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Long-term effects on cirrhosis and portal hypertension of direct antiviral agent (DAA)-based eradication of hepatitis C virus (HCV) are still under debate. We analysed dynamics of liver and spleen elastography to assess potential regression of cirrhosis and portal hypertension 3 years post-treatment. Fifty-four patients with HCV-associated cirrhosis and DAA-induced SVR were included. Liver and spleen stiffness were measured at baseline (BL), end of treatment (EOT), 24 weeks after EOT (FU24) and 1, 2 and 3 (FU144) years post-treatment by transient liver elastography (L-TE) and point shear wave elastography (pSWE) using acoustic radiation force impulse (ARFI) of the liver (L-ARFI) and spleen (S-ARFI). Biochemical, virological and clinical data were also obtained. Liver stiffness assessed by L-TE decreased between BL [median (range), 32.5(9.1–75) kPa] and EOT [21.3(6.7–73.5) kPa; p < .0001] and EOT and FU144 [16(4.1–75) kPa; p = .006]. L-ARFI values improved between EOT [2.5(1.2–4.1) m/s] and FU144 [1.7(0.9–4.1) m/s; p = .001], while spleen stiffness remained unchanged. Overall, L-TE improved in 38 of 54 (70.4%) patients at EOT and 29 of 38 (76.3%) declined further until FU144, whereas L-ARFI values decreased in 30/54 (55.6%) patients at EOT and continued to decrease in 28/30 (93.3%) patients at FU144. Low bilirubin and high albumin levels at BL were associated with improved L-ARFI values (p = .048) at EOT or regression of cirrhosis (

Background&aims The presence of baseline resistance-associated substitutions (RASs) reduced sustained virologic response (SVR) rates in chronic hepatitis C virus (HCV) genotype 1a infected patients treated with Elbasvir/Grazoprevir (EBR/GZR). This study aimed to evaluate the frequency of NS5A RASs and treatment outcomes in patients for whom EBR/GZR was intended. Methods We sequenced NS5A in 832 samples from German genotype1a-infected DAA-naive patients population-based, which were collected in the European Resistance Database. Treatment outcomes and clinical parameters were evaluated in 519 of these patients retrospectively. Results Overall, 6.5% of patients harbored EBR-specific NS5A RASs at baseline, including Q30H/R (3.3%), L31M (1.8%), Y93H (1.6%) and other individual variants. Antiviral treatment, including EBR/GZR, was initiated in 88% of patients. In the absence of RASs, the majority of patients received EBR/GZR for 12 weeks (57%) and the SVR rate was 97% compared to 99% SVR achieved using other DAA regimens (LDV/SOF±RBV, G/P, PrOD+RBV, VEL/SOF). Various regimens were used in the presence of RASs and SVR rates were high following treatment with LDV/SOF (100%), G/P (83%), PrOD/RBV (100%), VEL/SOF (100%), SMV/SOF (100%) and EBR/GZR+RBV for 16 weeks (100%). However, two patients received EBR/GZR for 16 weeks without RBV and one relapsed. Conclusions EBR/GZR treatment with or without RBV for 12 or 16 weeks according to a baseline RAS analysis was highly effective with ≥97% SVR in patients with genotype 1a. EBR/GZR without RBV should be avoided in patients with RASs. High SVR rates were also achieved using other 8 or 12 weeks DAA regimens.

Background and aim A number of studies were able to show a reduction of hypoxemia episodes during procedural sedation through the use of capnography (CA). The present study investigates the number of episodes of hypoxemia during percutaneous endoscopic gastrostomy (PEG) placement with propofol sedation comparing standard monitoring (SM) versus SM with additional CA surveillance. Methods In this single center randomized controlled trial, 150 patients were prospectively randomized 1:1 in either the SM group or the CA group after stratification for ASA class, PEG method (push or pull method), presence of head and neck tumor, and tracheostomy. CA analysis was performed for all patients but was blinded for the endoscopic team in the SM group. Results In the SM group, 57% episodes of hypoxemia (SpO2 15 s) and 41% episodes of severe hypoxemia (SpO2 15 s) were observed in comparison with 28% and 20% in the CA group, respectively. Odds ratios for hypoxemia and severe hypoxemia were 0.29 (confidence interval 0.15-0.57; P = 0.0005) and 0.35 (confidence interval 0.17-0.73; P = 0.008) in favor of the CA group. On average, CA was able to detect imminent mild and severe hypoxemia 83 and 99 s before standard monitoring. Standard monitoring represented an independent risk factor for hypoxemia and severe hypoxemia. Conclusions Respiratory complications of sedation during PEG placement are frequent events. CA is able to detect imminent hypoxemia at an early time point. This allows an early intervention and consecutively the avoidance of mild and severe hypoxemia. Therefore, CA monitoring can be recommended particularly during PEG insertion procedures.

BACKGROUND HBV DNA and quantitative (q)HBsAg levels as prognostic markers for HBV-related disease are mostly validated in Asia and their significance in Western populations is uncertain. AIM To analyse the impact of the HBV genotype and frequent mutations in precore (PC), basal core promoter (BCP) and preS on HBV DNA and qHBsAg levels. METHODS HBV DNA and qHBsAg serum levels of 465 patients with HBeAg-negative chronic HBV infection were correlated with the HBV genotype and mutations in PC, BCP and preS. For a detailed analysis of the molecular virology, genotype A2 genomes harbouring these mutations were analysed for replication efficacy and HBsAg release in cell culture. RESULTS While no impact of the HBV genotype on HBV DNA levels was observed, qHBsAg levels differed up to 1.4 log among the genotypes (P

SummaryBackground Direct antiviral therapies for chronic hepatitis C virus (HCV) infection have expanded treatment options for neglected patient populations, including elderly patients who are ineligible/intolerant to receive interferon (IFN)-based therapy. Aim To investigate the efficacy, tolerability and potential for drug–drug interactions (DDIs) of IFN-free treatment in patients aged ≥65 years in a large real-world cohort. Methods A total of 541 patients were treated with different combinations of direct antiviral agents (DAAs: ledipasvir/sofosbuvir ±ribavirin; daclatasvir/sofosbuvir ±ribavirin; paritaprevir/ombitasvir ±dasabuvir ±ribavirin or simeprevir/sofosbuvir ±ribavirin in genotype 1/4, and daclatasvir/sofosbuvir ±ribavirin or sofosbuvir/ribavirin in genotype 2/3). Efficacy, safety and potential DDIs were analysed and compared between patients aged

Soluble CD163 (sCD163), a marker for macrophage activation, was found to be associated with the severity of liver cirrhosis. The aim of the current study was to investigate whether serum sCD163 levels correlate with liver inflammation and fibrosis in patients with chronic hepatitis B virus (HBV) infection. In a retrospective cohort study, serum sCD163 levels were assessed by ELISA together with clinical and laboratory data in 186 patients with chronic HBV infection and 15 healthy controls. The relation between parameters for liver fibrosis and necroinflammation and sCD163 levels was analysed. Additionally, sCD163 was quantified in a subset of follow-up serum samples after initiation of antiviral treatment. sCD163 levels differed among phases of chronic HBV infection (P < 0.0001), and sCD163 concentrations were associated with inflammatory activity and fibrosis in the liver. sCD163 levels ≥ 1961 ng/l had a high specificity in the identification of subjects with substantial fibrosis (F ≥ 2). sCD163 concentrations decreased significantly after initiation of antiviral treatment. The correlation of sCD163 levels with necroinflammation and fibrosis and the sCD163 decline under treatment indicates that macrophage activation plays a role in HBV-related liver pathogenesis.

Acoustic radiation force impulse (ARFI) imaging is a new non-invasive, ultrasound-based method for the evaluation of liver fibrosis and cirrhosis.To determine the diagnostic accuracy of ARFI imaging, transient elastography (TE) and Fibrotest for the evaluation of complications in patients with cirrhosis.A total of 166 patients (109 male, mean age: 54 ± 11 years) with chronic liver disease and established cirrhosis were included in this study. ARFI-imaging of the liver and spleen, TE and Fibrotest were performed in all patients. In addition, clinical, laboratory and morphological parameters, including MELD/Child-Pugh scores, presence of oesophageal varices and hepatocellular carcinoma, history of variceal bleeding and history of hepatic encephalopathy were recorded.Acoustic radiation force impulse liver was significantly correlated with ARFI spleen (r = 0.48, P 0.001), TE (r = 0.75, P 0.001) and Fibrotest (r = 0.21, P = 0.006). The diagnostic accuracy (AUROC) for the diagnosis of large oesophageal varices was 0.58 (95% CI: 0.48-0.67), 0.58 (0.49-0.67), 0.53 (0.44-0.63) and 0.50 (0.41-0.59) for ARFI liver, spleen, TE and Fibrotest respectively (P 0.20). The AUROC for the detection of hepatocellular carcinoma (HCC) was 0.54 (0.39-0.70), 0.58 (0.44-0.73), 0.56 (0.40-0.73) and 0.72 (0.60-0.84) respectively (P 0.20). Multiple logistic regression analysis showed that ARFI spleen better predicted the presence of large oesophageal varices and HCC compared with ARFI liver.The diagnostic accuracy of ARFI liver and spleen was comparable to TE and Fibrotest for the detection of complications in patients with cirrhosis.

Summary. Treatment with hepatitis C virus (HCV)-NS3-protease inhibitors lead to the selection of resistant variants. Viral kinetics and resistance profiles in patients who are re-treated with the same protease inhibitor are unknown. Viral kinetics and NS3-resistance mutations obtained by clonal sequencing of the NS3-protease were analyzed in nine HCV-genotype-1-infected nonresponder patients who were sequentially treated with boceprevir (400 mg t.i.d.) for 1 week, peginterferon-alfa-2b for 2 weeks and combination of the two for 2 weeks in varying order. In addition to predominant wild-type isolates, previously described boceprevir-resistant mutations (V36, T54, R155, A156, V170) were observed. Furthermore, two resistant mutations (Q41, F43) were detected for the first time in vivo. In three patients, mutations selected after initial treatment with boceprevir were re-selected during subsequent boceprevir exposure. However, mutational patterns after the first and second exposure to boceprevir were different in five patients. In one patient, a viral variant (V55A) known to reduce susceptibility to boceprevir was the predominant variant observed at baseline and throughout treatment and was associated with a shallow viral decline. Different resistance mutations were selected during treatment with boceprevir ± peginterferon. Sequential short-term dosing of boceprevir was not associated with accumulation of resistant variants but pre-existing variants may impair virologic response.