Publications by authors named "Javier Ampuero"

80 Publications

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

Am J Gastroenterol 2021 Sep 9. Epub 2021 Sep 9.

Hospital Universitario Virgen del Rocio, Universidad de Sevilla, Spain.

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.
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http://dx.doi.org/10.14309/ajg.0000000000001503DOI Listing
September 2021

Inhibition of ATG3 ameliorates liver steatosis by increasing mitochondrial function.

J Hepatol 2021 Sep 21. Epub 2021 Sep 21.

University of Lübeck, Institute for Experimental and Clinical Pharmacology and Toxicology, Lübeck, Germany.

Background & Aims: Autophagy-related gene 3 (ATG3) is an enzyme mainly known for its actions in the LC3 lipidation process, which is essential for autophagy. Whether ATG3 plays a role in lipid metabolism or contributes to non-alcoholic fatty liver disease (NAFLD) remains unknown.

Methods: By performing proteomic analysis on livers from mice with genetic manipulation of hepatic p63, a regulator of fatty acid metabolism, we identified ATG3 as a new target downstream of p63. ATG3 was evaluated in liver samples from patients with NAFLD. Further, genetic manipulation of ATG3 was performed in human hepatocyte cell lines, primary hepatocytes and in the livers of mice.

Results: ATG3 expression is induced in the liver of animal models and patients with NAFLD (both steatosis and non-alcoholic steatohepatitis) compared with those without liver disease. Moreover, genetic knockdown of ATG3 in mice and human hepatocytes ameliorates p63- and diet-induced steatosis, while its overexpression increases the lipid load in hepatocytes. The inhibition of hepatic ATG3 improves fatty acid metabolism by reducing c-Jun N-terminal protein kinase 1 (JNK1), which increases sirtuin 1 (SIRT1), carnitine palmitoyltransferase 1a (CPT1a), and mitochondrial function. Hepatic knockdown of SIRT1 and CPT1a blunts the effects of ATG3 on mitochondrial activity. Unexpectedly, these effects are independent of an autophagic action.

Conclusions: Collectively, these findings indicate that ATG3 is a novel protein implicated in the development of steatosis.

Lay Summary: We show that autophagy-related gene 3 (ATG3) contributes to the progression of non-alcoholic fatty liver disease in humans and mice. Hepatic knockdown of ATG3 ameliorates the development of NAFLD by stimulating mitochondrial function. Thus, ATG3 is an important factor implicated in steatosis.
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http://dx.doi.org/10.1016/j.jhep.2021.09.008DOI Listing
September 2021

Wilson's disease: Revisiting an old friend.

World J Hepatol 2021 Jun;13(6):634-649

Department of Unit of Digestive Diseases, Hospital Universitario Virgen del Rocio, Sevilla 41014, Spain.

Wilson's disease (WD) is a rare condition caused by copper accumulation primarily in the liver and secondly in other organs, such as the central nervous system. It is a hereditary autosomal recessive disease caused by a deficiency in the ATP7B transporter. This protein facilitates the incorporation of copper into ceruloplasmin. More than 800 mutations associated with WD have been described. The onset of the disease frequently includes manifestations related to the liver (as chronic liver disease or acute liver failure) and neurological symptoms, although it can sometimes be asymptomatic. Despite it being more frequent in young people, WD has been described in all life stages. Due to its fatal prognosis, WD should be suspected in all patients with unexplained biochemical liver abnormalities or neurological or psychiatric symptoms. The diagnosis is established with a combination of clinical signs and tests, including the measurement of ceruloplasmin, urinary copper excretion, copper quantification in liver biopsy, or genetic assessment. The pharmacological therapies include chelating drugs, such as D-penicillamine or trientine, and zinc salts, which are able to change the natural history of the disease, increasing the survival of these patients. In some cases of end-stage liver disease or acute liver failure, liver transplantation must be an option to increase survival. In this narrative review, we offer an overview of WD, focusing on the importance of clinical suspicion, the correct diagnosis, and treatment.
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http://dx.doi.org/10.4254/wjh.v13.i6.634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239488PMC
June 2021

Management of NAFLD patients with advanced fibrosis.

Liver Int 2021 06;41 Suppl 1:95-104

Institute of Biomedicine of Seville (IBiS), SeLiver Group, Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain.

The prevalence of non alcoholic fatty liver disease (NAFLD) has increased to 25% in the general population and could double by 2030. Liver fibrosis is the main indicator of morbidity and mortality and recent estimations suggest a substantial number of individuals with undiagnosed advanced liver disease. Strategies to monitor advanced fibrosis are essential for early detection, referral, diagnosis and treatment in primary care and endocrine units, where NAFLD and consequently liver fibrosis are more prevalent. Blood-based non-invasive methods could be used to stratify patients according to the risk of the progression of fibrosis and combined with imaging techniques to improve stratification. Powerful new diagnostic tools such as MRE and PDFF are emerging and might prevent the need for liver biopsy in the near future. The current therapeutic landscape of NAFLD is rapidly evolving with an increasing number of molecules that treat key factors involved in its progression, but that still have a limited or no ability to effectively reverse fibrosis. Management of this disease will probably require a combination of sequential and personalized treatments as a result of its complex and dynamic pathophysiology. Lifestyle interventions are still the most effective therapeutic option and should be better integrated into patient management together with specific programs of bariatric endoscopy/surgery for morbidly obese patients.
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http://dx.doi.org/10.1111/liv.14847DOI Listing
June 2021

An Experimental DUAL Model of Advanced Liver Damage.

Hepatol Commun 2021 Jun 11;5(6):1051-1068. Epub 2021 Mar 11.

Department of Immunology, Ophthalmology and ENT Complutense University School of Medicine Madrid Spain.

Individuals exhibiting an intermediate alcohol drinking pattern in conjunction with signs of metabolic risk present clinical features of both alcohol-associated and metabolic-associated fatty liver diseases. However, such combination remains an unexplored area of great interest, given the increasing number of patients affected. In the present study, we aimed to develop a preclinical DUAL (alcohol-associated liver disease plus metabolic-associated fatty liver disease) model in mice. C57BL/6 mice received 10% vol/vol alcohol in sweetened drinking water in combination with a Western diet for 10, 23, and 52 weeks (DUAL model). Animals fed with DUAL diet elicited a significant increase in body mass index accompanied by a pronounced hypertrophy of adipocytes, hypercholesterolemia, and hyperglycemia. Significant liver damage was characterized by elevated plasma alanine aminotransferase and lactate dehydrogenase levels, extensive hepatomegaly, hepatocyte enlargement, ballooning, steatosis, hepatic cell death, and compensatory proliferation. Notably, DUAL animals developed lobular inflammation and advanced hepatic fibrosis. Sequentially, bridging cirrhotic changes were frequently observed after 12 months. Bulk RNA-sequencing analysis indicated that dysregulated molecular pathways in DUAL mice were similar to those of patients with steatohepatitis. Our DUAL model is characterized by obesity, glucose intolerance, liver damage, prominent steatohepatitis and fibrosis, as well as inflammation and fibrosis in white adipose tissue. Altogether, the DUAL model mimics all histological, metabolic, and transcriptomic gene signatures of human advanced steatohepatitis, and therefore serves as a preclinical tool for the development of therapeutic targets.
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http://dx.doi.org/10.1002/hep4.1698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183170PMC
June 2021

Long-term outcomes and predictive ability of non-invasive scoring systems in patients with non-alcoholic fatty liver disease.

J Hepatol 2021 10 4;75(4):786-794. Epub 2021 Jun 4.

Department of Medical Sciences, Division of Gastroenterology and Hepatology, A.O. Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy. Electronic address:

Background & Aims: Non-invasive scoring systems (NSS) are used to identify patients with non-alcoholic fatty liver disease (NAFLD) who are at risk of advanced fibrosis, but their reliability in predicting long-term outcomes for hepatic/extrahepatic complications or death and their concordance in cross-sectional and longitudinal risk stratification remain uncertain.

Methods: The most common NSS (NFS, FIB-4, BARD, APRI) and the Hepamet fibrosis score (HFS) were assessed in 1,173 European patients with NAFLD from tertiary centres. Performance for fibrosis risk stratification and for the prediction of long-term hepatic/extrahepatic events, hepatocarcinoma (HCC) and overall mortality were evaluated in terms of AUC and Harrell's c-index. For longitudinal data, NSS-based Cox proportional hazard models were trained on the whole cohort with repeated 5-fold cross-validation, sampling for testing from the 607 patients with all NSS available.

Results: Cross-sectional analysis revealed HFS as the best performer for the identification of significant (F0-1 vs. F2-4, AUC = 0.758) and advanced (F0-2 vs. F3-4, AUC = 0.805) fibrosis, while NFS and FIB-4 showed the best performance for detecting histological cirrhosis (range AUCs 0.85-0.88). Considering longitudinal data (follow-up between 62 and 110 months), NFS and FIB-4 were the best at predicting liver-related events (c-indices>0.7), NFS for HCC (c-index = 0.9 on average), and FIB-4 and HFS for overall mortality (c-indices >0.8). All NSS showed limited performance (c-indices <0.7) for extrahepatic events.

Conclusions: Overall, NFS, HFS and FIB-4 outperformed APRI and BARD for both cross-sectional identification of fibrosis and prediction of long-term outcomes, confirming that they are useful tools for the clinical management of patients with NAFLD at increased risk of fibrosis and liver-related complications or death.

Lay Summary: Non-invasive scoring systems are increasingly being used in patients with non-alcoholic fatty liver disease to identify those at risk of advanced fibrosis and hence clinical complications. Herein, we compared various non-invasive scoring systems and identified those that were best at identifying risk, as well as those that were best for the prediction of long-term outcomes, such as liver-related events, liver cancer and death.
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http://dx.doi.org/10.1016/j.jhep.2021.05.008DOI Listing
October 2021

Definite and indeterminate nonalcoholic steatohepatitis share similar clinical features and prognosis: A longitudinal study of 1893 biopsy-proven nonalcoholic fatty liver disease subjects.

Liver Int 2021 09 7;41(9):2076-2086. Epub 2021 May 7.

Digestive Department, Hospital Universitario San Cecilio, Granada, Spain.

Background And Aim: Histological score systems may not fully capture the essential nonalcoholic steatohepatitis (NASH) features, which is one of the leading causes of screening failure in clinical trials. We assessed the NASH distribution and its components across the fibrosis stages and their impact on the prognosis and their relationship with the concept of metabolic-associated fatty liver disease (MAFLD).

Methods: Spanish multicenter study including 1893 biopsy-proven nonalcoholic fatty liver disease (NAFLD) patients from HEPAmet registry. NASH was diagnosed by NAS score ≥4 (including steatosis, ballooning and lobular inflammation) and fibrosis by Kleiner score. The presence of MAFLD was determined. Progression to cirrhosis, first episode of decompensated cirrhosis and death were collected during the follow-up (4.7 ± 3.8 years).

Results: Fibrosis was F0 34.3% (649/1893), F1 27% (511/1893), F2 16.5% (312/1893), F3 15% (284/1893) and F4 7.2% (137/1893). NASH diagnosis 51.9% (982/1893), and its individual components (severe steatosis, ballooning and lobular inflammation), increased from F0 (33.6%) to F2 (68.6%), and decreased significantly in F4 patients (51.8%) (P = .0001). More than 70% of non-NASH patients showed some inflammatory activity (ballooning or lobular inflammation), showing a similar MAFLD rate than NASH (96.2% [945/982] vs. 95.2% [535/562]) and significantly higher than nonalcoholic fatty liver (NAFL) subjects (89.1% [311/349]) (P < .0001). Progression to cirrhosis was similar between NASH (9.5% [51/539]) and indeterminate NASH (7.9% [25/316]), and higher than steatosis (5% [14/263]) (logRank 8.417; P = .015). Death and decompensated cirrhosis were similar between these.

Conclusions: The prevalence of steatohepatitis decreased in advanced liver disease. However, most of these patients showed some inflammatory activity histologically and had metabolic disturbances. These findings should be considered in clinical trials whose main aim is to prevent cirrhosis progression and complications, liver transplant and death.
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http://dx.doi.org/10.1111/liv.14898DOI Listing
September 2021

Development and Validation of a Clinical-Genetic Risk Score to Predict Hepatic Encephalopathy in Patients With Liver Cirrhosis.

Am J Gastroenterol 2021 06;116(6):1238-1247

SeLiver Group at Institute of Biomedicine of Seville (IBiS), Virgen del Rocio University Hospital/CSIC/University of Seville, Seville, Spain.

Introduction: We aimed to define the impact of the genetic background on overt hepatic encephalopathy (HE) in patients with liver cirrhosis by developing a combined clinical-genetic risk score.

Methods: Patients suffering from liver cirrhosis from the outpatient clinics of 4 hospitals (n = 600) were included and followed up for at least 5 years until HE bouts, liver transplant, or death. Patients were genotyped for 60 candidate single nucleotide polymorphisms together with the microsatellite in the promoter region of the gene GLS.

Results: Single nucleotide polymorphisms rs601338 (FUT2), rs5743836 (TRL9), rs2562582 (SLC1A3), rs313853 (SLC1A5), and GLS microsatellite did predict independently the incidence and severity of overt HE and were included as genetic score. Competing risk analysis revealed that bilirubin (subhazard ratio [sHR] 1.30 [1.15-1.48], P < 0.001), albumin (sHR 0.90 [0.86-0.93], P < 0.001), genetic score (sHR 1.90 [1.57-2.30], P < 0.001), and previous episodes of overt HE (sHR 2.60 [1.57-4.29], P < 0.001) were independently associated to HE bouts during the follow-up with an internal (C-index 0.83) and external validation (C-index 0.74). Patients in the low-risk group had 5% and 12% risk of HE at 1 (log-rank 92.1; P < 0.001) and 5 (log-rank 124.1; P < 0.001) years, respectively, whereas 36% and 48% in the high-risk group.

Discussion: The genetic background influenced overt HE risk and severity. The clinical-genetic HE Risk score, which combined genetic background together with albumin, bilirubin, and previous episodes of overt HE, could be a useful tool to predict overt HE in patients with cirrhosis.
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http://dx.doi.org/10.14309/ajg.0000000000001164DOI Listing
June 2021

Looking for a new name for non-alcoholic fatty liver disease in Spanish: esteatosis hepática metabólica (EHmet).

Rev Esp Enferm Dig 2021 Mar;113(3):161-163

UGC Aparato Digestivo, Instituto de Biomedicina de Sevilla. Universidad de Sevilla, España.

The name of a disease does not follow any defined protocol and the scientific community's acceptance of several variants based on the customs of every location is usual. There are examples of prevalent entities with curious naming processes, such as diabetes mellitus. The first word, "diabetes", comes from the Greek dia (through), be (to go), and tes (factor), while the second word, "mellitus", comes from Latin melli (honey). As a consequence, diabetes mellitus literally means "the sweet factor that goes through…", pertaining to an excessive and sweet diuresis. Thus, we could deduce that a definition representing exactly the pathophysiology of the particular disease is not required.
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http://dx.doi.org/10.17235/reed.2021.7862/2021DOI Listing
March 2021

COVID-19 and the liver: the chicken or the egg dilemma.

Rev Esp Enferm Dig 2021 07;113(7):555

Hospital Universitario Virgen del Rocío.

After the publication of our meta-analysis, in which we demonstrated that aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total bilirubin were related to a poor prognosis in patients suffering COVID-19, some authors raised the question about whether these findings are directly linked, or they are epiphenomena.
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http://dx.doi.org/10.17235/reed.2021.7861/2021DOI Listing
July 2021

Simple non-invasive scoring systems and histological scores in predicting mortality in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis.

J Gastroenterol Hepatol 2021 Jul 19;36(7):1754-1768. Epub 2021 Mar 19.

Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China.

Background And Aim: There is debate among the hepatology community regarding the simple non-invasive scoring systems and histological scores (even it was developed for histological classification) in predicting clinical outcomes in patients with non-alcoholic fatty liver disease (NAFLD). This study aimed to determine whether the presence of simple non-invasive scoring systems and histological scores could predict all-cause mortality, liver-related mortality, and liver disease decompensation (liver failure, cirrhosis, hepatocellular carcinoma, or decompensated liver disease).

Methods: The pooled hazard ratio of prognostic factors and incidence rate per 1000 person-years in patients with NAFLD was calculated and further adjusted by two different models of handling the duplicated data.

Results: A total of 19 longitudinal studies were included. Most simple non-invasive scoring systems (Fibrosis-4 Score, BARD, and aspartate aminotransferase-to-platelet ratio index ) and histological scores (NAFLD activity score, Brunt, and "steatosis, activity, and fibrosis" ) failed in predicting mortality, and only the NAFLD fibrosis score > 0.676 showed prognostic ability to all-cause mortality (four studies, 7564 patients, 118 352 person-years followed up, pooled hazard ratio 1.44, 95% confidence interval [CI] 1.05-1.96). The incidence rate per 1000 person-years of all-cause mortality, liver-related mortality, cardiovascular-related mortality, and liver disease decompensation resulted in a pooled incidence rate per 1000 person-years of 22.65 (14 studies, 95% CI 9.62-53.31), 3.19 (7 studies, 95% CI 1.14-8.93), 6.02 (6 studies, 95% CI 4.69-7.74), and 11.46 (4 studies, 95% CI 5.33-24.63), respectively.

Conclusion: Non-alcoholic fatty liver disease fibrosis score showed promising prognostic value to all-cause mortality. Most present simple non-invasive scoring systems and histological scores failed to predict clinical outcomes.
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http://dx.doi.org/10.1111/jgh.15431DOI Listing
July 2021

Caucasian lean subjects with non-alcoholic fatty liver disease share long-term prognosis of non-lean: time for reappraisal of BMI-driven approach?

Gut 2021 Feb 4. Epub 2021 Feb 4.

UCM Digestive Diseases and SeLiver Group, Virgen del Rocio University Hospital, Institute of Biomedicine of Seville, University of Seville, Seville, Spain.

Objective: The full phenotypic expression of non-alcoholic fatty liver disease (NAFLD) in lean subjects is incompletely characterised. We aimed to investigate prevalence, characteristics and long-term prognosis of Caucasian lean subjects with NAFLD.

Design: The study cohort comprises 1339 biopsy-proven NAFLD subjects from four countries (Italy, UK, Spain and Australia), stratified into lean and non-lean (body mass index (BMI)
Results: Lean patients represented 14.4% of the cohort and were predominantly of Italian origin (89%). They had less severe histological disease (lean vs non-lean: non-alcoholic steatohepatitis 54.1% vs 71.2% p<0.001; advanced fibrosis 10.1% vs 25.2% p<0.001), lower prevalence of diabetes (9.2% vs 31.4%, p<0.001), but no significant differences in the prevalence of the I148M variant (p=0.57). During a median follow-up of 94 months (>10 483 person-years), 4.7% of lean vs 7.7% of non-lean patients reported liver-related events (p=0.37). No difference in survival was observed compared with non-lean NAFLD (p=0.069).

Conclusions: Caucasian lean subjects with NAFLD may progress to advanced liver disease, develop metabolic comorbidities and experience cardiovascular disease (CVD) as well as liver-related mortality, independent of longitudinal progression to obesity and genotype. These patients represent one end of a wide spectrum of phenotypic expression of NAFLD where the disease manifests at lower overall BMI thresholds.

Lay Summary: NAFLD may affect and progress in both obese and lean individuals. Lean subjects are predominantly males, have a younger age at diagnosis and are more prevalent in some geographic areas. During the follow-up, lean subjects can develop hepatic and extrahepatic disease, including metabolic comorbidities, in the absence of weight gain. These patients represent one end of a wide spectrum of phenotypic expression of NAFLD.
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http://dx.doi.org/10.1136/gutjnl-2020-322564DOI Listing
February 2021

Sofosbuvir improves HCV-induced insulin resistance by blocking IRS1 degradation.

Clin Transl Med 2021 01;11(1):e275

Unidad de Investigación, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria del Hospital Universitario de La Princesa, Madrid, Spain.

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http://dx.doi.org/10.1002/ctm2.275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810262PMC
January 2021

Reply to: "The predictive value of significant fibrosis for metabolic disturbances in patients with NAFLD".

J Hepatol 2021 04 24;74(4):971-972. Epub 2020 Dec 24.

Hospital Universitario Virgen del Rocío, Sevilla, Spain; SeLiver group, Instituto de Biomedicina de Sevilla, Spain; CIBERehd, Spain.

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http://dx.doi.org/10.1016/j.jhep.2020.12.020DOI Listing
April 2021

Effectiveness and safety of obeticholic acid in a Southern European multicentre cohort of patients with primary biliary cholangitis and suboptimal response to ursodeoxycholic acid.

Aliment Pharmacol Ther 2021 02 12;53(4):519-530. Epub 2020 Dec 12.

Madrid, Spain.

Background: Obeticholic acid (OCA) was recently approved as the only on-label alternative for patients with primary biliary cholangitis (PBC) with intolerance or suboptimal response to ursodeoxycholic acid (UDCA). However, few data are available outside clinical trials.

Aim: To assess the effectiveness and safety of OCA in a real-world cohort of patients with non-effective UDCA therapy.

Methods: Open-label, prospective, real-world, multicentre study, enrolling consecutive patients who did not meet Paris II criteria, from 18 institutions in Spain and Portugal. Effectiveness was assessed by the changes in GLOBE and UK-PBC scores from baseline. POISE and Paris II criteria were evaluated after 12 months of OCA . Liver fibrosis was evaluated by FIB-4 and AST to platelet ratio index (APRI).

Results: One hundred and twenty patients were eligible, median time since PBC diagnosis 9.3 (4.0-13.8) years, 21.7% had cirrhosis, and 26.7% received had previous or concomitant treatment with fibrates. Seventy-eight patients completed at least 1 year of OCA. The Globe-PBC score decreased to 0.17 (95% CI 0.05 to 0.28; P = 0.005) and the UK-PBC score decreased to 0.81 (95% CI -0.19 to 1.80; P = 0.11). There was a significant decrease in alkaline phosphatase of 81.3 U/L (95% CI 42.5 to 120; P < 0.001), ALT 22.1 U/L (95% CI 10.4 to 33.8; P < 0.001) and bilirubin 0.12 mg/dL (95% CI 0 to 0.24; P = 0.044). FIB-4 and APRI remained stable. According to the POISE criteria, 29.5% (23 out of 78) achieved response. The adverse events rate was 35%; 11.67% discontinued (8.3% due to pruritus).

Conclusions: This study supports data from phase III trials with significant improvement of PBC-Globe continuous prognostic marker score among OCA-treated patients with good tolerability.
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http://dx.doi.org/10.1111/apt.16181DOI Listing
February 2021

Impact of liver injury on the severity of COVID-19: a systematic review with meta-analysis.

Rev Esp Enferm Dig 2021 02;113(2):125-135

UCM Digestive Diseases and CIBERehd, Instituto de Biomedicina de Sevilla (IBiS), SeLiver Group, Virgen del Rocío/CSIC/US.

Background And Aims: SARS-CoV-2 is mainly a respiratory virus that has relevant systemic effects. We assessed the impact of baseline liver function (aspartate aminotransferase [AST], alanine aminotransferase [ALT], bilirubin) on COVID-19-related outcomes, including mortality, intensive care unit (ICU) admissions, and non-fatal severe complications.

Methods: after a systematic review of the relevant studies the odds ratio (OR), mean difference, sensitivity, specificity, and both positive and negative likelihood ratios were calculated for the prediction of relevant COVID-19 outcomes by performing a meta-analysis using fixed and random effects models. A Fagan nomogram was used to assess clinical usefulness. Heterogeneity was explored by sensitivity analysis and univariate meta-regression.

Results: twenty-six studies were included (22 studies and 5,271 patients for AST, 20 studies and 5,440 subjects for ALT, and nine studies and 3,542 patients for bilirubin). The outcomes assessed by these studies were: survival (n = 8), ICU admission (n = 4), and non-fatal severe complications (n = 16). AST > upper limit of normal (ULN) (OR: 3.10 [95 % CI, 2.61-3.68]), ALT > ULN (OR: 2.15 [95 % CI, 1.43-3.23]), and bilirubin > ULN (OR: 2.78 [95 % CI, 1.88-4.13]) were associated with an increased prevalence of severe complications with a specificity of 78 %, 77 %, and 94 %, respectively. The mean difference between mild and severe COVID-19 was 10.7 U/l (95 % CI, 5.8-15.6) for AST, 8 U/l (95 % CI, 1.0-15) for ALT, and 0.3 mg/dl (95 % CI, 0.16-0.45) for bilirubin.

Conclusions: patients showing liver injury had a significantly higher risk of developing severe COVID-19 as compared to those with normal liver function tests at admission. We should include the assessment of AST, ALT, and total bilirubin (TB) routinely in the workup of patients affected by SARS-CoV-2 in order to predict those at risk of developing COVID-19-related outcomes.
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http://dx.doi.org/10.17235/reed.2020.7397/2020DOI Listing
February 2021

Hepatitis C Virus Clearance by Direct-Acting Antivirals Agents Improves Endothelial Dysfunction and Subclinical Atherosclerosis: HEPCAR Study.

Clin Transl Gastroenterol 2020 08;11(8):e00203

SeLiver Group, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, España.

Introduction: Hepatitis C virus (HCV) infection has been related to increased cardiovascular (CV) risk. The aim of this study was to analyze the impact of sustained virological response (SVR) on endothelial dysfunction and subclinical atherosclerosis in patients with hepatitis C virus treated with direct-acting antiviral agents.

Methods: A total of 114 patients were prospectively recruited and underwent CV risk assessment including (i) endothelial dysfunction determined through laser Doppler flowmetry and (ii) subclinical atherosclerosis, elucidated by the ankle-brachial index (ABI). Atherogenic lipid profile (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides); markers of oxidative stress (oxidized low-density lipoprotein antibodies [OLAbs]), soluble markers of adhesion (vascular cell adhesion molecule [VCAM], e-selectin, and soluble markers of angiogenesis; and vascular endothelial growth factor, endothelial [EMPs] and platelet [PMPs] apoptotic microparticles, and cell-free DNA [cfDNA]) were measured. All determinations were performed at baseline, 12 weeks (SVR time), and 1 year after treatment.

Results: In patients with endothelial dysfunction, area of hyperemia improved after virus clearance (P = 0.013) and was related to significant decrease in VCAM, e-selectin (P < 0.001), and cfDNA (P = 0.017) and to increased OLAb levels (P = 0.001). In patients with subclinical atherosclerosis at baseline, a significantly improved ABI was seen after HCV clearance (P < 0.001). Levels of both EMPs and PMPs also decreased after SVR and at follow-up (P = 0.006 and P = 0.002, respectively).

Discussion: HCV clearance improved not only liver function but also endothelial dysfunction and subclinical atherosclerosis promoted by decrease in levels of VCAM, e-selectin, cfDNA, and PMPs and EMPs.
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http://dx.doi.org/10.14309/ctg.0000000000000203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431267PMC
August 2020

Stratification of patients in NASH clinical trials: A pitfall for trial success.

JHEP Rep 2020 Oct 21;2(5):100148. Epub 2020 Jul 21.

Hospital Universitario Virgen del Rocío, Sevilla, Spain.

Identifying the most effective therapeutic intervention in patients with NAFLD is challenging. Precise stratification in clinical trials is key to ensuring the inclusion of patients who will benefit (and not those who will be harmed) and/or in whom the natural history can be improved. Clinical trials in NAFLD can provide useful information about the individual components that underlie this complex metabolic disorder and the concomitant medications that could interfere with responses to an experimental intervention. However, to date, clinical trial reporting for NAFLD has been suboptimal, limiting our understanding. Frequently dysmetabolic comorbidities and/or daily habits are not reported or adequately accounted for. Herein, we suggest new strategies to integrate the spectra of comorbidities usually present in patients with NAFLD, accounting for the impact of lifestyle, to develop personalised therapeutic approaches. First, the mechanism of action of the drug being explored should be considered. Second, the same proportion of patients with relevant metabolic comorbidities should be maintained from phase II to III clinical trials, if such comorbidities are expected to impact on the treatment response. Third, innovative trial designs, such as the adaptative, umbrella or basket strategies, could be used to increase the efficiency of clinical trials, potentially benefiting patients while reducing costs and enhancing the likelihood of finding a real benefit of the therapy being studied. Finally, alcohol intake and daily exercise should be assessed objectively not only in the screening period but also during follow-up.
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http://dx.doi.org/10.1016/j.jhepr.2020.100148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486452PMC
October 2020

Nonalcoholic fatty liver disease and the risk of metabolic comorbidities: how to manage in clinical practice.

Pol Arch Intern Med 2020 11 14;130(11):975-985. Epub 2020 Jul 14.

Nonalcoholic fatty liver disease (NAFLD) is a clinical condition that encompasses various forms of liver damage not caused by chronic alcohol consumption. In the absence of other etiologies, it ranges from steatosis to nonalcoholic steatohepatitis and cirrhosis. The prevalence of NAFLD has considerably increased over the last years owing to the current lifestyle (unhealthy diet and sedentarism). Besides, it is associated with metabolic risk factors such as obesity, arterial hypertension, dyslipidemia, and type 2 diabetes. Given the poor prognosis of patients with advanced NAFLD, a practical therapeutic approach is necessary to halt its natural history. However, no licensed drugs have been approved for this purpose to date. Nowadays, we are in a race to find the first drug able to stop the incidence of NAFLD and reverse the disease in patients at more advanced stages. Meanwhile, the management of the NAFLD metabolic overload, including weight loss, cardiovascular protection, insulin sensitization, and lipid reduction, is the only strategy to improve hepatic and extrahepatic outcomes. In this review, we aimed to describe the management of the main metabolic disorders related to NAFLD, such as type 2 diabetes, arterial hypertension, and dyslipidemia.
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http://dx.doi.org/10.20452/pamw.15510DOI Listing
November 2020

Monitoring Occurrence of Liver-Related Events and Survival by Transient Elastography in Patients With Nonalcoholic Fatty Liver Disease and Compensated Advanced Chronic Liver Disease.

Clin Gastroenterol Hepatol 2021 04 2;19(4):806-815.e5. Epub 2020 Jul 2.

Centre d'Investigation de la Fibrose Hépatique, INSERM U1053, Hôpital Haut-Lévêque, Bordeaux University Hospital, Pessac, France.

Background & Aims: Patients with advanced fibrosis related to nonalcoholic fatty liver disease (NAFLD) are at risk of developing hepatic and extrahepatic complications. We investigated whether, in a large cohort of patients with NAFLD and compensated advanced chronic liver disease, baseline liver stiffness measurements (LSMs) and their changes can be used to identify patients at risk for liver-related and extrahepatic events.

Methods: We performed a retrospective analysis of consecutive patients with NAFLD (n = 1039) with a histologic diagnosis of F3-F4 fibrosis and/or LSMs>10 kPa, followed for at least 6 months, from medical centers in 6 countries. LSMs were made by FibroScan using the M or XL probe and recorded at baseline and within 1 year from the last follow-up examination. Differences between follow up and baseline LSMs were categorized as: improvement (reduction of more than 20%), stable (reduction of 20% to an increase of 20%), impairment (an increase of 20% or more). We recorded hepatic events (such as liver decompensation, ascites, encephalopathy, variceal bleeding, jaundice, or hepatocellular carcinoma [HCC]) and overall and liver-related mortality during a median follow-up time of 35 months (interquartile range, 19-63 months).

Results: Based on Cox regression analysis, baseline LSM was independently associated with occurrence of hepatic decompensation (hazard ratio [HR], 1.03; 95% CI, 1.02-1.04; P < .001), HCC (HR, 1.03; 95% CI, 1.00-1.04; P = .003), and liver-related death (HR, 1.02; 95% CI, 1.02-1.03; P = .005). In 533 patients with available LSMs during the follow-up period, change in LSM was independently associated with hepatic decompensation (HR, 1.56; 95% CI, 1.05-2.51; P = .04), HCC (HR, 1.72; 95% CI, 1.01-3.02; P = .04), overall mortality (HR, 1.73; 95% CI, 1.11-2.69; P = .01), and liver-related mortality (HR, 1.96; 95% CI, 1.10-3.38; P = .02).

Conclusions: In patients with NAFLD and compensated advanced chronic liver disease, baseline LSM and change in LSM are associated with risk of liver-related events and mortality.
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http://dx.doi.org/10.1016/j.cgh.2020.06.045DOI Listing
April 2021

Reflex testing. A key tool for the elimination of hepatitis C.

Rev Esp Enferm Dig 2020 07;112(7):513-514

Aparato Digestivo, Hospital Universitario Fundación Alcorcón, España.

Hepatitis C is a major cause of liver cirrhosis and hepatocellular carcinoma, as well as the primary indication for liver transplant in Europe. The highly effective direct-acting antivirals currently available make it possible to achieve the hepatitis C elimination targets set by the World Health Organization. For this, population screening and reflect testing are fundamental strategies.
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http://dx.doi.org/10.17235/reed.2020.7201/2020DOI Listing
July 2020

Quality of life in patients with hepatitis C. Importance of treatment.

Gastroenterol Hepatol 2019 Sep 16;42 Suppl 1:20-25. Epub 2020 Jun 16.

Psiquiatría de Urgencias, Hospital Universitario Príncipe de Asturias, Madrid, España.

Chronic hepatitis C virus infection is a systemic disease that impairs the quality of life of affected individuals. The impairment is not only due to physiological factors, such as the non-hepatic manifestations of the disease or certain symptoms such as fatigue, weakness and nausea, but is also due to the substantial psychological impact of the infection. Treatment with direct-acting antivirals (DAA) has been demonstrated to substantially improve patient's quality of life, starting in the initial phases. Supplement information: This article is part of a supplement entitled "The value of simplicity in hepatitis C treatment", which is sponsored by Gilead. © 2019 Elsevier España, S.L.U. All rights reserved.
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http://dx.doi.org/10.1016/S0210-5705(20)30184-9DOI Listing
September 2019

Bacterial antigen translocation and age as BMI-independent contributing factors on systemic inflammation in NAFLD patients.

Liver Int 2020 09 1;40(9):2182-2193. Epub 2020 Jul 1.

CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.

Background & Aims: Low-grade systemic inflammation is a crucial landmark in NAFLD favouring disease progression and comorbidities. We evaluated the input of circulating bacterial antigens on systemic markers of inflammation in NAFLD patients.

Patients & Methods: Multicenter cross-sectional study including consecutive patients with biopsy-proven NAFLD. Demographic, metabolic and fibrosis-related variables were collected. Circulating bacterial antigens were quantified in blood. Toll-like receptor SNPs were genotyped. Serum cytokine levels were evaluated. Peripheral blood mononuclear cell response to bacterial antigens was evaluated in vitro.

Results: Three hundred and fifteen patients from five Spanish hospitals were distributed by BMI. At least, one bacterial antigenic type was found in 66 patients with BMI < 30 (63.4%) and 163 patients with BMI > 30 (77.3%) (P = .014). HOMA-IR was significantly higher in the presence of circulating antigens among patients with BMI < 30. NASH and significant fibrosis in non-obese patients were more frequent in the presence of at least two circulating antigenic types. Allelic frequencies of TLR variants were similar to controls and did not affect clinical or laboratory parameters. Pro-inflammatory cytokines were significantly increased in patients with bacterial antigens, regardless of BMI. TLR gene and protein expression levels were significantly increased in PBMCs from patients with bacterial antigens. Antigen concentrations independently influenced TNF-α and IL-6, in both BMI subgroups of patients. Age independently influenced TNF-α and IL-6 in non-obese patients, and TNF-α in obese patients.

Conclusion: Serum circulating bacterial antigens as well as age were BMI-independent factors related to increased systemic inflammation in NAFLD and provides insight on the multifaceted sources of inflammation in these patients.
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http://dx.doi.org/10.1111/liv.14571DOI Listing
September 2020

COVID-19 and the digestive system: protection and management during the SARS-CoV-2 pandemic.

Rev Esp Enferm Dig 2020 05;112(5):389-396

Aparato Digestivo, Hospital General Universitario Morales Meseguer, España.

The purpose of this rapid review is to provide an update on the impact of SARS-CoV-2 infection on Gastroenterology and Hepatology departments, our patients, and our new way of working. The gastrointestinal tract and the liver are affected by SARS-CoV-2, especially in patients with immunosuppressive therapies. Patients with liver transplantation should be followed closely. Digestive endoscopy is a high-risk procedure for the transmission of SARS-CoV-2. While the pandemic lasts, we must adapt its indications and promote protective measures for patients and healthcare professionals alike. The COVID-19 pandemic has changed our priorities and the way we work, although we do not know what the repercussions will be after normality is reinstated.
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http://dx.doi.org/10.17235/reed.2020.7128/2020DOI Listing
May 2020

Significant fibrosis predicts new-onset diabetes mellitus and arterial hypertension in patients with NASH.

J Hepatol 2020 07 6;73(1):17-25. Epub 2020 Mar 6.

Complejo Hospitalario de Pontevedra, Spain.

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) could play a catalytic role in the development of metabolic comorbidities, although the magnitude of this effect in metabolically healthy patients with NAFLD remains unclear. We assessed the role of biopsy-proven NAFLD on the risk of developing type 2 diabetes mellitus (T2DM) and other metabolic comorbidities (arterial hypertension [AHT], and dyslipidemia) in metabolically healthy patients.

Methods: We included 178 metabolically healthy-defined by the absence of baseline T2DM, AHT, dyslipidemia-patients with biopsy-proven NAFLD from the HEPAmet Registry (N = 1,030). Hepamet fibrosis score (HFS), NAFLD fibrosis score, and Fibrosis-4 were calculated. Follow-up was computed from biopsy to the diagnosis of T2DM, AHT, or dyslipidemia.

Results: During a follow-up of 5.6 ± 4.4 years, T2DM occurred in 9% (16/178), AHT in 8.4% (15/178), low HDL in 9.6% (17/178), and hypertriglyceridemia in 23.6% (42/178) of patients. In multivariate analysis, significant fibrosis predicted T2DM and AHT. Independent variables related to T2DM appearance were significant fibrosis (HR 2.95; 95% CI 1.19-7.31; p = 0.019), glucose levels (p = 0.008), age (p = 0.007) and BMI (p = 0.039). AHT was independently linked to significant fibrosis (HR 2.39; 95% CI 1.14-5.10; p = 0.028), age (p = 0.0001), BMI (p = 0.006), glucose (p = 0.021) and platelets (p = 0.050). The annual incidence rate of T2DM was higher in patients with significant fibrosis (4.4 vs. 1.2 cases per 100 person-years), and increased in the presence of obesity, similar to AHT (4.6 vs. 1.1 cases per 100 person-years). HFS >0.12 predicted the risk of T2DM (25% [4/16] vs. HFS <0.12 4.5% [4/88]; logRank 6.658, p = 0.010).

Conclusion: Metabolically healthy patients with NAFLD-related significant fibrosis were at greater risk of developing T2DM and AHT. HFS >0.12, but not NAFLD fibrosis score or Fibrosis-4, predicted the occurrence of T2DM.

Lay Summary: Patients with biopsy-proven non-alcoholic fatty liver disease and significant fibrosis were at risk of developing type 2 diabetes mellitus and arterial hypertension. The risk of metabolic outcomes in patients with significant fibrosis was increased in the presence of obesity. In addition to liver biopsy, patients at intermediate-to-high risk of significant fibrosis by Hepamet fibrosis score were at risk of type 2 diabetes mellitus.
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http://dx.doi.org/10.1016/j.jhep.2020.02.028DOI Listing
July 2020

Oral glutamine challenge is a marker of altered ammonia metabolism and predicts the risk of hepatic encephalopathy.

Liver Int 2020 04 1;40(4):921-930. Epub 2019 Dec 1.

Hospital Universitario Virgen del Rocío, Sevilla, Spain.

Background: The current therapies for hepatic encephalopathy (HE) are not completely effective in all patients, probably due to the physiopathological heterogeneity and the different conditions underlying the bout of HE. We hypothesized that oral glutamine challenge (OGC) is able to predict the risk of HE through the identification of various features and types of HE.

Methods: We included 238 cirrhotic patients (198 without and 40 with a previous HE episode) that underwent OGC, obtaining baseline and 60 minutes post-load ammonia levels. Combined evaluation of baseline hyperammonemia (>78 mcg/dL) and impaired OGC (Δ >32 mcg/dL) defined low-, intermediate- and high-risk groups. Patients were censored at HE, liver transplantation and death or 6 years of follow-up.

Results: The 28.3% (56/198) of the main cohort suffered from HE during the follow-up. In the competing risk analysis, both intermediate- (subhazard ratio (sHR) 2.01 (95% CI 1.00-4.14); P = .048) and high-risk groups (sHR 4.67 (95% CI 2.19-9.98); P = .0001) were associated with the first HE episode, together with age and albumin. Similar results were found for repeated HE events. The cumulative incidence for HE of the high-risk group was two and four times greater than the intermediate- and low-risk groups, respectively. The HE grade was also higher in individuals with the greatest risk (P = .035). The most common precipitant factor was diuretics in the high-risk group, while infections and electrolyte imbalance predominated in the rest of patients.

Conclusion: Oral glutamine challenge identified patients at risk of HE and defined specific features of the episodes. This tool could be useful in the decision-making process for the adequate management of HE.
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http://dx.doi.org/10.1111/liv.14297DOI Listing
April 2020

Development and Validation of Hepamet Fibrosis Scoring System-A Simple, Noninvasive Test to Identify Patients With Nonalcoholic Fatty Liver Disease With Advanced Fibrosis.

Clin Gastroenterol Hepatol 2020 01 11;18(1):216-225.e5. Epub 2019 Jun 11.

Hospital Universitario Virgen del Rocío de Sevilla, Instituto de Biomedicina de Sevilla, University of Sevilla, Biomedical Research Networking Center in Hepatic and Digestive Diseases, Sevilla, Spain.

Background & Aims: Fibrosis affects prognoses for patients with nonalcoholic fatty liver disease (NAFLD). Several non-invasive scoring systems have aimed to identify patients at risk for advanced fibrosis, but inconclusive results and variations in features of patients (diabetes, obesity and older age) reduce their diagnostic accuracy. We sought to develop a scoring system based on serum markers to identify patients with NAFLD at risk for advanced fibrosis.

Methods: We collected data from 2452 patients with NAFLD at medical centers in Italy, France, Cuba, and China. We developed the Hepamet fibrosis scoring system using demographic, anthropometric, and laboratory test data, collected at time of liver biopsy, from a training cohort of patients from Spain (n = 768) and validated the system using patients from Cuba (n = 344), Italy (n = 288), France (n = 830), and China (n = 232). Hepamet fibrosis score (HFS) were compared with those of previously developed fibrosis scoring systems (the NAFLD fibrosis score [NFS] and FIB-4). The diagnostic accuracy of the Hepamet fibrosis scoring system was assessed based on area under the receiver operating characteristic (AUROC) curve, sensitivity, specificity, diagnostic odds ratio, and positive and negative predictive values and likelihood ratios.

Results: Variables used to determine HFS were patient sex, age, homeostatic model assessment score, presence of diabetes, levels of aspartate aminotransferase, and albumin, and platelet counts; these were independently associated with advanced fibrosis. HFS discriminated between patients with and without advanced fibrosis with an AUROC curve value of 0.85 whereas NFS or FIB-4 did so with AUROC values of 0.80 (P = .0001). In the validation set, cut-off HFS of 0.12 and 0.47 identified patients with and without advanced fibrosis with 97.2% specificity, 74% sensitivity, a 92% negative predictive value, a 76.3% positive predictive value, a 13.22 positive likelihood ratio, and a 0.31 negative likelihood ratio. HFS were not affected by patient age, body mass index, hypertransaminasemia, or diabetes. The Hepamet fibrosis scoring system had the greatest net benefit in identifying patients who should undergo liver biopsy analysis and led to significant improvements in reclassification, reducing the number of patients with undetermined results to 20% from 30% for the FIB-4 and NFS systems (P < .05).

Conclusions: Using clinical and laboratory data from patients with NAFLD, we developed and validated the Hepamet fibrosis scoring system, which identified patients with advanced fibrosis with greater accuracy than the FIB-4 and NFS systems. the Hepamet system provides a greater net benefit for the decision-making process to identify patients who should undergo liver biopsy analysis.
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http://dx.doi.org/10.1016/j.cgh.2019.05.051DOI Listing
January 2020

Sofosbuvir/velpatasvir for 12 weeks in hepatitis C virus-infected patients with end-stage renal disease undergoing dialysis.

J Hepatol 2019 10 11;71(4):660-665. Epub 2019 Jun 11.

Auckland City Hospital, Auckland, New Zealand.

Background & Aims: Although off-label use of sofosbuvir-containing regimens occurs regularly in patients with hepatitis C virus (HCV) infection undergoing dialysis for severe renal impairment or end-stage renal disease (ESRD), these regimens are not licensed for this indication, and there is an absence of dosing recommendations in this population. This study evaluated the safety and efficacy of sofosbuvir/velpatasvir in patients with HCV infection with ESRD undergoing dialysis.

Methods: In this phase II, single-arm study, 59 patients with genotype 1-6 HCV infection with ESRD undergoing hemodialysis or peritoneal dialysis received open-label sofosbuvir/velpatasvir (400 mg/100 mg) once daily for 12 weeks. Patients were HCV treatment naive or treatment experienced without cirrhosis or with compensated cirrhosis. Patients previously treated with any HCV NS5A inhibitor were not eligible. The primary efficacy endpoint was the proportion of patients achieving sustained virologic response (SVR) 12 weeks after discontinuation of treatment (SVR12). The primary safety endpoint was the proportion of patients who discontinued study drug due to adverse events.

Results: Overall, 56 of 59 patients achieved SVR12 (95%; 95% CI 86-99%). Of the 3 patients who did not achieve SVR12, 2 patients had virologic relapse determined at post-treatment Week 4 (including 1 who prematurely discontinued study treatment), and 1 patient died from suicide after achieving SVR through post-treatment Week 4. The most common adverse events were headache (17%), fatigue (14%), nausea (14%), and vomiting (14%). Serious adverse events were reported for 11 patients (19%), and all were deemed to be unrelated to sofosbuvir/velpatasvir.

Conclusions: Treatment with sofosbuvir/velpatasvir for 12 weeks was safe and effective in patients with ESRD undergoing dialysis.

Lay Summary: Sofosbuvir/velpatasvir is a combination direct-acting antiviral that is approved for treatment of patients with hepatitis C virus (HCV) infection. Despite the lack of dosing recommendations, sofosbuvir-containing regimens (including sofosbuvir/velpatasvir) are frequently used for HCV-infected patients undergoing dialysis. This study evaluated the safety and efficacy of sofosbuvir/velpatasvir for 12 weeks in patients with HCV infection who were undergoing dialysis. Treatment with sofosbuvir/velpatasvir was safe and well tolerated, resulting in a cure rate of 95% in patients with HCV infection and end-stage renal disease. Clinical Trial Number: NCT03036852.
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http://dx.doi.org/10.1016/j.jhep.2019.05.028DOI Listing
October 2019

Metabolic characterization of two different non-alcoholic fatty liver disease pre-clinical mouse models.

Rev Esp Enferm Dig 2019 Apr;111(4):301-307

UCM Digestive Diseases and CIBERehd, Institute of Biomedicine of Seville (IBiS), SeLiver Group, Virgen del Rocío/CSIC/US.

Introduction: non-alcoholic fatty liver disease is one of the most prevalent liver disorders in the developed world. Currently, there is no approved pharmacological therapy except for lifestyle intervention. Therefore, there is a need to increase the knowledge of preclinical models in order to boost novel discoveries that could lead to a better therapeutic management.

Material And Methods: this study characterized the effects of two different diets, a long-term high-fat high-fructose diet (HF-HFD) and a choline-deficient, methionine supplemented high-fat diet (CDA-HFD) in C57BL/6J mice for 52 weeks or 16 weeks, respectively. Body weight, lipid and hepatic profile were analyzed and liver histology was subsequently evaluated.

Results: HF-HFD animals had an increased body weight and total cholesterol levels, whereas the opposite occurred in CDA-HFD. Both HF-HFD and CDA-HFD animals had higher ALT and AST levels. With regard to histology findings, HF-HFD and CDA-HFD diets induced an increased collagen deposit and intrahepatic steatosis accumulation.

Conclusion: in conclusion, the comparison of these models aided in the selection of a long-term, more physiological model for physiopathology studies or a more rapid NASH model for novel molecule testing.
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http://dx.doi.org/10.17235/reed.2019.6083/2018DOI Listing
April 2019
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