RESUMEN
BACKGROUND: The established use of non-selective beta-blockers (NSBB) in the primary and secondary prevention of esophageal varices has recently been questioned in the subgroup of patients with diuretic-refractory ascites. OBJECTIVE: Critically analyze the body of evidence on the topic in order to assist clinical decisions. METHODS: A literature review was carried out in the Pubmed® and Scielo® databases. In total, 20 articles between 2010 and 2023 were read by independent researchers. CONCLUSION: It remains doubtful whether the use of NSBB is deleterious in cirrhotic patients with refractory ascites, however our literature review allows us to conclude that these drugs should not be proscribed in these patients. On the contrary, a doctor-patient decision based on tolerability and hemodynamic parameters certainly seems to be a safe conduct.
Asunto(s)
Antagonistas Adrenérgicos beta , Ascitis , Várices Esofágicas y Gástricas , Cirrosis Hepática , Humanos , Ascitis/tratamiento farmacológico , Ascitis/etiología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Antagonistas Adrenérgicos beta/uso terapéutico , Várices Esofágicas y Gástricas/tratamiento farmacológico , Várices Esofágicas y Gástricas/complicacionesRESUMEN
BACKGROUND: Previous experimental and clinical studies suggested a beneficial effect of statins, metformin, angiotensin-converting-enzyme inhibitors and angiotensin II receptor blockers (RASi) on portal hypertension. Still, their effects on hard cirrhosis-related clinical endpoints, such as variceal bleeding and bleeding-related mortality, remain to be investigated. METHODS: Thus, we recorded the use of statins, metformin and RASi in a large cohort of cirrhotic patients undergoing endoscopic band ligation (EBL) for primary (PP, n = 440) and secondary bleeding prophylaxis (SP, n = 480) between 01/2000 and 05/2020. Variceal (re-) bleeding and survival rates were compared between patients with vs. without these co-medications. RESULTS: A total of 920 cirrhotic patients with varices were included. At first EBL, median MELD was 13 and 515 (56%) patients showed ascites. Statins, metformin and RASi were used by 49 (5.3%), 74 (8%), and 91 (9.9%) patients, respectively. MELD and platelet counts were similar in patients with and without the co-medications of interest. Rates of first variceal bleeding and variceal rebleeding at 2 years were 5.2% and 11.7%, respectively. Neither of the co-medications were associated with decreased first bleeding rates (log-rank tests in PP: statins p = 0.813, metformin p = 0.862, RASi p = 0.919) nor rebleeding rates (log-rank tests in SP: statin p = 0.113, metformin p = 0.348, RASi p = 0.273). Similar mortality rates were documented in patients with and without co-medications for PP (log-rank tests: statins p = 0.630, metformin p = 0.591, RASi p = 0.064) and for SP (statins p = 0.720, metformin p = 0.584, RASi p = 0.118). CONCLUSION: In clinical practice, variceal bleeding and mortality rates of cirrhotic patients were not reduced by co-medication with statins, metformin or RASi. Nevertheless, we recommend the use of these co-medications by indication, as they may still exert beneficial effects on non-bleeding complications in patients with liver cirrhosis.
Asunto(s)
Várices Esofágicas y Gástricas , Hemorragia Gastrointestinal , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Cirrosis Hepática , Metformina , Humanos , Metformina/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Cirrosis Hepática/complicaciones , Cirrosis Hepática/mortalidad , Cirrosis Hepática/tratamiento farmacológico , Hemorragia Gastrointestinal/mortalidad , Hemorragia Gastrointestinal/prevención & control , Hemorragia Gastrointestinal/tratamiento farmacológico , Hemorragia Gastrointestinal/etiología , Várices Esofágicas y Gástricas/tratamiento farmacológico , Várices Esofágicas y Gástricas/mortalidad , Várices Esofágicas y Gástricas/complicaciones , Anciano , Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Estudios de CohortesRESUMEN
Portal hypertension is the key mechanism driving the transition from compensated to decompensated cirrhosis. In this review, the authors described the pathophysiology of portal hypertension in cirrhosis and the rationale of pharmacologic treatment of portal hypertension. We discussed both etiologic and nonetiologic treatment of portal hypertension and the specific clinical scenarios how nonselective beta-blocker can be used in patients with cirrhosis. Finally, the authors summarized the evidence for emerging alternatives for portal hypertension in patients with cirrhosis.
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Antagonistas Adrenérgicos beta , Hipertensión Portal , Cirrosis Hepática , Hipertensión Portal/tratamiento farmacológico , Hipertensión Portal/fisiopatología , Hipertensión Portal/etiología , Humanos , Antagonistas Adrenérgicos beta/uso terapéutico , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/complicaciones , Cirrosis Hepática/fisiopatología , Antihipertensivos/uso terapéutico , Várices Esofágicas y Gástricas/etiología , Várices Esofágicas y Gástricas/tratamiento farmacológicoAsunto(s)
Várices Esofágicas y Gástricas , Hemorragia Gastrointestinal , Cirrosis Hepática , Lipresina , Terlipresina , Vasoconstrictores , Humanos , Terlipresina/administración & dosificación , Terlipresina/uso terapéutico , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Várices Esofágicas y Gástricas/tratamiento farmacológico , Hemorragia Gastrointestinal/tratamiento farmacológico , Hemorragia Gastrointestinal/etiología , Vasoconstrictores/administración & dosificación , Lipresina/análogos & derivados , Lipresina/administración & dosificación , Lipresina/uso terapéutico , Administración IntravenosaAsunto(s)
Várices Esofágicas y Gástricas , Hemorragia Gastrointestinal , Cirrosis Hepática , Lipresina , Terlipresina , Vasoconstrictores , Humanos , Terlipresina/administración & dosificación , Terlipresina/uso terapéutico , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Várices Esofágicas y Gástricas/tratamiento farmacológico , Hemorragia Gastrointestinal/tratamiento farmacológico , Hemorragia Gastrointestinal/etiología , Vasoconstrictores/administración & dosificación , Lipresina/análogos & derivados , Lipresina/administración & dosificación , Lipresina/uso terapéutico , Administración IntravenosaRESUMEN
Variceal bleeding is a major complication and the leading cause of death in patients with cirrhosis and portal hypertension. This study aims to compare the efficacy and safety of terlipressin vs octreotide as an adjuvant to endoscopic management of patients with esophageal variceal bleeding in a real-time scenario. We reviewed the medical records of patients with esophageal variceal bleeding from January 2005 to December 2020 at our tertiary care Aga Khan University Hospital. Mortality was assessed after 6 weeks. A total of 842 patients with variceal bleed were evaluated. 624 patients (74.1%) and 218 patients (25.9%) received Terlipressin and Octreotide respectively. On multiple regression analysis, cardiac events during hospital stay (OR: 11.22), presence of Porto-systemic encephalopathy (OR: 3.79), and elevated bilirubin levels at the time of presentation were found to be independent risk factors for increased six weeks mortality. Moreover, cardiac events during hospital stay (OR: 3.26), Porto-systemic encephalopathy at presentation (OR: 3.06), and octreotide administration (OR: 1.80) were identified as independent risk factors for increased length of hospital stay. Terlipressin and Octreotide have similar outcomes in terms of control of bleeding, hospital stay, mortality, and side effects when used as adjuvant therapy for the management of variceal bleeding.
Asunto(s)
Encefalopatías , Várices Esofágicas y Gástricas , Várices , Humanos , Terlipresina/uso terapéutico , Octreótido/efectos adversos , Hemorragia Gastrointestinal/tratamiento farmacológico , Hemorragia Gastrointestinal/etiología , Vasoconstrictores/efectos adversos , Lipresina/uso terapéutico , Várices Esofágicas y Gástricas/complicaciones , Várices Esofágicas y Gástricas/tratamiento farmacológico , Várices/complicaciones , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Encefalopatías/tratamiento farmacológicoRESUMEN
BACKGROUND AND AIMS: Patients with Child-Turcotte-Pugh class B and C cirrhosis with upper gastrointestinal bleeding (UGIB) have systemic as well as localized (in the mucosa of the esophagus and stomach) fibrinolysis. The aim of this study was to evaluate the efficacy and safety of tranexamic acid in the treatment of acute UGIB in patients with cirrhosis. APPROACH AND RESULTS: A total of 600 patients with advanced liver cirrhosis (Child-Turcotte-Pugh class B or C) presenting with UGIB were randomly allocated to either the tranexamic acid (n=300) or the placebo group (n=300). The primary outcome measure was the proportion of patients developing 5-day treatment failure. Failure to control bleeding by day 5 was seen in 19/300 (6.3%) patients in the tranexamic acid group and 40/300 (13.3%) patients in the placebo group ( p =0.006). Esophageal endoscopic variceal ligation (EVL) site as a source of failure to control bleeding by day 5 among patients undergoing first-time esophageal EVL (excluding patients with a previous post-EVL ulcer as a source of bleed) was seen in 11/222 (4.9%) patients in the tranexamic acid group and 27/225 (1212.0%) patients in the placebo group ( p =0.005). However, 5-day and 6-week mortality was similar in the tranexamic acid and placebo groups. CONCLUSIONS: Tranexamic acid significantly reduces the failure to control bleeding by day 5 and failure to prevent rebleeding after day 5 to 6 weeks in patients with advanced liver cirrhosis (Child-Turcotte-Pugh class B or C) presenting with UGIB, by preventing bleeding from the EVL site.
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Antifibrinolíticos , Hemorragia Gastrointestinal , Cirrosis Hepática , Ácido Tranexámico , Humanos , Ácido Tranexámico/uso terapéutico , Ácido Tranexámico/administración & dosificación , Masculino , Femenino , Cirrosis Hepática/complicaciones , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/prevención & control , Hemorragia Gastrointestinal/tratamiento farmacológico , Persona de Mediana Edad , Antifibrinolíticos/uso terapéutico , Antifibrinolíticos/administración & dosificación , Anciano , Adulto , Várices Esofágicas y Gástricas/etiología , Várices Esofágicas y Gástricas/complicaciones , Várices Esofágicas y Gástricas/tratamiento farmacológico , Método Doble Ciego , Resultado del TratamientoAsunto(s)
Antifibrinolíticos , Várices Esofágicas y Gástricas , Hemorragia Gastrointestinal , Ácido Tranexámico , Humanos , Ácido Tranexámico/uso terapéutico , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/tratamiento farmacológico , Várices Esofágicas y Gástricas/tratamiento farmacológico , Várices Esofágicas y Gástricas/etiología , Antifibrinolíticos/uso terapéuticoRESUMEN
BACKGROUND: Acute upper gastrointestinal bleeding (UGIB) is a common emergency requiring hospital-based care. Advances in care across pre-endoscopic, endoscopic and post-endoscopic phases have led to improvements in clinical outcomes. AIMS: To provide a detailed, evidence-based update on major aspects of care across pre-endoscopic, endoscopic and post-endoscopic phases. METHODS: We performed a structured bibliographic database search for each topic. If a recent high-quality meta-analysis was not available, we performed a meta-analysis with random effects methods and odds ratios with 95% confidence intervals. RESULTS: Pre-endoscopic management of UGIB includes risk stratification, a restrictive red blood cell transfusion policy unless the patient has cardiovascular disease, and pharmacologic therapy with erythromycin and a proton pump inhibitor. Patients with cirrhosis should be treated with prophylactic antibiotics and vasoactive medications. Tranexamic acid should not be used. Endoscopic management of UGIB depends on the aetiology. For peptic ulcer disease (PUD) with high-risk stigmata, endoscopic therapy, including over-the-scope clips (OTSCs) and TC-325 powder spray, should be performed. For variceal bleeding, treatment should be customised by severity and anatomic location. Post-endoscopic management includes early enteral feeding for all UGIB patients. For high-risk PUD, PPI should be continued for 72 h, and rebleeding should initially be evaluated with a repeat endoscopy. For variceal bleeding, high-risk patients or those with further bleeding, a transjugular intrahepatic portosystemic shunt can be considered. CONCLUSIONS: Management of acute UGIB should include treatment plans for pre-endoscopic, endoscopic and post-endoscopic phases of care, and customise treatment decisions based on aetiology and severity of bleeding.
Asunto(s)
Várices Esofágicas y Gástricas , Úlcera Péptica , Humanos , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/terapia , Várices Esofágicas y Gástricas/tratamiento farmacológico , Endoscopía Gastrointestinal , Inhibidores de la Bomba de Protones/uso terapéuticoRESUMEN
BACKGROUND AND AIMS: Treatment of type 2 diabetes (T2D) in patients with compensated cirrhosis is challenging due to hypoglycemic risk, altered pharmacokinetics, and the lack of robust evidence on the risk/benefit ratio of various drugs. Suboptimal glycemic control accelerates the progression of cirrhosis, while the frequent coexistence of nonalcoholic fatty liver disease (NAFLD) with T2D highlights the need for a multifactorial therapeutic approach. METHODS: A literature search was performed in Medline, Google Scholar and Scopus databases till July 2023, using relevant keywords to extract studies regarding the management of T2D in patients with compensated cirrhosis. RESULTS: Metformin, sodium-glucose co-transporter-2 inhibitors (SGLT2i), and glucagon-like peptide-1 receptor agonists (GLP-1 RA) are promising treatment options for patients with T2D and compensated liver cirrhosis, offering good glycemic control with minimal risk of hypoglycemia, while their pleiotropic actions confer benefits on NAFLD and body weight, and decrease cardiorenal risk. Sulfonylureas cause hypoglycemia, thus should be avoided, while in specific studies, dipeptidyl peptidase-4 inhibitors have been correlated with increased risk of decompensation and variceal bleeding. Despite the benefits of thiazolidinediones in nonalcoholic steatohepatitis, concerns about edema and weight gain limit their use in compensated cirrhosis. Insulin does not exert hepatotoxic effects and can be administered safely in combination with other drugs; however, the risk of hypoglycemia should be considered. CONCLUSIONS: The introduction of new hepatoprotective diabetes drugs into clinical practice, including tirzepatide, SGLT2i, and GLP-1 RA, sets the stage for future trials to investigate the ideal therapeutic regimen for people with T2D and compensated cirrhosis.
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Diabetes Mellitus Tipo 2 , Várices Esofágicas y Gástricas , Hipoglucemia , Enfermedad del Hígado Graso no Alcohólico , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/inducido químicamente , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Várices Esofágicas y Gástricas/inducido químicamente , Várices Esofágicas y Gástricas/complicaciones , Várices Esofágicas y Gástricas/tratamiento farmacológico , Hemorragia Gastrointestinal/inducido químicamente , Hemorragia Gastrointestinal/complicaciones , Hemorragia Gastrointestinal/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Hipoglucemia/inducido químicamente , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Péptido 1 Similar al Glucagón , Receptor del Péptido 1 Similar al GlucagónRESUMEN
Decompensated cirrhosis is associated with a significantly increased risk of mortality. Variceal hemorrhage (VH) further increases the risk of mortality, and of future variceal bleed events. Non-selective beta-blockers (NSBBs) are effective therapy for primary and secondary prophylaxis of VH and have become the cornerstone of pharmacologic therapy in cirrhosis. Beta-blockers are associated with reduced overall mortality and GI-bleeding related mortality in patients with decompensated cirrhosis; they may also confer hemodynamically independent beneficial effects. Long-term treatment with beta-blockers may improve decompensation-free survival in compensated cirrhosis with clinically significant portal hypertension (CSPH). Carvedilol more effectively lowers the hepatic vein portal gradient than traditional NSBBs and has been shown to improve survival in compensated cirrhosis. Treatment goals in compensated cirrhosis with CSPH should focus on early utilization of beta-blockers to prevent decompensation and reduce mortality.
Asunto(s)
Várices Esofágicas y Gástricas , Hipertensión Portal , Humanos , Várices Esofágicas y Gástricas/complicaciones , Várices Esofágicas y Gástricas/tratamiento farmacológico , Hemorragia Gastrointestinal/tratamiento farmacológico , Hemorragia Gastrointestinal/etiología , Antagonistas Adrenérgicos beta/uso terapéutico , Carvedilol/uso terapéutico , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Hipertensión Portal/tratamiento farmacológico , Hipertensión Portal/complicacionesRESUMEN
BACKGROUND: In cirrhosis patients with acute variceal bleeding (AVB), the optimal duration of vasoconstrictor therapy after endoscopic haemostasis is unclear. AIMS: We aimed to compare efficacy of 1-day versus 3-day terlipressin therapy in cirrhosis patients with AVB post-endoscopic intervention. The primary objective was to compare rebleeding at 5 days between the two arms. Secondary objectives included rebleeding and mortality rates at 6 weeks. METHODS: In this open-label, randomised controlled trial, cirrhosis patients with AVB were randomised to either 1-day or 3-day terlipressin therapy. RESULTS: A total of 150 cirrhosis patients with AVB were recruited to receive either 1 day (n = 75) or 3 days (n = 75) of terlipressin therapy. One patient from 1-day arm was excluded. Modified intention-to-treat analysis included 149 patients. Baseline characteristics were comparable between the two groups. Rebleeding at 5 days: 3 (4.1%; 95% confidence interval [CI]: 0.4-9.0) versus 4 (5.3%; 95% CI: 2.0-10.0), risk difference (RD) p = 0.726 and 5-day mortality rates: 1 (1.4%; 95% CI: 0-7.3) versus 1 (1.3%; 95% CI: 0.2-7.0), RD p = 0.960 were similar. Rebleeding at 42 days: 9 (12.2%; 95% CI: 7.0-20.0) versus 10 (13.3%; 95% CI: 7.0-20.0), RD p = 0.842 and mortality at 42 days: 5 (6.8%; 95% CI: 3.0-10.0) versus 4 (5.3%; 95% CI: 2.0-10.0), RD p = 0.704 were also similar. Patients in the 1-day terlipressin therapy arm experienced significantly fewer adverse effects compared with those receiving 3 days of terlipressin therapy: 28 (37.8%) versus 42 (56%), p = 0.026. CONCLUSIONS: Our results suggest that 1 day of terlipressin therapy is associated with similar 5-day and 42-day rebleeding rates, 42-day mortality and an overall superior safety profile compared with 3-day of terlipressin therapy. These findings require to be validated in double-blinded, larger, multiethnic and multicentre studies across the various stages of cirrhosis (CTRI/2019/10/021771).
Asunto(s)
Várices Esofágicas y Gástricas , Cirrosis Hepática , Terlipresina , Humanos , Várices Esofágicas y Gástricas/complicaciones , Várices Esofágicas y Gástricas/tratamiento farmacológico , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/inducido químicamente , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Proyectos Piloto , Terlipresina/administración & dosificación , Terlipresina/efectos adversos , Várices/complicaciones , Vasoconstrictores/administración & dosificación , Vasoconstrictores/efectos adversosRESUMEN
BACKGROUND & AIMS: Pre-emptive transjugular intrahepatic portosystemic shunt (TIPS) is the treatment of choice for high-risk acute variceal bleeding (AVB; i.e., Child-Turcotte-Pugh [CTP] B8-9+active bleeding/C10-13). Nevertheless, some 'non-high-risk' patients have poor outcomes despite the combination of non-selective beta-blockers and endoscopic variceal ligation for secondary prophylaxis. We investigated prognostic factors for re-bleeding and mortality in 'non-high-risk' AVB to identify subgroups who may benefit from more potent treatments (i.e., TIPS) to prevent further decompensation and mortality. METHODS: A total of 2,225 adults with cirrhosis and variceal bleeding were prospectively recruited at 34 centres between 2011-2015; for the purpose of this study, case definitions and information on prognostic indicators at index AVB and on day 5 were further refined in low-risk patients, of whom 581 (without failure to control bleeding or contraindications to TIPS) who were managed by non-selective beta-blockers/endoscopic variceal ligation, were finally included. Patients were followed for 1 year. RESULTS: Overall, 90 patients (15%) re-bled and 70 (12%) patients died during follow-up. Using clinical routine data, no meaningful predictors of re-bleeding were identified. However, re-bleeding (included as a time-dependent co-variable) increased mortality, even after accounting for differences in patient characteristics (adjusted cause-specific hazard ratio: 2.57; 95% CI 1.43-4.62; p = 0.002). A nomogram including CTP, creatinine, and sodium measured at baseline accurately (concordance: 0.752) stratified the risk of death. CONCLUSION: The majority of 'non-high-risk' patients with AVB have an excellent prognosis, if treated according to current recommendations. However, about one-fifth of patients, i.e. those with CTP ≥8 and/or high creatinine levels or hyponatremia, have a considerable risk of death within 1 year of the index bleed. Future clinical trials should investigate whether elective TIPS placement reduces mortality in these patients. IMPACT AND IMPLICATIONS: Pre-emptive transjugular intrahepatic portosystemic shunt placement improves outcomes in high-risk acute variceal bleeding; nevertheless, some 'non-high-risk' patients have poor outcomes despite the combination of non-selective beta-blockers and endoscopic variceal ligation. This is the first large-scale study investigating prognostic factors for re-bleeding and mortality in 'non-high-risk' acute variceal bleeding. While no clinically meaningful predictors were identified for re-bleeding, we developed a nomogram integrating baseline Child-Turcotte-Pugh score, creatinine, and sodium to stratify mortality risk. Our study paves the way for future clinical trials evaluating whether elective transjugular intrahepatic portosystemic shunt placement improves outcomes in presumably 'non-high-risk' patients who are identified as being at increased risk of death.
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Várices Esofágicas y Gástricas , Derivación Portosistémica Intrahepática Transyugular , Várices , Adulto , Humanos , Várices Esofágicas y Gástricas/complicaciones , Várices Esofágicas y Gástricas/cirugía , Várices Esofágicas y Gástricas/tratamiento farmacológico , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/prevención & control , Creatinina , Derivación Portosistémica Intrahepática Transyugular/efectos adversos , Várices/complicaciones , Antagonistas Adrenérgicos beta/uso terapéutico , Cirrosis Hepática/etiología , SodioRESUMEN
INTRODUCTION: Endoscopic variceal ligation (EVL) plus nonselective ß-blockers (NSBB) is the standard of care for secondary prophylaxis of esophageal variceal bleeding (EVB). This trial aimed to compare the rebleeding rates between EVL plus NSBB till eradication of esophageal varices (EEV) and EVL plus long-term NSBB. METHODS: After control of acute EVB, patients with cirrhosis were randomized into 2 groups, with group A patients receiving EVL plus propranolol till EEV, while group B patients received standard of care with continuation of propranolol. Recurrent varices were ligated at follow-up endoscopy in both groups. RESULTS: The median follow-up period was 23.0 months in group A (n = 106) and 23.6 months in group B (n = 106). Twelve patients (11.3%) in group A and 11 (10.4%) in group B had recurrent EVB. The difference in rebleeding rates and the 95% confidence interval (CI) was 0.9% (-7.5% to 9.3%). The upper 95% CI bound of the difference was within the margin of 13.2%, and the noninferiority of group A to group B was established. Thirty-eight patients (35.8%) in group A and 40 (37.7%) in group B had further decompensation, with the difference (95% CI) of -1.9% (-14.9% to 11.1%). Twenty-four patients (22.6%) in group A and 26 (24.5%) in group B expired, with the difference (95% CI) in mortality rates of -1.9% (-13.3% to 9.5%). DISCUSSION: EVL plus propranolol till EEV was noninferior to EVL plus continuing propranolol in secondary prophylaxis of EVB, but the impact on further decompensation and transplantation-free survival deserved further investigation.
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Várices Esofágicas y Gástricas , Propranolol , Humanos , Propranolol/uso terapéutico , Várices Esofágicas y Gástricas/complicaciones , Várices Esofágicas y Gástricas/cirugía , Várices Esofágicas y Gástricas/tratamiento farmacológico , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/prevención & control , Hemorragia Gastrointestinal/tratamiento farmacológico , Antagonistas Adrenérgicos beta/uso terapéutico , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Endoscopía Gastrointestinal , LigaduraRESUMEN
Nonselective beta-blockers (NSBBs) may exacerbate ascites by impairing cardiac function. This study evaluated the impact of achieving a heart rate target of 55-60 beats per minute (bpm) on ascites-related death and complications from worsening ascites in patients with cirrhosis and diuretic-responsive ascites using NSBBs. A retrospective study was conducted at the Faculty of Medicine Ramathibodi Hospital, Mahidol University (2012-2022) and analyzed patients with cirrhosis and diuretic-responsive ascites using NSBBs (propranolol/carvedilol) for variceal bleeding prophylaxis. The outcomes were incidence of ascites-related death and complications from worsening ascites, comparing the achievable target group (heart rate 55-60 bpm) and the unachievable target group (heart rate >60 bpm). A total of 206 patients were included in the study, with a median follow-up time of 20 months. The patients were divided into an achievable target group (n = 75, median heart rate = 58.0 bpm) and an unachievable target group (n = 131, median heart rate = 73.6 bpm). Propranolol was the most used NSBB (95.1%). The adjusted hazard ratio (HR) for ascites-related death from spontaneous bacterial peritonitis (SBP) or refractory ascites (RA) or hepatorenal syndrome (HRS) or hepatic encephalopathy (HE) showed no difference between the groups (adjusted HR 0.59 [0.23-1.54]; p = 0.28). Additionally, no significant difference was found in the incidence of complications between groups, including SBP, RA, HRS, and HE. Achieving a heart rate target of 55-60 bpm with NSBBs for variceal bleeding prophylaxis is safe in patients with diuretic-responsive ascites and cirrhosis.
Asunto(s)
Várices Esofágicas y Gástricas , Propranolol , Humanos , Estudios Retrospectivos , Várices Esofágicas y Gástricas/inducido químicamente , Várices Esofágicas y Gástricas/complicaciones , Várices Esofágicas y Gástricas/tratamiento farmacológico , Frecuencia Cardíaca , Ascitis/tratamiento farmacológico , Ascitis/epidemiología , Ascitis/etiología , Hemorragia Gastrointestinal/etiología , Cirrosis Hepática/tratamiento farmacológico , Antagonistas Adrenérgicos beta , Diuréticos/uso terapéuticoRESUMEN
DESCRIPTION: Cirrhosis is a major cause of morbidity and mortality in the United States and worldwide. It consists of compensated, decompensated, and further decompensated stages; median survival is more than 15 years, 2 years, and 9 months for each stage, respectively. With each stage, there is progressive worsening of portal hypertension and the vasodilatory-hyperdynamic circulatory state, resulting in a progressive decrease in effective arterial blood volume and renal perfusion. Vasoconstrictors reduce portal pressure via splanchnic vasoconstriction and are used in the management of variceal hemorrhage. Intravenous (IV) albumin increases effective arterial blood volume and is used in the prevention of acute kidney injury (AKI) and death after large-volume paracentesis and in patients with spontaneous bacterial peritonitis (SBP). The combination of vasoconstrictors and albumin is used in the reversal of hepatorenal syndrome (HRS-AKI), the most lethal complication of cirrhosis. Because a potent vasoconstrictor, terlipressin, was recently approved by the US Food and Drug Administration, and because recent trials have explored use of IV albumin in other settings, it was considered that a best practice update would be relevant regarding the use of vasoactive drugs and IV albumin in the following 3 specific scenarios: variceal hemorrhage, ascites and SBP, and HRS. METHODS: This expert review was commissioned and approved by the American Gastroenterological Association (AGA) Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership. It underwent internal peer review through standard procedures of Gastroenterology. These Best Practice Advice statements were drawn from a review of the published literature and from expert opinion. Some of the statements are unchanged from published guidelines because of lack of new evidence in the literature. Because systematic reviews were not performed, these Best Practice Advice statements do not carry formal ratings regarding the quality and evidence or strength of the presented considerations. Best Practice Advice Statements BEST PRACTICE ADVICE 1: Vasoactive drugs should be initiated as soon as the diagnosis of variceal hemorrhage is suspected or confirmed, preferably before diagnostic and/or therapeutic endoscopy. BEST PRACTICE ADVICE 2: After initial endoscopic hemostasis, vasoactive drugs should be continued for 2-5 days to prevent early rebleeding. BEST PRACTICE ADVICE 3: Octreotide is the vasoactive drug of choice in the management of variceal hemorrhage based on its safety profile. BEST PRACTICE ADVICE 4: IV albumin should be administered at the time of large-volume (>5 L) paracentesis. BEST PRACTICE ADVICE 5: IV albumin may be considered in patients with SBP. BEST PRACTICE ADVICE 6: Albumin should not be used in patients (hospitalized or not) with cirrhosis and uncomplicated ascites. BEST PRACTICE ADVICE 7: Vasoconstrictors should not be used in the management of uncomplicated ascites, after large-volume paracentesis or in patients with SBP. BEST PRACTICE ADVICE 8: IV albumin is the volume expander of choice in hospitalized patients with cirrhosis and ascites presenting with AKI. BEST PRACTICE ADVICE 9: Vasoactive drugs (eg, terlipressin, norepinephrine, and combination of octreotide and midodrine) should be used in the treatment of HRS-AKI, but not in other forms of AKI in cirrhosis. BEST PRACTICE ADVICE 10: Terlipressin is the vasoactive drug of choice in the treatment of HRS-AKI and use of concurrent albumin can be considered when accounting for patient's volume status. BEST PRACTICE ADVICE 11: Terlipressin treatment does not require intensive care unit monitoring and can be administered intravenously through a peripheral line. BEST PRACTICE ADVICE 12: Terlipressin use is contraindicated in patients with hypoxemia and in patients with ongoing coronary, peripheral, or mesenteric ischemia, and should be used with caution in patients with acute-on-chronic liver failure grade 3. The benefits may not outweigh the risks in patients with serum creatinine >5 mg/dL and in patients listed for transplantation with a Model for End-stage Liver Disease ≥35.
Asunto(s)
Lesión Renal Aguda , Enfermedad Hepática en Estado Terminal , Várices Esofágicas y Gástricas , Síndrome Hepatorrenal , Humanos , Terlipresina/efectos adversos , Preparaciones Farmacéuticas , Octreótido/uso terapéutico , Várices Esofágicas y Gástricas/diagnóstico , Várices Esofágicas y Gástricas/tratamiento farmacológico , Várices Esofágicas y Gástricas/etiología , Ascitis/tratamiento farmacológico , Enfermedad Hepática en Estado Terminal/complicaciones , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/inducido químicamente , Índice de Severidad de la Enfermedad , Vasoconstrictores/efectos adversos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Síndrome Hepatorrenal/diagnóstico , Síndrome Hepatorrenal/tratamiento farmacológico , Síndrome Hepatorrenal/etiología , Albúminas/efectos adversosRESUMEN
BACKGROUND: Patients with cirrhosis are at increased risk for osteoporosis, and those who suffer a fracture are at high risk for mortality. Despite this, osteoporosis is often overlooked and undertreated. This study aimed to evaluate osteoporosis screening, management, and adverse osteoporosis medication events in patients with cirrhosis. METHODS: We performed a retrospective chart review of adult outpatients with compensated and decompensated cirrhosis seen in single health system over a 6-year period. Patient demographics, liver and bone health comorbidities, DEXA scan results, and medications were abstracted. RESULTS: In total, 5398 patients met criteria. The cohort was predominately white (79.1%) and older (age 59). 44.4% were female. 64.6% had decompensated cirrhosis. Median MELD-Na score was 12.8. 23.5% had a DEXA scan ordered, approximately 50% completed this test. Patients who were older, female, white, with more severe liver disease, and other osteoporosis risk factors were more likely to have a DEXA scan ordered. 48.5% of patients had osteopenia and 30.2% had osteoporosis on DEXA scan. Only 22.6% of patients with osteoporosis received treatment, most commonly oral bisphosphonates. Oral bisphosphonate prescription was not associated with variceal bleeding (8.4% without vs. 4.8% with, p = 0.487). CONCLUSION: A minority of patients with cirrhosis were screened for osteoporosis. The majority screened had osteopenia or osteoporosis on DEXA scan. Less than a quarter of patients with osteoporosis were started on treatment. Real-world experience of oral bisphosphonate use did not reveal higher rates of gastrointestinal bleeding. There is room for improvement in all aspects of bone health care in cirrhosis.
Asunto(s)
Enfermedades Óseas Metabólicas , Várices Esofágicas y Gástricas , Osteoporosis , Adulto , Humanos , Femenino , Persona de Mediana Edad , Masculino , Estudios Retrospectivos , Prevalencia , Várices Esofágicas y Gástricas/tratamiento farmacológico , Absorciometría de Fotón/métodos , Hemorragia Gastrointestinal/tratamiento farmacológico , Osteoporosis/diagnóstico , Osteoporosis/epidemiología , Difosfonatos/uso terapéutico , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/epidemiologíaRESUMEN
BACKGROUND & AIMS: Non-selective ß-blockers (NSBBs) and endoscopic variceal-ligation (EVL) have similar efficacy preventing first variceal bleeding. Compensated and decompensated cirrhosis are markedly different stages, which may impact treatment outcomes. We aimed to assess the efficacy of NSBBs vs EVL on survival in patients with high-risk varices without previous bleeding, stratifying risk according to compensated/decompensated stage of cirrhosis. METHODS: By systematic review, we identified RCTs comparing NSBBs vs EVL, in monotherapy or combined, for primary bleeding prevention. We performed a competing-risk, time-to-event meta-analysis, using individual patient data (IPD) obtained from principal investigators of RCTs. Analyses were stratified according to previous decompensation of cirrhosis. RESULTS: Of 25 RCTs eligible, 14 failed to provide IPD and 11 were included, comprising 1400 patients (656 compensated, 744 decompensated), treated with NSBBs (N = 625), EVL (N = 546) or NSBB+EVL (N = 229). Baseline characteristics were similar between groups. Overall, mortality risk was similar with EVL vs. NSBBs (subdistribution hazard-ratio (sHR) = 1.05, 95% CI = 0.75-1.49) and with EVL + NSBBs vs either monotherapy, with low heterogeneity (I2 = 28.7%). In compensated patients, mortality risk was higher with EVL vs NSBBs (sHR = 1.76, 95% CI = 1.11-2.77) and not significantly lower with NSBBs+EVL vs NSBBs, without heterogeneity (I2 = 0%). In decompensated patients, mortality risk was similar with EVL vs. NSBBs and with NSBBs+EVL vs. either monotherapy. CONCLUSIONS: In patients with compensated cirrhosis and high-risk varices on primary prophylaxis, NSBBs significantly improved survival vs EVL, with no additional benefit noted adding EVL to NSBBs. In decompensated patients, survival was similar with both therapies. The study suggests that NSBBs are preferable when advising preventive therapy in compensated patients.