Search

Population screening; Liver fibrosis; Early diagnosis Cribratge de població; Fibrosi hepàtica; Diagnòstic precoç Cribado de población; Fibrosis hepática; Diagnóstico precoz Cirrhosis, highly prevalent worldwide, develops after years of hepatic inflammation triggering progressive fibrosis. Currently, the main etiologies of cirrhosis are non-alcoholic fatty liver disease and alcohol-related liver disease, although chronic hepatitis B and C infections are still major etiological factors in some areas of the world. Recent studies have shown that liver fibrosis can be assessed with relatively high accuracy noninvasively by serological tests, transient elastography, and radiological methods. These modalities may be utilized for screening for liver fibrosis in at-risk populations. Thus far, a limited number of population-based studies using noninvasive tests in different areas of the world indicate that a significant percentage of subjects without known liver disease (around 5% in general populations and a higher rate −18% to 27%-in populations with risk factors for liver disease) have significant undetected liver fibrosis or established cirrhosis. Larger international studies are required to show the harms and benefits before concluding that screening for liver fibrosis should be applied to populations at risk for chronic liver diseases. Screening for liver fibrosis has the potential for changing the current approach from diagnosing chronic liver diseases late when patients have already developed complications of cirrhosis to diagnosing liver fibrosis in asymptomatic subjects providing the opportunity of preventing disease progression. LiverScreen Consortium and the European Commission under the H20/20 program (847989); AGAUR (2017SGR-01281); Centro de Investigacion Biomedica en Enfermedades Hepaticas y Digestivas; Fundación de Investigación Sanitaria, cofunded by Instituto Carlos III–Subdirección General de Evaluación and the European Regional Development Fund (PI18/01330, PI18/00662, and PI18/00862); and Gilead’s Investigator–sponsored research program (IN-ES-989-5309)

Diabetes; Liver cirrhosis; Medical nutrition Diabetes; Cirrosis hepática; Tratamiento nutricional Diabetis; Cirrosi hepàtica; Tractament nutricional La cirrosis hepática es una enfermedad progresiva y crónica del hígado, de etiología diversa, que se asocia frecuentemente con intolerancia a la glucosa y en algunos casos concurre con diabetes tipo 2 (DM2). La DM2 se asocia con resultados adversos en pacientes con cirrosis, incluyendo una mayor tasa de ingresos hospitalarios, una mayor prevalencia de carcinoma hepatocelular y un mayor riesgo de mortalidad. La desnutrición es otra complicación frecuente en la cirrosis, cuya prevalencia aumenta con el grado de disfunción hepática, empeorando el pronóstico. El presente artículo describe los resultados del consenso de expertos y las respuestas de los panelistas sobre el manejo nutricional en la práctica clínica habitual de los pacientes con diabetes/hiperglucemia hospitalizados en planta (no críticos) con cirrosis hepática. Liver cirrhosis is a progressive and chronic disease of the liver, of diverse etiology, which is frequently associated with glucose intolerance and in some cases concurs with type 2 diabetes (DM2). DM2 is associated with adverse outcomes in patients with cirrhosis, including a higher rate of hospitalizations, a higher prevalence of hepatocellular carcinoma, and an increased risk of mortality. Malnutrition is another frequent complication of cirrhosis, the prevalence of which increases with the degree of liver dysfunction, worsening the prognosis. This article describes the results of the expert consensus and the responses of the panelists on the nutritional management in routine clinical practice of patients with diabetes/hyperglycemia hospitalized (non-critically ill) with liver cirrhosis.

Noninvasive predictors; Portal hypertension; Cirrhosis Predictores no invasivos; Hipertensión portal; Cirrosis Predictors no invasius; Hipertensió portal; Cirrosi Clinically significant portal hypertension (CSPH), defined as hepatic venous pressure gradient (HVPG) ≥ 10 mm Hg, identifies patients with compensated cirrhosis at a high risk of decompensation. However, HVPG is an invasive and nuanced method. The ANTICIPATE models, which include liver stiffness measurements by transient elastography (TE) and platelet count ± body mass index, are robust noninvasive surrogates of CSPH but required external validation in patients with nonalcoholic steatohepatitis (NASH) cirrhosis. Additionally, TE is not widely available worldwide. The aims of the study were: (1) to externally validate the ANTICIPATE models using baseline data from patients with compensated NASH cirrhosis screened/enrolled in a multicenter international randomized controlled trial; and (2) to develop and externally validate a model using only laboratory values. Regarding aim 1, both ANTICIPATE models showed good calibration and discrimination (area under the curve [AUC] > 0.8) in our cohort (n = 222). Regarding aim 2, a new lab-based model using the Fibrosis-4 index (FIB-4 [age, aspartate aminotransferase, alanine aminotransferase, platelet count]) plus serum albumin was developed. The discrimination in the training cohort (n = 309) was good (AUC of 0.78 [95% confidence interval [CI]:0.72–0.83]). It was then externally validated in a separate cohort of 245 patients with compensated NASH cirrhosis (AUC of 0.8 [95% CI: 0.75–0.86]). Given the difference in the prevalence of CSPH between training (74%) and validation (39%) cohorts, the model required an update of the baseline risk to achieve a good calibration. The updated model was named FIB4+. In conclusion, both ANTICIPATE models performed well in predicting the presence of CSPH in NASH cirrhosis. A model using FIB-4 plus albumin (FIB4+) can be used to predict CSPH where TE is not available. Supported by the Yale Liver Center, National Institutes of Health (P30 DK34989).

Although EASL guidelines recommend anti-HDV testing in all HBsAg-positive individuals, HDV infection remains an underdiagnosed condition. We describe the impact of an HDV screening program by reflex anti-HDV testing in all HBsAg-positive samples and compare the results before and after its implementation.In total, 2,236 HBsAg-positive determinations were included from January 2018 to December 2021. Only the first sample from each participant was evaluated: 1,492 samples before reflex anti-HDV testing (2018-2020) and 744 samples after (2021). Demographic and clinical characteristics of anti-HDV-positive patients were collected.Before reflex testing, anti-HDV had been tested in 7.6% (114/1492) of HBsAg-positive individuals: 23% (91/390) attended in an academic hospital and only 2% (23/1,102) in primary care centres. After reflex testing was established, 93% (691/744) of HBsAg-positive cases were evaluated for anti-HDV: 91% (533/586) in the academic hospital and 100% (158/158) in primary care. The anti-HDV-positive prevalence was similar before and after reflex testing: 9.6% (11/114) and 8.1% (56/691), respectively. However, the absolute number of anti-HDV-positive patients increased. Most anti-HDV-positive patients were young, HBeAg-negative, Caucasian males. HDV-RNA was detectable in 35 (65%) of 54 tested, HBV-DNA was undetectable in 64%, and alanine aminotransferase levels were normal in 48%.Anti-HDV reflex testing quintupled the absolute number of diagnoses of chronic hepatitis D infection. Before the reflex test, a large percentage of HBsAg-positive individuals had not undergone any anti-HDV determination. Implementation of reflex testing increases the diagnosis of patients with chronic hepatitis D.Chronic hepatitis delta (CHD) is a viral disease caused by HDV, which requires the presence of HBV to propagate. HDV infection can cause rapid progression to cirrhosis, among other severe complications. The prevalence of CHD worldwide is controversial, and the infection often goes unrecognised, mainly because of unawareness among physicians. Use of reflex testing in other viral hepatitis has proven to increase detection and linking-to-care of infected patients. Implementation of anti-HDV testing in all HBsAg-positive patients has led to a 5-fold increase in the number of HDV diagnoses in an academic hospital and primary care centres.

Chronic liver disease; Fibrosis 4 score Malaltia hepàtica crònica; Puntuació de fibrosi 4 Enfermedad crónica del hígado; Puntuación de fibrosis 4 Liver disease is frequently asymptomatic, challenging early identification in the primary care setting. The fibrosis 4 (FIB4) index is a liver fibrosis biomarker that is a potential alternative to liver biopsy for diagnosing and managing liver disease. This study aimed to calculate the FIB4 index for screening individuals at high risk of liver disease at the community level. This was a retrospective real-world study analyzing blood and serum test results from a central laboratory. The primary outcome was the number of individuals within each risk category for hepatic fibrosis: high risk (FIB4 ≥ 3.25) and low risk (FIB4 < 1.3). The analysis included samples from 31,753 patients, of which 18,102 were aged 40 to 75 years. In these patients, the FIB4 index had been explicitly requested in 1852 (10.2%) cases and estimated ad hoc in the rest. Of the 263 (1.5%) cases with FIB4 ≥ 3.25, the FIB4 index was requested in 46 (17.5%), and 52 (19.8%) showed evidence of liver fibrosis in their medical records, while the rest did not report any data regarding liver fibrosis. FIB4 is a simple score that can play a role as a “red flag” for early identification of patients at high risk of advanced liver fibrosis and their referral to specialized care.

Viral hepatitis; Liver cirrhosis Hepatitis viral; Cirrosis del hígado Hepatitis viral; Cirrosi del fetge

Background & Aims Prophylactic administration of platelets and fresh frozen plasma (FFP) has been recommended in patients with cirrhosis with low platelets and/or prolonged international normalized ratio (INR) without scientific evidence to support this practice. In this analysis, we evaluated the use of prophylactic administration of blood products in outpatients with cirrhosis undergoing endoscopic band ligation (EBL). Methods This is a multicenter retrospective analysis of consecutive EBL procedures in patients with cirrhosis at 4 hospitals in Spain from 01/2010-01/2017. FFP and/or platelet transfusion were given at the discretion of the physician if INR was >1.5 and/or platelet count, Graphical abstract, Highlights • Multicenter analysis of prophylactic administration of blood products in 536 outpatients with cirrhosis undergoing EBL. • The prophylactic transfusion protocol was only followed in 16% and 28% of procedures with high INR and/or low platelets, respectively. • Post EBL-bleeding occurred in 26 patients – 4.8% of patients and in 2.2% of procedures. • Patients that bled had higher Child-Pugh and MELD scores compared to those that did not bleed. • There was no clear relationship between post-EBL bleeding and the baseline INR/platelet count before the procedure.

Trombocitopènia greu; Malaltia hepàtica crònica; Lusutrombopag; Avatrombopag Trombocitopenia grave; Enfermedad hepática crónica; Lusutrombopag; Avatrombopag Severe thrombocytopenia; Chronic liver disease; Lusutrombopag; Avatrombopag La malaltia hepàtica crònica (MHC) es caracteritza per la destrucció progressiva, gradual i irreversible del fetge, la qual cosa resulta en cirrosi hepàtica i, finalment, en insuficiència hepatocel·lular. En els estadis més avançats, la malaltia s’associa a complicacions com icterícia, coagulopatia i hipertensió portal. L’etiologia de la MHC inclou malalties d’origen viral com l’hepatitis B i C, malalties causades per toxines com l’alcohol, trastorns del metabolisme com la malaltia de fetge gras no alcohòlic (FGNA) i trastorns autoimmunes com la colangitis esclerosant, entre d’altres.

Cirrhosis; Probiotic; Cognitive function Cirrosis; Probiòtic; Funció cognitiva Cirrosis; Probiótico; Función cognitiva Probiotics can modulate gut microbiota, intestinal permeability, and immune response and could therefore improve cognitive dysfunction and help avoid potential consequences, such as falls, in patients with cirrhosis. The aim of this study was to evaluate the effect of a multistrain probiotic on cognitive function, risk of falls, and inflammatory response in patients with cirrhosis. Consecutive outpatients with cirrhosis and cognitive dysfunction (defined by a Psychometric Hepatic Encephalopathy Score [PHES] < -4) and/or falls in the previous year were randomized to receive either a sachet of a high-concentration multistrain probiotic containing 450 billion bacteria twice daily for 12 weeks or placebo. We evaluated the changes in cognitive function (PHES); risk of falls (Timed Up and Go [TUG] test, gait speed, and incidence of falls); systemic inflammatory response; neutrophil oxidative burst; intestinal barrier integrity (serum fatty acid-binding protein 6 [FABP-6] and 2 [FABP-2] and zonulin and urinary claudin-3); bacterial translocation (lipopolysaccharide-binding protein [LBP]); and fecal microbiota. Thirty-six patients were included. Patients treated with the probiotic (n = 18) showed an improvement in the PHES (P = 0.006), TUG time (P = 0.015) and gait speed (P = 0.02), and a trend toward a lower incidence of falls during follow-up (0% compared with 22.2% in the placebo group [n = 18]; P = 0.10). In the probiotic group, we observed a decrease in C-reactive protein (P = 0.01), tumor necrosis factor alpha (P = 0.01), FABP-6 (P = 0.009), and claudin-3 (P = 0.002), and an increase in poststimulation neutrophil oxidative burst (P = 0.002). Conclusion: The multistrain probiotic improved cognitive function, risk of falls, and inflammatory response in patients with cirrhosis and cognitive dysfunction and/or previous falls.

Patients with cirrhosis often develop malnutrition and micronutrient deficiencies, leading to a worse prognosis and increased mortality. Our main goal was to assess the prevalence of micronutrient deficiencies in patients with decompensated cirrhosis. This was a prospective single-center study including 125 consecutive patients hospitalized for acute decompensation of cirrhosis (mostly of alcoholic etiology). A blood test including trace elements and vitamins was performed on admission. The main micronutrient deficiencies observed were vitamin D (in 94.5%), vitamin A (93.5%), vitamin B6 (60.8%) and zinc (85.6%). Patients in Child-Pugh class C had lower levels of vitamin A (p &lt, 0.0001), vitamin E (p = 0.01) and zinc (p &lt, 0.001), and higher levels of ferritin (p = 0.002) and vitamin B12 (p &lt, 0.001) than those in Child-Pugh class A and B. Patients with a higher model of end-stage liver disease (MELD) score had lower levels of vitamin A (p &lt, 0.0001), vitamin E (p &lt, 0.001), magnesium (p = 0.01) and zinc (p = 0.001), and higher levels of ferritin (p = 0.002) and vitamin B12 (p &lt, 0.0001). Severe hepatic insufficiency correlated with lower levels of zinc, vitamin E and vitamin A, and higher levels of vitamin B12 and ferritin.

Background & Aims Treatment with non-selective beta-blockers (NSBBs) reduces the risk of ascites, which is the most common decompensating event in cirrhosis. This study aimed to assess the ability of a serum microRNA (miRNA) signature to predict ascites formation and the hemodynamic response to NSBBs in compensated cirrhosis. Methods Serum levels of miR-452-5p, miR-429, miR-885-5p, miR-181b-5p, and miR-122-5p were analyzed in patients with compensated cirrhosis (N = 105). Hepatic venous pressure gradient (HVPG) was measured at baseline, after intravenous propranolol, and 1 year after randomization to NSBBs (n = 52) or placebo (n = 53) (PREDESCI trial). miRNAs were analyzed at baseline and at 1 year. Results Nineteen patients (18%) developed ascites, of whom 17 developed ascites after 1 year. miR-181b-5p levels at 1 year, but not at baseline, were higher in patients that developed ascites. The AUC of miR-181b-5p at 1 year to predict ascites was 0.7 (95% CI 0.59–0.78). miR-429 levels were lower at baseline in acute HVPG responders to NSBBs (AUC 0.65; 95% CI, 0.53–0.76), but levels at baseline and at 1 year were not associated with the HVPG response to NSBBs at 1 year. Conclusions Serum miR-181b-5p is a promising non-invasive biomarker to identify patients with compensated cirrhosis at risk of ascites development. Lay summary Ascites marks the transition from the compensated to decompensated stage in cirrhosis and indicates a worsening in prognosis. There are currently no easily accessible tools to identify patients with compensated cirrhosis at risk of developing ascites. We evaluated the levels of novel molecules termed microRNAs in the blood of patients with compensated cirrhosis and observed that miR-181b-5p can predict which patients are going to develop ascites., Graphical abstract, Highlights • miR-181b-5p appears to be a useful serum biomarker to anticipate ascites onset. • Low serum miR-181b-5p indicates low risk of ascites in compensated cirrhosis. • Low serum miR-429 reflects acute hemodynamic response to non-selective beta-blockers.

Clinical trials; Liver transplant; Quality of life Ensayos clínicos; Trasplante de hígado; Calidad de vida Assaigs clínics; Trasplantament de fetge; Qualitat de vida Management of decompensated cirrhosis is currently geared towards the treatment of complications once they occur. To date there is no established disease-modifying therapy aimed at halting progression of the disease and preventing the development of complications in patients with decompensated cirrhosis. The design of clinical trials to investigate new therapies for patients with decompensated cirrhosis is complex. The population of patients with decompensated cirrhosis is heterogeneous (i.e., different etiologies, comorbidities and disease severity), leading to the inclusion of diverse populations in clinical trials. In addition, primary endpoints selected for trials that include patients with decompensated cirrhosis are not homogeneous and at times may not be appropriate. This leads to difficulties in comparing results obtained from different trials. Against this background, the LiverHope Consortium organized a meeting of experts, the goal of which was to develop recommendations for the design of clinical trials and to define appropriate endpoints, both for trials aimed at modifying the natural history and preventing progression of decompensated cirrhosis, as well as for trials aimed at managing the individual complications of cirrhosis.

Background & Aims Health-related quality of life (HRQoL) determined by patient-reported outcomes (PROs) is impaired in chronic hepatitis B (CHB) and C patients, but there are no data regarding patients with chronic hepatitis D (CHD). The aim of this study was to assess PRO scores in untreated patients with CHD and compare them with those obtained for patients with CHB. Methods Patients with CHD completed 3 PRO instruments (Chronic Liver Disease Questionnaire [CLDQ], Functional Assessment of Chronic Illness Therapy–Fatigue [FACIT-F], and Work Productivity and Activity Impairment [WPAI]), and the results were compared with those of patients mono-infected with CHB. Results In total, 125 patients were included: 43 with CHD and 82 with CHB. Overall, baseline PROs showed differences between both groups. Several assessments, such as the worry score from CLDQ (p = 0.0118), functional well-being from FACIT-F (p = 0.0281), and activity impairment from WPAI (p = 0.0029) showed a significant trend to worse scores in patients with CHD than with CHB. In addition, the linear regression model supports the finding that having CHD as opposed to having CHB was a predictor of a higher worry score (CLDQ) and a higher activity impairment (WPAI). Conclusions In this first assessment in CHD, PROs recorded in patients with CHD showed a significant impairment in some domains of HRQoL questionnaires in comparison with those with CHB. Studies in larger cohorts with lengthier follow-up are needed to fully assess patient-reported quality of life over the course of CHD. Lay summary Chronic hepatitis D (CHD) is a viral disease that causes rapid evolution to liver cirrhosis, amongst other severe complications, when compared to patients with chronic hepatitis B (CHB). Health-related quality of life in chronic hepatitis C and CHB has been reported widely, but no studies have been performed on patient-reported outcomes in patients with CHD. Results showed that CHD patients reported worse outcomes in psychological domains such as worry and emotional well-being, as well as in physical domains such as abdominal symptoms, physical well-being, and activity impairment in comparison with patients with CHB., Graphical abstract, Highlights • Patient-reported outcomes (PROs) have been studied in patients with chronic hepatitis B and C. • There are no data on PROs for chronic hepatitis D. • Several scores of health-related quality of life are worse in patients with chronic hepatitis D than in those with chronic hepatitis B. • PROs are useful for evaluation of quality of life in clinical trials during and after treatment.

Carcinoma hepatocelular; Elastografía transitoria Carcinoma hepatocel·lular; Elastografia transitòria Hepatocellular carcinoma; Transient elastography Background: The potential role of non-invasive tests (NITs) for liver fibrosis for hepatocellular carcinoma (HCC) prediction remains poorly known. Methods: Retrospective analysis of a NAFLD cohort from a single university hospital in Barcelona, Spain. Incidence rates and cumulative incidence for the overall cohort, as well as cirrhotic and non-cirrhotic patients were calculated. Logistic regression analyses were carried out to investigate risk factors of HCC. Results: From the entire cohort of 1040 patients, 996 patients (95.8%) were analyzed, in whom 35 cases of HCC were detected, of which 26 (72.4%) HCC incident cases were newly diagnosed during a median follow-up of 2.5 (1.9–3.6) years. Two-hundred and thirty-one (23.2%) were cirrhotic at baseline. With the exception of 2 (7.7%) cases of HCC, the rest were diagnosed in cirrhotic patients. Overall HCC cumulative incidence was 9.49 (95% CI 6.4–13.9) per 1000 person-years. The incidence rate for cirrhotic patients was 41.2 (95% CI 27.6–61.6) per 1000 person-years and 0.93 (95% CI 0.23–3.7) per 1000 person-years for patients without cirrhosis. Overall mortality was significantly higher amongst patients with HCC (4.4% vs. 30.8%, p < 0.001). In patients with available liver biopsy (n = 249, 25%), advanced fibrosis (F3–F4) was significantly associated with higher HCC incidence, but not steatosis, lobular inflammation, nor ballooning. In the overall cohort, FIB-4 ≥1.3 (HR 8.46, 95% CI 1.06–67.4, p = 0.044) and older age (HR 1.06, 95% CI 1.01–1.11, p = 0.025) were associated with increasing risk of HCC over time, whereas in cirrhotic patients predictors of HCC included decreasing values of albumin (HR 0.34, 95% CI 0.13–0.87, p = 0.024), platelets (HR 0.98, 95% CI 0.98–0.99, p = 0.001), and increasing values of liver stiffness (HR 1.03, 95% CI 1.00–1.06, p = 0.016). Conclusions: In a Spanish cohort of NAFLD patients, HCC was rare in non-cirrhotic patients. NITs might play a relevant role at predicting HCC. The study was conducted in accordance with the Declaration of Helsinki and approved by the Vall d’Hebron University Hospital Campus Institutional Review Board (study protocol code PR(AG)626/2021).

Background: Patients with acutely decompensated cirrhosis (AD) may or may not develop acute-on-chronic liver failure (ACLF). ACLF is characterized by high-grade systemic inflammation, organ failures (OF) and high short-term mortality. Although patients with AD cirrhosis exhibit distinct clinical phenotypes at baseline, they have low short-term mortality, unless ACLF develops during follow-up. Because little is known about the association of profile of systemic inflammation with clinical phenotypes of patients with AD cirrhosis, we aimed to investigate a battery of markers of systemic inflammation in these patients. Methods: Upon hospital admission baseline plasma levels of 15 markers (cytokines, chemokines, and oxidized albumin) were measured in 40 healthy controls, 39 compensated cirrhosis, 342 AD cirrhosis, and 161 ACLF. According to EASL-CLIF criteria, AD cirrhosis was divided into three distinct clinical phenotypes (AD-1: Creatinine, SCOPUS: ar.j, info:eu-repo/semantics/published

Citocines; Malalties del fetge Citocinas, Enfermedades del hígado Cytokines; Liver diseases Probiotics can prevent pathological bacterial translocation by modulating intestinal microbiota and improving the gut barrier. The aim was to evaluate the effect of a fermented milk containing Lactobacillus paracasei subsp. paracasei CNCM I-1518 on bacterial translocation in rats with carbon tetrachloride (CCl4)-induced cirrhosis. Sprague-Dawley rats treated with CCl4 were randomized into a probiotic group that received fermented milk containing Lactobacillus paracasei subsp. paracasei CNCM I-1518 in drinking water or a water group that received water only. Laparotomy was performed one week after ascites development. We evaluated bacterial translocation, intestinal microbiota, the intestinal barrier and cytokines in mesenteric lymph nodes and serum. Bacterial translocation decreased and gut dysbiosis improved in the probiotic group compared to the water group. The ileal β-defensin-1 concentration was higher and ileal malondialdehyde levels were lower in the probiotic group than in water group. There were no differences between groups in serum cytokines but TNF-α levels in mesenteric lymph nodes were lower in the probiotic group than in the water group. Fermented milk containing Lactobacillus paracasei subsp. paracasei CNCM I-1518 decreases bacterial translocation, gut dysbiosis and ileal oxidative damage and increases ileal β-defensin-1 expression in rats treated with CCl4, suggesting an improvement in the intestinal barrier integrity. This study was partially funded by Danone Research (Palaiseau, Cedex, France), and grants PI08/0262 and PI14/00680 from the Instituto de Salud Carlos III, Madrid, Spain, and cofinanced by Fondos FEDER (Fondo Europeo de Desarrollo Regional), “Una manera de hacer Europa”, European Union, and CERCA Programme, Generalitat de Catalunya. The investigational product was provided by Danone Research. Silvia Vidal was supported by Fondo de Investigaciones Sanitarias (FIS) and is a participant in the Program for Stabilization of Investigators of the Direcció d’Estrategia i Coordinació del Departament de Salut, Generalitat de Catalunya. Pau Sancho-Bru is funded by Instituto de Salud Carlos III, Miguel Servet (CP11/00071).