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)

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".

Multi-organ Involvement in Non-pulmonary Sarcoidosis.

Isolated extrapulmonary involvement in sarcoidosis is uncommon and reported in 5-9% of systemic sarcoidosis, this constitutes a clinical challenge due to its extensive differential diagnosis. Extrapulmonary sarcoidosis affecting more than three organs is rarely reported and there are scarce literature data published on diagnosis, clinical course and management in those cases. We hereby discuss a case of a 41-year-old female with systemic non-pulmonary sarcoidosis affecting lacrimal gland, peripheral lymph nodes, parotid gland and the liver.

Multi-organ Involvement in Non-pulmonary Sarcoidosis / Afectación multiorgánica en sarcoidosis no pulmonar

Isolated extrapulmonary involvement in sarcoidosis is uncommon and reported in 5–9% of systemic sarcoidosis, this constitutes a clinical challenge due to its extensive differential diagnosis. Extrapulmonary sarcoidosis affecting more than three organs is rarely reported and there are scarce literature data published on diagnosis, clinical course and management in those cases.We hereby discuss a case of a 41-year-old female with systemic non-pulmonary sarcoidosis affecting lacrimal gland, peripheral lymph nodes, parotid gland and the liver.(AU)

La afectación extrapulmonar aislada en la sarcoidosis es infrecuente y se reporta en el 5 al 9% de las sarcoidosis sistémicas, lo que constituye un desafío clínico debido a su extenso diagnóstico diferencial. La sarcoidosis extrapulmonar que afecta a más de tres órganos es raramente reportada y hay pocos datos publicados sobre el diagnóstico, la evolución clínica y el manejo de estos casos. Presentamos el caso de una mujer de 41 años con sarcoidosis sistémica no pulmonar que afecta a la glándula lacrimal, los ganglios linfáticos periféricos, la glándula parótida y el hígado.(AU)

Microwave versus radiofrequency ablation for the treatment of liver malignancies: a randomized controlled phase 2 trial.

Microwave (MWA) and radiofrequency ablation (RFA) are main ablative techniques for hepatocellular carcinoma (HCC) and colorectal liver metastasis (MT). This randomized phase 2 clinical trial compares the effectiveness of MWA and RFA as well as morphology of corresponding ablation zones. HCC and MT patients with 1.5-4 cm tumors, suitable for ablation, were randomized into MWA or RFA Groups. The primary endpoint was short-to-long diameter ratio of ablation zone (SLR). Primary technical success (TS) and a cumulative local tumor progression (LTP) after a median 2-year follow-up were compared. Between June 2015 and April 2020, 82 patients were randomly assigned (41 patients per group). For the per-protocol analysis, five patients were excluded. MWA created larger ablation zones than RFA (p = 0.036) although without differences in SLR (0.5 for both groups, p = 0.229). The TS was achieved in 98% (46/47) and 90% (45/50) (p = 0.108), and LTP was observed in 21% (10/47) vs. 12% (6/50) (OR 1.9 [95% CI 0.66-5.3], p = 0.238) of tumors in MWA vs. RFA Group, respectively. Major complications were found in 5 cases (11%) vs. 2 cases (4%), without statistical significance. MWA and RFA show similar SLR, effectiveness and safety in liver tumors between 1.5 and 4 cm.

Multi-organ Involvement in Non-pulmonary Sarcoidosis.

Isolated extrapulmonary involvement in sarcoidosis is uncommon and reported in 5-9% of systemic sarcoidosis, this constitutes a clinical challenge due to its extensive differential diagnosis. Extrapulmonary sarcoidosis affecting more than three organs is rarely reported and there are scarce literature data published on diagnosis, clinical course and management in those cases. We hereby discuss a case of a 41-year-old female with systemic non-pulmonary sarcoidosis affecting lacrimal gland, peripheral lymph nodes, parotid gland and the liver.

Resistance-associated substitutions after sofosbuvir/velpatasvir/voxilaprevir triple therapy failure.

Direct-acting antivirals (DAAs) resolve chronic HCV infection in >95% of patients, but a small percentage do not respond to DAA-based therapy. These may be difficult to treat because of resistance-associated substitutions (RAS) emerging after treatment failure. Triple therapy with sofosbuvir (SOF)/velpatasvir (VEL)/voxilaprevir (VOX) is the recommended retreatment after DAA-based failure. However, in rare cases, failure to triple therapy occurs, and there is little information characterizing the viruses that relapse. To determine the RAS profile after failing SOF/VEL/VOX, and seek suitable alternatives for retreatment, samples from 5 patients were analysed using MiSeq Illumina deep sequencing before and after triple therapy. All patients were men, aged 59-78 years, 2 HCV genotype (G) 1b and 3 G3a. The most prevalent NS3 substitutions after SOF/VEL/VOX failure were Y56F and A166T. Four patients had the NS5A RAS, Y93H, after triple failure, and Y93H was observed in both G1b patients before retreatment and after SOF/ledipasvir failure. In 2 G3a patients, Y93H appeared at triple failure, and on the other G3a, A30K persisted in 100% of viral genomes. Finally, G1b patients showed C316N in NS5B, associated with SOF failure, but G3a patients had no known NS5B substitutions. HCV RAS analysis identified the following substitutions present at higher rates after triple failure: Y56F in NS3 (G1b), A166T in NS3 (G3a), A30K or Y93H in NS5A, and C316N in NS5B (G1b). A RAS-based salvage treatment (SOF + glecaprevir/pibrentasvir + RBV) was successfully used in one G3a patient.

Impact of HCV cure with drug-acting antivirals in the use of concomitant medication and lipid profile: follow-up data 2 years after the sustained virological response.

BACKGROUND AND AIM: Patients with chronic hepatitis C (CHC) frequently associated comorbidities and concomitant medication. Sustained virological response (SVR12) has been related to an increase in cholesterol serum levels and in peripheral vascular resistance. Our aim was to evaluate the impact of SVR12 on the use of concomitant medication and serum lipid profile. METHODS: Prospective study including patients treated with direct-acting antivirals who had achieved the SVR12. Clinical data and concomitant drugs were analysed at baseline and at least 1 year after SVR12. Differences from baseline to follow-up in the concomitant medication were evaluated by Stuart-Maxwell test and lipid profile by Wilcoxon signed-rank test. Patients were categorized according to the increase/decrease in the number of drugs included in each class (Anatomical Therapeutic Chemical classification system). RESULTS: Two hundred twenty-six patients with SVR12 were included, 73.5% were receiving concomitant drugs (49.6% with antihypertensive effect, 30.5% antacids, 16.4% anti-diabetic drugs, and 7.1% lipid-lowering agents). One year after SVR12, total cholesterol serum levels increased from 161 to 179 mg/dl (P < 0.001) and, after a median time of 25.7 months, the use of lipid-lowering drugs increased from 7.8 to 11.5% (P = 0.009). In addition, we observed a trend to use more antihypertensive drugs in older patients (P = 0.06), especially in those with cirrhosis. Anxiolytics decreased after SVR12 from 13.7 to 10.6% (P = 0.035). CONCLUSION: CHC cure is associated with a significant increase in cholesterol serum levels and the use of lipid-lowering agents, as well as the use of drugs with antihypertensive effect in older patients.

Significant decrease in the prevalence of hepatitis C infection after the introduction of direct acting antivirals.

BACKGROUND AND AIM: Accurate information on the epidemiology of hepatitis C and B infection is mandatory to establish a national/regional plan. We aim to update the prevalence of hepatitis C and B infection in Catalonia using point-of-care tests to analyze the risk factors related and to implement a linkage-to-care circuit. METHODS: This is a community-based study. A random list of adult individuals was retrieved from censuses of primary care centers. Point-of-care tests for anti-hepatitis C virus (HCV) and HBV surface antigen (HBsAg) and a questionnaire for risk factor assessment were performed. Positive results were validated and a circuit for linkage-to-care was established. RESULTS: A total of 3328 individuals were included. The anti-HCV and HBsAg overall prevalence were lower than expected [1.02%, 95% confidence interval (CI) 0.65-1.39; and 0.52%, 95% CI 0.26-0.77, respectively]. Anti-HCV positive subjects were mostly (88%) autochthonous. The prevalence increased with age; only 12% were under age 40. The associated risk factors were drug use, blood transfusion, relative with HCV, and diabetes. Notably, the prevalence of active infection was only 0.49% (95% CI 0.23-0.74), 40% less than previously reported, reflecting the impact of direct acting antiviral therapy. Differently, HBsAg positive subjects were mostly foreign migrants (53%) with no other risk factors. Despite the implementation of a linkage-to-care circuit, one third of HBsAg positive subjects were lost. CONCLUSIONS: The prevalence of HCV infection was lower than previously reported, showing a strong impact of direct acting antiviral therapy in the last years. Because of hepatitis B universal vaccination, HBV infection in Catalonia is mainly associated with migrant population. Linkage-to-care in patients with hepatitis B was challenging and warrants additional efforts.

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.

Deep-sequencing reveals broad subtype-specific HCV resistance mutations associated with treatment failure.

A percentage of hepatitis C virus (HCV)-infected patients fail direct acting antiviral (DAA)-based treatment regimens, often because of drug resistance-associated substitutions (RAS). The aim of this study was to characterize the resistance profile of a large cohort of patients failing DAA-based treatments, and investigate the relationship between HCV subtype and failure, as an aid to optimizing management of these patients. A new, standardized HCV-RAS testing protocol based on deep sequencing was designed and applied to 220 previously subtyped samples from patients failing DAA treatment, collected in 39 Spanish hospitals. The majority had received DAA-based interferon (IFN) α-free regimens; 79% had failed sofosbuvir-containing therapy. Genomic regions encoding the nonstructural protein (NS) 3, NS5A, and NS5B (DAA target regions) were analyzed using subtype-specific primers. Viral subtype distribution was as follows: genotype (G) 1, 62.7%; G3a, 21.4%; G4d, 12.3%; G2, 1.8%; and mixed infections 1.8%. Overall, 88.6% of patients carried at least 1 RAS, and 19% carried RAS at frequencies below 20% in the mutant spectrum. There were no differences in RAS selection between treatments with and without ribavirin. Regardless of the treatment received, each HCV subtype showed specific types of RAS. Of note, no RAS were detected in the target proteins of 18.6% of patients failing treatment, and 30.4% of patients had RAS in proteins that were not targets of the inhibitors they received. HCV patients failing DAA therapy showed a high diversity of RAS. Ribavirin use did not influence the type or number of RAS at failure. The subtype-specific pattern of RAS emergence underscores the importance of accurate HCV subtyping. The frequency of "extra-target" RAS suggests the need for RAS screening in all three DAA target regions.

Enfermedad hepática por alcohol. Guías de práctica clínica. Documento de consenso auspiciado por la AEEH / Alcohol-related liver disease. Clinical practice guidelines. Consensus document sponsored by AEEH

La enfermedad hepática alcohólica (EHA) es la causa más prevalente de enfermedad hepática avanzada y cirrosis hepática en Europa incluyendo a España. De acuerdo con la Organización Mundial de la Salud la fracción de cirrosis hepática atribuible al uso de alcohol en España es del 73,8% entre varones y del 56,3% entre mujeres. La EHA incluye diversos estadios como la esteatohepatitis, la cirrosis y el cáncer hepatocelular. Además, enfermos con EHA de base e ingesta abundante de alcohol pueden desarrollar hepatitis alcohólica, que cursa con una elevada mortalidad. Hasta la fecha, el único tratamiento efectivo para tratar la EHA es la abstinencia prolongada. No existen tratamientos específicos, y el único tratamiento que aumenta la esperanza de vida en la hepatitis alcohólica es la prednisolona. Para enfermos con hepatitis alcohólica que no responden al tratamiento, algunos centros ofrecen la posibilidad de un trasplante precoz. Estas guías de práctica clínica tienen como objetivo proponer recomendaciones sobre la EHA teniendo en cuenta su relevancia como causa de hepatopatía crónica avanzada y cirrosis hepática en nuestro medio. En el presente trabajo se propone como objetivo responder las preguntas claves para la práctica clínica de Gastroenterología, Hepatología, así como de Medicina Interna y centros de salud primaria, poniendo al servicio del profesional de la salud la información más actualizada respecto al manejo y tratamiento de la EHA. Estas guías proporcionan recomendaciones basadas en la evidencia para el manejo clínico de esta enfermedad

Alcohol-related liver disease (ARLD) is the most prevalent cause of advanced liver disease and liver cirrhosis in Europe, including Spain. According to the World Health Organization the fraction of liver cirrhosis attributable to alcohol use in Spain is 73.8% among men and 56.3% among women. ARLD includes various stages such as steatohepatitis, cirrhosis and hepatocellular cancer. In addition, patients with underlying ARLD and heavy alcohol intake may develop alcoholic hepatitis, which is associated with high mortality. To date, the only effective treatment to treat ARLD is prolonged withdrawal. There are no specific treatments, and the only treatment that increases life expectancy in alcoholic hepatitis is prednisolone. For patients with alcoholic hepatitis who do not respond to treatment, some centres offer the possibility of an early transplant. These clinical practice guidelines aim to propose recommendations on ARLD taking into account their relevance as a cause of advanced chronic liver disease and liver cirrhosis in our setting. This paper aims to answer the key questions for the clinical practice of Gastroenterology, Hepatology, as well as Internal Medicine and Primary Health Centres, making the most up-to-date information regarding the management and treatment of ARLD available to health professionals. These guidelines provide evidence-based recommendations for the clinical management of this disease

Alcohol-related liver disease. Clinical practice guidelines. Consensus document sponsored by AEEH. / Enfermedad hepática por alcohol. Guías de práctica clínica. Documento de consenso auspiciado por la AEEH.

Alcohol-related liver disease (ARLD) is the most prevalent cause of advanced liver disease and liver cirrhosis in Europe, including Spain. According to the World Health Organization the fraction of liver cirrhosis attributable to alcohol use in Spain is 73.8% among men and 56.3% among women. ARLD includes various stages such as steatohepatitis, cirrhosis and hepatocellular cancer. In addition, patients with underlying ARLD and heavy alcohol intake may develop alcoholic hepatitis, which is associated with high mortality. To date, the only effective treatment to treat ARLD is prolonged withdrawal. There are no specific treatments, and the only treatment that increases life expectancy in alcoholic hepatitis is prednisolone. For patients with alcoholic hepatitis who do not respond to treatment, some centres offer the possibility of an early transplant. These clinical practice guidelines aim to propose recommendations on ARLD taking into account their relevance as a cause of advanced chronic liver disease and liver cirrhosis in our setting. This paper aims to answer the key questions for the clinical practice of Gastroenterology, Hepatology, as well as Internal Medicine and Primary Health Centres, making the most up-to-date information regarding the management and treatment of ARLD available to health professionals. These guidelines provide evidence-based recommendations for the clinical management of this disease.

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.

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.

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.

Documento de consenso. Manejo de la enfermedad hepática grasa no alcohólica (EHGNA). Guía de práctica clínica / Consensus document. Management of non-alcoholic fatty liver disease (NAFLD). Clinical practice guideline

La enfermedad hepática grasa no alcohólica (EHGNA) es la causa más frecuente de hepatopatía crónica en nuestro medio y se prevé un incremento de su incidencia en los próximos años asociada al incremento de la obesidad y el síndrome metabólico. Esta guía de práctica clínica propone recomendaciones sobre el diagnóstico y en especial marcadores no invasivos, así como en el manejo y seguimiento de esta enfermedad. La intervención dietética basada en la dieta mediterránea y el cambio del estilo de vida constituyen el pilar del tratamiento de la EHGNA, pero aún falta por elucidar si la composición de la dieta puede influir en la mejoría de la enfermedad más allá de la pérdida de peso. El tratamiento con fármacos debe restringirse a los pacientes con esteatohepatitis y fibrosis significativa que no consiguen resolución de la esteatohepatitis después de una intervención con dieta y ejercicio físico durante un año. Nuevos fármacos aún en fases iniciales de desarrollo han demostrado ser superiores a placebo. Por último, el impacto de la EHGNA en la indicación de trasplante hepático, la viabilidad del injerto y la recidiva de EHGNA de novo tras el trasplante, así como el incrementado riesgo cardiovascular determinan todo el proceso peritrasplante hepático. Esta guía de práctica clínica se ha elaborado tras la I Reunión de Consenso sobre EHGNA con un panel de experto nacionales e internaciones en Sevilla y tienen como objetivo proponer recomendaciones basadas en la evidencia científica disponible para el manejo de estos pacientes

Non-alcoholic fatty liver disease (NAFLD) is the main cause of liver diseases in Spain and the incidence is raising due to the outbreak of type 2 diabetes and obesity. This CPG suggests recommendation about diagnosis, mainly non-invasive biomarkers, and clinical management of this entity. Life-style modifications to achieve weight loss is the main target in the management of NAFLD. Low caloric Mediterranean diet and 200 minutes/week of aerobic exercise are encouraged. In non-responders patients with morbid obesity, bariatric surgery or metabolic endoscopy could be indicated. Pharmacological therapy is indicated in patients with NASH and fibrosis and non-responders to weight loss measures. NAFLD could influence liver transplantation, as a growing indication, the impact of steatosis in the graft viability, de novo NAFLD rate after OLT and a raised cardiovascular risk that modify the management of this entity. The current CPG was the result of the First Spanish NAFLD meeting in Seville