Liver and cardiovascular mortality after hepatitis C virus eradication by DAA: Data from RESIST-HCV cohort.

Real-world evidence on the course of Hepatitis C Virus (HCV) chronic liver disease after Sustained Virologic Response (SVR) obtained with direct-acting antiviral drugs (DAAs) are still limited, and the effects on mortality remain unclear. We evaluated the post-treatment survival of 4307 patients in the RESIST-HCV cohort (mean age 66.3 ± 11.6 years, 56.9% males, 24.7% chronic hepatitis, 66.9% Child-Pugh A cirrhosis and 8.4% Child-Pugh B cirrhosis) treated with DAAs between March 2015 and December 2016 and followed for a median of 73 weeks (range 16-152). Proportional cause-specific hazard regression for competing risks was used to evaluate the survival and to assess the predictors of liver and cardiovascular death. Overall, 94.7% of patients achieved SVR while 5.3% were HCV RNA-positive at last follow-up. Sixty-three patients (1.4%) died during the observation period. SVR was associated with a decreased risk of liver mortality (hazard ratio,HR0.09, beta -2.37, p < .001). Also, platelet count (HR 0.99, beta-0.01, p = .007) and albumin value (HR 0.26, beta -1.36 p = .001) were associated with liver mortality by competing risk analysis. SVR was associated with a reduced risk of cardiovascular mortality regardless of presence of cirrhosis (HR 0.07, beta-2.67, p < .001). Presence of diabetes (HR 3.45, beta 1.24, p = .014) and chronic kidney disease class ≥3 (HR 3.60, beta 1.28, p = 0.016) were two factors independently associated with higher risk of cardiovascular mortality. Patients with SVR to a DAA therapy have a better liver and cardiovascular survival, and the effects of HCV eradication are most evident in patients with compensated liver disease.

Incidence of Hepatocellular Carcinoma in Patients With HCV-Associated Cirrhosis Treated With Direct-Acting Antiviral Agents.

BACKGROUND & AIMS: Studies have produced conflicting results of the incidence of hepatocellular carcinoma (HCC) in patients with hepatitis C virus-associated cirrhosis treated with direct-acting antivirals (DAAs). Data from clinics are needed to accurately assess the occurrence rate of HCC in patients with cirrhosis in the real world. METHODS: We collected data from a large prospective study of 2,249 consecutive patients (mean age = 65.4 years, 56.9% male) with hepatitis C virus-associated cirrhosis (90.5% with Child-Pugh class A and 9.5% with Child-Pugh class B) treated with DAAs from March 2015 through July 2016 at 22 academic and community liver centers in Sicily, Italy. HCC occurrence was evaluated by Kaplan-Meier curves. Cox regression analysis was used to identify variables associated with HCC development. RESULTS: A sustained virologic response (SVR) was achieved by 2,140 patients (total = 95.2%; 95.9% with Child Pugh class A and 88.3% with Child Pugh class B; P < .001). Seventy-eight patients (3.5%) developed HCC during a mean follow-up of 14 months (range = 6-24 months). At 1 year after exposure to DAAs, HCC developed in 2.1% of patients with Child-Pugh class A with an SVR and 6.6% of patients with no SVR and in 7.8% of patients with Child-Pugh class B with an SVR and 12.4% of patients with no SVR (P < .001 by log-rank test). Albumin level below 3.5 g/dL (hazard ratio = 1.77, 95% confidence interval = 1.12-2.82, P = .015), platelet count below 120 × 109/L (hazard ratio = 3.89, 95% confidence interval = 2.11-7.15, P < .001), and absence of an SVR (hazard ratio = 3.40, 95% confidence interval = 1.89-6.12, P < .001) were independently associated increased risk for HCC. The mean interval from exposure to DAAs to an HCC diagnosis was 9.8 months (range = 2-22 months) and did not differ significantly between patients with (n = 64, 9.2 months) and without (n = 14, 12.0 months) an SVR (P = .11). A larger proportion of patients with an SVR had a single HCC lesion (78% vs 50% without an SVR; P = .009) or an HCC lesion smaller than 3 cm (58% vs 28% without an SVR; P = .07). CONCLUSIONS: In an analysis of data from a large prospective study of patients with hepatitis C virus-associated compensated or decompensated cirrhosis, we found that the SVR to DAA treatment decreased the incidence of HCC over a mean follow-up of 14 months.

Is Transient Elastography Needed for Noninvasive Assessment of High-Risk Varices? The REAL Experience.

INTRODUCTION: The Baveno VI consensus guidelines and an expanded algorithm suggest that transient elastography (TE) and platelet (PLT) count can be used to identify patients with cirrhosis who can avoid esophagogastroduodenoscopy (EGD). The primary aims of this study were to assess the ability of a simple algorithm, which uses only laboratory parameters, to predict medium/large esophageal varices (EV) in patients with hepatitis C virus (HCV) and cirrhosis from the Rete Sicilia Selezione Terapia-HCV (RESIST-HCV) cohort and to compare the performance of the algorithm with Baveno VI and Expanded Baveno VI criteria. The secondary aim was to assess the role of TE in ruling out large EV. METHODS: In total, 1,381 patients with HCV-associated cirrhosis who had EGD and TE within 1 year of starting treatment with direct-acting antivirals were evaluated. Using multivariate logistic analysis, laboratory variables were selected to determine which were independently associated with medium/large EV to create the RESIST-HCV criteria. These criteria were tested in a training cohort with patients from a single center (Palermo) and validated with patients from the 21 other centers of the RESIST-HCV program (validation cohort). RESULTS: In the entire cohort, medium/large EV were identified in 5 of 216 patients (2.3%) using the Baveno VI criteria and 13 of 497 patients (2.6%) using the Expanded Baveno VI criteria. PLT count and albumin level were independently associated with medium/large EV. The best cut-off values were a PLT count greater than 120 × 10 cells/µL and serum albumin level greater than 3.6 g/dL; negative predictive values (NPVs) were 97.2% and 94.7%, respectively. In the training cohort of 326 patients, 119 (36.5%) met the RESIST-HCV criteria and the NPV was 99.2%. Among 1,055 patients in the validation cohort, 315 (30%) met the RESIST-HCV criteria and the NPV was 98.1%. Adding TE to the RESIST-HCV criteria reduced the avoided EGDs for approximately 25% of patients and the NPV was 98.2%. DISCUSSION: The "easy-to-use" RESIST-HCV algorithm avoids EGD for high-risk EV screening for more than 30% of patients and has the same performance criteria as TE. Using these criteria simplifies the diagnosis of portal hypertension.

[Quantitative imaging in nephrology: limits and potentials of elastosonography].

Chronic kidney disease is characterized by increasingly amplified fibrotic processes regardless of etiology. The severity of renal fibrosis seems to correlate with an increased risk of end-stage renal disease; therefore, monitoring of renal fibrosis over time may play an important role in the follow-up of both focal and diffuse renal diseases and in evaluating the response to treatments. Renal biopsy is the only method capable of providing objective and comparable information on the extent of fibrosis, but it is not suitable for outpatient monitoring of chronic kidney disease due to its invasiveness. Elastosonography is an innovative and non-invasive ultrasound method that allows the measurement of tissue elasticity through the transmission of mechanical waves and the measurement of their propagation speed. Although some authors have demonstrated the usefulness of elastosonographic techniques for the quantification of liver fibrosis, few studies have investigated the applications of elastosonography in renal pathology. Furthermore, the depth of native kidneys, the high anisotropy of the renal tissue, and the possibility of examining only a small region of interest currently limit its spread in clinical practice. The aim of this review is to examine the physical principles of elastosonography and to review the latest evidence about the possible applications of the ARFI (acoustic radiation force impulse) technique in the study of kidney diseases.