Non-Selective Beta-Blockers in Liver Cirrhosis: the Effect of the "Therapeutic Window" and Patient Survival

Objectives of the study: to analyze the survival rate of patients who received and did not receive various drugs of the class of non-selective beta-blockers (NSBB) while waiting for liver transplantation (LT) on the waiting list for liver transplantation (WLLT), depending on the presence or absence of a "therapeutic window" for the appointment of NSBB; to determine risk factors for death when prescribing various representatives of the NSBB class in patients with refractory ascites (RA). Material and methods. The retrospective case-control study was conducted. The "case" group included 278 adult patients with decompensated liver diseases of various etiologies included in the WLLT, who were treated with NSBB while waiting for LT. The "control" group consisted of 72 patients with decompensated liver diseases of various etiologies included in the WLLT, who did not receive NSBB therapy during the waiting period for LT. For the subsequent analysis, the group of patients receiving NSBB (n = 278) was divided into two subgroups: with the presence of a "therapeutic window" (n = 175), and without it (n = 103). The survival rate of patients was determined by the Kaplan - Mayer method. Predictors of mortality of patients receiving NSBB in the absence of a" therapeutic window "for NSBB were determined using the Cox proportional hazards model in the groups of patients with RA (n = 103) and non-RA (n = 175). Results. The survival rate of patients receiving NSBB in the presence of a" therapeutic window "for NSBB is significantly higher than in the group of patients receiving NSBB in WLLP while waiting for LT in the absence of a" therapeutic window " for NSBB (Log-Rank < 0.0001). The risk of death in patients with RA treated with NSBB was significantly higher than in patients with non-RA (HR = 2.285; CI 1.237 4.220; p = 0.008). The risk of death for patients treated with propranol was significantly different from carvedilol (HR = 2,152 and HR = 0.765; p = 0.042, respectively). Conclusion. The results of the study confirmed the hypothesis that there is a "therapeutic window" for NSBB when they are prescribed to patients with decompensated cirrhosis of the liver and included in the WLLP. The use of NSBB contributes to an increase in the mortality of patients with RA, regardless of the type of drug, in the case when the "closed therapeutic window" phase develops. In order to reduce the mortality of patients waiting for LT for several years due to acute organ deficiency, doctors who lead patients to WLLT should assess the risk and benefit of using NSBB

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Impact of cardiac function, refractory ascites and beta blockers on the outcome of patients with cirrhosis listed for liver transplantation

Journal of Hepatology ◽

10.1016/j.jhep.2019.10.002 ◽

2020 ◽

Vol 72 (3) ◽

pp. 463-471 ◽

Cited By ~ 8

Author(s):

Valerio Giannelli ◽

Olivier Roux ◽

Cédric Laouénan ◽

Pauline Manchon ◽

Floriane Ausloos ◽

...

Keyword(s):

Liver Transplantation ◽

Cardiac Function ◽

Beta Blockers ◽

Refractory Ascites

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The Impact of Share 35 Policy on Patient Survival in Patients Undergoing Liver Transplantation With Gender- and Race-Mismatched Donors

Progress in Transplantation ◽

10.1177/1526924818765802 ◽

2018 ◽

Vol 28 (2) ◽

pp. 151-156

Author(s):

Yefei Zhang ◽

Maha R. Boktour

Keyword(s):

Liver Transplantation ◽

Proportional Hazards Model ◽

Patient Survival ◽

Research Question ◽

Cox Proportional Hazards Model ◽

Future Research ◽

Gender And Race ◽

Risk Of Death ◽

Share 35 Policy ◽

The Impact

Introduction: The United Network for Organ Sharing (UNOS) instituted the Share 35 policy in June 2013 in order to reduce death on liver transplant waitlist. The effect of this policy on patient survival among patients with gender- and race-mismatched donors has not been examined. Research Question: To assess the impact of Share 35 policy on posttransplantation patient survival among patients with end-stage liver disease (ESLD) transplanted with gender- and race-mismatched donors. Design: A total of 16 467 adult patients with ESLD who underwent liver transplantation between 2012 and 2015 were identified from UNOS. An overall Cox proportional hazards model adjusting for demographic, clinical, and geographic factors and separate models with a dummy variable of pre- and post-Share 35 periods as well as its interaction with other factors were performed to model the effect of gender and race mismatch on posttransplantation patient survival and to compare the patient survival differences between the first 18 months of Share 35 policy to an equivalent time period before. Results: Comparison of the pre- and post-Share 35 periods did not show significant changes in the numbers of gender- and race-mismatched transplants, or the risk of death for gender-mismatched recipients. However, black recipients with Hispanic donors (hazard ratio: 0.51, 95% confidence interval, 0.29-0.90) had significantly increased patient survival after Share 35 policy took effect. Conclusion: The Share 35 policy had a moderate impact on posttransplantation patient survival among recipients with racially mismatched donors according to the first 18-month experience. Future research is recommended to explore long-term transplantation.

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Non-selective beta blocker use is associated with improved short-term survival in patients with cirrhosis referred for liver transplantation

BMC Gastroenterology ◽

10.1186/s12876-019-1155-1 ◽

2020 ◽

Vol 20 (1) ◽

Cited By ~ 2

Author(s):

Taiwo Ngwa ◽

Eric Orman ◽

Eduardo Vilar Gomez ◽

Raj Vuppalanchi ◽

Chandrashekhar Kubal ◽

...

Keyword(s):

Liver Transplantation ◽

Beta Blockers ◽

Kidney Injury ◽

Refractory Ascites ◽

Short Term ◽

Term Survival ◽

Bacterial Peritonitis ◽

Stage 1 ◽

Short Term Survival

Abstract Background Recent evidence cautions against the use of non-selective beta-blockers (NSBB) in patients with refractory ascites or spontaneous bacterial peritonitis while other data suggests a survival benefit in patients with advanced liver disease. The aim of this study was to describe the use and impact of NSBB in patients with cirrhosis referred for liver transplantation. Methods A single-center cohort of patients with cirrhosis, who were referred and evaluated for liver transplantation between January and June 2012 were studied for baseline characteristics and clinical outcomes. Patients were grouped according to the use of NSBB at initial evaluation, with the endpoint of 90-day mortality. Results Sixty-five (38%) of 170 consecutive patients evaluated for liver transplantation were taking NSBB. Patients taking NSBB had higher MELD and Child Pugh score. NSBB use was associated with lower 90-day mortality (6% vs. 15%) with a risk adjusted hazard ratio of 0.27 (95%CI .09–0.88, p = .03). Patients taking NSBB developed acute kidney injury (AKI) within 90 days more frequently than patients not taking NSBB (22% vs 11%), p = 0.048). However, this was related to increased stage 1 AKI episodes, all of which resolved. Twelve (27%) of 45 patients with > 90 day follow up discontinued NSBB, most commonly for hypotension and AKI, had increased subsequent MELD and mortality. Conclusions NSBB use in patients with cirrhosis undergoing liver transplant evaluation is associated with better short-term survival. Nevertheless, ongoing tolerance of NSBB in this population is dynamic and may select a subset of patients with better hemodynamic reserve.

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The simple maneuver to safely extend the anhepatic time to 30 minutes for rat liver transplantation

10.21203/rs.3.rs-118171/v2 ◽

2021 ◽

Author(s):

Gaofeng Tang ◽

jiabin zhang ◽

Huibo Zhao ◽

Sidong Wei ◽

Shaotang Zhou ◽

...

Keyword(s):

Liver Transplantation ◽

Survival Rate ◽

Rat Liver ◽

Tolerance Induction ◽

Brown Norway ◽

Control Group ◽

Sprague Dawley ◽

Once Daily ◽

Rat Liver Transplantation ◽

Group Control Group

Abstract Background Orthotopic rat liver transplantation (OLT) is widely used; it remains to be challenging although many renovations have been made. Methods For tolerance induction, we performed OLT including whole graft OLT from close Sprague Dawley (SD) rat to SD (whole graft group, control group, n = 21) and 30 minute anhepatic time (AHT) group (AHT group, n = 11). For good outcomes of AHT group and generalization of this maneuver, partial OLT was performed from 50% Lewis allograft to Brown Norway (BN) rats to induce tolerance (half graft group, n = 28), Cyclosporine A was injected once daily for 14 days. Results For whole graft group, 30-day survival rate was 85.5% (18/21), the reasons of death were gas embolism due to the missed suturing in 2 cases, blood loss in 1 case. For AHT group and tolerance group, 30-day survival rate was 72.7% (8/11), 64.3% (18/28), the causes of death were diverse. There were no differences in survival in 3 groups (p = 0.289). Conclusion The anhepatic time can be extended simply through the change of clamping the diaphragm, which facilitates its application in the research.

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The Simple Maneuver to Safely Extend the Anhepatic Time to 30 Minutes for Rat Liver Transplantation

10.21203/rs.3.rs-118171/v1 ◽

2020 ◽

Author(s):

Gaofeng Tang ◽

Jiabin Zhang ◽

Huibo Zhao ◽

Sidong Wei ◽

shaotang zhou ◽

...

Keyword(s):

Liver Transplantation ◽

Survival Rate ◽

Rat Liver ◽

Tolerance Induction ◽

Brown Norway ◽

Control Group ◽

Sprague Dawley ◽

Once Daily ◽

Rat Liver Transplantation ◽

Group Control Group

Abstract Background: Orthotopic rat liver transplantation (OLT) is widely used; it remains to be challenging although many renovations have been made. Methods: For tolerance induction, we performed OLT including whole graft OLT from close Sprague Dawley (SD) rat to SD (whole graft group, control group, n=21) and 30 minute anhepatic time (AHT) group (AHT group, n=11). For good outcomes of AHT group and generalization of this maneuver, partial OLT was performed from 50% Lewis allograft to Brown Norway (BN) rats to induce tolerance (half graft group, n=28), Cyclosporine A was injected once daily for 14 days. Results: For whole graft group, 30-day survival rate was 85.5% (18/21), the reasons of death were gas embolism due to the missed suturing in 2 cases, blood loss in 1 case. For AHT group and tolerance group, 30-day survival rate was 72.7% (8/11), 64.3% (18/28), the causes of death were diverse. There were no differences in survival in 3 groups (p=0.289). Conclusion: The anhepatic time can be extended simply through the change of clamping the diaphragm, which facilitates its application in the research.

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Rare cause of non-immune hemolytic anemia in end-stage liver disease

Case Reports in Internal Medicine ◽

10.5430/crim.v7n2p7 ◽

2020 ◽

Vol 7 (2) ◽

pp. 7

Author(s):

Maheep Singh Sangha ◽

Aakash Aggarwal ◽

Japmehr Sandhu

Keyword(s):

Liver Transplantation ◽

Liver Diseases ◽

Cell Formation ◽

Decompensated Cirrhosis ◽

Severe Anemia ◽

Multidrug Therapy ◽

Bile Acid Sequestrants ◽

End Stage Liver Disease ◽

Immune Hemolytic Anemia ◽

End Stage

Spur cells are reportedly linked to advanced end-stage liver diseases and may lead to accelerated hemolysis. In this case report, we discuss one of these rare instances when a 45-year-old female with decompensated cirrhosis was admitted for severe anemia. Extensive workup revealed non-immune hemolysis secondary to spur cell formation. Orthotopic liver transplantation remains the only treatment of choice for reversal of spur cell anemia. Alternatively, multidrug therapy has also been explored, including usage of bile acid sequestrants; however, success is rare.

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Systemic arterial blood pressure determines the therapeutic window of non-selective beta blockers in decompensated cirrhosis

Alimentary Pharmacology & Therapeutics ◽

10.1111/apt.15439 ◽

2019 ◽

Vol 50 (6) ◽

pp. 696-706 ◽

Cited By ~ 10

Author(s):

Tammo L. Tergast ◽

Markus Kimmann ◽

Hans Laser ◽

Svetlana Gerbel ◽

Michael P. Manns ◽

...

Keyword(s):

Blood Pressure ◽

Arterial Blood Pressure ◽

Beta Blockers ◽

Therapeutic Window ◽

Decompensated Cirrhosis ◽

Systemic Arterial Blood Pressure ◽

Arterial Blood

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Which Incision is Better for Orthotopic Rat Liver Transplantation, Transverse or Midline?

10.21203/rs.3.rs-691424/v1 ◽

2021 ◽

Author(s):

Gaofeng Tang ◽

Zhongwu Zou ◽

Huibo Zhao ◽

Weiwei Wang ◽

Guoyong Chen ◽

...

Keyword(s):

Liver Transplantation ◽

Survival Rate ◽

Acute Rejection ◽

Rat Liver ◽

Brown Norway ◽

Control Group ◽

Sprague Dawley ◽

Transverse Incision ◽

Rat Liver Transplantation ◽

Biting Behavior

Abstract Orthotopic rat liver transplantation (OLT) is a complex procedure extensively applicable to basic science, myriad complications can occur, incision-related self-biting has not been reported after liver transplantation. For the project of tolerance induction through stem cells, OLT was performed from inbred Sprague Dawley (SD) rat to SD (control group, n = 9), SD to Lewis (chronic rejection, n = 11), and OLT from Lewis allograft to Brown Norway (BN) rats (acute rejection, n = 63), the acute rejection group was sub-grouped into the transverse incision group(n = 26) and midline group(n = 37), Cyclosporine A was injected at 2mg/kg into the rejection groups once daily for 14 days, lidocaine cream alone or with naloxone was used for pain-relieving. The recipient survival and wound status were the primary endpoint of this study. For SD→SD, 30-day survival rate was 88.9%, no self-biting behavior occurred; for SD→Lewis, 30-day survival rate was 54.5%, the degree II of self-biting occurred in 2 cases. For Lewis→BN with transverse incision, 30-day survival rate was 51.8%, severe self-biting occurred in 16 cases in 8–27 days and 5 more cases over 30 days, which caused death or euthanasia, the degree 2 of biting occurred in 2 cases. For Lewis→BN with midline incision, 30-day survival rate was 86.0%, no severe self-biting occurred, mild self-biting in 2 cases. There was difference in the biting–related survival between two sub-groups (p = 0.003). In conclusion, incision-related self-biting behavior is species-specific for rats, the transverse incision is the pain-causing reason; the midline one is effective to avert occurrences.

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Komplikationen der Leberzirrhose – medikamentöse versus interventionelle Therapie

DMW - Deutsche Medizinische Wochenschrift ◽

10.1055/a-0753-6051 ◽

2019 ◽

Vol 144 (18) ◽

pp. 1259-1266

Author(s):

Lukas Sturm ◽

Martin Rössle ◽

Michael Schultheiß

Keyword(s):

Liver Transplantation ◽

Liver Cirrhosis ◽

Variceal Bleeding ◽

Hepatorenal Syndrome ◽

Beta Blockers ◽

Therapeutic Option ◽

Treatment Options ◽

Refractory Ascites ◽

Effective Therapeutic Option ◽

Intrahepatic Portosystemic Shunt

AbstractThe prognosis of patients with liver cirrhosis is impaired by complications such as variceal bleeding, ascites, hepatorenal syndrome, hepatic encephalopathy and hepatocellular carcinoma. A steadily increasing array of treatment options for these complications is available, including pharmaceutical treatment (e. g. beta blockers for varices or diuretics for ascites), endoscopic treatment (e. g. band ligation of varices), radiological interventions (e. g. transjugular shunt, transarterial chemoembolization) and liver transplantation. Most of the complications occur due to portal hypertension. Therefore, decompressive treatment by implantation of a transjugular intrahepatic portosystemic shunt (TIPS) an effective therapeutic option for many complications of liver cirrhosis. Its main indications are acute and recurrent variceal bleeding in patients with advanced disease as well as refractory ascites. The TIPS does not affect options of abdominal surgery and may therefore be used as a bridge to liver transplantation.

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