The biochemical pattern defines MASLD phenotypes linked to distinct histology and prognosis.

BACKGROUND: MASLD can manifest as hepatocellular damage, which can result in mild elevation of aminotransferases. However, in some patients, MASLD presents with cholestatic pattern. OBJECTIVE: To assess the impact of the biochemical pattern on the natural course of MASLD, including liver damage in histology, the accuracy of non-invasive tests(NITs), and prognosis. METHODS: Multicenter study enrolling 2156 patients with biopsy-proven MASLD, who were classified based on their[ALT/ULN)]/[(ALP/ULN)] levels at the time of biopsy: (a) hepatocellular pattern(H), > 5; (b) mixed pattern(M),2-5; (c) cholestatic pattern(C), < 2. OUTCOMES: (a) histological evaluation of the single components of NAS, MASH, and fibrosis; (b) NITs and transient elastography assessing advanced fibrosis; (c) prognosis determined by the appearance of decompensated cirrhosis and death. RESULTS: Out of the 2156 patients, 22.9% exhibited the H-pattern, whilst 31.7% exhibited the C-pattern. Severe steatosis, ballooning, lobular inflammation, and MASH (56.4% H vs. 41.9% M vs. 31.9% C) were more common in H-pattern (p = 0.0001),whilst C-pattern was linked to cirrhosis (5.8% H vs. 5.6% M vs. 10.9% C; p = 0.0001). FIB-4(0.74(95% CI 0.69-0.79) vs. 0.83 (95% CI 0.80-0.85); p = 0.005) and Hepamet Fibrosis Score(0.77 (95% CI 0.69-0.85) vs. 0.84 (95% CI 0.80-0.87); p = 0.044)exhibited lower AUROCs in the H-pattern. The C-pattern[HR 2.37 (95% CI 1.12-5.02); p = 0.024], along with age, diabetes, and cirrhosis were independently associated with mortality. Most patients maintained their initial biochemical pattern during the second evaluation. CONCLUSIONS: The H-pattern exhibited greater necro-inflammation in the histology than the C-pattern, whereas the latter showed more cirrhosis. The accuracy of NITs in detecting fibrosis was decreased in H-pattern. The occurrence of decompensated events and mortality was predominant in C-pattern. Therefore, identifying MASLD phenotypes based on the biochemical presentation could be relevant for clinical practice.

Further decompensation in cirrhosis: Results of a large multicenter cohort study supporting Baveno VII statements.

BACKGROUND AND AIMS: The prognostic weight of further decompensation in cirrhosis is still unclear. We investigated the incidence of further decompensation and its effect on mortality in patients with cirrhosis. APPROACH AND RESULTS: Multicenter cohort study. The cumulative incidence of further decompensation (development of a second event or complication of a decompensating event) was assessed using competing risks analysis in 2028 patients. A 4-state model was built: first decompensation, further decompensation, liver transplant, and death. A cause-specific Cox model was used to assess the adjusted effect of further decompensation on mortality. Sensitivity analyses were performed for patients included before or after 1999. In a mean follow-up of 43 months, 1192 patients developed further decompensation and 649 died. Corresponding 5-year cumulative incidences were 52% and 35%, respectively. The cumulative incidences of death and liver transplant after further decompensation were 55% and 9.7%, respectively. The most common further decompensating event was ascites/complications of ascites. Five-year probabilities of state occupation were 24% alive with first decompensation, 21% alive with further decompensation, 7% alive with a liver transplant, 16% dead after first decompensation without further decompensation, 31% dead after further decompensation, and <1% dead after liver transplant. The HR for death after further decompensation, adjusted for known prognostic indicators, was 1.46 (95% CI: 1.23-1.71) ( p <0.001). The significant impact of further decompensation on survival was confirmed in patients included before or after 1999. CONCLUSIONS: In cirrhosis, further decompensation occurs in ~60% of patients, significantly increases mortality, and should be considered a more advanced stage of decompensated cirrhosis.

Documento de posicionamiento de la «Societat Catalana de Digestologia» sobre elastografía hepática 2022 / Clinical practice guidelines of the Catalan Society of Gastroenterology about hepatic elastography 2022

Introducción: Después de casi 20 años utilizando la elastografía de transición para el diagnóstico no invasivo de la fibrosis hepática, su uso se ha extendido al cribado poblacional, la evaluación de la esteatosis y las complicaciones de la cirrosis. Por ello, la «Societat Catalana de Digestologia» encargó a un grupo de expertos actualizar el primer Documento realizado en 2011. Material y métodos: El grupo de trabajo (8 médicos y 4 enfermeras) elaboró un panel de preguntas en base a la encuesta online «Elastografía Hepática en Cataluña 2022» siguiendo la estructura PICO y el método Delphi. Resultados: Las respuestas se presentan con el nivel de evidencia, el grado de recomendación y el consenso final tras ser evaluadas por 2 revisores externos. Conclusión: La elastografía de transición utiliza el método elastográfico más sencillo y fiable para cuantificar la fibrosis hepática, evaluar la esteatosis y conocer el riesgo de complicaciones en pacientes con cirrosis. El documento ha sido avalado por la «Societat Catalana de Digestologia» y el «Col legi Oficial d’Infermeres i Infermers de Barcelona». (AU)

Introduction: After almost 20 years using transient elastography (TE) for the non-invasive diagnosis of liver fibrosis, its use has been extended to population screening, evaluation of steatosis and complications of cirrhosis. For this reason, the «Catalan Society of Gastroenterology» commissioned a group of experts to update the first document carried out in 2011. Material and methods: The working group (8 doctors and 4 nurses) prepared a panel of questions based on the online survey «Hepatic Elastography in Catalonia 2022» following the PICO structure and the Delphi method. Results: The answers are presented with the level of evidence, the degree of recommendation and the final consensus after being evaluated by two external reviewers. Conclusion: Transient elastography uses the simplest and most reliable elastographic method to quantify liver fibrosis, assess steatosis, and determine the risk of complications in patients with cirrhosis. The document has been endorsed by the “Catalan Society of Gastroenterology” and the “Col·legi Oficial d’Infermeres i Infermers de Barcelona”. (AU)

Tenofovir Disoproxil Fumarate Reduces the Severity of COVID-19 in Patients with Chronic Hepatitis B.

BACKGROUND AND AIMS: HIV-positive patients on tenofovir hydroxyl fumarate (TDF)/emtricitabine have a lower risk of COVID-19 and hospitalization than those given other treatments. Our aim was to analyze the severity of COVID-19 in patients with chronic hepatitis B (CHB) on TDF or entecavir (ETV). METHODS: Spanish hospital databases (n = 28) including information regarding adult CHB patients on TDF or ETV for the period February 1st to November 30th 2020 were searched for COVID-19, defined as a positive SARS-CoV-2 polymerase chain reaction, and for severe COVID-19. RESULTS: Of 4736 patients, 117 had COVID-19 (2.5%), 67 on TDF and 50 on ETV. Compared to patients on TDF, those on ETV showed (p < 0.05) greater rates of obesity, diabetes, ischemic cardiopathy, and hypertension. COVID-19 incidence was similar in both groups (2.3 vs. 2.6%). Compared to TDF, patients on ETV more often (p < 0.01) had severe COVID-19 (36 vs. 6%), required intensive care unit (ICU) (10% vs. 0) or ventilatory support (20 vs. 3%), were hospitalized for longer (10.8 ± 19 vs. 3.1 ± 7 days) or died (10 vs. 1.5%, p = 0.08). In an IPTW propensity score analysis adjusted for age, sex, obesity, comorbidities, and fibrosis stage, TDF was associated with a sixfold reduction in severe COVID-19 risk (adjusted-IPTW-OR 0.17, 95%CI 0.04-0.67, p = 0.01). CONCLUSION: Compared to ETV, TDF seems to play a protective role in CHB patients with SARS-CoV-2 whereby the risk of severe COVID-19 is lowered.

Clinical practice guidelines of the Catalan Society of Gastroenterology about hepatic elastography 2022. / Documento de posicionamiento de la «Societat Catalana de Digestologia¼ sobre elastografía hepática 2022.

INTRODUCTION: After almost 20 years using transient elastography (TE) for the non-invasive diagnosis of liver fibrosis, its use has been extended to population screening, evaluation of steatosis and complications of cirrhosis. For this reason, the «Catalan Society of Gastroenterology¼ commissioned a group of experts to update the first document carried out in 2011. MATERIAL AND METHODS: The working group (8 doctors and 4 nurses) prepared a panel of questions based on the online survey «Hepatic Elastography in Catalonia 2022¼ following the PICO structure and the Delphi method. RESULTS: The answers are presented with the level of evidence, the degree of recommendation and the final consensus after being evaluated by two external reviewers. CONCLUSION: Transient elastography uses the simplest and most reliable elastographic method to quantify liver fibrosis, assess steatosis, and determine the risk of complications in patients with cirrhosis. The document has been endorsed by the "Catalan Society of Gastroenterology" and the "Col·legi Oficial d'Infermeres i Infermers de Barcelona".

Prevalence and outcomes of acute-on-chronic liver failure among cirrhotic patients admitted for an acute decompensation / Prevalencia y evolución de fracaso hepático crónico agudizado en pacientes cirróticos ingresados por descompensación aguda

Background: Acute-on-chronic liver failure (ACLF) is a common syndrome that occurs in patients with advanced chronic liver disease. It consists of the rapid failure of various organs and is associated with high short-term mortality. We aim to describe the main features and outcomes of inpatients who developed ACLF and to identify the factors associated with in-hospital and 28-day mortality. Patients and methods: All patients meeting ACLF criteria with advanced chronic liver disease admitted for decompensation from January 2014 to December 2016 were identified. Clinical and biological data were collected at the time of ACLF diagnosis and at 3–7 days thereafter, as well as in-hospital and 28-day mortality. Results: Eighty nine out of 354 admission episodes (28%) developed ACLF, which was present at the time of admission in 72% of cases. A precipitating factor was identified in 83% of cases, the most frequent being infection (53%) and gastrointestinal bleeding (19%). In the multivariate regression analysis, the ACLF grade at 3–7 days after diagnosis was predictive of in-hospital mortality and 28-day mortality, and lower creatinine and bilirubin levels at the time of ACLF diagnosis and a precipitating factor other than bacterial infection were associated with ACLF reversion at 3–7 days. Conclusions: ACLF is a frequent complication among patients with chronic liver disease admitted for acute decompensations and is associated with a high mortality rate and is related to the number of organs involved. Bacterial infection is the most frequent precipitating factor of ACLF and probably entails a worse prognosis.(AU)

Introducción: La insuficiencia hepática crónica agudizada (IHCA) es una complicación frecuente en pacientes con enfermedad hepática crónica avanzada. Consiste en el fracaso de varios órganos y se asocia a una elevada mortalidad a corto plazo. El objetivo fue describir las características y evolución de los pacientes ingresados que desarrollan IHCA e identificar los factores asociados con mortalidad intrahospitalaria y a 28 días.Pacientes y métodos: Se identificaron los pacientes que cumplían criterios de IHCA con enfermedad hepática avanzada ingresados por descompensación de Enero 2014 a Diciembre 2016. Se recogieron datos clínicos y analíticos en el momento de presentar IHCA y a los 3-7 días así como mortalidad intrahospitalaria y a los 28 días. Resultados: Ochenta y nueve de 354 ingresos (28%) desarrollaron IHCA, el 72% de los casos IHCA era presente al ingreso. Se identificó un factor precipitante en el 83% de los casos, el más frecuentes fue la infección (53%). En el análisis multivariante, el grado de IHCA a los 3-7 días del diagnóstico se asoció a mortalidad intrahospitalaria y a los 28 días. Niveles de creatinina y bilirrubina en el momento del diagnóstico de IHCA y un factor precipitante distinto de infección bacteriana, se asoció con mejoría del grado de IHCA a los 3-7 días. Conclusiones: IHCA es una complicación frecuente en los pacientes con enfermedad hepática crónica avanzada ingresados por descompensación aguda y se asocia a una elevada mortalidad. Las infecciones bacterianas es el factor precipitante mas frecuente de IHCA y probablemente conlleva un peor pronóstico.(AU)

Prevalence and outcomes of acute-on-chronic liver failure among cirrhotic patients admitted for an acute decompensation.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is a common syndrome that occurs in patients with advanced chronic liver disease. It consists of the rapid failure of various organs and is associated with high short-term mortality. We aim to describe the main features and outcomes of inpatients who developed ACLF and to identify the factors associated with in-hospital and 28-day mortality. PATIENTS AND METHODS: All patients meeting ACLF criteria with advanced chronic liver disease admitted for decompensation from January 2014 to December 2016 were identified. Clinical and biological data were collected at the time of ACLF diagnosis and at 3-7 days thereafter, as well as in-hospital and 28-day mortality. RESULTS: Eighty nine out of 354 admission episodes (28%) developed ACLF, which was present at the time of admission in 72% of cases. A precipitating factor was identified in 83% of cases, the most frequent being infection (53%) and gastrointestinal bleeding (19%). In the multivariate regression analysis, the ACLF grade at 3-7 days after diagnosis was predictive of in-hospital mortality and 28-day mortality, and lower creatinine and bilirubin levels at the time of ACLF diagnosis and a precipitating factor other than bacterial infection were associated with ACLF reversion at 3-7 days. CONCLUSIONS: ACLF is a frequent complication among patients with chronic liver disease admitted for acute decompensations and is associated with a high mortality rate and is related to the number of organs involved. Bacterial infection is the most frequent precipitating factor of ACLF and probably entails a worse prognosis.

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

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.

Impact of sustained virological response with DAAs on gastroesophageal varices and Baveno criteria in HCV-cirrhotic patients.

BACKGROUND: Direct-acting antivirals (DAAs) show high efficacy and safety in HCV-cirrhotic patients, but most maintain clinically significant portal hypertension after sustained virological response (SVR). Non-invasive Baveno and expanded-Baveno criteria can identify patients without high-risk gastroesophageal varices (GEV) who have no need for endoscopic surveillance. However, data after SVR are scarce. We performed a multicenter study to evaluate SVR effects over GEV and diagnostic accuracy of non-invasive criteria after SVR. METHODS: HCV-cirrhotic patients receiving DAAs and baseline endoscopic evaluation were included (November 2014-October 2015). GEV were classified as low risk (LR-GEV) (< 5 mm) or high risk (HR-GEV) (≥ 5 mm or with risk signs). Transient elastography (TE) and endoscopy were performed during follow-up. RESULTS: SVR was achieved in 230 (93.1%) of 247 included patients, 151 (65.7%) with endoscopic follow-up. Among 64/151 (42.4%) patients without baseline GEV, 8 (12.5%) developed GEV after SVR. Among 50/151 (33.1%) with baseline LR-GEV, 12 (24%) developed HR-GEV. Patients with GEV progression showed TE ≥ 25 kPa before treatment (64.7%) or ≥ 20 kPa after SVR (66.7%). Only 6% of patients without GEV and LSM < 25 kPa before treatment, and 10% of those with baseline LSM < 25 kPa and LSM < 20 kPa after SVR showed GEV progression after 36 months. The negative predictive value of Baveno and expanded-Baveno criteria to exclude HR-GEV was maintained after SVR (100% and 90.7%, respectively). CONCLUSIONS: HCV-cirrhotic patients can develop HR-GEV after SVR. Surveillance is especially recommended in those with GEV before antiviral treatment. Baveno and expanded-Baveno criteria can be safely applied after SVR. https://clinicaltrials.gov: NCT02758509.

Recomendaciones para la detección, diagnóstico y seguimiento de los pacientes con enfermedad por hígado graso no alcohólico en atención primaria y hospitalaria / Recommendations for the detection, diagnosis and follow-up of patients with non-alcoholic fatty liver disease in primary and hospital care

La enfermedad por hígado graso no alcohólico (EHGNA) es una de las enfermedades hepáticas crónicas más frecuentes, con una prevalencia del 20-30% en la población general y del 60-80% en poblaciones de riesgo. En un porcentaje no despreciable de pacientes la EHGNA progresa desde la esteatosis hacia a diferentes estadios de fibrosis y cirrosis. Por su alta prevalencia, la EHGNA se ha convertido en un problema de salud relevante que requiere de acciones específicas para su detección, diagnóstico, seguimiento y tratamiento. Además, dado que la EHGNA presenta un riesgo aumentado de morbimortalidad cardiovascular requiere un enfoque multidisciplinar para su tratamiento y seguimiento. Los pacientes en estadios iniciales de la enfermedad, sin fibrosis, pueden ser evaluados y recibir tratamiento en el ámbito de Atención Primaria, mientras que aquellos con enfermedad hepática avanzada se benefician de un seguimiento especializado en el ámbito hospitalario para prevenir y tratar las complicaciones hepáticas. El presente documento de consenso, elaborado por las Sociedades Catalanas de Digestología, Atención Primaria, Endocrinología, Diabetes y Medicina Interna nace de la necesidad de diseñar estrategias que guíen los flujos de los pacientes entre el ámbito de Atención Primaria y Hospitalaria para poder ofrecer a los pacientes con EHGNA la mejor atención según el estadio de su enfermedad. En el documento de consenso se describen los métodos diagnósticos no invasivos más utilizados para el diagnóstico de los pacientes y se han diseñado dos algoritmos para el tratamiento de los pacientes tanto en ámbito de atención primaria como de atención hospitalaria

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases, with a prevalence of 20-30% in the general population and 60-80% in at-risk populations. In a not negligible percentage of patients, NAFLD progresses from steatosis to different stages of fibrosis and cirrhosis. Due to its high prevalence, NAFLD has become a significant health problem that requires specific action in detection, diagnosis, follow-up and treatment. Furthermore, given that NAFLD presents an increased risk of cardiovascular morbidity and mortality, a multidisciplinary approach is required for its treatment and follow-up. Patients with early stages of the disease, without fibrosis, can be diagnosed and receive treatment in the Primary Care setting, while those with more advanced liver disease benefit from specialised follow-up in the hospital setting to prevent and treat liver complications. This consensus document, prepared by the Catalan Societies of Digestology, Primary Care, Endocrinology, Diabetes and Internal Medicine, arises from the need to design strategies to guide patient flows between Primary and Hospital Care in order to offer patients with NAFLD the best care according to the stage of their disease. The consensus document describes the most commonly used non-invasive diagnostic methods for patient diagnosis and two algorithms have been designed for patient management in both Primary Care and Hospital Care

Recommendations for the detection, diagnosis and follow-up of patients with non-alcoholic fatty liver disease in primary and hospital care. / Recomendaciones para la detección, diagnóstico y seguimiento de los pacientes con enfermedad por hígado graso no alcohólico en atención primaria y hospitalaria.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases, with a prevalence of 20-30% in the general population and 60-80% in at-risk populations. In a not negligible percentage of patients, NAFLD progresses from steatosis to different stages of fibrosis and cirrhosis. Due to its high prevalence, NAFLD has become a significant health problem that requires specific action in detection, diagnosis, follow-up and treatment. Furthermore, given that NAFLD presents an increased risk of cardiovascular morbidity and mortality, a multidisciplinary approach is required for its treatment and follow-up. Patients with early stages of the disease, without fibrosis, can be diagnosed and receive treatment in the Primary Care setting, while those with more advanced liver disease benefit from specialised follow-up in the hospital setting to prevent and treat liver complications. This consensus document, prepared by the Catalan Societies of Digestology, Primary Care, Endocrinology, Diabetes and Internal Medicine, arises from the need to design strategies to guide patient flows between Primary and Hospital Care in order to offer patients with NAFLD the best care according to the stage of their disease. The consensus document describes the most commonly used non-invasive diagnostic methods for patient diagnosis and two algorithms have been designed for patient management in both Primary Care and Hospital Care.

Reactivación de la hepatitis B asociada a agentes inmunodepresores y a quimioterapia. Historia natural, factores de riesgo y recomendaciones para prevenirla / Reactivation of hepatitis B associated with immunosuppressants and chemotherapy. Natural history, risk factors and recommendations for prevention

A pesar de que el riesgo de reactivación de la hepatitis B en los pacientes tratados con inmunosupresores es conocido desde hace años y de la existencia de recomendaciones, los datos procedentes de algunas encuestas indican que el estudio del perfil serológico de la infección por el VHB antes de iniciar el tratamiento inmunosupresor no es una práctica universal. Teniendo en cuenta las consecuencias graves que puede comportar la reactivación de la infección por el VHB, creemos que es necesario divulgar la importancia de este problema entre los profesionales sanitarios que prescriben estos tratamientos así como de las recomendaciones a seguir. De hecho, en los últimos años, es cada vez más frecuente el empleo de quimioterapia e inmunosupresores potentes en pacientes con procesos neoplásicos y en patología no neoplásica de diversas especialidades, aumentando la población de pacientes con riesgo de reactivación del VHB

Although the risk of reactivation of hepatitis B in patients treated with immunosuppressants has been known for years and, if there are recommendations, data from some surveys indicate that the study of the serological profile of HBV infection before starting immunosuppressive treatment is not universal practice. Taking into account the serious consequences that the reactivation of the infection with HBV may entail, we believe that it is necessary to disclose the importance of this problem among the health professionals who prescribe these treatments as well as the recommendations to be followed. In fact, in recent years, the use of chemotherapy and potent immunosuppressants in patients with neoplastic processes and in non-neoplastic pathology of various specialties has been increasingly frequent, increasing the population of patients at risk of reactivation of HBV

Time association between hepatitis C therapy and hepatocellular carcinoma emergence in cirrhosis: Relevance of non-characterized nodules.

BACKGROUND & AIMS: Despite direct-acting antivirals being highly effective at eradicating hepatitis C virus infection, their impact on the development of hepatocellular carcinoma (HCC) remains controversial. We analyzed the clinical and radiological outcome of cirrhotic patients treated with interferon-free regimens to estimate the risk of developing HCC. METHODS: This was a retrospective multicenter study focusing on cirrhotic patients treated with direct-acting antivirals until December 2016. Clinical and radiologic characteristics were collected before the start of antiviral therapy, at follow-up and at HCC development. Diagnosis of HCC was centrally validated and its incidence was expressed as HCC/100 person-years. RESULTS: A total of 1,123 patients were included (60.6% males, 83.8% Child-Pugh A) and 95.2% achieved a sustained virologic response. Median time of follow-up was 19.6 months. Seventy-two patients developed HCC within a median of 10.3 months after starting antiviral treatment. HCC incidence was 3.73 HCC/100 person-years (95% CI 2.96-4.70). Baseline liver function, alcohol intake and hepatic decompensation were associated with a higher risk of HCC. The relative risk was significantly increased in patients with non-characterized nodules at baseline 2.83 (95% CI 1.55-5.16) vs. absence of non-characterized nodules. When excluding these patients, the risk remained increased. CONCLUSION: These data expose a clear-cut time association between interferon-free treatment and HCC. The mechanisms involved in the increased risk of HCC emergence in the short term require further investigation. LAY SUMMARY: In this cohort of cirrhotic patients, interferon-free therapies achieved a high rate of sustained virologic response (>95%); however, we reported a risk of de novo hepatocellular carcinoma of 3.73 per 100 person-years and a clear-cut time association with antiviral therapy. The time association between starting direct-acting antivirals and developing hepatocellular carcinoma, together with the association with the presence of non-characterized nodules at baseline ultrasound, suggests that antiviral therapy elicits a mechanism (probably immune-related) that primes the growth and clinical recognition of hepatocellular carcinoma early during follow-up. As a result, short-term liver cancer risk is significantly increased.

Reactivation of hepatitis B associated with immunosuppressants and chemotherapy. Natural history, risk factors and recommendations for prevention. / Reactivación de la hepatitis B asociada a agentes inmunodepresores y a quimioterapia. Historia natural, factores de riesgo y recomendaciones para prevenirla.

Although the risk of reactivation of hepatitis B in patients treated with immunosuppressants has been known for years and, if there are recommendations, data from some surveys indicate that the study of the serological profile of HBV infection before starting immunosuppressive treatment is not universal practice. Taking into account the serious consequences that the reactivation of the infection with HBV may entail, we believe that it is necessary to disclose the importance of this problem among the health professionals who prescribe these treatments as well as the recommendations to be followed. In fact, in recent years, the use of chemotherapy and potent immunosuppressants in patients with neoplastic processes and in non-neoplastic pathology of various specialties has been increasingly frequent, increasing the population of patients at risk of reactivation of HBV.

Efficacy of Sofosbuvir and Velpatasvir, With and Without Ribavirin, in Patients With Hepatitis C Virus Genotype 3 Infection and Cirrhosis.

BACKGROUND & AIMS: In phase 3 trials and real-world settings, smaller proportions of patients with genotype 3 hepatitis C virus (HCV) infection and cirrhosis have a sustained virologic response 12 weeks after treatment (SVR12) with the combination of sofosbuvir and velpatasvir than in patients without cirrhosis. It is unclear whether adding ribavirin to this treatment regimen increases SVRs in patients with genotype 3 HCV infection and cirrhosis. METHODS: We performed a phase 2 trial of 204 patients with genotype 3 HCV infection and compensated cirrhosis (mean age 51 ± 7.4 years) at 29 sites in Spain from August 19, 2016 through April 18, 2017. Patients were assigned to groups given sofosbuvir and velpatasvir for 12 weeks (n = 101) or sofosbuvir and velpatasvir plus ribavirin for 12 weeks (n = 103). The primary efficacy end point was SVR12. RESULTS: The overall rates of SVR12 were 91% (92 of 101; 95% CI 84-96) for the sofosbuvir-velpatasvir group and 96% (99 of 103; 95% CI 90-99) for the sofosbuvir-velpatasvir plus ribavirin group. In the sofosbuvir-velpatasvir group, a smaller proportion of patients with baseline resistance-associated substitutions (RASs) in nonstructural protein 5A (NS5A) achieved an SVR12 (84%) than did patients without (96%). In the sofosbuvir-velpatasvir plus ribavirin group, baseline RASs had less effect on the proportion of patients with an SVR12 (96% for patients with baseline RASs; 99% for patients without). The most common adverse events (which occurred in ≥10% of patients) were asthenia (12%) in the sofosbuvir-velpatasvir group and asthenia (27%), headache (24%), and insomnia (12%) in the sofosbuvir-velpatasvir plus ribavirin group. CONCLUSIONS: Consistent with findings from previous studies, a high rate of patients (91% and 96%) with genotype 3 HCV infection and compensated cirrhosis achieved an SVR12 with sofosbuvir and velpatasvir, with or without ribavirin. Of patients treated with sofosbuvir and velpatasvir without ribavirin, fewer patients with baseline NS5A RASs achieved an SVR12 compared with patients without baseline NS5A. ClinicalTrials.govNCT02781558.

Papel de la ribavirina en la terapia libre de interferón frente al virus de la hepatitis C / Role of ribavirin in interferon-free therapy for the treatment of hepatitis C virus

Los regímenes libres de interferón ofrecen tasas de respuesta virológica sostenida (RVS) por encima del 90%, efectos adversos generalmente bien tolerados y duraciones de tratamiento de 12 semanas para la mayoría de pacientes con hepatitis C crónica, incluyendo pacientes naive o previamente tratados y pacientes con o sin cirrosis. Sin embargo, algunas de las opciones de tratamiento recomendadas por las guías requieren la adición de ribavirina (RBV) o extender la duración del tratamiento para aumentar la eficacia. El uso de RBV es una herramienta útil en aquellos pacientes difíciles de curar como los pacientes con cirrosis descompensada o infectados por el genotipo 3 y aquellos que no han logrado una RVS después de un tratamiento con antivirales de acción directa (AAD). Globalmente, la adición de RBV a las diferentes combinaciones causa efectos adversos relacionados con una disminución de la hemoglobina y añade inconvenientes como su posología, por la que los pacientes deben tomar varios comprimidos dos veces al día. Sin embargo, la anemia grave es rara y fácilmente manejable con una reducción de dosis. Además, la RBV es teratogénica. En la práctica, debido a que la RBV es barata y bien tolerada cuando se combina con un régimen sin interferón, sigue siendo una herramienta útil para optimizar los resultados de algunos regímenes de tratamiento contra el VHC. Los regímenes libres de RBV eliminan los efectos adversos relacionados con la misma, resultando en una mejor tolerabilidad, mejorando la adherencia y la calidad de vida del paciente y disminuyendo el coste del tratamiento (AU)

Interferon-free regimens achieve sustained virologic response (SVR) rates of over 90%, have generally well-tolerated adverse effects and involve 12-week treatment durations for most patients with chronic hepatitis C, including naive or previously treated patients and patients with or without cirrhosis. However, some of the treatment options recommended by the guidelines require the addition of ribavirin (RBV) or extend the duration of treatment to increase efficacy. The use of RBV is a useful tool in those difficult-to-cure patients such as patients with decompensated or genotype-3-infected cirrhosis and those who have not achieved SVR after treatment with direct-acting antivirals (DAA). Overall, adding RBV to the different combinations causes adverse effects related to a decrease in haemoglobin and involves inconveniences such as its dosage, which requires patients to take several tablets twice daily. However, severe anaemia is rare and easily manageable with a dose reduction. In addition, RBV is teratogenic. In practice, because RBV is inexpensive and well tolerated when combined with an interferon-free regimen, it continues to be a useful tool to optimise the results of some HCV treatment regimens. RBV-free regimens eliminate RBV-related adverse effects related, resulting in better tolerability, improving patient adherence and quality of life and reducing the cost of treatment (AU)

Manifestaciones neurológicas del alcoholism / Neurological manifestations of excessive alcohol consumption

En este artículo se revisan las distintas manifestaciones neurológicas del consumo excesivo de alcohol, que pueden ser agudas o crónicas y afectar al sistema nervioso central o periférico. El mecanismo por el cual se producen varía de un grupo de trastornos a otro. Destacan factores nutricionales, efectos tóxicos del alcohol, factores metabólicos e incluso inmunológicos. Estas manifestaciones pueden conllevar una gran morbilidad y un aumento significativo de la mortalidad, por lo que es importante reconocerlas y tratarlas precozmente (AU)

This article reviews the different acute and chronic neurological manifestations of excessive alcohol consumption that affect the central or peripheral nervous system. Several mechanisms can be implicated depending on the disorder, ranging from nutritional factors, alcohol-related toxicity, metabolic changes and immune-mediated mechanisms. Recognition and early treatment of these manifestations is essential given their association with high morbidity and significantly increased mortality (AU)

Role of ribavirin in interferon-free therapy for the treatment of hepatitisC virus. / Papel de la ribavirina en la terapia libre de interferón frente al virus de la hepatitisC.

Interferon-free regimens achieve sustained virologic response (SVR) rates of over 90%, have generally well-tolerated adverse effects and involve 12-week treatment durations for most patients with chronic hepatitis C, including naive or previously treated patients and patients with or without cirrhosis. However, some of the treatment options recommended by the guidelines require the addition of ribavirin (RBV) or extend the duration of treatment to increase efficacy. The use of RBV is a useful tool in those difficult-to-cure patients such as patients with decompensated or genotype-3-infected cirrhosis and those who have not achieved SVR after treatment with direct-acting antivirals (DAA). Overall, adding RBV to the different combinations causes adverse effects related to a decrease in haemoglobin and involves inconveniences such as its dosage, which requires patients to take several tablets twice daily. However, severe anaemia is rare and easily manageable with a dose reduction. In addition, RBV is teratogenic. In practice, because RBV is inexpensive and well tolerated when combined with an interferon-free regimen, it continues to be a useful tool to optimise the results of some HCV treatment regimens. RBV-free regimens eliminate RBV-related adverse effects related, resulting in better tolerability, improving patient adherence and quality of life and reducing the cost of treatment.