Contrast imaging techniques to diagnose hepatocellular carcinoma in cirrhotics outside regular surveillance.

INTRODUCTION AND AIM: The American Association for the Study of the Liver (AASLD) recommends contrast computerized tomography (CT-scan) and magnetic resonance (MRI) to diagnose hepatocellular carcinoma (HCC) arising in cirrhotic patients under semiannual surveillance with abdominal ultrasound (US). A US guided fine needle biopsy (FNB) serves the same purpose in radiologically undiagnosed tumors and incidentally detected nodules in cirrhotics outside surveillance. In this population, we evaluated the performance of radiological diagnosis of HCC according to 2010 AASLD recommendations. MATERIALS AND METHODS: All cirrhotic patients with a liver nodule incidentally detected by US were prospectively investigated with a sequential application of CT-scan/MRI examination and a FNB. RESULTS: Between 2011 and 2015, 94 patients (mean age 67 years) had a liver nodule (total 120) detected by US in the context of histologically confirmed cirrhosis. Mean nodules diameter was 40 (10-160) mm, 87 (73%) <5cm. At histology, 84 (70%) nodules were HCC, 8 (7%) intrahepatic cholangiocarcinoma, 6 (5%) metastases, 2 (2%) neuroendocrine tumors and 20 (16%) benign lesions. Hyperenhancement in arterial phase followed by wash-out in venous phases on at least one radiological technique was demonstrated in 62 nodules (61 HCC, 1 high grade dysplastic nodule), with a specificity of 97% (IC95%: 85-100%), sensitivity 73% (IC95%: 62-81%) and diagnostic accuracy 80%, being 64% for ≥5cm HCC. Sensitivity of AFP >200ng/mL was 12% (IC95%: 6-23%). CONCLUSION: A single contrast imaging technique showing a typical contrast pattern confidently identifies HCC also in cirrhotic patients with an incidental liver nodule, thereby reducing the need for FNB examinations.

Efficacy of telaprevir-based therapy in stable liver transplant patients with chronic genotype 1 hepatitis C.

UNLABELLED:  Background and rationale. The REPLACE study (NCT01571583) investigated telaprevir-based triple therapy in patients who have recurrent genotype 1 hepatitis C virus (HCV) infection following liver transplantation and are on a stable immunosuppressant regimen of tacrolimus or cyclosporin A. Patients received telaprevir 750 mg 8-hourly with pegylated interferon 180 ?g weekly and ribavirin 600 mg daily, followed by a further 36 weeks of pegylated interferon and ribavirin alone and 24 weeks of follow-up. Efficacy (sustained virological response [SVR] 12 weeks after last planned study dose), safety and tolerability of telaprevir throughout the study were assessed. Pharmacokinetics of telaprevir, tacrolimus and cyclosporin A were also examined. RESULTS: In total, 74 patients were recruited. Overall, 72% (53/74; 95% CI: 59.9 to 81.5) of patients achieved SVR at 12 weeks following completion of treatment. Anticipated increases in plasma concentrations of tacrolimus and cyclosporin A occurred during telaprevir treatment and were successfully managed through immunosuppressant dose reduction and, for tacrolimus, reduced dosing frequency. Safety and tolerability of telaprevir-based triple therapy were generally comparable with previous data in non-transplant patients, although rates of reported anemia (55% [41/74]) were higher. Elevated plasma creatinine (46% [34/74]) was observed during REPLACE - consistent with the post-liver transplant population and the co-administered immunosuppressants. CONCLUSION: Telaprevir-based triple therapy in patients with recurrent genotype 1 HCV infection following liver transplantation produced high rates of SVR. Therapeutic concentrations of immunosuppressants were maintained successfully through dose modification during telaprevir treatment.

Diagnosis of liver nodules within and outside screening programs.

Evaluation of a liver nodule detected with ultrasound includes the recovery of a detailed medical history, a physical exam, appropriate contrast imaging examinations and, in selected cases, histopathology. In this setting, identification of liver disease accompanying a liver nodule helps distinction between benign nodules and metastatic malignant nodules from primary liver cancer, as recommended by scientific liver societies. Diagnostic algorithms for a liver nodule in patients with liver disease involve contrast CT scan, magnetic resonance imaging or contrast enhanced ultrasounds to show the typical neoplastic pattern of early arterial hyperenhancement wash-in followed by hypoenhancement in the late portal phase wash out. The flow charts developed by western societies utilize the discriminant criterion of tumor size i.e. the radiological diagnosis being endorsed in a nodule equal or greater than 1 cm whereas eastern societies rely on the recognition of a typical vascular pattern of the node, independently of size. Differential diagnosis should be obtained to differentiate liver related nodules like regenerative macronodules (more than 20% of the cases) and the less frequent intrahepatic cholangiocarcinoma (~2% of the cases) from liver disease unrelated nodules like hemangioma (~4%), neuroendocrine metastatic nodules (~1%) and focal nodular hyperplasia. In patients without liver disease, the most common liver nodules in the liver are hemangioma (~1.5%), focal nodular hyperplasia (0.03%) and hepatocellular adenoma (up to 0.004% in long term users of oral contraceptives). Optimization of management of patients with a liver nodule requires establishment of a multidisciplinary clinic.

ABT-450, ritonavir, ombitasvir, and dasabuvir achieves 97% and 100% sustained virologic response with or without ribavirin in treatment-experienced patients with HCV genotype 1b infection.

BACKGROUND & AIMS: The interferon-free regimen of ABT-450 (a protease inhibitor), ritonavir, ombitasvir (an NS5A inhibitor), dasabuvir (a non-nucleoside polymerase inhibitor), and ribavirin has shown efficacy in patients with hepatitis C virus (HCV) genotype 1b infection-the most prevalent subgenotype worldwide. We evaluated whether ribavirin is necessary for ABT-450, ritonavir, ombitasvir, and dasabuvir to produce high rates of sustained virologic response (SVR) in these patients. METHODS: We performed a multicenter, open-label, phase 3 trial of 179 patients with HCV genotype 1b infection, without cirrhosis, previously treated with peginterferon and ribavirin. Patients were assigned randomly (1:1) to groups given ABT-450, ritonavir, ombitasvir, and dasabuvir, with ribavirin (group 1) or without (group 2) for 12 weeks. The primary end point was SVR 12 weeks after treatment (SVR12). We assessed the noninferiority of this regimen to the rate of response reported (64%) for a similar population treated with telaprevir, peginterferon, and ribavirin. RESULTS: Groups 1 and 2 each had high rates of SVR12, which were noninferior to the reported rate of response to the combination of telaprevir, peginterferon, and ribavirin (group 1: 96.6%; 95% confidence interval, 92.8%-100%; and group 2: 100%; 95% confidence interval, 95.9%-100%). The rate of response in group 2 was noninferior to that of group 1. No virologic failure occurred during the study. Two patients (1.1%) discontinued the study owing to adverse events, both in group 1. The most common adverse events in groups 1 and 2 were fatigue (31.9% vs 15.8%) and headache (24.2% vs 23.2%), respectively. Decreases in hemoglobin level to less than the lower limit of normal were more frequent in group 1 (42.0% vs 5.5% in group 2; P < .001), although only 2 patients had hemoglobin levels less than 10 g/dL. CONCLUSIONS: The interferon-free regimen of ABT-450, ritonavir, ombitasvir, and dasabuvir, with or without ribavirin, produces a high rate of SVR12 in treatment-experienced patients with HCV genotype 1b infection. Both regimens are well tolerated, as shown by the low rate of discontinuations and generally mild adverse events. ClinicalTrials.gov number: NCT01674725.

Maintenance therapy with peginterferon alfa-2b does not prevent hepatocellular carcinoma in cirrhotic patients with chronic hepatitis C.

BACKGROUND & AIMS: Several studies have reported that low doses of interferon can delay the development of hepatocellular carcinoma (HCC) and progression of chronic hepatitis C. We investigated the incidence of clinical events among participants of the Evaluation of PegIntron in Control of Hepatitis C Cirrhosis (EPIC)3 program. METHODS: Data were analyzed from an open-label randomized study of patients with chronic hepatitis C who had failed to respond to interferon alfa plus ribavirin. All patients had compensated cirrhosis with no evidence of HCC. Patients received peginterferon alfa-2b (0.5 µg/kg/week; n=311) or no treatment (controls, n=315) for a maximum period of 5 years or until 98 patients had a clinical event (hepatic decompensation, HCC, death, or liver transplantation). The primary measure of efficacy was time until the first clinical event. RESULTS: There was no significant difference in time to first clinical event among patients who received peginterferon alfa-2b compared with controls (hazard ratio [HR], 1.452; 95% confidence interval [CI]: 0.880-2.396). There was no decrease in the development of HCC with therapy. The time to disease progression (clinical events or new or enlarged varices) was significantly longer for patients who received peginterferon alfa-2b compared with controls (HR, 1.564; 95% CI: 1.130-2.166). In a prospectively defined subanalysis of patients with baseline portal hypertension, peginterferon alfa-2b significantly increased the time to first clinical event compared with controls (P=.016). There were no new safety observations. CONCLUSIONS: Maintenance therapy with peginterferon alfa-2b is not warranted in all patients and does not prevent HCC. However, there is a potential clinical benefit of long-term suppressive therapy in patients with preexisting portal hypertension.