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Pizzo E, Avşar TS, Abraldes JG, Genesca J, Tsochatzis EA. Cost-Effectiveness of the Baveno VI Criteria Compared With Endoscopy for High-Risk Varices in Patients With Child-Pugh A Cirrhosis. Clin Gastroenterol Hepatol 2024; 22:2053-2061. [PMID: 38777174 DOI: 10.1016/j.cgh.2024.05.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2024] [Revised: 05/07/2024] [Accepted: 05/09/2024] [Indexed: 05/25/2024]
Abstract
BACKGROUND & AIMS Although upper gastrointestinal endoscopy (EGD) remains the gold standard for detecting varices in cirrhosis, the Baveno VI criteria proposed a combination of transient elastography and platelet count that could rule out high-risk varices, therefore sparing the need for an endoscopy, with significant potential cost savings. We performed a cost-effectiveness analysis of the Baveno VI criteria compared with EGD in the diagnosis of high-risk varices in cirrhosis. METHODS We built an analytical decision model to estimate the cost and benefits of using the Baveno VI criteria compared with EGD in patients with Child-Pugh A cirrhosis. The analysis was performed from the UK National Health Service perspective, over 1, 5, and 20 years. A Markov model was populated with data from published evidence. Outcomes were measured in terms of quality-adjusted life years (QALYs) and avoided deaths. The analyses were repeated for Canada and Spain, using relevant cost inputs. RESULTS The Baveno VI criteria were cost effective compared with endoscopy in all analyses. For 1000 patients, they produced 0.16 additional QALYs at an incremental cost of £326 ($443.41) over 5 years, resulting in an incremental cost of £2081 ($2830) per additional QALY gained. The incremental net monetary benefit of Baveno VI compared with EGD was £2808 ($3819) over 5 years per patient. Baveno VI criteria also were cost effective in Canada and Spain. Deterministic and probabilistic sensitivity analysis supported these findings. CONCLUSIONS The findings demonstrate that the Baveno VI criteria are cost effective, suggesting that they should be considered for widespread implementation on the basis of safety, appropriateness, and economic grounds.
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Affiliation(s)
- Elena Pizzo
- Department of Applied Health Research, University College London, London, United Kingdom.
| | - Tuba Saygın Avşar
- Department of Applied Health Research, University College London, London, United Kingdom
| | - Juan G Abraldes
- Division of Gastroenterology, Liver Unit, University of Alberta, Edmonton, Canada
| | - Joan Genesca
- Liver Unit, Digestive Diseases Division, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain
| | - Emmanuel A Tsochatzis
- University College London Institute for Liver and Digestive Health, Royal Free Hospital and University College London, London, United Kingdom.
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Nouh MAEL, Abd-Elmageed MK, Amer AAM, ELhamouly MS. Role of portal color Doppler ultrasonography as noninvasive predictive tool for esophageal varices in cirrhotic patients. THE EGYPTIAN JOURNAL OF RADIOLOGY AND NUCLEAR MEDICINE 2022. [DOI: 10.1186/s43055-021-00681-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Esophageal varices (EV) is the most common apprehensive complication of portal hypertension in patients with cirrhotic liver. Guidelines recommend Upper gastro-intestinal endoscopic screening for EV in patients with newly diagnosed chronic cirrhosis (Imperiale et al. in Hepatology 45(4):870–878, 2007). Yet, it is invasive, time consuming and costly. To avoid unnecessary endoscopy, some studies have suggested Doppler ultrasound examination as simple, and noninvasive tool in prediction and assessment of severity of EV (Agha et al. in Dig Dis Sci 54(3):654–660, 2009). Our study was to assess the role of different Doppler indices of portal vein, hepatic and splenic arteries as a noninvasive tool for prediction of esophageal varices in cirrhotic patients.
Results
This prospective case control study was conducted on 100 cirrhotic liver patients and 100 of healthy volunteers as control group. Patients were subjected to clinical examination, upper gastrointestinal tract endoscopy, abdominal ultrasonography with duplex Doppler evaluation of different portal Doppler hemodynamic indices were done for each patient. The results revealed that portal vein diameter, hepatic artery pulsatility index, portal hypertensive index, portal vein flow velocity, portal congestion index have high sensitivity for prediction of EV. However, Splenic artery resistance index, hepatic artery resistance index HARI, liver vascular index and platelet count/spleen diameter have less sensitivity for prediction of EV.
Conclusion
Measuring the portal hemodynamic indices can help physicians as noninvasive predictors of EV in cirrhotic patients to restrict the need for unnecessary endoscopic screening especially when endoscopic facilities are limited.
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Cost-effectiveness of cardio-oncology clinical assessment for prevention of chemotherapy-induced cardiotoxicity. Rev Port Cardiol 2021; 40:475-483. [PMID: 34274093 DOI: 10.1016/j.repce.2021.07.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Accepted: 09/30/2020] [Indexed: 11/21/2022] Open
Abstract
INTRODUCTION Cancer chemotherapy increases the risk of heart failure. This cost-effectiveness study analyzes cardio-oncology imaging assessment of left ventricular ejection fraction (LVEF) using a Portuguese healthcare payer perspective and a five-year time horizon. METHODS Two cardioprotective strategies were assessed: universal cardioprotection (UCP) for all patients and cardioprotection initiated on diagnosis of LVEF-defined cardiotoxicity (EF-CTX). A Markov model, informed by the retrospective clinical course of breast cancer patients followed in a Portuguese public hospital, was developed to assess the cost-effectiveness of LVEF cardio-oncology imaging assessment. Data on transition probabilities, costs and utilities were retrieved from both the retrospective data and published literature to assess the cost-effectiveness of LVEF echocardiographic assessment. Costs and utilities of the cardioprotective strategies were assessed over a five-year range, using probabilistic sensitivity analyses. RESULTS In the reference case of a 63-year-old breast cancer patient treated with cardioprotection initiated on diagnosis of EF-CTX, the five-year time horizon (4.22 QALYs and €2594 cost over five years) dominated UCP (3.42 QALYS and €3758 cost over five years). Under a time horizon of five years at a willingness-to-pay threshold of €22 986, over 65.7% of simulations provided additional QALYs. Monte Carlo simulation of the Markov model had no effect on the model's conclusions. CONCLUSION In the Portuguese public healthcare system and under specific hypotheses, from a healthcare payer perspective, EF-CTX-guided cardioprotection for patients at risk of chemotherapy-related cardiotoxicity provides more QALYs at lower cost than UCP.
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de Mello Sampayo F, Fiuza M, Pinto F, Fontes J. Cost-effectiveness of cardio-oncology clinical assessment for prevention of chemotherapy-induced cardiotoxicity. Rev Port Cardiol 2021. [PMID: 34052079 DOI: 10.1016/j.repc.2020.09.012] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
Abstract
INTRODUCTION Cancer chemotherapy increases the risk of heart failure. This cost-effectiveness study analyzes cardio-oncology imaging assessment of left ventricular ejection fraction (LVEF) using a Portuguese healthcare payer perspective and a five-year time horizon. METHODS Two cardioprotective strategies were assessed: universal cardioprotection (UCP) for all patients and cardioprotection initiated on diagnosis of LVEF-defined cardiotoxicity (EF-CTX). A Markov model, informed by the retrospective clinical course of breast cancer patients followed in a Portuguese public hospital, was developed to assess the cost-effectiveness of LVEF cardio-oncology imaging assessment. Data on transition probabilities, costs and utilities were retrieved from both the retrospective data and published literature to assess the cost-effectiveness of LVEF echocardiographic assessment. Costs and utilities of the cardioprotective strategies were assessed over a five-year range, using probabilistic sensitivity analyses. RESULTS In the reference case of a 63-year-old breast cancer patient treated with cardioprotection initiated on diagnosis of EF-CTX, the five-year time horizon (4.22 QALYs and €2594 cost over five years) dominated UCP (3.42 QALYS and €3758 cost over five years). Under a time horizon of five years at a willingness-to-pay threshold of €22 986, over 65.7% of simulations provided additional QALYs. Monte Carlo simulation of the Markov model had no effect on the model's conclusions. CONCLUSION In the Portuguese public healthcare system and under specific hypotheses, from a healthcare payer perspective, EF-CTX-guided cardioprotection for patients at risk of chemotherapy-related cardiotoxicity provides more QALYs at lower cost than UCP.
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Affiliation(s)
- Felipa de Mello Sampayo
- ISCTE-Instituto Universitário de Lisboa, BRU_ISCTE Business Research Unit, Lisboa, Portugal.
| | - Manuela Fiuza
- Universidade de Lisboa, Faculdade de Medicina, Centro Cardiovascular da Universidade de Lisboa, Cardio-Oncology Unit, Lisboa, Portugal
| | - Fausto Pinto
- Universidade de Lisboa, Faculdade de Medicina, Centro Cardiovascular da Universidade de Lisboa, Cardio-Oncology Unit, Lisboa, Portugal
| | - Joana Fontes
- ISCTE-Instituto Universitario de Lisboa, Lisboa, Portugal
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Zhang X, Wang J, Shi J, Jia X, Dang S, Wang W. Cost-effectiveness of Atezolizumab Plus Bevacizumab vs Sorafenib for Patients With Unresectable or Metastatic Hepatocellular Carcinoma. JAMA Netw Open 2021; 4:e214846. [PMID: 33825837 PMCID: PMC8027915 DOI: 10.1001/jamanetworkopen.2021.4846] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Accepted: 02/08/2021] [Indexed: 02/06/2023] Open
Abstract
IMPORTANCE Atezolizumab plus bevacizumab as a first-line therapy for patients with unresectable or metastatic hepatocellular carcinoma has been shown to improve overall and progression-free survival compared with standard sorafenib treatment. However, because of the high cost of atezolizumab plus bevacizumab, assessment of its value by considering both efficacy and cost is needed. OBJECTIVE To evaluate the cost-effectiveness of atezolizumab plus bevacizumab vs sorafenib for patients with unresectable or metastatic hepatocellular carcinoma from a US payer perspective. DESIGN, SETTING, AND PARTICIPANTS This economic evaluation was performed from June through September 2020, with a 6-year investment time period. Hypothetical patients were male and female adults 18 years or older who had a diagnosis of locally advanced metastatic or unresectable hepatocellular carcinoma confirmed by histologic or clinical features. MAIN OUTCOMES AND MEASURES Health care costs (adjusted to 2020 US dollars), life-years, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) of atezolizumab plus bevacizumab vs sorafenib were examined using a partitioned survival model. One-way deterministic and probabilistic sensitivity analyses were used to examine model uncertainty. The model was also used to estimate price reductions of atezolizumab plus bevacizumab that would achieve more favorable cost-effectiveness. RESULTS In the base case analysis of a hypothetical sample of 424 patients, atezolizumab plus bevacizumab was associated with an increase of 0.623 life-years (1.840 vs 1.218 life-years) and 0.484 QALYs (1.412 vs 0.928 QALYs) and with an incremental cost of $156 210 per patient compared with sorafenib. The ICER was $322 500 per QALY (5th to 95th percentile, $149 364-$683 744 per QALY), with 0.6% and 5.1% chance of being cost-effective at willingness-to-pay thresholds of $100 000 and $150 000 per QALY, respectively. The ICER never decreased below $150 000 per QALY in the 1-way sensitivity analyses. To achieve more favorable cost-effectiveness under the thresholds of $150 000 to $100 000 per QALY, the prices of atezolizumab and bevacizumab would need to be reduced by 37% to 47%. CONCLUSIONS AND RELEVANCE In this economic evaluation, atezolizumab plus bevacizumab was associated with clinical benefit but was not cost-effective compared with sorafenib for first-line treatment of unresectable or metastatic hepatocellular carcinoma from a US payer perspective. A substantial reduction in price for atezolizumab plus bevacizumab would be needed to achieve favorable cost-effectiveness for this new therapy.
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Affiliation(s)
- Xin Zhang
- Department of Hepatology and Infectious Diseases,
Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Jingjing Wang
- Department of Pediatrics, Second Affiliated Hospital
of Xi’an Jiaotong University, Xi’an, China
| | - Juanjuan Shi
- Department of Hepatology and Infectious Diseases,
Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Xiaoli Jia
- Department of Hepatology and Infectious Diseases,
Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Shuangsuo Dang
- Department of Hepatology and Infectious Diseases,
Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Wenjun Wang
- Department of Hepatology and Infectious Diseases,
Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
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Piccolo Serafim L, Simonetto DA. Primary Prophylaxis of Variceal Bleeding in Liver Cirrhosis. VARICEAL BLEEDING IN LIVER CIRRHOSIS 2021:67-75. [DOI: 10.1007/978-981-15-7249-4_6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Williams MJ, Hayes P. Improving the management of gastrointestinal bleeding in patients with cirrhosis. Expert Rev Gastroenterol Hepatol 2016; 10:505-15. [PMID: 26581713 DOI: 10.1586/17474124.2016.1122523] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Gastrointestinal bleeding remains a major cause of mortality in patients with cirrhosis. The most common source of bleeding is from gastroesophageal varices but non-variceal bleeding from peptic ulcer disease also carries a significant risk in patients with liver disease. The prognosis is related to the severity of the underlying liver disease, and deaths often occur due to liver failure, infection or renal failure. Optimal management should therefore not only achieve haemostasis but address these complications as well. The management of gastrointestinal bleeding in patients with cirrhosis includes a range of medical, endoscopic and radiological interventions. This article updates the recent developments in this area and highlights topics where further research is still required.
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Affiliation(s)
- Michael J Williams
- a Centre for Liver and Digestive Diseases , Royal Infirmary of Edinburgh , Edinburgh , UK
| | - Peter Hayes
- a Centre for Liver and Digestive Diseases , Royal Infirmary of Edinburgh , Edinburgh , UK
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8
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Nolan MT, Plana JC, Thavendiranathan P, Shaw L, Si L, Marwick TH. Cost-effectiveness of strain-targeted cardioprotection for prevention of chemotherapy-induced cardiotoxicity. Int J Cardiol 2016; 212:336-45. [DOI: 10.1016/j.ijcard.2016.02.137] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2015] [Revised: 02/05/2016] [Accepted: 02/28/2016] [Indexed: 12/13/2022]
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Saab S, Alper T, Sernas E, Pruthi P, Alper MA, Sundaram V. Hospitalized Patients with Cirrhosis Should Be Screened for Clostridium difficile Colitis. Dig Dis Sci 2015; 60:3124-9. [PMID: 25986524 DOI: 10.1007/s10620-015-3707-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2015] [Accepted: 05/06/2015] [Indexed: 02/08/2023]
Abstract
BACKGROUND Clostridium difficile infection (CDI) is an important public health problem in hospitalized patients. Patients with cirrhosis are particularly at risk of increased associated morbidity, mortality, and healthcare utilization from CDI. AIM The aim of this study was to assess the pharmacoeconomic impact of CDI screening on hospitalized patients with cirrhosis. METHODS A Markov model was used to compare costs and outcomes of two strategies for the screening of CDI. The first strategy consisted of screening all patients for CDI and treating if detected (screening). In the second strategy, only patients found to have symptomatic CDI were treated (no screening). The probability of underlying CDI prevalence, symptomatic CDI infection, and likelihood of recurrent infection were varied in a sensitivity analysis. The costs of antibiotics and hospitalization were also assessed. Differences in outcome were expressed in ratio of the total costs associated with screening to the total costs associated without screening. RESULTS The results of our model showed that screening for CDI was consistently associated with improved healthcare outcomes and decreased healthcare utilization across all variables in the one- and two-way sensitivity analyses. Using baseline assumptions, the costs associated with the no screening strategy were 3.54 times that of the screening strategy. Moreover, the mortality for symptomatic CDI was lower in the screening strategy than the no screening strategy. CONCLUSION The screening strategy results in less healthcare utilization and improved clinical outcomes. Screening for CDI measures favorably.
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Affiliation(s)
- Sammy Saab
- Department of Medicine, University of California at Los Angeles, Los Angeles, CA, USA. .,Department of Surgery, University of California at Los Angeles, Los Angeles, CA, USA. .,Pfleger Liver Institute, 200 Medical Plaza, Suite 214, Los Angeles, CA, 90095, USA.
| | - Theodore Alper
- Department of Surgery, University of California at Los Angeles, Los Angeles, CA, USA
| | - Ernesto Sernas
- Department of Surgery, University of California at Los Angeles, Los Angeles, CA, USA
| | - Paridhima Pruthi
- Department of Surgery, University of California at Los Angeles, Los Angeles, CA, USA
| | | | - Vinay Sundaram
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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10
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Abstract
Gastroesophageal varices are present in almost half of patients with cirrhosis at the time of initial diagnosis. Variceal bleeding occurs in 25% to 35% of patients with cirrhosis. Effective and timely care can prevent variceal bleeding (primary prophylaxis). For example, clinical studies demonstrate that both beta-blockers and endoscopic variceal ligation are effective in preventing a first episode of variceal bleeding. The major challenge is to screen patients in a timely manner and institute a form of therapy that has the highest chance of success in terms of patient compliance and effectiveness.
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11
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Di Pascoli L, Buja A, Bolognesi M, Montagnese S, Gatta A, Gregori D, Merkel C. Cost-effectiveness analysis of beta-blockers vs endoscopic surveillance in patients with cirrhosis and small varices. World J Gastroenterol 2014; 20:10464-10469. [PMID: 25132763 PMCID: PMC4130854 DOI: 10.3748/wjg.v20.i30.10464] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2013] [Revised: 02/09/2014] [Accepted: 05/05/2014] [Indexed: 02/07/2023] Open
Abstract
AIM: To evaluate the most cost-effectiveness strategy for preventing variceal growth and bleeding in patients with cirrhosis and small esophageal varices.
METHODS: A stochastic analysis based on decision trees was performed to compare the cost-effectiveness of beta-blockers therapy starting from a diagnosis of small varices (Strategy 1) with that of endoscopic surveillance followed by beta-blockers treatment when large varices are demonstrated (Strategy 2), for preventing variceal growth, bleeding and death in patients with cirrhosis and small esophageal varices. The basic nodes of the tree were gastrointestinal endoscopy, inpatient admission and treatment for bleeding, as required. All estimates were performed using a Monte Carlo microsimulation technique, consisting in simulating observations from known probability distributions depicted in the model. Eight-hundred-thousand simulations were performed to obtain the final estimates. All estimates were then subjected to Monte Carlo Probabilistic sensitivity analysis, to assess the impact of the variability of such estimates on the outcome distributions.
RESULTS: The event rate (considered as progression of varices or bleeding or death) in Strategy 1 [24.09% (95%CI: 14.89%-33.29%)] was significantly lower than in Strategy 2 [60.00% (95%CI: 48.91%-71.08%)]. The mean cost (up to the first event) associated with Strategy 1 [823 £ (95%CI: 106 £-2036 £)] was not significantly different from that of Strategy 2 [799 £ (95%CI: 0 £-3498 £)]. The cost-effectiveness ratio with respect to this endpoint was equal to 50.26 £ (95%CI: -504.37 £-604.89 £) per event avoided over the four-year follow-up. When bleeding episodes/deaths in subjects whose varices had grown were included, the mean cost associated with Strategy 1 was 1028 £ (95%CI: 122 £-2581 £), while 1699 £ (95%CI: 171 £-4674 £) in Strategy 2.
CONCLUSION: Beta-blocker therapy turn out to be more effective and less expensive than endoscopic surveillance for primary prophylaxis of bleeding in patients with cirrhosis and small varices.
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Karadsheh Z, Allison H. Primary prevention of variceal bleeding: pharmacological therapy versus endoscopic banding. NORTH AMERICAN JOURNAL OF MEDICAL SCIENCES 2014; 5:573-9. [PMID: 24350068 PMCID: PMC3842697 DOI: 10.4103/1947-2714.120791] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Variceal bleeding is one of the most feared complications in patients with liver cirrhosis. It continues to be a leading cause of death among patients with liver cirrhosis. Although its prognosis has improved over the last several decades, it still carries substantial mortality. Preventing variceal bleeding has been extensively studied and evaluated in several studies in the recent years and the comparison between the different modalities available to prevent variceal bleeding has been an area of discussion. Currently the two most widely used modalities to prevent variceal bleeding are pharmacologic (non-selective beta-blockers [NSBB]) and endoscopic (variceal band ligation [VBL]) which have replaced sclerotherapy in the recent years. In addition to NSBB and recent carvedilol, different other medications have been evaluated including isosorbide mononitrates, spironolactone and angiotensin blocking agents. Comparing the outcomes and adverse effects of these two modalities has been evaluated in different studies. Some studies have showed superiority of VBL until recently, when carvedilol has been included, however; overall mortality has been similar in most trials. Despite that, NSBB remain the first line treatment, as they are cheaper and relatively effective in preventing both esophageal and gastric bleeding. The following sections discuss the primary prevention of variceal bleeding with a focus on NSBB, carvedilol and VBL.
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Affiliation(s)
- Zeid Karadsheh
- Department of Medicine, Brockton Hospital, Brockton, USA
| | - Harmony Allison
- Division of Gastroenterology, Tufts Medical Center, Boston, MA, USA
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13
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Abstract
Primary prevention of variceal bleeding is an important and long-debated topic in the management of patients with cirrhosis and esophageal varices. Prophylaxis is recommended for high-risk patients with small esophageal varices (advanced liver disease and/or presence of red wale marks) and those with medium/large varices. Nonselective β-blockers and endoscopic band ligation have been shown to be equally effective in primary prevention of variceal bleeding and are the only currently recommended therapies. Controversy still exists, however, regarding which one of these strategies is preferred. This article reviews the established recommendations and recent advances in the prevention of first esophageal variceal bleeding.
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Affiliation(s)
- Douglas A Simonetto
- Gastroenterology Research Unit, Division of Gastroenterology and Hepatology, Department of Physiology, Advanced Liver Disease Study Group, Fiterman Center for Digestive Diseases, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA
| | - Vijay H Shah
- Gastroenterology Research Unit, Division of Gastroenterology and Hepatology, Department of Physiology, Advanced Liver Disease Study Group, Fiterman Center for Digestive Diseases, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA
| | - Patrick S Kamath
- Gastroenterology Research Unit, Division of Gastroenterology and Hepatology, Department of Physiology, Advanced Liver Disease Study Group, Fiterman Center for Digestive Diseases, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA.
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14
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Ge PS, Runyon BA. The changing role of beta-blocker therapy in patients with cirrhosis. J Hepatol 2014; 60:643-53. [PMID: 24076364 DOI: 10.1016/j.jhep.2013.09.016] [Citation(s) in RCA: 92] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2013] [Revised: 09/13/2013] [Accepted: 09/17/2013] [Indexed: 12/11/2022]
Abstract
Cirrhosis is a leading cause of death in the United States and worldwide. Beta-blockers have been established in numerous studies as part of the cornerstone of the medical management of cirrhosis, particularly in the primary and secondary prevention of variceal hemorrhage. However, new evidence has cautioned the use of beta-blockers in patients with end-stage cirrhosis and refractory ascites. In this article, we review the beneficial effects of beta-blocker therapy, the potential harms of aggressive beta-blocker therapy, and provide suggestions regarding the appropriate use of this class of medications in patients with cirrhosis.
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Affiliation(s)
- Phillip S Ge
- Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States
| | - Bruce A Runyon
- Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States.
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15
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de Franchis R, Dell’Era A. Pre-primary and Primary Prophylaxis of Variceal Hemorrhage. VARICEAL HEMORRHAGE 2014. [PMCID: PMC7121476 DOI: 10.1007/978-1-4939-0002-2_7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
Variceal hemorrhage is a life-threatening complication of portal hypertension. Thus, prevention of variceal formation (pre-primary prophylaxis) or at least prevention of variceal bleeding are important goals to improve life quality and—if possible—survival of patients with liver cirrhosis. Interruption of the underlying cause of liver disease is the most successful approach, which, however, often fails. For this situation interruption or modulation of different pathophysiological mechanisms leading to fibrosis, hyperdynamic circulation and portal hypertension have been shown effective in animal models. But few could be translated to humans. By contrast, different steps to prevent first bleeding from varices have proven successful in many clinical trials. These applied mainly drugs to lower portal pressure, such as nonselective β-blockers, or endoscopic obliteration of varices, while prophylactic shunt procedures are not advised.
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Affiliation(s)
| | - Alessandra Dell’Era
- Ospedale Universitario Luigi Sacco, Universitá degli Studi di Milano, UOC Gastroenterologia, Milano, Italy
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16
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Simonetto DA, Shah VH. Primary prophylaxis of esophageal variceal bleeding. Clin Liver Dis (Hoboken) 2012; 1:147-150. [PMID: 31186875 PMCID: PMC6499289 DOI: 10.1002/cld.92] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Affiliation(s)
- Douglas A. Simonetto
- Gastroenterology Research Unit, Advanced Liver Disease Study Group, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Vijay H. Shah
- Gastroenterology Research Unit, Advanced Liver Disease Study Group, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
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Goulart B, Ramsey S. A trial-based assessment of the cost-utility of bevacizumab and chemotherapy versus chemotherapy alone for advanced non-small cell lung cancer. VALUE IN HEALTH : THE JOURNAL OF THE INTERNATIONAL SOCIETY FOR PHARMACOECONOMICS AND OUTCOMES RESEARCH 2011; 14:836-845. [PMID: 21914503 DOI: 10.1016/j.jval.2011.04.004] [Citation(s) in RCA: 71] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/17/2010] [Revised: 03/29/2011] [Accepted: 04/25/2011] [Indexed: 05/31/2023]
Abstract
OBJECTIVES Bevacizumab is approved for treatment of advanced non-small cell lung cancer (NSCLC) in combination with chemotherapy based on a 2-month median survival benefit demonstrated in one randomized trial. The cost-utility of adding bevacizumab to chemotherapy in advanced NSCLC remains unknown. We evaluated the cost-utility of bevacizumab added to chemotherapy in patients with advanced NSCLC. METHODS We developed a Markov model to estimate quality-adjusted life years (QALYs) and direct medical costs from the US payer perspective in patients treated with bevacizumab plus chemotherapy and compared these outcomes with patients treated with chemotherapy alone. We populated the model with survival and toxicity data from the clinical trial that compared the two strategies. We obtained utilities from a literature search and unit costs from Medicare. We discounted QALYs and costs at 3% per year. We addressed uncertainty with one-way and probabilistic sensitivity analyzes. RESULTS Compared with chemotherapy alone, bevacizumab and chemotherapy increased mean QALYs by 0.13, at an incremental life-time cost of US$72,000 per patient. The incremental cost-utility ratio (ICUR) was US$560,000/QALY. The ICUR was most sensitive to the survival on bevacizumab treatment, the drug costs of bevacizumab, and the utility of stable disease on treatment. At a threshold of US$100,000/QALY, the addition of bevacizumab had a 0.2% probability of being cost-effective. CONCLUSIONS Bevacizumab does not appear to be cost-effective when added to chemotherapy in patients with advanced NSCLC, based on approximate cost-effectiveness thresholds that have been identified in the United States. These results may inform decision-makers about resource allocation for NSCLC care.
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Zhang C, Thabut D, Kamath PS, Shah VH. Oesophageal varices in cirrhotic patients: from variceal screening to primary prophylaxis of the first oesophageal variceal bleeding. Liver Int 2011; 31:108-19. [PMID: 20946450 DOI: 10.1111/j.1478-3231.2010.02351.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Bleeding from oesophageal varices is still a lethal complication in cirrhotic patients with portal hypertension. Approximately 5-10% of patients with cirrhosis will develop oesophageal varices per year, and about 25-30% of cirrhotic patients with oesophageal varices and without previous variceal haemorrhage will bleed from ruptured varices. To date, data on preventing the formation/growth of oesophageal varices (preprimary prophylaxis) are conflicting, with insufficient evidence to use β-blockers. There is evidence for the need for primary prophylaxis, and both β-blockers and endoscopic variceal ligation have shown the same efficacy in preventing first bleeding, but which one to prefer is still controversial. The present article reviews the established and potential therapeutic strategies for preventing the development and rupture of oesophageal varices.
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Affiliation(s)
- Chunqing Zhang
- Department of Gastroenterology, Provincial Hospital Affiliated to Shandong University, Jinan Shandong, China
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19
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Direct costs of care in a randomized controlled trial of endoscopic sclerotherapy versus emergency portacaval shunt for bleeding esophageal varices in cirrhosis--Part 4. J Gastrointest Surg 2011; 15:38-47. [PMID: 20824373 PMCID: PMC3023018 DOI: 10.1007/s11605-010-1332-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2010] [Accepted: 08/12/2010] [Indexed: 01/31/2023]
Abstract
BACKGROUND Emergency treatment of bleeding esophageal varices (BEV) in cirrhotic patients is of prime importance because of the high mortality rate surrounding the episode of acute bleeding. Nevertheless, there is a paucity of randomized controlled trials of emergency surgical therapy and no reports of the costs of any of the widely used forms of emergency treatment. The important issue of direct costs of care was examined in a randomized controlled trial that compared endoscopic sclerotherapy (EST) to emergency portacaval shunt (EPCS). METHODS Two hundred eleven unselected consecutive patients with ultimately biopsy-proven cirrhosis and endoscopically proven acute BEV were randomized to EST (n = 106) or EPCS (n = 105). Diagnostic workup was completed, and EST or EPCS was initiated within 8 h. Criteria for failure of EST or EPCS were clearly defined, and crossover rescue treatment was applied, when primary therapy failed. Ninety-six percent of patients underwent more than 10 years follow-up, or until death. Complete charges for all aspects of care were obtained continuously for more than 10 years. RESULTS Direct charges for all aspects of care were significantly lower in patients treated by EPCS than in patients treated by emergency EST followed by long-term repetitive sclerotherapy. Charges per patient, per year of treatment, and per year in each child's risk class were significantly lower in patients randomized to EPCS. Charges in patients who failed endoscopic sclerotherapy and underwent a rescue portacaval shunt were significantly higher than the charges in both the unshunted sclerotherapy patients and the patients randomized to EPCS. This result was particularly noteworthy given the widespread practice of using surgical portacaval shunt as rescue treatment only when all other forms of therapy have failed. CONCLUSIONS In this randomized controlled trial of emergency treatment of acute BEV, EPCS was significantly superior to EST with regard to direct costs of care as reflected in charges for care as well as in survival rate, control of bleeding, and incidence of portal-systemic encephalopathy. These results provide support for the use of EPCS as a first line of emergency treatment of BEV in cirrhosis.
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Abstract
Gastroesophageal variceal hemorrhage is a major complication of portal hypertension in 50% to 60% of patients with liver cirrhosis and is a frequent cause of mortality in these patients. The prevalence of variceal hemorrhage is approximately 5% to 15% yearly, and early variceal rebleeding has a rate of occurrence of 30% to 40% within the first 6 weeks. More than 50% of patients who survive after the first bleeding episode will experience recurrent bleeding within 1 year. Management of gastroesophageal varices should include prevention of initial and recurrent bleeding episodes and control of active hemorrhage. Therapies used in the management of gastroesophageal variceal hemorrhage may include pharmacologic therapy (vasoactive agents, nonselective b-blockers, and antibiotic prophylaxis), endoscopic therapy, transjugular intrahepatic portosystemic shunt, and shunt surgery. This article focuses primarily on pharmacologic management of acute variceal hemorrhage.
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Affiliation(s)
- Tram B Cat
- Critical Care, Department of Pharmacy, Antelope Valley Hospital, 1600 West Avenue, Lancaster, CA 93534, USA.
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Laine L. Primary prophylaxis of esophageal variceal bleeding: an endoscopic approach. J Hepatol 2010; 52:944-5. [PMID: 20381891 DOI: 10.1016/j.jhep.2009.12.035] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2009] [Accepted: 12/17/2009] [Indexed: 01/07/2023]
Affiliation(s)
- Loren Laine
- Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, 2025 Zonal Ave., Los Angeles, CA 90033, USA.
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Albillos A, Peñas B, Zamora J. Role of endoscopy in primary prophylaxis for esophageal variceal bleeding. Clin Liver Dis 2010; 14:231-50. [PMID: 20682232 DOI: 10.1016/j.cld.2010.03.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Cirrhosis is the leading cause of portal hypertension in the Western world. From a clinical standpoint, the most significant consequence of portal hypertension is the development of esophageal varices. Despite the many advances in the management of variceal bleeding, it remains a life-threatening complication of portal hypertension. Primary prophylaxis to prevent the first bleeding episode in patients with cirrhosis and esophageal varices is therefore critically important in the management of patients with cirrhosis.
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Affiliation(s)
- Agustín Albillos
- Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Madrid, Spain.
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PillCam ESO versus esophagogastroduodenoscopy in esophageal variceal screening: A decision analysis. J Clin Gastroenterol 2009; 43:975-81. [PMID: 19661814 DOI: 10.1097/mcg.0b013e3181a7ed09] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES PillCam ESO has been evaluated as a possible strategy to screen patients with cirrhosis for esophageal varices, but current guidelines recommend patients undergo screening with esophagogastroduodenoscopy (EGD), as it is currently the gold standard. Although recent data have suggested that PillCam ESO may be an acceptable alternative for screening, there is limited data on its cost-effectiveness compared with other screening modalities. This study was performed to compare the cost-effectiveness of PillCam ESO versus EGD for esophageal variceal screening. METHODS Markov models were constructed to compare 2 screening strategies: PillCam ESO versus EGD. In each arm, patients were followed for a time horizon of 15 years in 1-year transition intervals. All variables, transition probabilities, and costs were derived from the medical literature, and sensitivity analyses were performed on the different variables in the model. RESULTS Base-case analysis shows that PillCam ESO is associated with an average expected cost of $22,589 and an average expected effectiveness measure of 12.81 life-years. EGD is associated with an average expected cost of $23,083 and an average expected effectiveness measure of 12.67 life-years. PillCam ESO was found to dominate EGD as a screening strategy for patients with cirrhosis. Sensitivity analyses found several variables within the model to have influential effects on the results. CONCLUSIONS PillCam ESO is the dominant strategy for screening patients with cirrhosis for esophageal varices. However, based on a small difference in costs and effectiveness between each strategy, the results would suggest that PillCam ESO and EGD are essentially equivalent strategies.
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Garcia-Tsao G, Lim JK. Management and treatment of patients with cirrhosis and portal hypertension: recommendations from the Department of Veterans Affairs Hepatitis C Resource Center Program and the National Hepatitis C Program. Am J Gastroenterol 2009; 104:1802-1829. [PMID: 19455106 DOI: 10.1038/ajg.2009.191] [Citation(s) in RCA: 170] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Cirrhosis represents the end stage of any chronic liver disease. Hepatitis C and alcohol are currently the main causes of cirrhosis in the United States. Although initially cirrhosis is compensated, it eventually becomes decompensated, as defined by the presence of ascites, variceal hemorrhage, encephalopathy, and/or jaundice. These management recommendations are divided according to the status, compensated or decompensated, of the cirrhotic patient, with a separate section for the screening, diagnosis, and management of hepatocellular carcinoma (HCC), as this applies to patients with both compensated and decompensated cirrhosis. In the compensated patient, the main objective is to prevent variceal hemorrhage and any practice that could lead to decompensation. In the decompensated patient, acute variceal hemorrhage and spontaneous bacterial peritonitis are severe complications that require hospitalization. Hepatorenal syndrome is also a severe complication of cirrhosis but one that usually occurs in patients who are already in the hospital and, as it represents an extreme of the hemodynamic alterations that lead to ascites formation, it is placed under treatment of ascites. Recent advances in the pathophysiology of the complications of cirrhosis have allowed for a more rational management of cirrhosis and also for the stratification of patients into different risk groups that require different management. These recommendations are based on evidence in the literature, mainly from randomized clinical trials and meta-analyses of these trials. When few or no data exist from well-designed prospective trials, emphasis is given to results from large series and consensus conferences with involvement of recognized experts. A rational management of cirrhosis will result in improvements in quality of life, treatment adherence, and, ultimately, in outcomes.
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Abstract
PURPOSE OF REVIEW Esophageal variceal bleeding is a life-threatening complication of liver cirrhosis. The aim of this review is to discuss the most important studies published in 2007 concerning diagnosis of esophageal varices, primary and secondary prophylaxis and treatment of variceal bleeding. RECENT FINDINGS The specific areas reviewed are the noninvasive or minimally invasive diagnosis of oesophageal varices, prevention of the formation of varices and their progression from small to large, prevention of the first variceal hemorrhage, treatment of acute bleeding episodes and prevention of rebleeding, assessment of costs related to prophylaxis and treatment of variceal bleeding. Multidetector computed tomographic esophagography was found to identify the presence and grade the size of esophageal varices. Portal vein thrombosis was found to be an independent predictor of the aggravation of esophageal varices in patients with cirrhosis and hepatocellular carcinoma. The role of hepatic vein pressure gradient measurement in the prediction of decompensation of cirrhosis has been elucidated. SUMMARY Relevant studies are reviewed on the diagnosis and the natural history of esophageal varices, prevention of their formation and growth, prevention of the first variceal bleed, use of hepatic vein pressure gradient to predict the evolution of portal hypertension and to estimate the response to pharmacological treatment, prediction of bleeding, treatment of variceal bleeding and prevention of rebleeding, and cost strategies.
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Bosch J, Berzigotti A, Garcia-Pagan JC, Abraldes JG. The management of portal hypertension: rational basis, available treatments and future options. J Hepatol 2008; 48 Suppl 1:S68-92. [PMID: 18304681 DOI: 10.1016/j.jhep.2008.01.021] [Citation(s) in RCA: 195] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Variceal bleeding is the last step in a chain of events initiated by an increase in portal pressure, followed by the development and progressive dilation of varices until these finally rupture and bleed. This sequence of events might be prevented - and reversed - by achieving a sufficient decrease in portal pressure. A different approach is the use of local endoscopic treatments at the varices. This article reviews the rationale for the management of patients with cirrhosis and portal hypertension, the current recommendations for the prevention and treatment of variceal bleeding, and outlines the unsolved issues and the perspectives for the future opened by new research developments.
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Affiliation(s)
- Jaime Bosch
- Hepatic Hemodynamic Laboratory, Liver Unit, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), University of Barcelona, Hospital Clínic, C.Villarroel 170, 08036 Barcelona, Spain.
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Portal hypertension: pre-primary and primary prophylaxis of variceal bleeding. Dig Liver Dis 2008; 40:318-27. [PMID: 18291732 DOI: 10.1016/j.dld.2007.12.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2007] [Accepted: 12/05/2007] [Indexed: 12/11/2022]
Abstract
In liver cirrhosis, variceal bleeding is the last in a chain of events initiated by the increase in portal pressure (estimated in clinical practice by the hepatic venous pressure gradient). When hepatic venous pressure gradient goes above 10 mmHg the patient is at risk of developing varices, and when hepatic venous pressure gradient reaches 12 mmHg variceal bleeding might develop. Currently, there is not any effective therapy for the prevention of the development of varices. When varices are small, beta-adrenergic blockers might prevent the enlargement of the varices, and may reduce the risk of variceal bleeding. In patients with medium to large varices, beta-blockers are clearly effective in reducing the risk of variceal bleeding. Endoscopic band ligation might be more effective than beta-blockers, but available evidence is still very weak.
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Garcia-Tsao G, Bosch J, Groszmann RJ. Portal hypertension and variceal bleeding--unresolved issues. Summary of an American Association for the study of liver diseases and European Association for the study of the liver single-topic conference. Hepatology 2008; 47:1764-72. [PMID: 18435460 DOI: 10.1002/hep.22273] [Citation(s) in RCA: 191] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Guadalupe Garcia-Tsao
- Section of Digestive Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
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Kumagi T, Heathcote EJ. Primary biliary cirrhosis. Orphanet J Rare Dis 2008; 3:1. [PMID: 18215315 PMCID: PMC2266722 DOI: 10.1186/1750-1172-3-1] [Citation(s) in RCA: 81] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2007] [Accepted: 01/23/2008] [Indexed: 12/15/2022] Open
Abstract
Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic liver disease of autoimmune etiology characterized by injury of the intrahepatic bile ducts that may eventually lead to liver failure. Affected individuals are usually in their fifth to seventh decades of life at time of diagnosis, and 90% are women. Annual incidence is estimated between 0.7 and 49 cases per million-population and prevalence between 6.7 and 940 cases per million-population (depending on age and sex). The majority of patients are asymptomatic at diagnosis, however, some patients present with symptoms of fatigue and/or pruritus. Patients may even present with ascites, hepatic encephalopathy and/or esophageal variceal hemorrhage. PBC is associated with other autoimmune diseases such as Sjogren's syndrome, scleroderma, Raynaud's phenomenon and CREST syndrome and is regarded as an organ specific autoimmune disease. Genetic susceptibility as a predisposing factor for PBC has been suggested. Environmental factors may have potential causative role (infection, chemicals, smoking). Diagnosis is based on a combination of clinical features, abnormal liver biochemical pattern in a cholestatic picture persisting for more than six months and presence of detectable antimitochondrial antibodies (AMA) in serum. All AMA negative patients with cholestatic liver disease should be carefully evaluated with cholangiography and liver biopsy. Ursodeoxycholic acid (UDCA) is the only currently known medication that can slow the disease progression. Patients, particularly those who start UDCA treatment at early-stage disease and who respond in terms of improvement of the liver biochemistry, have a good prognosis. Liver transplantation is usually an option for patients with liver failure and the outcome is 70% survival at 7 years. Recently, animal models have been discovered that may provide a new insight into the pathogenesis of this disease and facilitate appreciation for novel treatment in PBC.
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Affiliation(s)
- Teru Kumagi
- Department of Medicine, Toronto Western Hospital (University Health Network/University of Toronto), Toronto, Ontario, Canada.
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Abstract
Variceal bleeding is still a life-threatening complication of portal hypertension responsible for an appreciable rate of morbidity and mortality. The most appropriate treatment approach, whether drugs (nonselective beta-blockers) or endoscopic (variceal band ligation) therapy, to prevent the initial bleed, or primary prophylaxis, is an issue of controversy. Meta-analysis of randomized controlled trials indicates that banding seems to be somehow slightly more effective than beta-blockers at preventing a first bleeding episode, but this does not translate to improved survival. The firmness of this conclusion is, in addition, diminished by the small sample size and short follow-up of most studies. Moreover, adverse events due to banding are more severe than those associated with beta-blockers. Thus, beta-blockers remain as first-line therapy in patients with cirrhosis and large esophageal varices. Prophylactic therapy with beta-blockers can be considered in patients with small varices, especially in those with red signs or Child class C liver disease. The available evidence does not support the idea that organic nitrates improve the efficacy of beta-blockers in primary prophylaxis. The method used to establish the dose of beta-blockers and check its effect on hepatic venous pressure gradient (HVPG) has also been disputed. An attractive strategy is to measure the HVPG response to beta-blockers as a guide to primary prophylaxis, with the aim of switching to another therapy, that is, band ligation, in HVPG nonresponders. However, no study has yet demonstrated that banding as rescue therapy in nonresponders lowers the risk of first bleeding and improves survival.
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