Recurrence of hepatitis C after liver transplantation (LT) is the main cause of graft loss and retransplantation. Frequent liver biopsies are essential to follow-up hepatitis C virus (HCV)-induced liver damage. However, liver biopsy is an invasive and expensive procedure. We evaluated prospectively the diagnostic accuracy of noninvasive measurement of liver stiffness (by transient elastography) to assess the severity of hepatitis C recurrence after LT. For this purpose, we included 124 HCV-infected liver transplant recipients who underwent 169 liver biopsies and 129 hepatic hemodynamic studies with determination of hepatic venous pressure gradient (HVPG). Simultaneously, patients underwent measurement of liver stiffness. Liver fibrosis was mild (F0-F1) in 96 cases (57%) and significant (F2-F4) in 73 (43%). HVPG was normal (Ͻ6 mm Hg) in 69 cases (54%) and elevated (Ն6 mm Hg) in 60 (46%). Using a liver stiffness cutoff value of 8.5 kilopascals, the sensitivity, specificity, negative predictive value, and positive predictive value for diagnosis of fibrosis ՆF2 were 90%, 81%, 79%, and 92%, respectively. The area under the curve (AUC) for diagnosis of fibrosis ՆF2, ՆF3 and F4 were 0.90, 0.93, and 0.98, respectively. There was a close direct correlation between liver stiffness and HVPG (Pearson coefficient, 0.84; P Ͻ 0.001) and the AUC for diagnosis of portal hypertension (HVPG Ն6 mm Hg) was 0.93. Importantly, none of the individuals with liver stiffness below the cutoff value had either bridging fibrosis (F3) or cirrhosis (F4) or significant portal hypertension (HVPG Ն10 mm Hg). In conclusion, determination of liver stiffness is an extremely valuable tool to assess the severity of HCV recurrence after LT and in reducing the need of follow-up liver biopsies.

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Liver biopsy is essential in the follow-up of HCV-infected liver transplant recipients. The aim of this study was to prospectively compare percutaneous (PLB) versus transjugular liver biopsy (TLB) in the assessment of liver damage. We also explored the diagnostic value of hepatic venous pressure gradient (HVPG) to identify patients at risk of severe HCV disease recurrence after liver transplantation (LT). One hundred sixteen paired PLB and TLB (with HVPG measurement) were performed 3 or 12 months after LT in 80 patients. Concordance for necroinflammation and fibrosis was fair or good, particularly 1 year after LT (kappa > 0.6). At this point, a significant positive association was seen between the median HVPG and the fibrosis stage C hronic hepatitis C virus (HCV) infection leading to liver cirrhosis and hepatocellular carcinoma is the main indication for liver transplantation (LT) in Western countries and Japan. 1 Regretfully, recurrence of HCV infection is universal after LT, 2 and disease progression is significantly faster in immunosuppressed than in immunocompetent individuals. In liver transplant recipients, chronic HCV infection may lead to cirrhosis in as much as 30% of individuals only 5 years after LT. [3][4][5] Once liver cirrhosis is established, the cumulative probability of developing clinical decompensation is close to 50% 1 year after diagnosis and, more importantly, survival after decompensation is extremely short. 6 As a result of this accelerated course of HCV infection, longterm graft and patient survival are significantly reduced in patients undergoing LT for HCV-related cirrhosis compared with other groups. 7 Frequent liver biopsies are essential to monitor HCV-induced liver damage and are part of the routine follow-up of HCV-infected liver transplant recipients. Early histological damage after transplantation correlates with long-term outcome; in fact, the presence of significant liver fibrosis in 1-year liver biopsies identifies patients at high risk of graft loss. 3,8 In addition, assessment of liver damage is relevant to adopt therapeutic decisions, particularly because of the low efficacy and high incidence of adverse events of current antiviral therapy in this group of patients. 3,9,10

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Significant liver fibrosis (F > 2) and portal hypertension (hepatic venous pressure gradient[HVPG] > 6 mmHg) at 1 year after liver transplantation (LT) identify patients with severe hepatitis C recurrence. We evaluated whether repeated liver stiffness measurements (LSM) following LT can discriminate between slow and rapid "fibrosers" (fibrosis stage F2-F4 at 1 year after LT). Eighty-four patients who had undergone LT and who were infected with hepatitis C virus (HCV) and 19 LT controls who were not infected with HCV underwent LSM at 3, 6, 9, and 12 months after LT. All HCV-infected patients underwent liver biopsy 12 months after LT (paired HVPG measurements in 74); 31 (37%) were rapid fibrosers. Median LSM (in kilopascal) at months 6, 9, and 12 were significantly higher in rapid fibrosers (9.9, 9.5, 12.1) than in slow fibrosers (6.9, 7.5, 6.6) (P < 0.01 all time points). The slope of liver stiffness progression (kPa ؋ month) in rapid fibrosers (0.42) was significantly greater than in slow fibrosers (0.05) (P < 0.001), suggesting two different speeds of liver fibrosis progression. H epatitis C virus (HCV) infection recurs universally after liver transplantation (LT) 1 and graft cirrhosis develops in a significant proportion of patients within the first years after LT. 2-4 As a result of this accelerated course, hepatitis C recurrence is the first cause of graft loss and reduction in patient survival in most liver transplant programs. 5 Thus, identification of patients at risk of severe recurrence at an early stage, in order to adopt therapeutic decisions, 6-8 becomes crucial. It is well known that early histological damage after transplantation corre-

Consistent with findings from previous studies, a high rate of patients (91% and 96%) with genotype 3 HCV infection and compensated cirrhosis achieved an SVR12 with sofosbuvir and velpatasvir, with or without ribavirin. Of patients treated with sofosbuvir and velpatasvir without ribavirin, fewer patients with baseline NS5A RASs achieved an SVR12 compared with patients without baseline NS5A. ClinicalTrials.govNCT02781558.

Jordi Llaneras (1), Mar Riveiro-Barciela (1)(2), Sabela Lens (2)(3), Moisés Diago (4), Alba Cachero (5), Javier García-Samaniego (2)(6), Isabel Conde (7), Ana Arencibia (8), Juan Arenas (9), Francisco Gea (10), Xavier Torras (2)(11), José Luis Calleja (12), José Antonio Carrión (13), Inmaculada Fernández (14), Rosa María Morillas (2)(15), José Miguel Rosales (16), Isabel Carmona (17), Conrado Fernández-Rodríguez (18), Manuel Hernández-Guerra (19), Susana Llerena (20), Vanesa Bernal (21), Juan Turnes (22), Jesús M. González-Santiago (23), Silvia Montoliu (24), Blanca Figueruela (25), Ester Badia (26), Manuel Delgado (27), Miguel Fernández-Bermejo (28), Mercedes Iñarrairaegui (2)(29), Juan Manuel Pascasio (2)(30), Rafael Esteban (1)(2), Zoe Mariño (2)(3), Maria Buti (1)(2).

Highlights Meta-analysis of real-world data from 12,583 patients taking glecaprevir/pibrentasvir. Glecaprevir/pibrentasvir achieved 96.7% virologic cure overall. Virologic cure was > − 95% across subgroups of interest. Serious adverse events were reported in 1.0% of patients.