Doppler imaging assessment can show and facilitate the correct diagnosis of those changes, thus avoiding the need for a more invasive modality such as endoscopic retrograde cholangiopancreatography or a more expensive investigation such as magnetic resonance cholangiopancreatography.

Is the model of end-stage liver disease (MELD) valid in Israel? A critical analysis of liver transplant waiting list mortality.

BACKGROUND: The model for end-stage liver disease is the best available predictor of waiting list mortality among liver transplant candidates. OBJECTIVES: To validate the applicability of MELD in Israel. METHODS: All candidates awaiting liver transplantation in our institution were followed prospectively since 2002. We measured the concordance (c-statistic) equivalent to the area under the receiver operating characteristic curve in order to assess the predictive power of MELD. Other independent mortality risk factors were identified by a separate multivariate analysis. Mortality rates within different MELD and Child-Pugh-Turcotte scores were compared to the original (United States) MELD data. RESULTS: Of 86 patients listed for transplantation, 40 were transplanted (36 in Israel and 4 abroad). Of the other 46 patients, 24 are alive and still listed, and 22 died (25%, approximately 7%/year). The area under the ROC curve for MELD score was 0.79 (0.83 USA) compared to a CPT score of 0.71 (0.76 USA). High MELD scores, occurrence of spontaneous bacterial peritonitis, and diagnosis of hepatocellular carcinoma were independent risk factors of mortality. Death rates per mid-MELD score (20-29) were significantly higher than the USA results. CONCLUSIONS: MELD is valid in Israel and superior to CPT in predicting waiting list mortality. Although longer waiting time due to organ scarcity is a key factor, death rates in the mid-range (10-29) MELD groups indicate further audit of the care of patients with end-stage liver disease.

Donor recruitment and selection for adult-to-adult living donor liver transplantation in urgent and elective circumstances.

BACKGROUND: Adult-to-adult living donor liver transplantation is becoming an alternative to cadaveric transplantation in urgent and elective settings. Donor selection crucially affects donor safety and recipient outcome. OBJECTIVE: To present our algorithm of urgent and elective donor selection. METHODS: Urgent selection is expeditious and protocol-based. Elective selection permits a comprehensive process. Both include medical, psychosocial and surgical-anatomic evaluations. Liver volumes and vascular anatomy are evaluated with computerized tomographic angiography. Informed consent is obtained after painstaking explanations. Independent institutional committees review and approve all cases. RESULTS: Between July 2003 and June 2004 we evaluated 43 potential live donors for 12 potential recipients (fulminant hepatic failure, n = 5; chronic end-stage liver disease, n = 6; primary graft non-function, n = 1). Thirty-three candidates (76%) were excluded due to blood type incompatibility (n = 14, 42%), incompatible anatomy (n = 8, 24%)--including problematic volume distribution (n = 2) or vascular anatomy (n = 6)--psychosocial issues (n = 4, 12%), or medical co-morbidity (n = 7, 22%). Five recipients (FHF, n = 4; chronic ESLD, n = 1) were successfully transplanted from living donors. In the acute setting, two patients (FHF, PGNF) died in the absence of an appropriate donor (cadaveric or living donor). In the elective group, one patient died of unexpected variceal bleeding and one received a cadaveric graft just before the planned living donor transplantation was performed. One candidate was transplanted overseas and two cases are scheduled. The ratio of compatibility for donation was 34% (10/29) for blood type-compatible candidates. CONCLUSIONS: Donor selection for living donor liver transplantation is a complex, labor-intensive multidisciplinary process. Most exclusions are due to blood type incompatibility or anatomic details. Psychosocial aspects of these donations warrant special attention.

Initial experience with urgent adult-to-adult living donor liver transplantation in fulminant hepatic failure.

BACKGROUND: The prognosis of patients with fulminant hepatic failure without timely liver transplantation is dismal. Given the limited availability of cadaveric organs for urgent transplantation in Israel, adult-to-adult living donor segmental liver transplantation may be the only alternative. OBJECTIVES: To report our initial experience with urgent lifesaving LDLT in this unique scenario. METHODS: Three adult patients with FHF (two of unknown etiology, one with paracetamol intoxication) were transferred from other institutions and admitted to our intensive care unit. Initial treatment and monitoring included intracranial pressure monitoring and hepatic dialysis using the Molecular Adsorbent Recirculating System. Expeditious potential donor selection included medical, psychosocial and surgical evaluation. Liver volume and vascular anatomic compatibility were assessed with computed tomography angiography. RESULTS: Between July and October 2003 we performed three procedures of urgent adult-to-adult LDLT. The donors (two uncles, one sister) underwent hepatic resection (two right lobes, one left lateral segment) and recovered well. The recipients underwent total hepatectomy with caval preservation, followed by lobar grafting. All recipients recovered and are alive with good liver function and without any neurologic complications. CONCLUSIONS: Urgent adult-to-adult living donor segmental liver transplantation can be performed safely and timely as a lifesaving procedure in the setting of comatose patients with FHF.