A new year and a new roadmap for the journal in challenging times.

Sixteen months have passed since I had the honor of being appointed editor-in-chief of Revista Española de Enfermedades Digestivas (The Spanish Journal of Gastroenterology) (REED) and thank the Spanish Society of Digestive Diseases (SEPD) for trusting me in this new phase of the REED history. Four months later, in November 2021, Dr Juan-Ramon Larrubia joined the journal as Executive Editor. We thank the former Editor-in-Chief and deputy-editor Enrique Peéez-Cuadrado and Javier A. Cienfuegos, respectively, their devoted work putting the journal on an upward trajectory since 2016, one year before the REED centenary, they set the bar very high.

Hepatocellular carcinoma risk in hepatitis C stage-3 fibrosis after sustained virological response with direct-acting antivirals.

BACKGROUND & AIMS: Patients with chronic hepatitis C and stage 3 fibrosis are thought to remain at risk of hepatocellular carcinoma after sustained virological response. We investigated this risk in a large cohort of patients with well-defined stage 3 fibrosis. METHODS: We performed a multicentre, ambispective, observational study of chronic hepatitis C patients with sustained virological response after treatment with direct-acting antivirals started between January and December 2015. Baseline stage 3 was defined in a two-step procedure: we selected patients with transient elastography values of 9.5-14.5 kPa and subsequently excluded those with nodular liver surface, splenomegaly, ascites or collaterals on imaging, thrombopenia or esophago-gastric varices. Patients were screened twice-yearly using ultrasound. RESULTS: The final sample comprised 506 patients (median age, 57.4 years; males, 59.9%; diabetes, 17.2%; overweight, 44.1%; genotype 3, 8.9%; HIV coinfection, 18.4%; altered liver values, 15.2%). Median follow-up was 33.7 (22.1-39.1) months. Five hepatocellular carcinomas and 1 cholangiocarcinoma were detected after a median of 29.4 months (95% CI: 26.8-39.3), with an incidence of 0.47/100 patients/year (95% CI: 0.17-1.01). In the multivariate analysis, only males older than 55 years had a significant higher risk (hazard ratio 7.2 [95% CI: 1.2-41.7; P = .029]) with an incidence of 1.1/100 patients/year (95% CI: 0.3-2.8). CONCLUSIONS: In a large, well-defined cohort of patients with baseline hepatitis C stage-3 fibrosis, the incidence of primary liver tumours was low after sustained virological response and far from the threshold for cost-effectiveness of screening, except in males older than 55 years.

Obeticholic Acid and Fibrates in Primary Biliary Cholangitis: Comparative Effects in a Multicentric Observational Study.

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.

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

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.

Coordinated assistance plan for the elimination of hepatitis C virus at the centro de ayuda integral al drogodependiente (CAID (Comprehensive Care Centre for Drug Addicts)). / Plan asistencial coordinado para la eliminación del virus de la hepatitis C en el centro de ayuda integral al drogodependiente (CAID).

INTRODUCTION: The drug-injecting population has a high prevalence of hepatitis C virus (HCV) and high risk of transmission. It is a priority to establish an agile diagnostic and treatment plan. OBJECTIVES: 1) Assess the effectiveness of a new coordinated care plan of referral from the Comprehensive Care Centre for Drug Addicts (CAID) to specialised care and 2) Determine the prevalence of HCV, clinical characteristics, effectiveness and safety of treatment in this population. METHODS: 1,300 serologies requested by the CAID between 1998 and 2018 were retrospectively analysed, the seroprevalence of HCV was calculated and the efficiency of the traditional CAID-specialised care referral system was evaluated. A care plan was designed and coordinated among specialists involved in diagnosis and treatment. Since October 2018, 11 patients have been included in the new plan and the performance of both referral systems was compared. RESULTS: With the traditional system, 48.2% (83/172) of the patients were lost. 14.5% (172/1,300) presented positive HCV serology, compared to the general population OR = 19; 95% CI 14.3-25. The prevalence of active infection was 80.3% (90/112). The prevalence of active infection was 80.3% (90/112). Of the 11 patients referred by the new plan, 76.9% (8/11) had active infection and 100% (8/8) were treated with Direct Antiviral Agents successfully. CONCLUSIONS: The new coordinated CAID-specialised care plan presents high effectiveness in comparison with the traditional referral system. The seroprevalence and prevalence of active infection in the CAID population is very high. Treatments with Direct Antiviral Agents are effective and safe.

A Model Based on Noninvasive Markers Predicts Very Low Hepatocellular Carcinoma Risk After Viral Response in Hepatitis C Virus-Advanced Fibrosis.

BACKGROUND AND AIMS: Patients with hepatitis C virus (HCV) and advanced fibrosis remain at risk of hepatocellular carcinoma (HCC) after sustained viral response (SVR) and need lifelong surveillance. Because HCC risk is not homogenous and may decrease with fibrosis regression, we aimed to identify patients with low HCC risk based on the prediction of noninvasive markers and its changes after SVR. APPROACH AND RESULTS: This is a multicenter cohort study, including patients with HCV and compensated advanced fibrosis that achieved SVR after direct antivirals. Clinical and transient elastography (TE) data were registered at baseline, 1 year, and 3 years after the end of treatment (EOT). All patients underwent liver ultrasound scan every 6 months. Patients with clinical evaluation 1 year after EOT were eligible. Univariate and multivariate Cox regression analysis were performed, and predictive models were constructed. HCC occurrence rates were evaluated by Kaplan-Meier. Nine hundred and ninety-three patients were eligible (56% male; 44% female; median age 62 years), 35 developed HCC (3.9%), and the median follow-up was 45 months (range 13-53). Baseline liver stiffness measurement (LSM) (HR 1.040; 95% CI 1.017-1.064), serum albumin (HR 0.400; 95% CI 0.174-0.923), 1-year DeltaLSM (HR 0.993; 95% CI 0.987-0.998), and 1-year FIB-4 score (HR 1.095; 95% CI 1.046-1.146) were independent factors associated with HCC. The TE-based HCC risk model predicted 0% of HCC occurrence at 3 years in patients with score 0 (baseline LSM ≤ 17.3 kPa, albumin >4.2 g/dL, and 1-year DeltaLSM > 25.5%) versus 5.2% in patients with score 1-3 (Harrell's C 0.779; log-rank 0.002). An alternative model with FIB-4 similarly predicted HCC risk. CONCLUSIONS: A combination of baseline and dynamic changes in noninvasive markers may help to identify patients with a very low risk of HCC development after SVR.

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

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.

Digestive units in the National Health System of the 21st century. Organizational and management standards for a patient-centered service.

The Spanish Society of Digestive Pathology has set a consensus document on the standards and recommendations for gastroenterology units (GU). These standards are considered as relevant in the organization and management of the unit to develop their activities with efficiency and quality. Four key groups of processes have been identified: a) care for the acutely ill adult patient; b) outpatient digestive endoscopy; c) in-hospital support to other services and outpatient clinics; and d) management of patients with chronic complex digestive pathology. Standards for organization and management of the unit were classified within the group of support processes, and training and research as strategic processes. Standards have also been developed for some functional and monographic units such as endoscopy, hepatology and inflammatory bowel disease; as well as for certain procedures including endoscopic retrograde cholangiopancreatography, colonoscopy and gastroscopy. The standards will be set for other units and procedures as they are developed. The standards developed must be reviewed within a maximum period of five years.

Clinical Outcome Event Adjudication in a 10-Year Prospective Study of Nucleos(t)ide Analogue Therapy for Chronic Hepatitis B.

Background and Aims: In the REALM (Randomized, Observational Study of Entecavir to Assess Long-Term Outcomes Associated with Nucleoside/Nucleotide Monotherapy for Patients with Chronic HBV Infection) study, 12,378 patients with chronic hepatitis B virus (HBV) infection received up to 10 years of randomized therapy with entecavir or another HBV nucleos(t)ide analogue. Monitored clinical outcome events (COEs) included malignant neoplasms, HBV disease progression events, and deaths. An external event adjudication committee (EAC) was convened to provide real-time review of reported COEs to optimize data quality, and minimize potential adverse effects of the large cohort, interdisciplinary outcome assessments, geographic scope, and long duration. Methods: The EAC comprised an international group of hepatologists and oncologists with expertise in diagnosis of targeted COEs. The EAC reviewed and adjudicated COEs according to prospectively defined diagnostic criteria captured in the EAC charter. Operational processes, including data collection and query procedures, were implemented to optimize efficiency of data recovery to maximize capture of adjudicated COEs, the primary study outcome measure. Results: A total of 1724 COEs were reported and 1465 of these events were adjudicated by the EAC as reported by the investigators (85.0% overall concordance). Concordance by COE type varied: deaths, 99.6%; hepatocellular carcinoma (HCC), 83.3%; non-HCC malignancies, 88.0%; non-HCC HBV disease progression, 68.2%. Reasons for lack of concordance were most commonly lack of adequate supporting data to support an adjudicated diagnosis or evidence that the event pre-dated the study. Conclusions: The REALM EAC performed a critical role in ensuring data quality and consistency; EAC performance was facilitated by well-defined diagnostic criteria, effective data capture, and efficient operational processes. Trial registration: ClinicalTrials.gov NCT00388674.

The contribution of telemedicine to hepatitis C elimination in a correctional facility.

BACKGROUND: micro-elimination has been recently proposed as an efficient strategy to achieve global hepatitis C virus (HCV) elimination. The Spanish Health Ministry Strategic Plan for hepatitis C infection highlighted intervention in prisons as a priority action. However, there are important barriers associated with the specialized care provision to the penitentiary population. AIMS: to assess the contribution of telemedicine for HCV elimination in a correctional facility in Spain. METHODS: an open label program of HCV elimination via telemedicine was started on February 3rd, 2015 in a large penitentiary of 1,200 inmates, as an alternative to referring patients to specialists. An anonymous satisfaction survey was performed among a random sample of inmates and all participating doctors. RESULTS: the prevalence of HCV viremia prior to program initiation was 12.4%. One hundred and thirty-one patients received DAA HCV treatment during the period 2015-2018; 42.74% had a HCV-HIV co-infection. Overall, 97% achieved a sustained virological response (SVR). A second regime of DAA successfully rescued non-responder patients and the HCV prevalence was zero at the end of the program. Satisfaction was high or very high according to 67% of inmates and all participating doctors. CONCLUSION: telemedicine is an effective tool for HCV elimination in penitentiary correctional facilities where referral to specialists is difficult. The extensive use of this technology should be recommended in this setting in order to facilitate equitable access to specialized care.

Higher levels of serum uric acid influences hepatic damage in patients with non-alcoholic fatty liver disease (NAFLD).

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.

Hepatitis B virus in patients with chronic hepatitis C treated with direct antiviral agents.

INTRODUCTION: cases of hepatitis B virus (HBV) reactivation have been reported in patients with hepatitis C virus (HCV) treated with direct antiviral agents (DAA). OBJECTIVES AND METHODS: the main objectives of the present study are: a) to determine the prevalence of HBV/HCV coinfection in HCV patients treated with DAAs in the Autonomous Community of Madrid (CM) and also to determine the incidence and clinical relevance of HBV reactivation; and b) to determine the HBV screening rates in HCV patients in our region. For that purpose, 1,337 HCV patients were consecutively treated with DAAs in two hospitals located in South CM between January 2015 and June 2017. RESULTS: nine of the 1,337 (0.67%) participants were HBsAg positive and 356 (26.6%) had previous HBV infection markers. Two of the four (50%) HBsAg positive patients with untreated HBV developed a virological reactivation, but not a biochemical reaction. Of the 356 patients with previous HBV infection markers, all had normal transaminases at the end of treatment and during follow-up. The HBV screening rate amounted to 92.9% of the cohort. CONCLUSIONS: the prevalence of HBV (HBsAg positive) infection in patients with chronic hepatitis C in the southern area of the CM is low. HBV reactivation in HBsAg positive patients treated with DAAs is common, although without clinical relevance. In our region, there is a high rate of HBV screening in patients with HCV that are likely treated with DAAs.

RECALAD. Patient care at National Health System Digestive Care Units - A pilot study, 2015.

OBJECTIVES: To reach a situation diagnosis on the status of patient management at digestive care units (DCUs) in Spain. MATERIAL AND METHODS: A cross-sectional descriptive study across DCUs in general acute care hospitals within the Spanish National Health System (data referred to 2015). The study variables were collected with a questionnaire including items on structure, services portfolio, activity, education, research, and good practice. Hospital discharge rates for digestive diseases were also assessed using the minimum basic data set (2005-2014). RESULTS: Two hundred and nine hospitals invited, 55 responders (26.3%). Average discharges from hospital were 1,139 ± 653 per DCU/year, and 100 ± 66 per year per dedicated gastroenterologist. In 2014, admission rate to DCUs per 1,000 population and year was 280, with a mean stay of 7.4 days. The analysis of the MBDS for 2005-2014 reveals a progressive increase in the number of discharges (37% more in 2014 versus 2005), with a 28% decrease in hospital gross mortality rate (3.7% in 2014) and a slightly reduced (14%) mean stay (7.6 days in 2014). Considerable variability may be seen in structure, activity, and results indicators. Mortality and readmission rates, as well as mean stay, vary more than 100% amongst DCUs, and major dispersions also exist in frequentation and results amongst autonomous communities. CONCLUSIONS: The RECALAD 2015 survey unveiled relevant aspects related to DCUs organization, structure, and management. The notable variability encountered likely reflects relevant differences in efficiency and productivity, and thus points out there is ample room for improvement.

Upcoming pharmacological developments in chronic hepatitis B: can we glimpse a cure on the horizon?

BACKGROUND: Hepatitis B virus (HBV) chronic infection affects up to 240 million people in the world and it is a common cause of cirrhosis and hepatocellular carcinoma (HCC). HBV covalently closed circular DNA (cccDNA) plays an essential role in HBV persistence and replication. Current pharmacological treatment with nucleos(t)ide analogues (NA) may suppress HBV replication with little or no impact on cccDNA, hence lifelong treatment is required in the vast majority of patients. Clearances of intrahepatic cccDNA and/or HBsAg are critical endpoints for future antiviral therapy in chronic HBV. Recent promising developments targeting different molecular HBV life cycle steps are being pre-clinically tested or have moved forward in early clinical trials. METHODS: We review the current state of the art of these pharmacological developments, mainly focusing on efficacy and safety results, which are expected to lay the ground for future HBV eradication. An inclusive literature search on new treatments of HBV using the following electronic databases: Pubmed/MEDLINE, AMED, CINAHL and the Cochrane Central Register of Controlled Trials. Full-text manuscripts and abstracts published over the last 12 years, from 2005 to March 2011 were reviewed for relevance and reference lists were crosschecked for additional applicable studies regarding new HBV antiviral treatment. RESULTS: HBV entry inhibitors, HBV core inhibitors, HBV cccDNA transcripts RNA interference, HBV cell apoptosis inducers, HBV RNA, viral proteins and DNA knock down agents, HBV release inhibitors, anti-sense nucleosides, exogenous interferon stimulation, interferon response stimulation and HBV therapeutic vaccines were reviewed. CONCLUSION: This review will provide readers with an updated vision of current and foreseeable therapeutic developments in chronic hepatitis B.

Disruptive therapeutic innovation and the opportunity to eliminate a chronic disease - The issue of chronic hepatitis C in Spain.

Public funding decisions must be guided by criteria of scientific evidence, cost-effectiveness and economic evaluation. As an increase in health-effectiveness provided by therapeutic innovations can also substantially raise the cost, the cost-effectiveness analysis estimating this increase in the cost per unit of health gained compared to the previous technologies should be part of the economic evaluation. The measure of effectiveness most frequently used in health economic evaluations is the Quality Adjusted Life Year (QALY). Data from a Markov analysis presented by Turnes et al. in the last issue of this journal comparing two scenarios, pre-DAA and post-DAA in Spain is discussed in this document.

Risk of cirrhosis-related complications in patients with advanced fibrosis following hepatitis C virus eradication.

BACKGROUND & AIMS: The risk of hepatocellular carcinoma (HCC) is reduced but not eradicated among patients with hepatitis C virus (HCV)-induced advanced hepatic fibrosis who attained sustained viral response (SVR). We aimed to assess the risk of cirrhosis-related complications in this specific group of patients. METHODS: Data from previously reported Western cohort studies including patients with chronic HCV infection and bridging fibrosis or cirrhosis who attained SVR were pooled for survival analyses on the individual patient level. The primary endpoint was HCC and the secondary endpoint was clinical disease progression, defined as liver failure, HCC or death. RESULTS: Included were 1000 patients with SVR. Median age was 52.7 (IQR 45.1-59.7) years, 676 (68%) were male and 842 (85%) had cirrhosis. Median follow-up was 5.7 (IQR 2.9-8.0) years. Fifty-one patients developed HCC and 101 had clinical disease progression. The cumulative 8-year HCC incidence was 1.8 (95% CI 0.0-4.3) among patients with bridging fibrosis and 8.7% (95% CI 6.0-11.4) among those with cirrhosis (p=0.058). Within the cirrhosis group, the 8-year HCC incidence was 2.6% (95% CI 0.0-5.5) among patients <45years, 9.7% (95% CI 5.8-13.6) among patients from 45-60years, and 12.2% (95% CI 5.3-19.1) among patients >60years of age at start of therapy (p=0.006). Multivariable Cox analyses indicated that higher age, lower platelet count and diabetes mellitus were independently associated with development of HCC. After 8years 4.2% (95% CI 0.1-8.3) of patients with bridging fibrosis and 15.8% (95% CI 12.3-19.3) of patients with cirrhosis experienced clinical disease progression (p=0.007). CONCLUSIONS: Patients with HCV-induced cirrhosis and SVR showed an annual risk of approximately 1% for HCC and 2% for clinical disease progression. Therefore, to prevent HCC surveillance, chronic HCV infection should preferably be treated before cirrhosis has developed. LAY SUMMARY: Patients with cirrhosis who were able to eradicate their chronic HCV infection remain at substantial risk of primary liver cancer. The risk of liver cancer increases with higher age, laboratory makers suggesting more severe liver disease, and presence of diabetes mellitus. Also after successful antiviral therapy patients with HCV-induced cirrhosis should thus remain included in follow-up for early detection of liver cancer.

Factores de riesgo de la enfermedad hepática grasa no alcohólica / Risk factors for non-alcoholic fatty liver disease

Prevalence of non-alcoholic fatty liver disease (NAFLD) may be 10%-15% worldwide, and these figures are even higher in obese and in type 2 diabetes mellitus patients. The most important risk factor is metabolic syndrome, especially central obesity. Even though the majority of patients with macrovesicular steatohepatitis will not progress to advanced liver disease, a subgroup of patients will evolve to non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma. Independent risk factors associated with NASH are older age, type 2 diabetes mellitus and obesity. Patients with significant hepatocellular lesion, such as hepatocyte ballooning, Mallory hyalline or fibrosis, have a higher risk of cirrhosis and are more likely to have a high liver-related mortality, although higher global mortality has not been demonstrated. Although NASH related cirrhosis may have better prognosis compared to hepatitis C cirrhosis, recent series suggest that it may be the third cause of liver transplantation. Steatosis, NASH and cirrhosis recurrence post-liver transplantation is common. The risk of hepatocellular carcinoma (HCC) is increased in patients with NAFLD, and all patients with cryptogenic cirrhosis should be screened for HCC

La enfermedad hepática grasa no alcohólica puede afectar al 15%-25% de la población, con cifras mayores en pacientes obesos y con diabetes mellitus tipo 2. El principal factor de riesgo es el síndrome metabólico, especialmente la obesidad central. Aunque la mayoría de los pacientes con esteatosis macrovacuolar simple no presentan progresión de su enfermedad, existe un subgrupo que progresa a esteatohepatitis no alcohólica, y aunque se desconocen los factores de riesgo para esta progresión, la mayoría de los estudios reconocen la edad, la presencia de diabetes mellitas tipo 2 y la obesidad como predictores de riesgo independientes de EHNA. La presencia de lesión hepatocelular significativa, como el abalonamiento hepatocitario o la hialina de Mallory y la fibrosis, incrementan significativamente el riesgo de cirrosis. Los pacientes que tienen esta lesión histopatológica presentan una mortalidad de causa hepática superior, si bien no se ha demostrado una mortalidad global aumentada. Aunque la cirrosis secundaria a esteatohepatitis no alcohólica parece tener un pronóstico ligeramente mejor que la secundaria a hepatitis C, en muchas series es la tercera causa de trasplante ortotópico de hígado. La recurrencia postrasplante de la esteatosis, de la esteatohepatitis no alcohólica y de la cirrosis es frecuente. Existe un aumento del riesgo de hepatocarcinoma en pacientes con enfermedad hepática grasa no alcohólica. En la actualidad se recomienda el seguimiento para la detección precoz de este tumor en todos los pacientes con cirrosis criptogénica

Acute-on-chronic liver failure: Pathogenesis, prognostic factors and management.

Acute-on-chronic liver failure (ACLF) is increasingly recognized as a complex syndrome that is reversible in many cases. It is characterized by an acute deterioration of liver function in the background of a pre-existing chronic liver disease often associated with a high short-term mortality rate. Organ failure (OF) is always associated, and plays a key role in determining the course, and the outcome of the disease. The definition of ACLF remains controversial due to its overall ambiguity, with several disparate criteria among various associations dedicated to the study of liver diseases. Although the precise pathogenesis needs to be clarified, it appears that an altered host response to injury might be a contributing factor caused by immune dysfunction, ultimately leading to a pro-inflammatory status, and eventually to OF. The PIRO concept (Predisposition, Insult, Response and Organ Failure) has been proposed to better approach the underlying mechanisms. It is accepted that ACLF is a different and specific form of liver failure, where a precipitating event is always involved, even though it cannot always be ascertained. According to several studies, infections and active alcoholism often trigger ACLF. Viral hepatitis, gastrointestinal haemorrhage, or drug induced liver injury, which can also provoke the syndrome. This review mainly focuses on the physiopathology and prognostic aspects. We believe these features are essential to further understanding and providing the rationale for improveddisease management strategies.

Alcohol liver disease: A review of current therapeutic approaches to achieve long-term abstinence.

Harmful alcohol drinking may lead to significant damage on any organ or system of the body. Alcoholic liver disease (ALD) is the most prevalent cause of advanced liver disease in Europe. In ALD, only alcohol abstinence was associated with a better long-term survival. Therefore, current effective therapeutic strategy should be oriented towards achieving alcohol abstinence or a significant reduction in alcohol consumption. Screening all primary care patients to detect those cases with alcohol abuse has been proposed as population-wide preventive intervention in primary care. It has been suggested that in patients with mild alcohol use disorder the best approach is brief intervention in the primary care setting with the ultimate goal being abstinence, whereas patients with moderate-to-severe alcohol use disorder must be referred to specialized care where detoxification and medical treatment of alcohol dependence must be undertaken.

Labour productivity losses caused by premature death associated with hepatitis C in Spain.

BACKGROUND AND AIMS: Hepatitis C virus (HCV) infection places a huge burden on healthcare systems. There is no study assessing the impact of HCV infection on premature deaths in Spain. The aim of this study was to estimate productivity losses because of premature deaths attributable to hepatitis C occurring in Spain during 2007-2011. MATERIALS AND METHODS: We use data from several sources (Registry of Deaths, Labour Force Survey and Wage Structure Survey) to develop a simulation model based on the human capital approach and to estimate the flows in labour productivity losses in the period considered. The attributable fraction method was used to estimate the numbers of deaths associated with HCV infection. Two sensitivity analyses were developed to test the robustness of the results. RESULTS: Our model shows total productivity losses attributable to HCV infection of 1054.7 million euros over the period analysed. The trend in productivity losses is decreasing over the period. This result is because of improvements in health outcomes, reflected in the reduction of the number of years of potential productive life lost. Of the total estimated losses, 18.6% were because of hepatitis C, 24.6% because of hepatocellular carcinoma, 30.1% because of cirrhosis, 15.9% because of other liver diseases and 10.7% because of HIV-HCV coinfection. CONCLUSION: The results show that premature mortality attributable to hepatitis C involves significant productivity losses. This highlights the need to extend the analysis to consider other social costs and obtain a more complete picture of the actual economic impact of hepatitis C infection.