Dynamic Changes in Non-Invasive Markers of Liver Fibrosis Are Predictors of Liver Events after SVR in HCV Patients.

Objectives: The course of progressive liver damage after achieving sustained virological response (SVR) with direct-acting antivirals (DAAs) remains undetermined. We aimed to determine risk factors associated with the development of liver-related events (LREs) after SVR, focusing on the utility of non-invasive markers. Methods: An observational, retrospective study that included patients with advanced chronic liver disease (ACLD) caused by hepatitis C virus (HCV), who achieved SVR with DAAs between 2014 and 2017. Patients were followed-up until December 2020. LREs were defined as the development of portal hypertension decompensation and the occurrence of hepatocellular carcinoma (HCC). Serological markers of fibrosis were calculated before treatment and one and two years after SVR. Results: The study included 321 patients, with a median follow-up of 48 months. LREs occurred in 13.7% of patients (10% portal hypertension decompensation and 3.7% HCC). Child-Pugh [HR 4.13 (CI 95% 1.74; 9.81)], baseline FIB-4 [HR 1.12 (CI 95% 1.03; 1.21)], FIB-4 one year post-SVR [HR 1.31 (CI 95% 1.15; 1.48)] and FIB-4 two years post-SVR [HR 1.42 (CI 95% 1.23; 1.64)] were associated with portal hypertension decompensation. Older age, genotype 3, diabetes mellitus and FIB-4 before and after SVR were associated with the development of HCC. FIB-4 cut-off values one and two years post-SVR to predict portal hypertension decompensation were 2.03 and 2.21, respectively, and to predict HCC were 2.42 and 2.70, respectively. Conclusions: HCV patients with ACLD remain at risk of developing liver complications after having achieved SVR. FIB-4 evaluation before and after SVR may help to predict this risk, selecting patients who will benefit from surveillance.

A 2-Step Strategy Combining FIB-4 With Transient Elastography and Ultrasound Predicted Liver Cancer After HCV Cure.

INTRODUCTION: Despite the direct-acting antiviral therapy has dramatically decreased the likelihood of having liver-related complications and extrahepatic outcomes, the risk of developing hepatocellular carcinoma (HCC) is not totally eliminated after sustained virological response (SVR). We aimed to develop an easy-to-apply strategy to be adopted in clinical practice for accurately classifying the HCC risk in hepatitis C virus patients after SVR. METHODS: Prospective and multicenter study enrolling hepatitis C virus patients with advanced fibrosis (transient elastography [TE] > 10 kPa) or cirrhosis by ultrasound showing SVR. They were followed up until HCC, liver transplantation, death, or until October 2020, which occurred first, with a minimum follow-up period of 6 months after SVR (follow-up: 49 [interquartile range 28-59] months). RESULTS: Patients with cirrhosis by ultrasound represented 58% (611/1,054) of the overall cohort. During the study, HCC occurrence was 5.3% (56/1,054). Multivariate analyses revealed that Fibrosis-4 (FIB-4) > 3.25 (hazard ratio [HR] 2.26 [1.08-4.73]; P = 0.030), TE (HR 1.02 [1.00-1.04]; P = 0.045) and cirrhosis by ultrasound (HR 3.15 [1.36-7.27]; P = 0.007) predicted HCC occurrence. Baseline HCC screening criteria (TE > 10 kPa or cirrhosis) identified patients at higher risk of HCC occurrence in presence of FIB-4 > 3.25 (8.8%; 44/498) vs FIB-4 < 3.25 (2.4%; 12/506), while those with only FIB > 3.25 had no HCC (0%; 0/50) (logRank 22.129; P = 0.0001). A combination of baseline FIB-4 > 3.25 and HCC screening criteria had an annual incidence >1.5 cases per 100 person-years, while the rest of the groups remained <1 case. Patients who maintained post-treatment FIB-4 > 3.25 and HCC screening criteria remained at the highest risk of HCC occurrence (13.7% [21/153] vs 4.9% [9/184]; logRank 7.396, P = 0.007). DISCUSSION: We demonstrated that a two-step strategy combining FIB-4, TE, and ultrasound could help stratify HCC incidence risk after SVR.

HCV microelimination strategies: An interventional study in diagnosed patients without access to the system.

Hepatitis C virus (HCV) one-step diagnosis improves recovery in patients with active infection. However, patients with previous anti-HCV+ may be excluded. We aimed to identify and retrieve non-referred or lost-to-follow-up HCV-infected patients. All anti-HCV+ patients seen in our hospital between 2013 and 2018 were included. In the first phase, we identified anti-HCV+ patients who were not referred to the Gastroenterology Unit (GU) or lost-to-follow-up. In the second phase, recovered patients were invited for a one-step visit for liver evaluation. A total of 1330 anti-HCV+ patients were included: 21.7% had not been referred to GU, and 23.1% were lost-to-follow-up. In the second phase, 49.6% of patients were contacted, and 92.8% attended a medical consultation: 62.7% had active infection, 92.2% were treated, and 86.5% achieved SVR (ITT). We concluded that screening microbiological data and referring unidentified patients with active HCV infection directly to specialists is an effective tool in achieving HCV microelimination.

Liver manifestations in COVID-19 and the influence of pre-existing liver disease in the course of the infection.

INTRODUCTION: patients with advanced chronic liver disease (CLD) may be at an increased risk of a severe course due to cirrhosis-associated immune dysfunction. The aim of this study was to determine the prevalence of CLD in COVID-19 patients and to analyze the course of the infection, compared with patients with non-liver disease. MATERIALS AND METHODS: this was a retrospective single center study of all patients with a positive SARS-CoV-2 polymerase chain reaction (PCR) test from March 23rd to April 30th, 2020. Clinical and biochemical data of patients with and without CLD and COVID-19 were collected from the medical records. RESULT: four hundred and forty-seven patients with a SARS-CoV-2 positive PCR were included, 6.3 % had CLD; 69.7 % of patients with CLD were male, with a median age of 65.5 years and active alcohol consumption and smoking; 75 % had non-advanced liver fibrosis and most had non-alcoholic fatty liver disease (NAFLD). The hospital admission rate (92.9 % vs 47.7 %, p < 0.001), concomitant comorbidities (diabetes 38.5 vs 16.5 %, p = 0.011; obesity 30.8 vs 8.5 %, p = 0.033; cancer 23.1 vs 5 %, p = 0.027; and chronic obstructive pulmonary disease (COPD) 19.2 vs 9 %, p = 0.009) and concomitant antibiotics treatment (19.3 vs 5 %, p = 0.018) were higher in patients with CLD than in those without CLD. In-patient hospital mortality rates were similar in both groups (30.8 vs 19.6 %, p = 0.289). The presence of CLD was not associated with mortality (OR = 1.06; 95 % CI = 0.35-3.18; p = 0.924). However, patients with CLD and COVID-19 who were male, obese or under concomitant antibiotic treatment had the highest risk of mortality according to the univariate analysis. CONCLUSION: patients with CLD had a higher risk of hospital admission, with worse outcomes during the COVID-19 infection associated to other concomitant comorbidities and a suspicion of bacterial co-infection.

An esophageal neuroendocrine tumor in a Barrett's esophagus successfully treated with endoscopic resection.

Neuroendocrine tumors rarely occur in the esophagus because the neuroendocrine system is not well developed in the esophagus. The case of a neuroendocrine esophageal tumor developed in a patient with Barret's esophagus is presented. It was successfully trated by endoscopy.

Index of the Mayo Endoscopy and Ulcerative Colitis Endoscopy Index of Severity: are they equally valid?

INTRODUCTION: endoscopy plays an essential role in the management of patients with ulcerative colitis (UC), as it allows us to visualize and assess the severity of the disease. Different scores have been devised to standardize the findings because such assessments are not always objective. AIMS: the aim of this study was to assess the interobserver variability between the Index of Mayo Endoscopy (IME) and the Ulcerative Colitis Endoscopy Index of Severity (UCEIS), analyzing the severity of the endoscopic lesions in patients with UC. The secondary aim was to analyze if the cathartic preparation affected the degree of concordance amongst the endoscopists. MATERIAL AND METHODS: this was a single-cohort observational, comparative study in which a colonoscopy was performed in patients with UC, as the normal clinical practice. The results were classified according to the IME and the UCEIS by three endoscopic specialists. In order to assess the degree of interobserver correlation, the Kappa index for IME was used and the intraclass correlation coefficient was used for UCEIS. RESULTS: sixty-seven patients were included in the study. The average age was 51 (SD ± 16.7) and the average Mayo Clinic index was 3.07 (SD ± 2.54). The weighted Kappa index between endoscopists A and B for the IME was 0.8, 0.52 between A and C and 0.49 between B and C. The intraclass correlation coefficient for UCEIS was 0.922 between the three endoscopists (95 % CI: 0.832-0.959). A better interobserver correlation was found when the cathartic preparation was ≥ 8 based on the Boston Scale. CONCLUSIONS: there was a higher correlation between the different endoscopists for the UCEIS than for the IME. Thus, this should be considered to be the best index to use in the clinical practice. A good cleansing preparation is important to improve the interobserver correlation.

Cut-off ranges of infliximab serum levels in Crohn's disease in the clinical practice.

INTRODUCTION: between 30 % and 40 % of patients treated with infliximab lose response during maintenance. Therapeutic drug monitoring could be used to optimize management in these situations. However, infliximab serum levels are not well defined. The aim of this study was to determine the cut-off range of infliximab serum levels in Crohn's disease patients in remission in the clinical practice. METHODS: an observational retrospective study was performed from 2016 to 2017. Patients were included with established Crohn's disease, who had been on a maintenance dose schedule of infliximab. Infliximab levels and antibodies to infliximab were measured at least twice in all patients, after induction and after six months of treatment. Clinical remission was defined as ≤ 4 using the Harvey-Bradshaw index. Cluster analysis was used to analyze the results. RESULTS: one hundred and five Crohn's disease patients were included in the study; 57.1 % were male with a mean age of 39 years (SD ± 12.9). The median (range) time of the disease was eleven years (7-15) and the median (range) time of follow-up was 32 months (22-38). Patients who achieved remission had infliximab serum levels between 4.26-8.26 ug/ml versus 0.06-1.43 ug/ml in patients who did not achieve remission after induction. Infliximab serum levels were 2.84-7.75 ug/ml and 0.05-2.69 ug/ml in patients who achieved remission versus those who did not achieve remission after six months of treatment. Overall, 4.26-8.26 ug/ml was found to be the best cut-off range for remission. CONCLUSIONS: in our clinical practice, serum levels of infliximab in Crohn's disease patients should be higher than 4 ug/ml to achieve clinical remission.

Clip Closure After Resection of Large Colorectal Lesions With Substantial Risk of Bleeding.

BACKGROUND & AIMS: It is not clear whether closure of mucosal defects with clips after colonic endoscopic mucosal resection (EMR) prevents delayed bleeding, although it seems to have no protective effects when risk is low. We performed a randomized trial to evaluate the efficacy of complete clip closure of large (≥2 cm) nonpedunculated colorectal lesions after EMR in patients with an estimated average or high risk of delayed bleeding. METHODS: We performed a single-blind trial at 11 hospitals in Spain from May 2016 through June 2018, including 235 consecutive patients who underwent EMR for large nonpedunculated colorectal lesions with an average or high risk of delayed bleeding (based on Spanish Endoscopy Society Endoscopic Resection Group score). Participants were randomly assigned to groups that received closure of the scar with 11-mm through-the-scope clips (treated, n = 119) or no clip (control, n = 116). The primary outcome was proportion of patients in each group with delayed bleeding, defined as evident hematochezia that required medical intervention within 15 days after colonoscopy. RESULTS: In the clip group, complete closure was achieved in 68 (57%) cases, with partial closure in 33 (28%) cases and failure to close in 18 (15%) cases. Delayed bleeding occurred in 14 (12.1%) patients in the control group and in 6 (5%) patients in the clip group (absolute risk difference, reduction of 7% in the clip group; 95% confidence interval, -14.7% to 0.3%). After completion of the clip closure, there was only 1 (1.5%) case of delayed bleeding (absolute risk difference, reduction of 10.6%; 95% confidence interval, -4.3% to 17.9%). CONCLUSIONS: In a randomized trial of patients with large nonpedunculated colorectal lesions undergoing EMR, we found that clip closure of mucosal defects in patients with a risk of bleeding can be a challenge, but also reduces delayed bleeding. Prevention of delayed bleeding required complete clip closure. ClinicalTrials.gov ID: NCT02765022.

Switching from reference infliximab to CT-P13 in patients with inflammatory bowel disease: results of a multicenter study after 12 months.

BACKGROUND AND AIMS: infliximab has changed the natural history of inflammatory bowel disease (IBD). The advent of biosimilar treatments such as CT-P13 will hopefully improve the availability of biological therapies. Data with regard to drug switching are currently limited. The objective of the study was to assess the effectiveness and safety of switching from the reference product (RP), infliximab, to CT-P13 in patients with IBD. METHODS: this was a multicenter prospective observational study in patients with Crohn's disease (CD) and ulcerative colitis (UC). All patients had switched from infliximab RP (Remicade®) to CT-P13 treatment and were followed up for 12 months. The efficacy endpoint was the change in clinical remission assessed at 0 and 12 months, according to the Harvey-Bradshaw score and partial Mayo score for patients with CD and UC, respectively. Adverse events were monitored and recorded throughout the study. RESULTS: a total of 167 patients (116 CD/51 UC) were included; 88.8% (103/116) of patients with CD were in remission at the time of the drug switch and 69.7% were in remission at 12 months. The Harvey-Bradshaw (HB) score significantly changed at 12 months (p = 0.001); 84.3% (43/51) of patients with UC were in remission at the time of the drug switch and 76.7% were in remission at 12 months. No significant changes in the median partial Mayo score (p = 0.87) were observed at 12 months. Serious adverse events related to medication were reported in 12/167 (7.2%) cases. CONCLUSION: switching from infliximab RP to CT-P13 is safe and effective at 12 months. The loss of efficacy at 12 months was 15.7%.

Late migration of a metal stent after EUS-drainage of a pancreatic pseudocyst abscess.

Endoscopic ultrasound (EUS)-guided drainage of pancreatic collections has replaced surgery as the first line of treatment due its accuracy and safety profile. A higher success rate and fewer adverse events has been observed using fully covered metal stent for the drainage. However, complications of EUS-guided drainage can appear. We present a case of late migration of the stent.

Switching from reference infliximab to CT-P13 in patients with inflammatory bowel disease: 12 months results.

BACKGROUND: Biological agents, such as infliximab, have transformed the outcomes of patients with immune-mediated inflammatory diseases. The advent of biosimilar treatment options such as CT-P13 promises to improve the availability of biological therapy, yet real-world switching data are currently limited. Here, we assess the effectiveness and safety of switching to CT-P13 from infliximab reference product (RP) in patients with inflammatory bowel disease. MATERIALS AND METHODS: This was a prospective single-center observational study in patients with moderate to severe Crohn's disease (CD) and ulcerative colitis (UC). All patients were switched from infliximab RP (Remicade) to CT-P13 treatment and followed up for up to 12 months. The efficacy endpoint was the change in clinical response assessed at 3-monthly intervals, according to the Harvey-Bradshaw score and partial Mayo score for patients with CD and UC, respectively. C-reactive protein (CRP) was also measured. Adverse events were monitored and recorded throughout the study. RESULTS: A total of 98 patients with inflammatory bowel disease (67 CD/31 UC) were included. A total of 83.6% (56/67) of patients with CD were in remission at the time of the switch and 62.7% were in remission at 12 months. The Harvey-Bradshaw score showed a significant change at 12 months (P=0.007) but no significant change was observed in median CRP at this timepoint (P=0.364). A total of 80.6% (25/31) of patients with UC were in remission at the time of the switch and 65.3% (18/28) were in remission at 12 months. No significant changes in the median partial Mayo score (P=0.058) or CRP (P=0.329) were observed at 12 months. Serious adverse events related to medication were reported in 11 (11.2%) patients. CONCLUSION: Switching from infliximab RP to CT-P13 is efficacious and well tolerated in patients with CD or UC for up to 12 months.

Evolution of the incidence of inflammatory bowel disease in Southern Spain.

BACKGROUND: The incidence of inflammatory bowel disease is increasing in Europe and in Spain. However, there is no recent data from Southern Spain. OBJECTIVES: To determine the evolution of the hospital incidence of inflammatory bowel disease in Southern Spain. MATERIAL AND METHODS: A retrospective study was performed in two hospitals in Southern Spain. Data was collected from inflammatory bowel disease patients, divided into two periods (1995-2000 and 2001-2014) and compared. The reference population from both areas was 1,011,555 inhabitants. RESULTS: A total of 430 patients were registered during the first period (1995-2000); 50% (215) had Crohn's disease that resulted in a cumulative incidence rate of 7.08 cases/100,000 inhabitants per year. The overall inflammatory bowel disease incidence was 3.54 cases/100,000 inhabitants per year. During the second period (2001-2014), 2,089 patients were collected; 51.7% had ulcerative colitis (1,081). The rate of cumulative incidence of inflammatory bowel disease was 14.7 cases/100,000 inhabitants per year (7.6 cases of ulcerative colitis/100,000 inhabitants/year and 7.1 cases of Crohn´s disease/100,000 inhabitants/year). CONCLUSIONS: The incidence of inflammatory bowel disease in Southern Spain has doubled in the last decade and is similar to that of the rest of the country and Europe.