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Limited screening and delays in diagnosis and linkage-to-care are barriers for hepatitis C virus (HCV) elimination. The LiverTAI study focused on patients tested for HCV using AI technologies to describe their demographic and clinical characteristics and pre-testing patient journeys, reflecting clinical practice in hospitals.LiverTAI is a retrospective, secondary analysis of electronic health records (EHRs) from 6 tertiary Spanish hospitals, extracting unstructured clinical data using natural language processing (NLP) EHRead® technology. Adult subjects with an HCV testing procedure from January 2014 to December 2018 were grouped according to HCV seropositivity and viremia.From 2,440,358 patients, 16,261 patients were tested for HCV (13,602 [83.6%] HCV seronegative; 2659 [16.4%] seropositive). Active HCV viremia appeared in 37.7% (n=1003) of patients, 18.6% (n=494) had negative viremia, and 43.7% (n=1162) unknown viremia. Patient journeys showed core departments (Gastroenterology, Internal Medicine, and Infectious Disease) and others including Emergency perform ample HCV testing in Spanish hospitals, whereas Medical Oncology lags. Patients were PCR-tested and genotyped significantly faster in core departments (p.001).Our results highlight hospital departments responsible for HCV testing. However, further testing was sub-optimal during the study period. Therefore, we underscore the need for HCV screening and reflex testing to accelerate diagnosis and linkage-to-care.

The formation of biofilm by pathogenic microorganisms has become a problem in the livestock industry since it is considered a potential source of infection for farm animals while increasing microbial resistance to physical and chemical agents. Some plant extracts, such as soluble wheat extract, have been shown to be effective in inhibiting or destroying the biofilm of certain micro-organisms under specific conditions. The objective of this study is to evaluate the capacity of the pathogen to form biofilm on different surfaces used in livestock, as well as to evaluate the anti-biofilm capacity of the soluble wheat extract against S. aureus on these surfaces. The inhibition potential of inhibition or destruction of biofilm was tested in vitro. Wheat extract at a concentration of 0.29 mg/100mL showed anti-biofilm activity on S. aureus, inhibiting its formation, as well as destroying it greatly after a contact time of 24 hours, on those surfaces where the microorganism presents more adhesion capacity.

Clinically significant portal hypertension (CSPH), defined as a hepatic venous pressure gradient (HVPG) ≥10 mmHg, persists 24 weeks after sustained virological response (SVR) in up to 78% of patients with HCV-related cirrhosis treated with direct-acting antivirals. These patients remain at risk of decompensation. However, long-term paired clinical and hemodynamic data are not available for this population.We conducted a prospective multicenter study in 226 patients with HCV-related cirrhosis and CSPH who achieved SVR after antiviral therapy. Patients with CSPH 24 weeks after end of treatment (SVR24) were offered another hemodynamic assessment 96 weeks after end of treatment (SVR96).All patients were clinically evaluated. Out of 176 patients with CSPH at SVR24, 117 (66%) underwent an HVPG measurement at SVR96. At SVR96, 55/117 (47%) patients had HVPG10 mmHg and 53% had CSPH (65% if we assume persistence of CSPH in all 59 non-evaluated patients). The proportion of high-risk patients (HVPG ≥16 mmHg) diminished from 41% to 15%. Liver stiffness decreased markedly after SVR (median decrease 10.5 ± 13 kPa) but did not correlate with HVPG changes (30% of patients with liver stiffness measurement13.6 kPa still had CSPH). Seventeen (7%) patients presented with de novo/additional clinical decompensation, which was independently associated with baseline HVPG ≥16 mmHg and history of ascites.Patients achieving SVR experienced a progressive reduction in portal pressure during follow-up. However, CSPH may persist in up to 53-65% of patients at SVR96, indicating persistent risk of decompensation. History of ascites and high-risk HVPG values identified patients at higher risk of de novo or further clinical decompensation.As a major complication of cirrhosis, clinically significant portal hypertension (CSPH) is associated with adverse clinical outcomes. Herein, we show that CSPH persists at 96 weeks in just over half of patients with HCV-related cirrhosis, despite HCV elimination by direct-acting antivirals. Despite viral cure, patients with CSPH at the start of antiviral treatment remain at long-term risk of hepatic complications and should be managed accordingly.

Despite secondary-prophylaxis with β-blockers and endoscopic-variceal-ligation rebleeding is frequent, particularly within the first-6-weeks. Early-rebleeding may have greater impact on death-risk than late rebleeding, which may affect therapy. We assessed whether the influence of rebleeding on long-term survival of patients on secondary-prophylaxis is greater in patients with early-rebleeding.369 patients with cirrhosis were consecutively included once recovered from first variceal-bleeding. The impact of rebleeding on survival was investigated according to whether it occurred within 6-weeks (early-rebleeding) or later (late-rebleeding).During 46-months of follow-up (IQR: 14-61), 45 patients (12%) had early-rebleeding, 74(20%) had late-rebleeding and 250(68%) had not rebleeding. Mortality risk was higher in early-rebleeding group vs. late-rebleeding (HR = 0.476, 95%CI = 0.318-0.712, p 0.001) and was similar in late-rebleeding group vs. no-rebleeding (HR = 0.902, 95%CI = 0.749-1.086, p = 0.271). Adjusting for baseline risk-factors, early-rebleeding was independently associated with mortality-risk (HR = 1.58, 95%CI = 1.02-2.45; p = 0.04). Child-PughMELD scores improved at 3rd-4th-week only in patients without early-rebleeding (p 0.05). Presence of ascites or encephalopathy, MELD-score12 and HVPG20 mmHg identified patients at risk of early-rebleeding.Patients with early-rebleeding have higher risk of death than patients without rebleeding and even than those rebleeding later. Our results suggest that patients at risk of early rebleeding might benefit from preemptive therapies such as early-TIPS.

Background Direct-acting antivirals (DAAs) show high efficacy and safety in HCV-cirrhotic patients, but most maintain clinically significant portal hypertension after sustained virological response (SVR). Non-invasive Baveno and expanded-Baveno criteria can identify patients without high-risk gastroesophageal varices (GEV) who have no need for endoscopic surveillance. However, data after SVR are scarce. We performed a multicenter study to evaluate SVR effects over GEV and diagnostic accuracy of non-invasive criteria after SVR. Methods HCV-cirrhotic patients receiving DAAs and baseline endoscopic evaluation were included (November 2014-October 2015). GEV were classified as low risk (LR-GEV) (< 5 mm) or high risk (HR-GEV) (>= 5 mm or with risk signs). Transient elastography (TE) and endoscopy were performed during follow-up. Results SVR was achieved in 230 (93.1%) of 247 included patients, 151 (65.7%) with endoscopic follow-up. Among 64/151 (42.4%) patients without baseline GEV, 8 (12.5%) developed GEV after SVR. Among 50/151 (33.1%) with baseline LR-GEV, 12 (24%) developed HR-GEV. Patients with GEV progression showed TE >= 25 kPa before treatment (64.7%) or >= 20 kPa after SVR (66.7%). Only 6% of patients without GEV and LSM < 25 kPa before treatment, and 10% of those with baseline LSM < 25 kPa and LSM < 20 kPa after SVR showed GEV progression after 36 months. The negative predictive value of Baveno and expanded-Baveno criteria to exclude HR-GEV was maintained after SVR (100% and 90.7%, respectively). Conclusions HCV-cirrhotic patients can develop HR-GEV after SVR. Surveillance is especially recommended in those with GEV before antiviral treatment. Baveno and expanded-Baveno criteria can be safely applied after SVR. : NCT02758509.

[Background & Aims] The interferon‐free regimen paritaprevir/ritonavir, ombitasvir + dasabuvir (PTV /r/OBV /DSV ) has shown high efficacy in patients with hepatitis C virus (HCV ) genotype 1b infection when administered for 8 or 12 weeks, but data regarding the 8‐week treatment are scarce. The aim of our study was to assess the efficacy and safety of the 8‐week administration of PTV /r/OBV /DSV in a real‐world cohort., [Methods] We performed a multicentre observational study from Spanish Hepa‐C database including patients receiving 8 weeks of PTV /r/OBV /DSV (October 2016‐November 2017). Those with advanced fibrosis, with non‐genotype 1b or who were treatment‐experienced were excluded., [Results] A total of 211 patients were registered from 23 Spanish centres; eleven were excluded. At baseline, 42.5% (n = 85) were male, median (range) age was 57 (23‐86), ALT was 45 (11‐494) IU/mL, viral load was 6.1 (3.3‐8.2) log10 IU/mL, and 74.5% had mild liver fibrosis (F0‐F1) and 25.5% moderate fibrosis (F2). At the end of treatment (EOT ), HCV viral load was undetectable in 100% (200/200). Seven patients relapsed after treatment discontinuation. Sustained virological response (SVR 12) rates by intention‐to‐treat analysis were 96% (192/200). Regarding treatment safety, 2 patients developed ALT elevation >5x ULN, but there were no treatment discontinuations. One patient died 7 weeks after EOT., [Conclusion] Treatment with PTV/r/OBV/DSV in genotype 1b‐infected treatment‐naive patients with mild‐moderate fibrosis shows excellent efficacy and safety in real life, similarly to clinical trials. Clinicaltrials.gov, number: NCT 03122132., JAC has received a grant from Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (PI14/00540), co‐funded by Fondo Europeo de Desarrollo Regional (FEDER), Unión Europea, Una manera de hacer Europa.

[Abstract] A percentage of hepatitis C virus (HCV)-infected patients fail direct acting antiviral (DAA)-based treatment regimens, often because of drug resistance-associated substitutions (RAS). The aim of this study was to characterize the resistance profile of a large cohort of patients failing DAA-based treatments, and investigate the relationship between HCV subtype and failure, as an aid to optimizing management of these patients. A new, standardized HCV-RAS testing protocol based on deep sequencing was designed and applied to 220 previously subtyped samples from patients failing DAA treatment, collected in 39 Spanish hospitals. The majority had received DAA-based interferon (IFN) α-free regimens; 79% had failed sofosbuvir-containing therapy. Genomic regions encoding the nonstructural protein (NS) 3, NS5A, and NS5B (DAA target regions) were analyzed using subtype-specific primers. Viral subtype distribution was as follows: genotype (G) 1, 62.7%; G3a, 21.4%; G4d, 12.3%; G2, 1.8%; and mixed infections 1.8%. Overall, 88.6% of patients carried at least 1 RAS, and 19% carried RAS at frequencies below 20% in the mutant spectrum. There were no differences in RAS selection between treatments with and without ribavirin. Regardless of the treatment received, each HCV subtype showed specific types of RAS. Of note, no RAS were detected in the target proteins of 18.6% of patients failing treatment, and 30.4% of patients had RAS in proteins that were not targets of the inhibitors they received. HCV patients failing DAA therapy showed a high diversity of RAS. Ribavirin use did not influence the type or number of RAS at failure. The subtype-specific pattern of RAS emergence underscores the importance of accurate HCV subtyping. The frequency of “extra-target” RAS suggests the need for RAS screening in all three DAA target regions. Ministerio de Economía y Empresa; IDI-20151125 Ministerio de Ciencia, Innovación y Universidades; SAF SAF 2017-87846-R

Cases of portopulmonary hypertension (PoPH) developing after DAA therapy for hepatitis C virus (HCV) infection have been reported. The purpose of the study was to assess the effects of DAA treatment for HCV infection on pulmonary hemodynamics. 91 patients with liver cirrhosis and clinically significant portal hypertension (hepatic venous pressure gradient, HVPG≥10 mmHg) were evaluated. Right heart catheterization and HVPG measurement were performed at baseline (BL), 6 months (6m) and 2 years (2y) after finishing DAA treatment. Results: All patients achieved sustained viral response. Results on pulmonary hemodynamics and HVPG are shown in Table 1. Mean Pulmonary artery pressure (PAP) increase by 2 mmHg at 6m and remained stable at 2y assessment. One patient (1.1%) had PoPH (PAP>20mmHg, PVR >3UWood) at BL, 2 (2.1%) at 6m, and 4(4.4%) at 2y after finishing DAA therapy. The HVPG decreased significantly after 6m and decreased further after 2y. At 2y 20(22%) patients had HVPG Conclusions: DAA treatment for HCV infection produces an increase in PAP that in a reduce proportion of patients leads to the development of pulmonary hypertension. Evaluation with echocardiography before starting DAA therapy and up to 2 years after finishing it is recomended.

Background and Aim Accurate information on the epidemiology of hepatitis C and B infection is mandatory to establish a national/regional plan. We aim to update the prevalence of hepatitis C and B infection in Catalonia using point-of-care tests to analyze the risk factors related and to implement a linkage-to-care circuit. Methods This is a community-based study. A random list of adult individuals was retrieved from censuses of primary care centers. Point-of-care tests for anti-hepatitis C virus (HCV) and HBV surface antigen (HBsAg) and a questionnaire for risk factor assessment were performed. Positive results were validated and a circuit for linkage-to-care was established. Results A total of 3328 individuals were included. The anti-HCV and HBsAg overall prevalence were lower than expected [1.02%, 95% confidence interval (CI) 0.65-1.39; and 0.52%, 95% CI 0.26-0.77, respectively]. Anti-HCV positive subjects were mostly (88%) autochthonous. The prevalence increased with age; only 12% were under age 40. The associated risk factors were drug use, blood transfusion, relative with HCV, and diabetes. Notably, the prevalence of active infection was only 0.49% (95% CI 0.23-0.74), 40% less than previously reported, reflecting the impact of direct acting antiviral therapy. Differently, HBsAg positive subjects were mostly foreign migrants (53%) with no other risk factors. Despite the implementation of a linkage-to-care circuit, one third of HBsAg positive subjects were lost. Conclusions The prevalence of HCV infection was lower than previously reported, showing a strong impact of direct acting antiviral therapy in the last years. Because of hepatitis B universal vaccination, HBV infection in Catalonia is mainly associated with migrant population. Linkage-to-care in patients with hepatitis B was challenging and warrants additional efforts.

Este artículo contiene 10 páginas, 7 figuras, 5 tablas., The cartography of shallow water macroalgal assemblages allows the assessment of water quality in coastal water bodies through the application of CARLIT. In this study, we have applied CARLIT to assess the ecological status of Algerian coastal water bodies for the first time. The surveyed zone is still in a good ecological status since 52% have a good to a high ecological Status. CARLIT index is well correlated with anthropogenic pressures and has proved suitable for the evaluation of the ecological status of coastal waters. Comparison between EQR values and EEI-c shows a similar pattern of change. CARLIT method allowed the collection of accurate information on the distribution and abundance of shallow-water communities. We also provide a cartographic baseline of the coastal assemblages useful for further evaluations on their geographic extension and for the implementation of a monitoring project on water quality in Algerian coast.

Background & Aims Drug-drug interactions (DDIs) with ombitasvir/paritaprevir/ritonavir with or without dasabuvir and with or without ribavirin (OBV/PTV/r ± DSV ± RBV) are common in clinical trials. Our aim was to analyze the prevalence and management of potential DDIs and adverse events (AEs) related to DDIs in patients with chronic hepatitis C (CHC) receiving OBV/PTV/r ± DSV ± RBV in clinical practice. Methods 177 CHC patients started OBV/PTV/r ± DSV ± RBV in 4 Spanish hospitals and were screened for potential DDIs using the University of Liverpool database. Patients were classified according to the most serious potential DDIs at baseline and AEs during therapy. Results At least one potential DDI was found in 110 (62.1%) patients: 100 (56.5%) had at least one manageable potential DDI and 10 (5.6%) at least one contraindicated. Patients with potential DDIs received a higher number of concomitant drugs (4 vs. 2, p

OBJECTIVES: Interferon-free therapies have an improved safety and efficacy profile. However, data in elderly patients, who have frequently advanced liver disease, associated comorbidities, and use concomitant medications are scarce. The im of this study was to assess the effectiveness and tolerability of all-oral regimens in elderly patients in real-life clinical practice. METHODS: Retrospective analysis of hepatitis C virus (HCV) patients aged >= 65 years receiving interferon-free regimens within the Spanish National Registry (Hepa-C). RESULTS: Data of 1,252 patients were recorded. Of these, 955 (76%) were aged 65-74 years, 211 (17%) were aged 75-79 years, and 86 (7%) were aged >= 80 years at the start of antiviral therapy. HCV genotype-1b was predominant (88%) and 48% were previous non-responders. A significant proportion of patients had cirrhosis (922; 74%), of whom 11% presented decompensated liver disease. The most used regimens were SOF/LDV (33%), 3D (28%), and SOF/SMV (26%). Ribavirin was added in 49% of patients. Overall, the sustained virological response (SVR12) rate was 94% without differences among the three age categories. Albumin = 75 years (2.59 (1.16-5.83); P = 0.02) and albumin = 75 years) or those with advanced liver disease (albumin

Background & Aims: Clinical trials evaluating second-generation direct-acting antiviral agents (DAAs) have shown excellent rates of sustained virologic response (SVR) and good safety profiles in patients with chronic hepatitis C virus (HCV) genotype 1 infection. We aimed to investigate the effectiveness and safety of two oral DAA combination regimens, ombitasvir/paritaprevir/rito navir plus dasabuvir (OMV/PTV/r + DSV) and ledipasvir/sofosbuvir (LDV/SOF), in a real-world clinical practice. Methods: Data from HCV genotype 1 patients treated with either OMV/PTV/r + DSV +/- ribavirin (RBV) (n = 1567) or LDV/SOF +/- RBV (n = 1758) in 35 centers across Spain between April 1, 2015 and February 28, 2016 were recorded in a large national database. Demographic, clinical and virological data were analyzed. Details of serious adverse events (SAEs) were recorded. Results: The two cohorts were not matched with respect to baseline characteristics and could not be compared directly. The SVR12 rate was 96.8% with OMV/PTVr/DSV +/- RBV and 95.8% with LDV/SOF +/- RBV. No significant differences were observed in SVR according to HCV subgenotype (p = 0.321 [OMV/PTV/r + DSV +/- RBV] and p = 0.174 [LDV/SOF]) or degree of fibrosis (c0.548 [OMV/PTV/r/DSV +/- RBV] and p = 0.085 [LDV/SOF]). Only baseline albumin level was significantly associated with failure to achieve SVR (p < 0.05) on multivariate analysis. Rates of SAEs and SAE-associated treatment discontinuation were 5.4% and 1.7%, in the OMV/PTV/r + DSV subcohort and 5.5% and 1.5% in the LDV/SOF subcohort, respectively. Hepatocellular carcinoma (HCC) recurred in 30% of patients with a complete response to therapy for previous HCC. Incident HCC was reported in 0.93%. Conclusions: In this large cohort of patients managed in the real-world setting in Spain, OMV/PTV/r + DSV and LDV/SOF achieved high rates of SVR12, comparable to those observed in randomized controlled trials, with similarly good safety profiles. Lay summary: In clinical trials, second-generation direct-acting antiviral agents (DAAs) have been shown to cure over 90% of patients chronically infected with the genotype 1 hepatitis C virus and have been better tolerated than previous treatment regimens. However, patients enrolled in clinical trials do not reflect the real patient population encountered in routine practice. The current study, which includes almost 4,000 patients, demonstrates comparable rates of cure with two increasingly used DAA combinations as those observed in the clinical trial environment, confirming that clinical trial findings with DAAs translate into the real-world setting, where patient populations are more diverse and complex. (c) 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Whether the effect of β-blockers on arterial pressure and/or cardiac function may offset the benefit of reducing portal pressure in advanced cirrhosis is controversial. Herein, we aimed to evaluate the systemic and splanchnic hemodynamic effects of β-blockers in decompensated vs. compensated cirrhosis and to investigate the influence of systemic hemodynamic changes on survival times in decompensated cirrhosis.Patients with cirrhosis and high-risk esophageal varices, without previous bleeding, were consecutively included and grouped according to the presence or absence of decompensation (ascites with or without overt encephalopathy). Systemic and hepatic hemodynamic measurements were performed before starting β-blockers and again after 1 to 3 months of treatment (short-term).Four hundred and three patients were included (190 decompensated and 213 compensated). At baseline, decompensated patients had higher portal pressure than compensated patients and were more hyperdynamic, with higher cardiac output (CO) and lower arterial pressure. Under β-blockers, decompensated patients had lower portal pressure decrease (10 ± 18% vs. 15 ± 12%; p0.05) and had greater reductions in heart rate (p0.001) and CO (17 ± 15% vs. 10 ± 21%; p0.01). Among patients with decompensated cirrhosis, those who died had a greater decrease in CO with β-blockers than survivors (21 ± 14% vs. 15 ± 16%; p0.05) and CO under β-blockers independently predicted death by competing-risk regression analysis, with good diagnostic accuracy (C-index 0.74; 95% CI 0.66-0.83). Death risk was higher in decompensated patients with CO5 L/min vs. CO ≥5 L/min (subdistribution hazard ratio 0.44; 95% CI 0.25-0.77; p = 0.004).In patients with high-risk varices treated to prevent first bleeding, the systemic hemodynamic response to β-blockers is greater and the portal pressure decrease is smaller in those with decompensated cirrhosis. The short-term effect of β-blockers on CO might adversely influence survival in decompensated cirrhosis.β-blockers are often used to reduce the risk of variceal bleeding in patients with cirrhosis. However, it is not known whether the effect of β-blockers on arterial pressure and/or cardiac function may offset the benefit of reducing portal pressure. Herein, we show that in patients with decompensated cirrhosis the potentially detrimental systemic effects of β-blockers are greater than in compensated patients, while the beneficial pressure lowering effects are reduced. The short-term effect of β-blockers on cardiac output may adversely influence survival in patients with decompensated cirrhosis.

Este artículo contiene 18 páginas, 8 figuras, 1 tabla., Historical information on marine organisms needs to be incorporated to develop effective management plans and conservation targets. In the Mediterranean Sea most species of brown seaweeds of the order Fucales are threatened or endangered and need protection. Here we merge data on historical and current records to create the first reference dataset on past and present distributions of Fucales from shallow and sheltered shores of Catalonia (NW Mediterranean Sea). Most Cystoseira sensu lato populations were found in the northern shores, where the most suitable environments exist. Carpodesmia mediterranea and Cystoseira compressa are far more abundant in exposed than in shallow, sheltered shores. Populations of most of the taxa (i.e. Carpodesmia crinita, Treptacantha elegans, T. sauvageauana, T. barbata f. aurantia) have suffered an important regression and two taxa have apparently become locally extinct (Cystoseira foeniculacea, Treptacantha barbata f. barbata). Carpodesmia caespitosa is still widespread in sheltered environments from the northern shores and a previously unreported taxon has been found (T. ballesterosii var. tenuior). Our regional-scale study makes available a solid, comprehensive baseline for future monitoring and application of conservation measures for the several threatened species of Fucales., Financial support to this research came from the projects ‘‘Cartografia dels Hàbitats Litorals a Catalunya’’ (Departament de Territori i Sosteniblitatand Institut Cartogàfic, Generalitat de Catalunya, Spain), CTN1500528 of the Agència Catalana de l’Aigua, Spain, and the INTRAMURAL CSIC PIE201730E033. Jana Verdura and Alba Medrano benefitted of funding from the Horizon 2020 EU Research and Innovation Program under grant agreement No. 689518 (MERCES). Partial funding came from the Sustainable Blue Economy program, European Union under the grant agreement AFRIMED EASME/EMFF/2017/1.2.1.12/S4/01/SI2.789059 to Jana Verdura.

Background & Aims: Despite direct-acting antivirals being highly effective at eradicating hepatitis C virus infection, their impact on the development of hepatocellular carcinoma (HCC) remains controversial. We analyzed the clinical and radiological outcome of cirrhotic patients treated with interferon-free regimens to estimate the risk of developing HCC. Methods: This was a retrospective multicenter study focusing on cirrhotic patients treated with direct-acting antivirals until December 2016. Clinical and radiologic characteristics were collected before the start of antiviral therapy, at follow-up and at HCC development. Diagnosis of HCC was centrally validated and its incidence was expressed as HCC/100 person-years. Results: A total of 1,123 patients were included (60.6% males, 83.8% Child-Pugh A) and 95.2% achieved a sustained virologic response. Median time of follow-up was 19.6 months. Seventy-two patients developed HCC within a median of 10.3 months after starting antiviral treatment. HCC incidence was 3.73 HCC/100 person-years (95% CI 2.96-4.70). Baseline liver function, alcohol intake and hepatic decompensation were associated with a higher risk of HCC. The relative risk was significantly increased in patients with non-characterized nodules at baseline 2.83 (95% CI 1.55-5.16) vs. absence of non-characterized nodules. When excluding these patients, the risk remained increased. Conclusion: These data expose a clear-cut time association between interferon-free treatment and HCC. The mechanisms involved in the increased risk of HCC emergence in the short term require further investigation. Lay summary: In this cohort of cirrhotic patients, interferonfree therapies achieved a high rate of sustained virologic response (>95%); however, we reported a risk of de novo hepatocellular carcinoma of 3.73 per 100 person-years and a clearcut time association with antiviral therapy. The time association between starting direct-acting antivirals and developing hepatocellular carcinoma, together with the association with the presence of non-characterized nodules at baseline ultrasound, suggests that antiviral therapy elicits a mechanism (probably immune-related) that primes the growth and clinical recognition of hepatocellular carcinoma early during follow-up. As a result, short-term liver cancer risk is significantly increased. (C) 2019 Published by Elsevier B.V. on behalf of European Association for the Study of the Liver.

Background & Aims: Around 5% of patients with chronic hepatitis C virus (HCV) infection treated with direct-acting antiviral (DAA) agents do not achieve sustained virological response (SVR). The currently approved retreatment regimen for prior DAA failure is a combination of sofosbuvir, velpatasvir, and voxilaprevir (SOF/VEL/VOX), although there is little data on its use in clinical practice. The aim of this study was to analyse the effectiveness and safety of SOF/VEL/VOX in the real-world setting. Methods: This was a prospective multicentre study assessing the efficacy of retreatment with SOF/VEL/VOX in patients who had experienced a prior DAA treatment failure. The primary endpoint was SVR 12 weeks after the completion of treatment (SVR12). Data on safety and tolerability were also recorded. Results: A total of 137 patients were included: 75% men, 35% with liver cirrhosis. Most were infected with HCV genotype (GT) 1 or 3. The most common prior DAA combinations were sofosbuvir plus an NS5A inhibitor or ombitasvir/paritaprevirtr +dasabuvir. A total of 136 (99%) patients achieved undetectable HCV RNA at the end of treatment. Overall SVR12 was 95% in the 135 patients reaching this point. SVR12 was lower in patients with cirrhosis (89%, p = 0.05) and those with GT3 infection (80%, p

Marino, Z., Darnell, A., Lens, S., Sapena, V., Diaz, A., Belmonte, E., Perello, C., Calleja, J.L., Varela, M., Rodriguez, M., Rodriguez de Lope, C., Llerena, S., Torras, X., Gallego, A., Sala, M., Morillas, R.M., Minguez, B., Llaneras, J., Coll, S., Carrion, J.A., Inarrairaegui, M., Sangro, B., Vilana, R., Sole, M., Ayuso, C., Rios, J., Forns, X., Bruix, J., Reig, M.

Pivotal phase studies of telaprevir (TLV) and boceprevir (BOV) showed 10-56% rates of early treatment interruption. However, there have been no reports on the sustained virological response (SVR) rates of these patients.To assess the SVR rate in a large cohort of patients who discontinued triple therapy with TLV or BOV for reasons other than stopping rules and to identify variables predicting SVR.A survey was sent to 15 hospitals in Catalonia asking them to report all TLV/BOV treatments finished by 31 May 2014. Demographic, clinical, laboratory, liver fibrosis and therapeutic data were recorded for treatments with early discontinuation. Logistic regression analysis, ROC curves and prognostic assessment of the variables identified were calculated.Twelve hospitals responded to the survey, representing 467 treatments and 121 (21.2%) early discontinuations, 76 (62.8%) due to stopping rules and 45 (37.2%) for other reasons. Early discontinuation was more frequent with BOV [38.2% (50/131) versus 21.1% (71/336) p0.005], mainly due to stopping rules [78% (39/50) versus 52.1% (37/71); p=0.004]. SVR was achieved in 21/121 patients (17.4%), 19/71 (26.8%) treated with TLV and 2/50 (4.0%) treated with BOV. In patients discontinuing treatment for reasons other than stopping rules, SVR was achieved in 19/37 (55.9%) treated with TLV and in 2/11 (18.2%) treated with BOV. The SVR rate in patients treated with TLV who discontinued due to a severe adverse event was 61.5% (16/26). A logistic regression analysis was performed only with triple therapy with TLV and early discontinuation. The predictive variables of SVR were undetectable HCV-RNA at treatment week 4 and treatment length longer than 11 weeks. Treatment duration longer than 11 weeks showed the best accuracy (0.794), with a positive predictive value of 0.928.Early discontinuation of TLV-based triple therapy due to reasons other than stopping rules still have a significant SVR rate (55.9%). Undetectable HVC-RNA at week 4 of treatment and treatment duration longer than 11 weeks are predictive of SVR in this subset of patients.

Background Current treatment combinations for chronic hepatitis C virus infection still include pegylated interferon and ribavirin despite the new therapeutic options available. Interferon-based treatments are associated with a high incidence of adverse effects. Central nervous system events are among the most frequent adverse drug reactions and their influence on treatment adherence and effectiveness is controversial. Objective The aim of the study was to evaluate neuropsychiatric adverse effects of interferon-based treatment for chronic hepatitis C in standard multidisciplinary clinical practice. Risk factors for these adverse effects and their impact on adherence and sustained viral response were also evaluated. Setting Ambulatory care pharmacy in coordination with the liver unit and the infectious diseases unit at a 650-bed tertiary university hospital. Methods We included all consecutive patients with chronic hepatitis C who completed treatment with pegylated interferon and ribavirin between 2005 and 2013. All patients underwent a multidisciplinary follow-up during treatment. Main outcome measures Neuropsychiatric adverse effects were evaluated in relation to severity, management and outcome. The presence of anxiety and depression was evaluated by means of specific tests. Results A total of 717 treatments in 679 patients were included. During treatment, we detected 1679 neuropsychiatric adverse effects in 618 patients (86.2 %), generating 1737 clinical interventions. Fifty-seven (3.3 %) neuropsychiatric adverse effects were severe and 2 (0.1 %) were life-threatening (suicidal attempts). Most neuropsychiatric adverse effects (1555 events, 92.6 %) resolved without sequelae. Psychiatric medication was required in 289 patients (40.3 %). Sustained viral response was achieved in 400 cases (55.8 %) and was associated with adherence (OR = 1.942, 95 % CI = 1.235-3.052, p = 0.004). A multivariate analysis did not show any relationship between neuropsychiatric adverse effects and treatment adherence or sustained viral response. A psychiatric history was a strong risk factor for depression, anxiety and other psychiatric disorders during treatment. Conclusion Neuropsychiatric adverse effects during interferon-based treatments in patients with chronic hepatitis C were common but mostly mild or moderate. Early detection and accurate multidisciplinary management avoided treatment discontinuation, ensuring adherence and attaining sustained viral response. The identified risk factors could be used to determine patients eligible for interferon-free combinations, thus optimizing health system economics.

Drug-drug interactions (DDIs) with ombitasvir/paritaprevir/ritonavir with or without dasabuvir and with or without ribavirin (OBV/PTV/r ± DSV ± RBV) are common in clinical trials. Our aim was to analyze the prevalence and management of potential DDIs and adverse events (AEs) related to DDIs in patients with chronic hepatitis C (CHC) receiving OBV/PTV/r ± DSV ± RBV in clinical practice.177 CHC patients started OBV/PTV/r ± DSV ± RBV in 4 Spanish hospitals and were screened for potential DDIs using the University of Liverpool database. Patients were classified according to the most serious potential DDIs at baseline and AEs during therapy.At least one potential DDI was found in 110 (62.1%) patients: 100 (56.5%) had at least one manageable potential DDI and 10 (5.6%) at least one contraindicated. Patients with potential DDIs were receiving a higher number of concomitant drugs (4 vs. 2, P 0.001). Routine medication was modified at baseline due to potential DDIs in 49 (27.7%) patients. During antiviral treatment, 67 (37.9%) patients presented at least one AE. In 9 (4.5%) patients, a DDI was suspected between OBV/PTV/r ± DSV ± RBV and the concomitant drug, requiring antiviral discontinuation in 4 patients.Potential DDIs are frequent with OBV/PTV/r ± DSV ± RBV, although a change in baseline medication is made in only one-quarter of patients. More than half of potential DDIs were only followed, and only 5% of patients developed AEs in which the implication of DDIs could not be excluded.

[Abstract] Background and Aims. Hepatitis C (HCV) therapy with Sofosbuvir (SOF)/Simeprevir (SMV) in clinical trials and real‐world clinical practice, showed high rates of sustained virological response (SVR) in non‐cirrhotic genotype (GT)‐1 and GT‐4 patients. These results were slightly lower in cirrhotic patients. We investigated real‐life effectiveness and safety of SOF/SMV with or without ribavirin (RBV) in a large cohort of cirrhotic patients. Methods. This collaborative multicentre study included data from 968 patients with cirrhosis infected with HCV‐GT1 or 4, treated with SOF/SMV±RBV in 30 centres across Spain between January‐2014 and December‐2015. Demographic, clinical, virological and safety data were analysed. Results. Overall SVR was 92.3%; the majority of patients were treated with RBV (62%) for 12 weeks (92.4%). No significant differences in SVR were observed between genotypes (GT1a:94.3%; GT1b:91.7%; GT4:91.1%). Those patients with more advanced liver disease (Child B/C, MELD≥10) or portal hypertension (platelet count≤100×109/L, transient elastography≥21 Kpa) showed significantly lower SVR rates (84.4%‐91.9%) than patients with less advanced liver disease (93.8%‐95.9%, P

Background and study aims: Meta-analyses suggest that an intravenous bolus or a high dose continuous infusion of somatostatin reduces the incidence of acute pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). Clinical guidelines, however, do not recommend this prophylaxis. The aim of this randomized, double-blind clinical trial was to evaluate the effect of somatostatin on the incidence of post-ERCP pancreatitis. Patients and methods: Patients undergoing ERCP at a single center were randomized to either intravenous bolus of somatostatin followed by a short (4-hour) continuous infusion, or to a similar placebo regimen. The primary outcome was post-ERCP pancreatitis, defined as abdominal pain with an amylase level at least three times higher than the upper limit of normality 24 hours after the ERCP and requiring admission for at least 2 days. Results: A total of 510 patients were enrolled (255 patients per group) and all completed follow-up. The main indications for ERCP were choledocholithiasis (62 %), and biliary malignant stricture (31 %). Post-ERCP pancreatitis occurred in 19 patients (7.5 %) in the somatostatin group and 17 patients (6.7 %) in the placebo group (relative risk [RR] 1.12, 95 % confidence interval [95 %CI] 0.59 – 2.1; P = 0.73). The number of cases of moderate or severe acute pancreatitis was similar in the somatostatin (2.4 %) and the placebo (3.5 %) groups (RR 0.67, 95 %CI 0.24 – 1.85, P = 0.43). No side effects were observed related to the use of somatostatin. Conclusions: Administration of an intravenous bolus of somatostatin followed by a short continuous infusion does not reduce the incidence of post-ERCP pancreatitis. Clinical Trials.gov number: NCT01060826.

The progression of cirrhosis is associated with alterations in the composition of the gut microbiome. To assess microbial translocation, we compared the serum microbial composition of patients with and without ascites and characterized the ascitic fluid microbiome using 16S rDNA high-throughput sequencing data. A complex and specific microbial community was detected in the serum and ascitic fluid of patients with cirrhosis but barely detectable in the serum of healthy controls. The serum microbiome of patients with ascites presented higher levels of lipopolysaccharide binding protein, a marker of microbial translocation, associated with higher diversity and relative abundance of Clostridiales and an unknown genus belonging to the Cyanobacteria phylum compared to patients without ascites. The composition of the fecal microbiome was also more altered in patients with than without ascites, confirming previous studies on fecal microbiome. We propose that alteration of the serum and fecal microbiome composition be considered indicators of cirrhosis progression.

Monitoring the hemodynamic response of portal pressure (PP) to drug therapy accurately stratifies the risk of variceal rebleeding (VRB). We assessed whether guiding therapy with hepatic venous pressure gradient (HVPG) monitoring may improve survival by preventing VRB. Patients with cirrhosis with controlled variceal bleeding were randomized to an HVPG-guided therapy group (N = 84) or to a control group (N = 86). In both groups, HVPG and acute β-blocker response were evaluated at baseline and HVPG measurements were repeated at 2-4 weeks to determine chronic response. In the HVPG-guided group, acute responders were treated with nadolol and acute nonresponders with nadolol+nitrates. Chronic nonresponders received nadolol+prazosin and had a third HVPG study. Ligation sessions were repeated until response was achieved. The control group was treated with nadolol+nitrates+ligation. Between-group baseline characteristics were similar. During long-term follow-up (median of 24 months), mortality was lower in the HVPG-guided therapy group than in the control group (29% vs. 43%; hazard ratio [HR] = 0.59; 95% confidence interval [CI] = 0.35-0.99). Rebleeding occurred in 19% versus 31% of patients, respectively (HR = 0.53; 95% CI = 0.29-0.98), and further decompensation of cirrhosis occurred in 52% versus 72% (HR = 0.68; 95% CI = 0.46-0.99). The survival probability was higher with HVPG-guided therapy than in controls, both in acute (HR = 0.59; 95% CI = 0.32-1.08) and chronic nonresponders (HR = 0.48; 95% CI = 0.23-0.99). HVPG-guided patients had a greater reduction of HVPG and a lower final value than controls (P

The most reliable indicators for post-ERCP acute pancreatitis are elevated amylase levels and abdominal pain 24 hours after ERCP. As ERCP is often performed on an outpatient basis, earlier diagnosis is important. We aimed to identify early predictors of post-ERCP pancreatitis. We prospectively analyzed IL-6, IL-10, TNFα, CRP, amylase and lipase before and 4 hours after ERCP, and studied their association with abdominal pain. We included 510 patients. Post-ERCP pancreatitis occurred in 36 patients (7.1%). IL-6, IL-10, TNFα and CRP were not associated with post-ERCP pancreatitis. Levels of amylase and lipase were higher in patients with pancreatitis (522 U/L and 1808 U/L vs. 78 U/L and 61 U/L, respectively; p 3 ULN. Amylase and lipase were the only markers of post-ERCP pancreatitis 4 hours after the procedure.

Falls are frequent among patients with debilitating disorders and can have a serious effect on health status. Mild cognitive disturbances associated with cirrhosis may increase the risk for falls. Identifying subjects at risk may allow the implementation of preventive measures. Our aim was to assess the predictive value of the Psychometric Hepatic Encephalopathy Score (PHES) in identifying patients likely to sustain falls. One hundred and twenty-two outpatients with cirrhosis were assessed using the PHES and were followed at specified intervals. One third of them exhibited cognitive dysfunction (CD) according to the PHES (

In compensated cirrhosis, a threshold value of hepatic venous pressure gradient (HVPG) ≥10 mm Hg is required for the development of decompensation. However, whether the treatment of portal hypertension (PHT) can prevent the transition into development of ascites once this level has been reached is unclear. Our aim was to assess the relationship between changes in HVPG induced by β-blockers and development of ascites in compensated cirrhosis with severe PHT.Eighty-three patients without any previous decompensation of cirrhosis, with large esophageal varices and HVPG ≥12 mm Hg were included. After baseline hemodynamic measurements nadolol was administered and a second hemodynamic study was repeated 1-3 months later.During 53±30 months of follow-up, decompensation occurred in 52 patients (62%) and in 81% of them ascites was the first manifestation. Using receiver operating characteristic curve analysis a decrease in HVPG ≥10% was the best cutoff to predict ascites. As compared with nonresponders, patients with an HVPG decrease ≥10% had a lower probability of developing ascites (19% vs. 57% at 3 years, P0.001), refractory ascites (P=0.007), and hepatorenal syndrome (P=0.027). By Cox regression analysis hemodynamic nonresponse was the best predictor of ascites. By stepwise logistic regression, development of ascites was independently associated with nonresponse, whereas refractory ascites, hepatorenal syndrome, and spontaneous bacterial peritonitis were not.In patients with compensated cirrhosis and large varices treated with β-blockers, an HVPG decrease ≥10% significantly reduces the risk of developing ascitic decompensation and other related complications such as refractory ascites or hepatorenal syndrome.

This document provides a detailed description of the position of the Catalan Society of Gastroenterology on the accuracy and utility of elastography in the non-invasive diagnosis of liver fibrosis. The document was written by a group of experts in chronic liver diseases and liver transplantation and reflects the consensus reached on the methodology and indications of transient elastography. This document was reviewed and presented in an abbreviated form at the XX Congress of the Catalan Society of Gastroenterology and included on the website http://www.scdigestologia.org/index.php?link=docs_posicio.

OBJECTIVES: Minimal hepatic encephalopathy (MHE) reduces quality of life and impacts daily functioning. It is known to impair fitness to drive, but deficits in attention and reaction may also be associated with falls. Falls may have important consequences in patients with cirrhosis due to coagulopathy, osteoporosis, and operative risk. However, the relationship between MHE and falls has not yet been evaluated. The objective of this study is to retrospectively investigate whether MHE is associated with falls in patients with cirrhosis. METHODS: We included 130 cirrhotic outpatients and 43 controls. MHE was diagnosed according to the results of the psychometric hepatic encephalopathy score (PHES). We recorded the reported incidence and number of falls in the 12 months before the study, the severity of injuries, and the need for healthcare services. RESULTS: Forty-five (34.6%) patients with cirrhosis exhibited MHE. The proportion of patients with MHE that reported falls (40%) was higher than those without MHE (12.9%, P < 0.001), which was similar to controls (11.6%). In patients with MHE, there was a higher need for primary healthcare services (8.8 vs. 0%, P = 0.004) and hospitalization (6.6 vs. 2.3%, P = 0.34) due to falls than in patients without MHE. Patients on psychoactive drugs (n = 21) showed a stronger association between MHE and falls: 6/8 (75%) patients with MHE presented falls vs. 2/13 (15.3%) patients without MHE (P = 0.01). In patients not receiving psychoactive drugs (n = 109), the incidence of falls was 12/37 (32.4%) in patients with MHE vs. 9/72 (12.5%) in those without MHE (P = 0.01). Multivariate analysis showed that MHE (odds ratio (OR): 2.91, 95% confidence interval (CI): 1.13-7.48, P = 0.02), previous encephalopathy (OR: 2.87, 95 % CI: 1.10-7.50, P = 0.03), and antidepressant therapy (OR: 3.91, 95 % CI: 0.96-15.9, P = 0.05) were independent factors associated to previous falls. CONCLUSIONS: Falls are more frequent in cirrhotic patients with MHE, particularly in those on treatment with psychoactive drugs, and are a significant cause for healthcare and hospitalization requirements.

Aliment Pharmacol Ther 2011; 33: 275–284 Summary Background Despite inoculation into blood culture bottles, ascitic fluid culture is negative in 50% of cases of spontaneous bacterial peritonitis (SBP). Aim To determine whether 16S rDNA gene detection by real-time polymerase chain reaction (PCR) and sequencing increases the efficacy of culture in microbiological diagnosis of spontaneous bacterial peritonitis. Methods We prospectively included 55 consecutive spontaneous bacterial peritonitis episodes in cirrhotic patients, 20 cirrhotic patients with sterile ascites and 27 patients with neoplasic ascites. Ascitic fluid was inoculated into blood culture bottles at the bedside and tested for bacterial DNA by real-time PCR and sequencing of 16S rDNA gene. Results Bacterial DNA was detected in 23/25 (92%) culture-positive SBP, 16/30 (53%) culture-negative SBP (P = 0.002 with respect to culture-positive SBP), 12/20 (60%) sterile ascites (P = 0.01 with respect to culture-positive SBP) and 0/27 neoplasic ascites (P

Background & Aims Patients with hepatitis C virus-associated cirrhosis and clinical significant portal hypertension (CSPH, hepatic venous pressure gradient [HVPG] 10 mmHg or greater), despite achieving sustained virological response (SVR) to therapy, remain at risk of liver decompensation. We investigated hemodynamic changes following SVR in patients with CSPH and whether liver stiffness measurements (LSMs) can rule out the presence of CSPH. Methods We performed a multicenter prospective study of 226 patients with hepatitis C virus-associated cirrhosis and CSPH who had SVR to interferon-free therapy at 6 Liver Units in Spain. The portal pressure gradient was determined based on HVPG at baseline and 24 weeks after therapy; patients also underwent right-heart catheterization and LSM at these time points. Primary outcomes were effects of SVR on the hepatic, pulmonary, and systemic hemodynamics; factors related to HVPG ≥10% reduction and to CSPH persistence; and whether LSMs can rule out the presence of CSPH after SVR. Results Most patients (75%) had esophageal varices, 21% were Child-B, and 29% had at least 1 previous episode of liver decompensation. Overall, HVPG decreased from 15 (IQR: 12–18) before treatment to 13 (10–16) mmHg after SVR (reduction of 2.1 ± 3.2 mmHg; P P Conclusions In a multicenter prospective study of patients with hepatitis C virus-associated cirrhosis, an SVR to all-oral therapy significantly reduced HVPG, compared with before treatment. Nevertheless, CSPH persists in most patients despite SVR, indicating persistent risk of decompensation. In this population, changes in LSM do not correlate with HVPG and cut-off values are not reliable in ruling out CSPH after SVR.