Characterizing Hepatitis Delta in Spain and the gaps in its management.

BACKGROUND AND AIMS: Chronic hepatitis D (CHD) is a severe form of chronic viral hepatitis. The estimated hepatitis delta prevalence in Spain is around 5% of patients with hepatitis B. Reimbursement of new antiviral therapies (Bulevirtide, BLV) was delayed in our country until February 2024. We aimed to characterize the clinical profile of patients with HDV/HBV infection in Spain and current barriers in their management at the time of BLV approval. METHOD: Multicenter registry including patients with positive anti-HDV serology actively monitored in 30 Spanish centers. Epidemiological, clinical and virological variables were recorded at the start of follow-up and at the last visit. RESULTS: We identified 329 anti-HDV patients, 41% were female with median age 51 years. The most common geographical origin was Spain (53%) and East Europe (24%). Patients from Spain were older and had HCV and HIV coinfection probably associated to past drug injection (p<0.01). HDV-RNA was positive in 138 of 221 assessed (62%). Liver cirrhosis was present at diagnosis in 33% and it was more frequent among viremic patients (58% vs 25%, p<0.01). After a median follow-up of 6 (3-12) years, 44 (16%) resolved infection (18 spontaneously and 26 after Peg-INF). An additional 10% of patients developed cirrhosis (n=137) during follow-up (45% had portal hypertension and 14% liver decompensation). Liver disease progression was associated to persisting viremia. CONCLUSION: One-third of the patients with CHD already have cirrhosis at diagnosis. Persistence of positive viremia is associated to rapid liver disease progression. Importantly, barriers to locally determine/quantify HDV-RNA were present.

Increased risk of MAFLD and Liver Fibrosis in Inflammatory Bowel Disease Independent of Classic Metabolic Risk Factors.

BACKGROUND & AIMS: There is conflicting evidence regarding the prevalence of and risk factors for metabolic-associated fatty liver disease (MAFLD) in patients with inflammatory bowel disease (IBD). We aimed to determine MAFLD prevalence and risk factors in IBD patients. METHODS: Cross-sectional, case-control study included all consecutive IBD patients treated at 2 different university hospitals. Controls were subjects randomly selected from the general population and matched by age, sex, type 2 diabetes status, and body mass index in a 1:2 ratio. MAFLD was confirmed by controlled attenuation parameter. Liver biopsies were collected when MAFLD with significant liver fibrosis was suspected. In addition, age- and fibrosis stage-paired non-IBD patients with biopsy-proven MAFLD served as a secondary control group. RESULTS: Eight hundred thirty-one IBD patients and 1718 controls were included. The prevalence of MAFLD and advanced liver fibrosis (transient elastography ≥9.7 kPa) was 42.00% and 9.50%, respectively, in IBD patients and 32.77% and 2.31%, respectively, in the general population (P < .001). A diagnosis of IBD was an independent predictor of MAFLD (adjusted odds ratio, 1.99; P < .001) and an independent risk factor for advanced liver fibrosis (adjusted odds ratio, 5.55; P < .001). Liver biopsies were obtained from 40 IBD patients; MAFLD was confirmed in all cases, and fibrosis of any degree was confirmed in 25 of 40 cases (62.5%). Body mass index and type 2 diabetes prevalence were significantly lower in IBD-MAFLD patients than in severity-paired patients with biopsy-proven MAFLD. CONCLUSIONS: MAFLD and liver fibrosis are particularly prevalent in IBD patients, regardless of the influence of classic metabolic risk factors.

Prevalence estimation of significant fibrosis because of NASH in Spain combining transient elastography and histology.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) has become a major public health problem, but the prevalence of fibrosis associated with non-alcoholic steatohepatitis (NASH) is largely unknown in the general population. This study aimed to provide an updated estimation of the prevalence of NASH fibrosis in Spain. METHODS: This was an observational, retrospective, cross-sectional, population-based study with merged data from two Spanish datasets: a large (N = 12 246) population-based cohort (ETHON), including transient elastography (TE) data, and a contemporary multi-centric biopsy-proven NASH cohort with paired TE data from tertiary centres (N = 501). Prevalence for each NASH fibrosis stage was estimated by crossing TE data from ETHON dataset with histology data from the biopsy-proven cohort. RESULTS: From the patients with valid TE in ETHON dataset (N = 11 440), 5.61% (95% confidence interval [95% CI]: 2.53-11.97) had a liver stiffness measurement (LSM) ≥ 8 kPa. The proportion attributable to NAFLD (using clinical variables and Controlled Attenuation Parameter) was 57.3% and thus, the estimated prevalence of population with LSM ≥ 8 kPa because of NAFLD was 3.21% (95% CI 1.13-8.75). In the biopsy-proven NASH cohort, 389 patients had LSM ≥ 8 kPa. Among these, 37% did not have significant fibrosis (F2-4). The estimated prevalence of NASH F2-3 and cirrhosis in Spain's adult population were 1.33% (95% CI 0.29-5.98) and 0.70% (95% CI 0.10-4.95) respectively. CONCLUSIONS: These estimations provide an accurate picture of the current prevalence of NASH-related fibrosis in Spain and can serve as reference point for dimensioning the therapeutic efforts that will be required as NASH therapies become available.

A nomogram as an indirect method to identify sarcopenia in patients with liver cirrhosis.

INTRODUCTION AND OBJECTIVES: Sarcopenia is one of the most common complications of cirrhosis, associated with an increased risk of morbidity and mortality. It is therefore necessary to perform a proper nutritional evaluation in these patients. Although CT scans are the gold standard for diagnosing sarcopenia, they are not widely used in clinical practice. There is thus a need to find indirect methods for identifying sarcopenia in patients with cirrhosis. MATERIAL AND METHODS: This is a cross-sectional study consecutively including all cirrhotic outpatients who underwent CT scans. RESULTS: A total of 174 patients met all the inclusion criteria and none of exclusion criteria. Fifty-five patients (31.6%) showed sarcopenia on CT scans. Multivariate analysis revealed that the factors that were independently associated with the presence of sarcopenia on CT scans were: male sex (OR 11.27, 95% CI 3.53-35.95; p<0.001), lower body mass index (BMI) (OR 1.22, 95% CI 1.11-1.34; p<0.001) and lower phase angle by bioelectrical impedance analysis (OR 2.83, 95% CI 1.74-4.6; p<0.001). With the variables identified from the multivariate study we developed a nomogram that allows ruling out the presence of sarcopenia. Our model rules out sarcopenia with an area under the receiver operating characteristic curve value of 0.8. The cutoff point of the probability to rule out sarcopenia was 0.6 (sensitivity 85%, specificity 73%, Youden index 0.58, PPV 82.5% and NPV 91.3%). CONCLUSION: Since CT scans involve exposure to radiation and their availability is limited, we propose using this nomogram as an indirect method to rule out sarcopenia in cirrhotic patients.

Adding Branched-Chain Amino Acids to an Enhanced Standard-of-Care Treatment Improves Muscle Mass of Cirrhotic Patients With Sarcopenia: A Placebo-Controlled Trial.

INTRODUCTION: The effect of branched-chain amino acid (BCAA) supplementation on muscle mass in patients with cirrhosis and sarcopenia is unknown. METHODS: This is a pilot, prospective, randomized, and double-blind study of a cohort of 32 patients with cirrhosis and sarcopenia diagnosed by computed tomography scan who underwent a nutritional and physical activity intervention for 12 weeks. They were divided into 2 groups (placebo: 17 patients; BCAA: 15 patients). The study protocol was registered at ClinicalTrials.gov (NCT04073693). RESULTS: Baseline characteristics were similar in both groups. After treatment, only the BCAA group presented a significant improvement in muscle mass (43.7 vs 46 cm2/m2; P = 0.023). Seventeen patients (63%) presented improvement in muscle mass overall, which was more frequent in the BCAA group (83.3 vs 46.7%; P = 0.056). Regarding frailty, there was a significant improvement in the Liver Frailty Index in the global cohort (n = 32) after the 12 weeks (4.2 vs 3.9; P < 0.001). This difference was significant in both groups: in the placebo group (4.2 vs 3.8; P < 0.001) and in the BCAA group (4.2 vs 3.9; P < 0.001). After treatment, the BCAA group had a higher increase in zinc levels than the placebo group (Δzinc: 12.3 vs 5.5; P = 0.026). In addition, there was a trend for greater improvement of albumin levels in the BCAA group (Δalbumin: 0.19 vs 0.04; P = 0.091). DISCUSSION: BCAA supplementation improves muscle mass in cirrhotic patients with sarcopenia.

Non-malignant portal vein thrombosis in a cohort of cirrhotic patients: Incidence and risk factors.

AIM: Non-malignant portal vein thrombosis (PVT) is a complication of liver cirrhosis. The aim of this study was to evaluate the annual incidence of PVT and related risk factors. METHODS: We retrospectively reviewed clinical, laboratory, and radiological data collected prospectively from September 2016 to September 2017. A follow-up of 36 months was performed in a subset of patients to determine the cumulative incidence of PVT and related complications. RESULTS: The study included 567 patients. The incidence of PVT at 12, 24, and 36 months was 3.7%, 0.8%, and 1.4%, respectively. Patients with PVT were compared with patients without PVT, and showed differences in albumin (p = 0.04), aspartate aminotransferase (p = 0.04), hemoglobin (p = 0.01), and prothrombin activity (p = 0.01). The presence of hydropic decompensation (57.1% vs. 30.1%; p 0.004), gastroesophageal varices (76.2% vs. 39.5%; p = 0.05), variceal bleeding (52.4% vs. 22.7%; p < 0.001), hepatic encephalopathy (38.1% vs. 9.9%; p = 0.01), spontaneous bacterial peritonitis (9.5% vs. 1.7%; p < 0.001), and use of beta-blockers (71.4% vs. 27.7%; p < 0.001) were significantly associated. In the multivariate analysis, use of beta-blockers and hepatic encephalopathy appeared as risk factors, and high albumin levels a protective factor. CONCLUSIONS: The incidence of PVT was 3.7%. Beta-blockers and hepatic encephalopathy were risks factors. High albumin levels were a protective factor.

Massive impact of coronavirus disease 2019 pandemic on gastroenterology and hepatology departments and doctors in Spain.

BACKGROUND AND AIM: Significant human and material resources have been diverted to coronavirus disease 2019 (COVID-19). Healthcare workers are at high risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We assess the impact of the COVID-19 pandemic on gastroenterology and hepatology departments and specialists in Spain. METHODS: This study involves a nationwide survey addressing the impact of COVID-19 on resources, procedures, and physicians of gastroenterology and hepatology departments in 81 hospitals representative of the Spanish National Health Service. RESULTS: Overall, 41.8% of hospital beds and 40.7% of gastroenterology and hepatology beds were allocated to COVID-19 patient care, as well as 24.8% of gastroenterologists and 58.3% of residents. Outpatient visits, abdominal ultrasounds, and endoscopies were reduced by 81.8-91.9%. Nine large university hospitals had 75% and 89% reductions in therapeutic endoscopies and hepatocellular carcinoma surgery, respectively, with cancelation of elective liver transplant and transjugular intrahepatic portosystemic shunt. Prevalence of infected physicians was 10.6% and was dependent on regional population incidence (r = 0.74, P = 0.001), with 11% hospitalized and one physician dying. Up to 63.4% of physicians may have been infected before or shortly after Spain entered lockdown, 57% of them having recently performed endoscopies. Adequate protection was acknowledged in > 80% hospitals, but only 2.9% performed regular SARS-CoV-2 testing. CONCLUSIONS: The impact of the COVID-19 pandemic on healthcare delivery has been massive. A wave of gastroenterology-related complications is expected because of resource diversion. Gastroenterologists have a high prevalence of infection, although they may have been infected during a first phase of lower awareness and protection. Regular SARS-CoV-2 screening, adequate protection, and quick reorganization of healthcare resources are still needed.

Accuracy of the Narrow-Band Imaging International Colorectal Endoscopic Classification System in Identification of Deep Invasion in Colorectal Polyps.

BACKGROUND & AIMS: T1 colorectal polyps with at least 1 risk factor for metastasis to lymph node should be treated surgically and are considered endoscopically unresectable. Optical analysis, based on the Narrow-Band Imaging International Colorectal Endoscopic (NICE) classification system, is used to identify neoplasias with invasion of the submucosa that require endoscopic treatment. We assessed the accuracy of the NICE classification, along with other morphologic characteristics, in identifying invasive polyps that are endoscopically unresectable (have at least 1 risk factor for metastasis to lymph node). METHODS: We performed a multicenter, prospective study of data collected by 58 endoscopists, from 1634 consecutive patients (examining 2123 lesions) at 17 university and community hospitals in Spain from July 2014 through June 2016. All consecutive lesions >10 mm assessed with narrow-band imaging were included. The primary end point was the accuracy of the NICE classification for identifying lesions with deep invasion, using findings from histology analysis as the reference standard. Conditional inference trees were fitted for the analysis of diagnostic accuracy. RESULTS: Of the 2123 lesions analyzed, 89 (4.2%) had features of deep invasion and 91 (4.3%) were endoscopically unresectable. The NICE classification system identified lesions with deep invasion with 58.4% sensitivity (95% CI, 47.5-68.8), 96.4% specificity (95% CI, 95.5-97.2), a positive-predictive value of 41.6% (95% CI, 32.9-50.8), and a negative-predictive value of 98.1% (95% CI, 97.5-98.7). A conditional inference tree that included all variables found the NICE classification to most accurately identify lesions with deep invasion (P < .001). However, pedunculated morphology (P < .007), ulceration (P = .026), depressed areas (P < .001), or nodular mixed type (P < .001) affected accuracy of identification. Results were comparable for identifying lesions that were endoscopically unresectable. CONCLUSIONS: In an analysis of 2123 colon lesions >10 mm, we found the NICE classification and morphologic features identify those with deep lesions with >96% specificity-even in non-expert hands and without magnification. ClinicalTrials.gov number NCT02328066.

Epidemiology of hepatitis C virus infection in a country with universal access to direct-acting antiviral agents: Data for designing a cost-effective elimination policy in Spain.

Accurate HCV prevalence estimates are necessary for guiding elimination policies. Our aim was to determine the HCV prevalence and assess the cost-effectiveness of a screen-and-treat strategy in the Spanish population. A population-based, cross-sectional study (PREVHEP-ETHON Cohort, Epidemiological sTudy of Hepatic infectiONs; NCT02749864) was performed from July 2015-April 2017. Participants from three Spanish regions were selected using two-stage conglomerate sampling, and stratified by age, with randomized subject selection. Anthropometric and demographic data were collected, and blood samples were taken to detect anti-HCV antibodies/quantify HCV RNA. The cost-effectiveness of the screening strategies and treatment were analysed using a Markov model. Among 12 246 participants aged 20-74 (58.4% females), the overall anti-HCV prevalence was 1.2% (95% CI 1.0-1.4), whereas the detectable HCV-RNA prevalence was 0.3% (0.2-0.4). Infection rates were highest in subjects aged 50-74 years [anti-HCV 1.6% (1.3-1.9), HCV RNA 0.4% (0.3-0.6]. Among the 147 anti-HCV + subjects, 38 (25.9%) had active infections while 109 (74.1%) had been cleared of infection; 44 (40.4%) had cleared after antiviral treatment, whereas 65 (59.6%) had cleared spontaneously. Overall, 59.8% of the anti-HCV + participants were aware of their serological status. Considering a cost of treatment of €7000/patient, implementing screening programmes is cost-effective across all age cohorts, particularly in patients aged 50-54 (negative incremental cost-effectiveness ratio which indicates a cost-saving strategy). The current HCV burden is lower than previously estimated, with approximately 25% of anti-HCV + individuals having an active infection. A strategy of screening and treatment at current treatment prices in Spain is cost-effective across all age cohorts.

Update on epidemiology of hepatitis B in a low-endemic European country: There is still much to do.

The latest epidemiological data in Spain were obtained a decade ago and revealed a prevalence of hepatitis B surface antigen (HBsAg) of 0.7%; hence, updated epidemiological data are necessary. Our aim was to determine the prevalence of hepatitis B virus (HBV) infection, and to analyse associated factors and characterize chronic infection. A population-based, cross-sectional study was performed in Spain between July 2015 and April 2017. Participants from three regions were selected using two-stage conglomerate sampling and stratified by age. Anthropometric and demographic data were collected, and blood samples were taken to detect serological markers of HBV infection and to quantify HBV-DNA. The characterization of chronic HBV infection was based on ALT (alanine aminotransferase) values, HBV-DNA levels, and results of transient elastography. The overall prevalence rates of HBsAg and antibody to hepatitis B core antigen (anti-HBc) among 12 246 participants aged 20-74 years (58.4% females) were 0.6% (95% CI [0.4-0.7]) and 8.2% (7.7-8.7), respectively. The risk factors for HBV infection identified in the multivariate analysis were age, nosocomial risk, and non-Spanish nationality. Moreover, most patients HBsAg positive (76.6%) presented as hepatitis B e antigen (HBeAg)-negative chronic infection (formerly 'inactive carriers') and only 6 (9.4%) HBsAg carriers fulfilled current criteria for treatment. The current HBV burden in Spain remains low but virtually unchanged over the past 15 years. Increased efforts are still needed to reach the goal set forth by the World Health Organization (WHO) for HBV elimination by 2030.

Effectiveness and safety of elbasvir/grazoprevir therapy in patients with chronic HCV infection: Results from the Spanish HEPA-C real-world cohort.

In randomized controlled trials of patients with chronic HCV infection, elbasvir/grazoprevir (EBR/GZR) demonstrated high cure rates and a good safety profile. This study assessed the effectiveness and safety of EBR/GZR, with and without ribavirin, in a real-world HCV patient cohort. HEPA-C is a collaborative, monitored national registry of HCV patients directed by the Spanish Association for the Study of the Liver and the Networked Biomedical Research Centre for Hepatic and Digestive Diseases. Patients entered into HEPA-C between December 2016 and May 2017, and treated with EBR/GZR with at least end-of-treatment response data, were included. Demographic, clinical and virologic data were analysed, and adverse events (AEs) recorded. A total of 804 patients were included in the study. The majority were male (57.9%), with a mean age of 60 (range, 19-92) years. Genotype (GT) distribution was GT 1, 86.8% (1a, 14.3%; 1b, 72.5%); GT 4, 13.2% and 176 patients (21.9%) were cirrhotic. Overall, among 588 patients with available data, 570 (96.9%) achieved sustained virologic response at 12 weeks post-treatment (SVR12). SVR12 rates by genotype were GT 1a, 97.7%; GT 1b, 98.6%; and GT 4, 98.1%. No significant differences in SVR12 according to fibrosis stage were observed. Eighty patients experienced an AE, resulting in treatment discontinuation in three. In this large cohort of patients with chronic HCV managed in a real-world setting in Spain, EBR/GZR achieved high rates of SVR12, comparable to those observed in randomized controlled trials, with a similarly good safety profile.

Impact of sustained viral response in the evolution of minimal hepatic encephalopathy: A prospective pilot study.

INTRODUCTION AND AIMS: To determine the prevalence of minimal hepatic encephalopathy(MHE) in patients with liver cirrhosis (LC) due to hepatitis C virus (HCV) infection and to evaluate the impact of sustained viral response (SVR) on MHE. MATERIALS AND METHODS: We performed a prospective study using MHE screening and follow-up on patients with HCV and LC. The patients were evaluated at the beginning of treatment and 24 weeks after treatment. RESULTS: 64 patients were included. 51.6% were male, the median age was 62 years, Child-Pugh classification A/B/C 93.8%/4.7%/1.6% and median MELD was 8.3. Prior hydropic decompensation was present in 11 patients. Median values of liver stiffness, as measured by transient elastography (TE) were 22.8kPa. Indirect signs of portal hypertension (PH) were present in 53.1% of patients, with a mean of 11.9mmHg among the ones with a measurement of the hepatic venous pressure gradient. The prevalence of MHE before treatment was 26.6%. After treatment, 98.4% of patients achieved SVR. The presence of MHE at 24 weeks post-treatment had an statistically significant association with the presence of pre-treatment MHE (80% vs. 21.6%; p<0.01), higher MELD scores at 24-weeks post-treatment (9.8 vs. 8; p=0.02), higher Child-Pugh scores at 24-weeks post-treatment (p=0.04), higher baseline INR levels (1.4 vs. 1.1; p<0.001) and with the presence of indirect signs of PH (100% vs. 47.1%; p=0.02). During follow-up, those patients without MHE at 24 weeks post-treatment had a higher probability of experiencing an improvement in post-treatment TE (80.9% vs. 40%, p=0.04). CONCLUSION: We found that SVR may lead to MHE resolution in a considerable proportion of patients, which has potential implications for disease prognosis.

Impact of Sustained Viral Response in the Evolution of Minimal Hepatic Encephalopathy: a Prospective Pilot Study.

INTRODUCTION AND AIMS: To determine the prevalence of minimal hepatic encephalopathy (MHE) in patients with liver cirrhosis (LC) due to hepatitis C virus (HCV) infection and to evaluate the impact of sustained viral response (SVR) on MHE. MATERIAL AND METHODS: We performed a prospective study using MHE screening and follow-up on patients with HCV and LC. The patients were evaluated at the beginning of treatment and 24 weeks after treatment. RESULTS: 64 patients were included. 51.6% were male, the median age was 62years, Child-Pugh classification A/B/C 93.8%/4.7%/1.6% and median MELD was 8.3. Prior hydropic decompensation was present in 11 patients. Median values of liver stiffness, as measured by transient elastography (TE) were 22.8 KPa. Indirect signs of portal hypertension (PH) were present in 53.1% of patients, with a mean of 11.9 mmHg among the ones with a measurement of the hepatic venous pressure gradient. The prevalence of MHE before treatment was 26.6%. After treatment, 98.4% of patients achieved SVR. The presence of MHE at 24weeks post-treatment had an statistically significant association with the presence of pre-treatment MHE (80% vs. 21.6%; p < 0.01), higher MELD scores at 24-weeks post-treatment (9.8 vs. 8; p = 0.02), higher Child-Pugh scores at 24-weeks post-treatment (p = 0.04), higher baseline INR levels (1.4 vs. 1.1; p < 0.001) and with the presence of indirect signs of PH (100% vs. 47.1%; p = 0.02). During follow-up, those patients without MHE at 24weeks post-treatment had a higher probability of experiencing an improvement in post-treatment TE (80.9% vs. 40%, p = 0.04). CONCLUSION: We found that SVR may lead to MHE resolution in a considerable proportion of patients, which has potential implications for disease prognosis.

Clinical guidelines for endoscopic mucosal resection of non-pedunculated colorectal lesions.

This document summarizes the contents of the Clinical Guidelines for the Endoscopic Mucosal Resection of Non-Pedunculated Colorectal Lesions that was developed by the working group of the Spanish Society of Digestive Endoscopy (GSEED of Endoscopic Resection). This document presents recommendations for the endoscopic management of superficial colorectal neoplastic lesions.

Clinical guidelines for endoscopic mucosal resection of non-pedunculated colorectal lesions. / Guía clínica para la resección mucosa endoscópica de lesiones colorrectales no pediculadas.

This document summarizes the contents of the Clinical Guidelines for the Endoscopic Mucosal Resection of Non-Pedunculated Colorectal Lesions that was developed by the working group of the Spanish Society of Digestive Endoscopy (GSEED of Endoscopic Resection). This document presents recommendations for the endoscopic management of superficial colorectal neoplastic lesions.

Real-World Effectiveness and Safety of Oral Combination Antiviral Therapy for Hepatitis C Virus Genotype 4 Infection.

Patients with hepatitis C virus (HCV) genotype 4 infection are poorly represented in clinical trials of second-generation direct-acting antiviral agents (DAAs). More data are needed to help guide treatment decisions. We investigated the effectiveness and safety of DAAs in patients with genotype 4 infection in routine practice. In this cohort study, HCV genotype 4-infected patients treated with ombitasvir/paritaprevir/ritonavir (OMV/PTVr) + ribavirin (RBV) (n=122) or ledipasvir/sofosbuvir (LDV/SOF) ± RBV (n=130) included in a national database were identified and prospectively followed up. Demographic, clinical and virologic data and serious adverse events (SAEs) were analyzed. Differences between treatment groups mean that data cannot be compared directly. Overall sustained virologic response at Week 12 post treatment (SVR12) was 96.2% with OMV/PTVr+RBV and 95.4% with LDV/SOF±RBV. In cirrhotic patients, SVR12 was 91.2% with OMV/PTVr+RBV and 93.2% with LDV/SOF±RBV. There was no significant difference in SVR12 according to degree of fibrosis in either treatment group (P = .243 and P = .244, respectively). On multivariate analysis, baseline albumin <3.5 g/dL (OMV/PTVr) and bilirubin >2 mg/dL (both cohorts) were significantly associated with failure to achieve SVR (P < .05). Rates of SAEs and SAE-associated discontinuation were 5.7% and 2.5%, respectively, in the OMV/PTVr subcohort and 4.6% and 0.8%, respectively, in the LDV/SOF subcohort. DAA-based regimens returned high rates of SVR12, comparable to limited data from clinical trials, in cirrhotic and non-cirrhotic HCV genotype 4 patients managed in a realworld setting. Safety profiles of both regimens were good and comparable to those reported for other HCV genotypes.

Reactivation of Herpesvirus in Patients With Hepatitis C Treated With Direct-Acting Antiviral Agents.

We performed a case-series analysis of reactivation of herpesvirus in patients with hepatitis C virus (HCV) infection treated with direct-acting antiviral (DAA) agents. We collected data from 576 patients with HCV infection treated with DAA combinations at 3 hospitals in Spain, from November 2014 through November 2015. We also collected data from a control population (230 HCV-infected patients, matched for sex and age; 23 untreated and 213 treated with interferon-based regimens). Herpesvirus was reactivated in 10 patients who received DAA therapy (7 patients had cirrhosis and 3 patients had received liver transplants), a median of 8 weeks after the therapy was initiated. None of the controls had herpesvirus reactivation. Patients with herpesvirus reactivation were receiving the DAA agents sofosbuvir with ledipasvir (with or without ribavirin, 7/10), ombitasvir with paritaprevir and ritonavir plus dasabuvir (with or without ribavirin, 2/10), or sofosbuvir with simeprevir plus ribavirin (1/10). Two of the 10 patients developed postherpetic neuralgia and 1 patient developed kerato-uveitis. All 10 patients with herpesvirus reactivation achieved a sustained virologic response. Immune changes that follow clearance of HCV might lead to reactivation of other viruses, such as herpesvirus. Patients with HCV infection suspected of having herpesvirus infection should be treated immediately. Some groups also might be screened for herpesvirus infection.

Prevalence and outcome of portal thrombosis in a cohort of cirrhotic patients undergoing liver transplantation.

INTRODUCTION: The prevalence of portal vein thrombosis (PVT) in patients that have undergone liver transplantation (LT) is 9.7% (SD 4.5). The aim of our study was to determine the prevalence, assess the factors that are associated with PVT and clarify their association with prognosis in patients with liver cirrhosis (LC) and LT. AIMS AND METHODS: From 2005 to 2014, laboratory, radiological and surgical data were collected from patients with LC in our center who had undergone LT for the first time. RESULTS: One hundred and ninety-one patients were included. The mean age was 55 (SD 9), 75.4% of patients were male and 48.7% had HCV. The Child-Pugh scores were A/B/C 41.9%/35.9%/25.5% and the MELD score was 15 (SD 6). Previous decompensations were: ascites (61.4%), hepatic encephalopathy (34.4%), variceal bleeding (25.4%), hepatocellular carcinoma (48.9%) and spontaneous bacterial peritonitis (SPB) (14.3%). The mean post-transplant follow-up was 42 months (0-113). PVT was diagnosed at LT in 18 patients (9.4%). Six patients were previously diagnosed using imaging tests (33.3%): 2 patients (11.1%) by DU and 4 patients (22.2%) by CT scan. All patients with PVT had DU in a mean time of 6 months before LT (0-44) and 90 patients (47.1%) had a CT scan in a median time of 6 months before LT (0-45). PVT was significantly related to the presence of SBP (33.3% vs 12.6%; p = 0.02) and lower levels of albumin (3.1g/dl vs 3.4g/dl; p = 0.05). MELD was higher in patients with PVT (16.6 vs 14.9; p = 0.3). There were no significant differences with regard to the need for transfusion of blood components. Moreover, the surgery time was similar in both groups. PVT correlated with a higher mortality in the first 30 days (8.8% vs 16.7%; p = 0.2). CONCLUSION: Prior history of SBP and lower levels of albumin were identified as factors associated with PVT. The pre-transplant diagnosis rate is very low and the presence of PVT may have implications for short-term mortality.

High liver stiffness values by transient elastography related to metabolic syndrome and harmful alcohol use in a large Spanish cohort.

BACKGROUND AND AIMS: Transient elastography (TE) to estimate liver stiffness has proved to be very useful in the diagnosis of chronic liver disease. Here, we intend to evaluate its use in a large Spanish cohort. METHOD: Nested study within the PREVHEP-ETHON (Epidemiological sTudy of Hepatic infectiONs; NCT02749864) population-based, cross-sectional study performed between July 2015 and April 2017. An epidemiological questionnaire, laboratory tests and TE and anthropometric measurements were obtained. RESULTS: Data from 11,440 subjects were analyzed. Mean age was 50.3 (SD 12.4), of which 58.1% were women. 15.4% showed metabolic syndrome (NCEP ATP-III), 1.3% were positive for hepatitis C antibodies, 0.8% positive for HBsAg, 9.1% reported harmful use of alcohol. The prevalence of significant fibrosis (LSM > 8 kPa), suggestive compensated advanced chronic liver disease (cACLD) (LSM ≥ 10 kPa) and highly suggestive cACLD (LSM > 15 kPa) was 5.6%, 2.9%, and 1.2% respectively. Risk factors associated with significant fibrosis were age (OR 1.03 [1.02-1.04; p < 0.001]), sex (OR 0.8 [0.6-0.95; p = 0.02]), AST (OR 1.01 [1.01-1.02; p < 0.001]), GGT (OR 1.005 [1.003-1.006; p < 0.001]) and metabolic syndrome (OR 2.1 [1.7-2.6; p < 0.001]); risk factors associated with suggestive cACLD were age (OR 1.04 [1.02-1.05; p < 0.001]), AST (OR 1.01 [1.01-1.02; p < 0.001]), GGT (OR 1.006 [1.004-1.008; p < 0.001]), low platelets (OR 0.997 [0.994-0.999; p = 0.02]) and metabolic syndrome (OR 2.2 [1.6-2.9; p < 0.001]); and risk factors associated with highly suggestive cACLD were age (OR 1.04 [1.02-1.06; p = 0.001]), AST (OR 1.02 [1.01-1.03; p < 0.001]), GGT (OR 1.005 [1.003-1.007; p < 0.001]), low platelets (OR 0.993 [0.989-0.997; p < 0.001]), metabolic syndrome (OR 2.1 [1.4-3.3; p = 0.001]) and alcohol consumption (OR 1.8 [1.05-3.1; p = 0.03]). A non-negligible proportion of patients with normal transaminase levels, even with healthy transaminase levels, showed significant fibrosis and suggestive and highly suggestive cACLD 4.6% (95% CI 2.4-3.0), 2.1% (95% CI 1.9-2.5) and 1% (95% CI 0.7-1.1), respectively. CONCLUSION: We found high proportion of significant fibrosis and cACLD measured by TE. The most relevant factor associated with significant fibrosis was metabolic syndrome, however TE is still an imperfect method since it overestimated the fibrosis stage in 50% of the histologically analyzed subjects.

Compound Endoscopic Morphological Features for Identifying Non-Pedunculated Lesions ≥20 mm with Intramucosal Neoplasia.

BACKGROUND: The major limitation of piecemeal endoscopic mucosal resection (EMR) is the inaccurate histological assessment of the resected specimen, especially in cases of submucosal invasion. OBJECTIVE: To classify non-pedunculated lesions ≥20 mm based on endoscopic morphological features, in order to identify those that present intramucosal neoplasia (includes low-grade neoplasia and high-grade neoplasia) and are suitable for piecemeal EMR. DESIGN: A post-hoc analysis from an observational prospective multicentre study conducted by 58 endoscopists at 17 academic and community hospitals was performed. Unbiased conditional inference trees (CTREE) were fitted to analyse the association between intramucosal neoplasia and the lesions' endoscopic characteristics. RESULT: 542 lesions from 517 patients were included in the analysis. Intramucosal neoplasia was present in 484 of 542 (89.3%) lesions. A conditional inference tree including all lesions' characteristics assessed with white light imaging and narrow-band imaging (NBI) found that ulceration, pseudodepressed type and sessile morphology changed the accuracy for predicting intramucosal neoplasia. In ulcerated lesions, the probability of intramucosal neoplasia was 25% (95%CI: 8.3-52.6%; p < 0.001). In non-ulcerated lesions, its probability in lateral spreading lesions (LST) non-granular (NG) pseudodepressed-type lesions rose to 64.0% (95%CI: 42.6-81.3%; p < 0.001). Sessile morphology also raised the probability of intramucosal neoplasia to 86.3% (95%CI: 80.2-90.7%; p < 0.001). In the remaining 319 (58.9%) non-ulcerated lesions that were of the LST-granular (G) homogeneous type, LST-G nodular-mixed type, and LST-NG flat elevated morphology, the probability of intramucosal neoplasia was 96.2% (95%CI: 93.5-97.8%; p < 0.001). CONCLUSION: Non-ulcerated LST-G type and LST-NG flat elevated lesions are the most common non-pedunculated lesions ≥20 mm and are associated with a high probability of intramucosal neoplasia. This means that they are good candidates for piecemeal EMR. In the remaining lesions, further diagnostic techniques like magnification or diagnostic +/- therapeutic endoscopic submucosal dissection should be considered.