Background We aimed to investigate the early changes in liver and spleen stiffness measurement(LSM, SSM) in hepatitis C virus (HCV) patients with compensated advanced chronic liverdisease (cACLD) ...treated with new antivirals (DAA) to elucidate factors determining theinitial change in stiffness and its implications for the long-term follow up ofHCV-cured patients. Methods: A total of 41 patients with cACLD who started DAA therapy underwent LSM and SSM atbaseline, week 4, end of treatment (EOT), 24 and 48 weeks of follow up using transientelastography. Results: LSM improved rapidly during the first 4 weeks of treatment (baseline: 20.8kPa; week 4:17.5kPa, p = 0.002), with no significant changes between week 4 and EOT(18.3kPa, p = 0.444) and between EOT and 48-week follow up (14.3kPa,p = 0.148). Likewise, SSM improved rapidly (baseline: 45.7kPa; week4: 33.8kPa, p = 0.047), with no significant changes between week 4 andEOT (30.8kPa, p = 0.153) and between EOT and 48-week follow up(31.2kPa, p = 0.317). A higher decrease in LSM was observed in patientswith baseline ALT ⩾ twofold upper limit normal (2 × ULN) than in those with ALT < 2 ×ULN (–5.7kPa versus –1.6kPa). Patients who presented a decrease in LSM⩾ 10% during treatment compared with those with LSM < 10% decrease, showed lower SSMvalues, higher platelet counts and lower bilirubin levels at 24-week follow up. Thosewith decrease in SSM ⩾ 10%, presented a higher increase in platelets than those with SSM< 10% change (p = 0.015). Conclusions: LSM and SSM decrease very rapidly during DAA treatment in cACLD patients suggestingthat it most probably reflects a reduction in inflammation rather than in fibrosis.cACLD patients should be maintained under surveillance independently of stiffnesschanges, because advanced fibrosis can still be present.
Alcoholic Liver Disease Ventura‐Cots, Meritxell; Ndugga, Nambi; Bataller, Ramon
Evidence‐based Gastroenterology and Hepatology 4e,
04/2019
Book Chapter
Alcoholic liver disease (ALD) is a major cause of liver‐related morbidity and mortality globally, and is a chief cause of death among adults with alcohol use disorders. This chapter describes the ...burden, pathogenesis, diagnosis, and therapy of ALD. It also discusses the fact that alcohol abuse can be a modifying factor for other liver diseases. The chapter further discusses some hot topics such as liver transplant for patients with ALD. Alcohol abuse is one of the main causes of preventable disease worldwide. Mortality in people with alcohol use disorders is markedly higher than previously thought, particularly with women who suffer from alcohol use disorders, who generally have a higher mortality risk than men. It is indicated in patients with aggressive forms of ALD such as alcoholic hepatitis which require specific therapies (e.g. corticosteroids and/or pentoxiphylline) and in patients with other cofactors suspected of contributing to liver disease.
Liver injury has been widely described in patients with Coronavirus disease 2019 (COVID-19). We aimed to study the effect of liver biochemistry alterations, previous liver disease, and the value of ...liver elastography on hard clinical outcomes in COVID-19 patients. We conducted a single-center prospective observational study in 370 consecutive patients admitted for polymerase chain reaction (PCR)-confirmed COVID-19 pneumonia. Clinical and laboratory data were collected at baseline and liver parameters and clinical events recorded during follow-up. Transient elastography with Controlled Attenuation Parameter (CAP) measurements was performed at admission in 98 patients. All patients were followed up until day 28 or death. The two main outcomes of the study were 28-day mortality and the occurrence of the composite endpoint intensive care unit (ICU) admission and/or death. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were elevated at admission in 130 patients (35%) and 167 (45%) patients, respectively. Overall, 14.6% of patients presented the composite endpoint ICU and/or death. Neither ALT elevations, prior liver disease, liver stiffness nor liver steatosis (assessed with CAP) had any effect on outcomes. However, patients with abnormal baseline AST had a higher occurrence of the composite ICU/death (21% versus 9.5%, p = 0.002). Patients ⩾65 years and with an AST level > 50 U/ml at admission had a significantly higher risk of ICU and/or death than those with AST ⩽ 50 U/ml (50% versus 13.3%, p < 0.001). In conclusion, mild liver damage is prevalent in COVID-19 patients, but neither ALT elevation nor liver steatosis influenced hard clinical outcomes. Elevated baseline AST is a strong predictor of hard outcomes, especially in patients ⩾65 years.
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.
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 (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.
La Enfermedad hepática alcohólica (EHA) es la causa más prevalente de enfermedad hepática avanzada y cirrosis hepática (CH) en Europa incluyendo a España. De acuerdo con la Organización Mundial de la Salud (OMS) la fracción de CH 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 (HA), 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 HA es la prednisolona. Para enfermos con HA 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 CH 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.
Background: The prevalence and impact of alcohol withdrawal syndrome (AWS) in patients with alcohol-associated hepatitis (AH) are unknown. In this study, we aimed to investigate the prevalence, ...predictors, management, and clinical impact of AWS in patients hospitalized with AH. Methods: A multinational, retrospective cohort study enrolling patients hospitalized with AH at 5 medical centres in Spain and in the USA was performed between January 1st, 2016 to January 31st, 2021. Data were retrospectively retrieved from electronic health records. Diagnosis of AWS was based on clinical criteria and use of sedatives to control AWS symptoms. The primary outcome was mortality. Multivariable models controlling for demographic variables and disease severity were performed to determine predictors of AWS (adjusted odds ratio OR) and the impact of AWS condition and management on clinical outcomes (adjusted hazard ratio HR). Findings: In total, 432 patients were included. The median MELD score at admission was 21.9 (18.3–27.3). The overall prevalence of AWS was 32%. Lower platelet levels (OR = 1.61, 95% CI 1.05–2.48) and previous history of AWS (OR = 2.09, 95% CI 1.31–3.33) were associated with a higher rate of incident AWS, whereas the use of prophylaxis decreased the risk (OR = 0.58, 95% CI 0.36–0.93). The use of intravenous benzodiazepines (HR = 2.18, 95% CI 1.02–4.64) and phenobarbital (HR = 2.99, 95% CI 1.07–8.37) for AWS treatment were independently associated with a higher mortality. The development of AWS increased the rate of infections (OR = 2.24, 95% CI 1.44–3.49), the need for mechanical ventilation (OR = 2.49, 95% CI 1.38–4.49), and ICU admission (OR = 1.96, 95% CI 1.19–3.23). Finally, AWS was associated with higher 28-day (HR = 2.31, 95% CI 1.40–3.82), 90-day (HR = 1.78, 95% CI 1.18–2.69), and 180-day mortality (HR = 1.54, 95% CI 1.06–2.24). Interpretation: AWS commonly occurs in patients hospitalized with AH and complicates the hospitalization course. Routine prophylaxis is associated with a lower prevalence of AWS. Prospective studies should determine diagnostic criteria and prophylaxis regimens for AWS management in patients with AH. Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Hepatic encephalopathy (HE) is a major complication of cirrhosis associated with high mortality and poor quality of life. Multiple risk factors have been classically associated with the development ...of HE, including upper gastrointestinal bleeding (UGIB). UGIB induces a status of hyperammonemia through the intraluminal digestion of blood nitrogenous compounds by colonic bacteria. In addition, the catabolic status caused by gastrointestinal bleeding provokes an increase in ammoniagenesis in different tissues. Ammonia and its transformation to glutamine in the astrocyte appear to be a key factor in HE development and pathogenesis. Current strategies for the treatment of HE have been focused on lowering ammonia production. Ornithine phenylacetate (OP) is a new drug proposed as an ammonia scavenger, our first trial proved that OP is a safe and well tolerated drug in decompensated cirrhotics, and confirmed the mechanism of action: decrease plasma ammonia by inducing its appearance as phenylacetylglutamine in urine. In the second trial we assess OP efficacy in lowering plasma ammonia levels vs. placebo in cirrhotic patients after UGIB. The primary outcome was a decrease in venous plasma ammonia during the first 24h of 25 µmol/L, this outcome was not archived, but dose of 10g/day proved to decreases plasma ammonia in cirrhotic patients, especially in Child-Pugh C patients, the data suggest that higher doses of OP might be required in Child-Pugh A and B patients to maximize ammonia elimination, and proved once again the proposed mechanism of action as well as the safety of the drug.
L’encefalopatia hepàtica (EH) és una complicació de la cirrosis hepática associada a un augment de la mortalitat i a una disminució en la qualitat de vida. El desenvolupament de l’EH s’ha associat amb múltiples factors de risc, entre ells destaca l’hemorràgia digestiva alta (HDA). L’HDA indueix un estat d’hiperamonièmia secundari a la digestió dels components nitrogenats de la sang arribada a nivell intestinal per part de la flora colònica. A més a més l’HDA provoca un estat catabòlic que causa un augment de l’amoniagènesi en diferents teixits. L’amoni a través de la seva transformació en glutamina a nivell astrocitari sembla el factor clau en el desenvolupament de l’EH. Fins ara els tractament per a l’EH s’han centrat en la disminució de la producció d’amoni. L’ornitina fenilacetat (OP) és un nou fàrmac que s’ha postulat com a eliminador d’amoni. El nostre primer assaig clínic demostra que l’OP és un fàrmac segur i ben tolerat en pacients amb cirrosis hepàtica descompensats per una HDA, a més amés en confirma el mecanisme d’acció: la disminució d’amoni plasmàtic a través de la formació de fenilacetilglutamina i posterior eliminació en orina. El segon assaig clínic compara l’eficàcia de l’OP contra placebo en disminuir l’amoni plasmàtic en pacients cirròtics descompensats per una HDA. L’objectiu principal era assolir una disminució de l’amoni plasmàtic, per part del grup que va rebre OP, durant les primeres 24h de 25 µmol/L. Aquest objectiu no va ser assolit, però la dosis administrada de 10g/24h va demostrar que disminuir l’amoni plasmàtic durant tot l’estudi, especialment en els pacients amb Child-Pugh C. Les dades obtingudes suggereixen que els pacient amb Child-Pugh A i B podrien necessitar dosis majors de fàrmac. L’estudi confirma un cop més el mecanisme d’acció del fàrmac, així com la seva seguretat i tolerabilitat.
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