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To analyze laboratory parameters, clinical and fibrosis evolution in F3-F4 patients cured with direct-acting antivirals (DAA).Unicenteric, observational and prospective study. All F3-F4 hepatitis C patients cured with DAA from 01/11/2014 to 31/08/2019 were included. A basal visit (BV) was performed and at 12 weeks (12w), 1, 2, 3 and 4 years after treatment. Demographic and laboratory variables, fibrosis measured by non-invasive tests, indirect markers of portal hypertension, the presence of esophageal varices, cirrhosis decompensation and hepatoceullar carcinoma were collected.169 patients were treated: 123 (72.8%) men, age 57.5±12 years; 117 (69.2%) with cirrhosis, 99 (84.6%) ChildA. 96,4% achieved SVR. The study was conducted for a median follow-up of 46.14 (2.89-62.55) months. It was observed a significant increase in platelets [155×10There is an improvement in laboratory parameters and fibrosis measured by non-invasive methods in F3-F4 patients cured with DAA. However, the risk of decompensation and the incidence/recurrence of hepatocellular carcinoma still remain, so there is a need to follow these patients.

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAM, To assess whether corticosteroids improve prognosis in patients with AS-AIH, and to identify factors at therapy initiation and during therapy predictive of the response to corticosteroids. Methods: This was a retrospective cohort study including all patients with AS-AIH admitted to 13 tertiary centres from January 2002 to January 2019. The composite primary outcome was death or liver transplantation within 90 days of admission. Kaplan–Meier and Cox regression methods were used for data analysis. Results: Of 242 consecutive patients enrolled (mean age [SD] 49.7 [16.8] years), 203 received corticosteroids. Overall 90-day transplant-free survival was 61.6% (95% confidence interval [CI] 55.4–67.7). Corticosteroids reduced the risk of a poor outcome (adjusted hazard ratio [HR] 0.25; 95% CI 0.2–0.4), but this treatment failed in 30.5%. An internally validated nomogram composed of older age, MELD, encephalopathy and ascites at the initiation of corticosteroids accurately predicted the response (C-index 0.82; [95% CI 0.8–0.9]). In responders, MELD significantly improved from days 3 to 14 but remained unchanged in non-responders. MELD on day 7 with a cut-off of 25 (sensitivity 62.5%[95% CI: 47.0–75.8]; specificity 95.2% [95% CI: 89.9–97.8]) was the best univariate predictor of the response. Prolonging corticosteroids did not increase the overall infection risk (adjusted HR 0.75; 95% CI 0.3–2.1). Conclusion: Older patients with high MELD, encephalopathy or ascites at steroid therapy initiation and during treatment are unlikely to show a favourable response and so prolonged therapy in these patients, especially if they are transplantation candidates, should be avoided, This study was supported in part by grants from the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III, number PI20/01302, awarded to Agustín Albillos and number PI 21/01310, awarded to Luis Téllez. CIBEREHD is funded by the Instituto de Salud Carlos III using grants cofinanced by the European Development Regional Fund “A way to achieve Europe” (EDRF). María Carlota Londoño received support from the Plan Nacional de I+D+I co- funded by ISCIII-Subdirección General de Evaluación and Fondo Europeo de Desarrollo Regional (FEDER-"Una manera de Hacer Europa") (PI17/00955)

OBJETIVO: Evaluar el resultado del cribado de hepatitis B y C en pacientes ingresados con COVID-19. PACIENTES Y MÉTODOS: Estudio transversal, prospectivo, realizado en dos hospitales españoles de tercer nivel. Se estudiaron marcadores de hepatitis B (HBsAg, anti-HBc) y C (anti-VHC, ARN VHC) a todos los pacientes hospitalizados con COVID-19 del 1 de marzo al 31 de diciembre de 2020. RESULTADOS: En este periodo ingresaron 4662 pacientes con COVID-19: 56,3% fueron varones, la edad mediana fue 76 (0-104) años. Se realizó serología de hepatitis B a 2915 (62,5%) pacientes; 253 (8,75%) presentaban anti-HBc+ y 11 (0,38%) HBsAg+. De los 11 pacientes, 4 desconocían el diagnóstico, 7 recibieron esteroides y uno recibió profilaxis. Hubo un caso de reactivación del VHB. Se determinaron anticuerpos anti-VHC a 2895 (62%) pacientes; 24 (0,83%) fueron positivos. De ellos, 13 pacientes estaban diagnosticados: 10 habían recibido tratamiento, uno se había curado espontáneamente y dos no habían sido tratados. De los 11 restantes, 10 tenían ARN VHC indetectable. En total, sólo 3 (0,10%) pacientes tenían carga viral detectable. Sin embargo, ninguno recibió tratamiento (2 > 90 años con comorbilidades, 1 falleció por COVID-19). CONCLUSIONES: El cribado de hepatitis C en pacientes ingresados por COVID-19 en nuestro medio ha mostrado menor utilidad de la esperada. La baja prevalencia de infección activa tras los tratamientos antivirales y la alta edad mediana de nuestra población limitan la detección de potenciales candidatos a tratamiento. El cribado de hepatitis B debería dirigirse a prevenir la reactivación en pacientes que precisen tratamientos inmunosupresores.

[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., This project has been partially funded by the ‘Consejería de Salud de la Junta de Andalucía’ (PI-0075-2014) and the ‘Spanish Ministry of Economy, Innovation and Competition, Instituto de Salud Carlos III’ (PI19/01404, PI16/01842, PI17/00535 and GLD19/00100).

INTRODUCTION: Obeticholic acid (OCA) and fibrates therapy results in biochemical improvement in placebo-controlled trials in patients with primary biliary cholangitis and insufficient response to ursodeoxycholic acid. There is scarce information outside of clinical trials. Therefore, we have assessed the effectiveness and adverse events of these treatments. METHODS: Data from patients included in the ColHai registry treated with OCA, fibrates, or both were recorded during a year, as well as adverse events and treatment discontinuation. RESULTS: Eighty-six patients were treated with OCA, 250 with fibrates (81% bezafibrate; 19% fenofibrate), and 15 with OCA plus fibrates. OCA group had baseline significantly higher alkaline phosphatase (ALP) (P = 0.01) and lower platelets (P = 0.03) than fibrates. Both treatments significantly decreased ALP, gamma-glutamyl transferase (GGT), and transaminases and improved Globe score. Albumin and immunoglobulin type M improved in the fibrates group. ALP decrease was higher under fibrates, whereas alanine aminotransferase decline was higher under OCA. Although baseline transaminases and GGT were higher in patients with OCA plus fibrates, significant ALP, GGT, alanine aminotransferase, and Globe score improvement were observed during triple therapy. Adverse events were reported in 14.7% of patients (21.3% OCA; 17.6% fenofibrate; 10.7% bezafibrate), mainly pruritus (10.1% with OCA). Discontinuation was more frequent in fenofibrate treatment mainly because of intolerance or adverse events. DISCUSSION: Second-line therapy with OCA or fibrates improves hepatic biochemistry and the GLOBE score in primary biliary cholangitis patients with suboptimal response to ursodeoxycholic acid. Simultaneous treatment with OCA and fibrates improved ALP as well.

It has come to our attention that there was a mistake in Fig. 2 in the published version of our manuscript. The mistake occurred during the publication process and has resulted in the lines being absent from the Kaplan-Meier plots in Fig. 2A,B. The y-axis was also incorrectly labelled in Fig. 2B. Please see the corrected figure below. We apologize for any inconvenience caused. This has been corrected in the online version. [Figure presented]

[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, [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., This project has been partially funded by the “Consejería de Salud de la Junta de Andalucía” (PI-0075-2014), the “Spanish Ministry of Economy, Innovation and Competition, Instituto de Salud Carlos III” (PI19/01404, PI16/01842 and PI17/00535) and “Gilead” (GLD19/00100).

HEPAmet Registry., [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.

[Background] recent evidence suggests a causal link between serum uric acid and the metabolic syndrome, diabetes mellitus, arterial hypertension, and renal and cardiac disease. Uric acid is an endogenous danger signal and activator of the inflammasome, and has been independently associated with an increased risk of cirrhosis., [Aim and methods] six hundred and thirty-four patients from the nation-wide HEPAMET registry with biopsy-proven NAFLD (53% NASH) were analyzed to determine whether hyperuricemia is related with advanced liver damage in patients with non-alcoholic fatty liver disease (NAFLD). Patients were divided into three groups according to the tertile levels of serum uric acid and gender., [Results] the cohort was composed of 50% females, with a mean age of 49 years (range 19-80). Patients in the top third of serum uric acid levels were older (p = 0.017); they had a higher body mass index (p < 0.01), arterial blood pressure (p = 0.05), triglyceridemia (p = 0.012), serum creatinine (p < 0.001) and total cholesterol (p = 0.016) and lower HDL-cholesterol (p = 0.004). According to the univariate analysis, the variables associated with patients in the top third were more advanced steatosis (p = 0.02), liver fibrosis (F2-F4 vs F0-1; p = 0.011), NASH (p = 0.002) and NAS score (p = 0.05). According to the multivariate logistic regression analysis, the top third of uric acid level was independently associated with steatosis (adjusted hazard ratio 1.7; CI 95%: 1.05-2.8) and NASH (adjusted hazard ratio 1.8; CI 95%: 1.08-3.0) but not with advanced fibrosis (F2-F4) (adjusted hazard ratio 1.09; CI 95%: 0.63-1.87)., [Conclusion] higher levels of serum uric acid were independently associated with hepatocellular steatosis and NASH in a cohort of patients with NAFLD. Serum uric acid levels warrants further evaluation as a component of the current non-invasive NAFLD scores of histopathological damage.

Background Metabolically healthy obesity (MHO) shows a reduced risk compared with obese patients with adverse metabolic conditions. Lean people suffering some metabolic derangements also have non-alcoholic fatty liver disease (NAFLD)-related outcomes compared with non-obese subjects with a few metabolic risks. Aim To define the impact of the metabolic status on the NAFLD-related outcomes, beyond the presence of obesity. Methods We designed a multicentre cross-sectional study, including 1058 biopsy-proven NAFLD patients. Metabolically healthy status was strictly defined by the lack of metabolic risk factors (diabetes mellitus, low HDL, hypertriglyceridemia, arterial hypertension). Non-alcoholic steatohepatitis (NASH) and significant fibrosis (F2-F4) were identified by liver biopsy. Chronic kidney disease epidemiology collaboration equation was calculated for kidney function and the atherogenic index of plasma (AIP) for cardiovascular risk. Results Metabolically healthy (OR 1.88; P = 0.050) and unhealthy obesity (OR 3.47: P < 0.0001), and unhealthy non-obesity (OR 3.70; P < 0.0001) were independently associated with NASH together with homeostatic model assessment (HOMA), ALT, and platelets. Significant fibrosis was more frequently observed in the presence of adverse metabolic conditions in obese (OR 3.89; P = 0.003) and non-obese patients (OR 3.92; P = 0.002), and independently associated with platelets, albumin, ALT, HOMA, and age. The number of metabolic factors determined the risk of NASH and significant fibrosis. Glomerular filtration rate was lower in unhealthy (91.7 +/- 18) than healthy metabolism (95.6 +/- 17) (P = 0.007). AIP was higher in adverse metabolic conditions (P = 0.0001). Metabolically unhealthy non-obesity showed higher liver damage (NASH 55.8% vs 42.4%; P P < 0.0001) and cardiovascular risk (P < 0.0001) than healthy obesity. Conclusions Metabolic unhealthy status showed a greater impact on NASH, significant fibrosis, kidney dysfunction, and atherogenic profile than obesity. However, metabolically healthy obesity was not a full healthy condition. We should focus our messages especially on patients with adverse metabolic conditions.

SUMMARY Background Hepatic venous pressure gradient (HVPG) has prognostic value in complications and survival of patients with liver cirrhosis. However, the relationship between HVPG and the outcome of acute alcoholic hepatitis (AAH), as well as the specific features of portal hypertension syndrome in this setting, have not been defined. Aims To evaluate the prognostic value of HVPG and to analyse the degree of portal hypertension and hyperdynamic circulation in patients with severe AAH. Methods Early measurements of HVPG were performed in 60 patients with severe AAH, and compared with the haemodynamic findings of 37 and 29 liver transplantation candidates with alcoholic or viral end-stage cirrhosis respectively. Results Twenty-three patients (38%) died during hospitalization. Portal hypertension and hyperdynamic circulation were more severe in AAH patients. HVPG was greater in non-survivors [26.9 (7.4) vs. 19.4 (5.2) mmHg, P 22 (P 25 (OR 7.4; CI 1.4–39.9) and HVPG > 22 mmHg (OR 6.7; CI 1.1–39.9) were independently associated to in-hospital mortality.

Diagnosis of portopulmonary hypertension (POPH) is based on the presence of portal hypertension and the same haemodynamic criteria as pulmonary arterial hypertension (PAH). However, the typical hyperdynamic circulation of cirrhosis may have some impact on the diagnosis of POPH. The aim was to compare the haemodynamic pattern of the pulmonary circulation between cirrhotics and non-cirrhotics, including patients with PAH.600 patients with cirrhosis [male 77.5%, age 54 (47-60) years, Child A: 14.7%, B: 54.3%, C: 31%] received right heart catheterization. For comparison, 118 non-cirrhotic patients [male 60%, age 64 (53-65) years] with right heart catheterization and PCWP20 mmHg were included. Both were divided into 3 groups, A: absence of pulmonary arterial hypertension; B or intermediate group: MPAP25 mmHg, PVR 120-240 dyn s cm(-5) and PCWP15 mmHg (or PCWP15 mmHg with TPG ≥12 mmHg); C: pulmonary arterial hypertension (same criteria as B except PVR ≥240 dyn s cm(-5) ).Distribution of patients with cirrhosis was A 583, B 7 and C 10. Prevalence of POPH was 1.7%. Cirrhotics had lower SVR and greater CO than non-cirrhotics (P0.05). Interestingly, patients with cirrhosis without PAH (groups A and B) had lower PVR (P0.05) when comparing with non-cirrhotics, while no differences in PVR were observed in group C. However, mean TPG was greater in group C of cirrhotics [36.6 mmHg (12.2) vs. 27.1 mmHg (10.1); P = 0.034].Patients with cirrhosis have lower PVR. TPG is greater in POPH than PAH. Characteristic haemodynamic changes of cirrhosis may influence the diagnosis of POPH.

Everolimus is a new immunosuppressant with antitumoral properties and few side effects, but limited use in liver transplantation. The aim of the present study was to evaluate the effect on survival and safety of everolimus in post liver transplantation neoplasms in a single center. Ten liver transplant recipients with a posttransplant diagnosis of neoplasm received everolimus during a median of 12.7 (5.5-27.5) months; median survival was 21.3 (7.5-40.5) months. The probability of survival of everolimus group was significantly greater than the observed in a historical cohort of 14 liver recipients with comparable tumors who did not receive everolimus (100%, 90%, 72% vs. 50%, 29%, 14%) at 6, 12, and 24 months, respectively (HR=4.6, 95% confidence interval: 1.3-16.4; P=0.008). During everolimus therapy no patients showed rejection. Renal function improved in three patients. Furthermore, severe adverse effects and infections were infrequent. In summary, everolimus seems safe for liver transplant recipients with cancer and may improve short-term survival, but further studies are needed to determine long-term benefits and safety.

OBJECTIVES: To estimate the prevalence of portal hypertensive duodenopathy (PHD) in patients with cirrhosis and portal hypertension, and to evaluate its relationship with clinical and haemodynamic parameters. PATIENTS AND METHODS: Endoscopy reports and clinical history of 549 consecutive patients with cirrhosis and portal hypertension were evaluated retrospectively. A diagnosis of PHD was obtained in those patients with a congestive vascular pattern of the duodenum. RESULTS: PHD was found in 46 patients (8.4%). Previous endoscopic band ligation and coexistence of severe gastropathy were significantly more frequent in PHD group. Systemic and hepatic haemodynamic evaluations were performed in 20 patients with PHD and 160 without PHD: the mean hepatic venous pressure gradient was higher in those cases with PHD (22.5 (5.4) vs. 19.8 (5.5) mmHg, P=0.045). Hypertensive colopathy was found in seven out of the 10 patients with PHD and a colonoscopic evaluation. In five of six patients PHD disappeared after liver transplant. CONCLUSIONS: PHD is an uncommon finding of portal hypertension in cirrhotic patients. It is associated with previous endoscopic band ligation, to manifestations of portal hypertension in other sites of the gastrointestinal tract and to greater values of hepatic venous pressure gradient. The clinical relevance of this syndrome remains to be determined. © 2006 Lippincott Williams & Wilkins.