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Surgical Risk Assessment in Patients with Chronic Liver Diseases

  • Shekhar S. Jadaun
    Affiliations
    Department of Gastroenterology and Hepatology, Centre for Liver and Biliary Sciences, Max Super Speciality Hospital, Saket, New Delhi, India
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  • Sanjiv Saigal
    Correspondence
    Address for correspondence. Sanjiv Saigal MD DM MRCP CCST, Principal Director and Head, Hepatology and Liver Transplant Medicine Centre for Liver and Biliary Sciences CLBS Max Super Speciality Hospital, Saket New Delhi, 110017, India.
    Affiliations
    Department of Gastroenterology and Hepatology, Centre for Liver and Biliary Sciences, Max Super Speciality Hospital, Saket, New Delhi, India
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Published:March 22, 2022DOI:https://doi.org/10.1016/j.jceh.2022.03.004
      Chronic liver diseases (CLD) is one of the leading causes of morbidity and mortality. The overall life span of patients with CLD has increased and so is the number of surgical procedures these patients undergo. Pathophysiological and hemodynamic changes in cirrhosis make these patients more susceptible to hypotension and hypoxia during surgery. They also have a high risk of drug induced liver injury, renal dysfunction and post-operative liver decompensation. Patients with CLD planned for elective or semi-elective surgery should undergo detailed preoperative risk assessment. Patients should be evaluated for the presence of clinically significant portal hypertension and cirrhosis. In the absence of both cirrhosis and clinically significant portal hypertension, patients with CLD can undergo surgery with minimal or low risk. Various risk assessment tools available for patients with advanced CLD are—CTP score, MELD Score, Mayo risk score, VOCAL-Penn score. A Child class C and/or Mayo risk score >15 in general is associated with high risk of post-operative mortality and elective surgery should be deferred in these patients. In patients with Child class, A and MELD 10–15 surgery is permissible with caution (except liver resection and cardiac surgery) while in Child A and MELD <10 surgery is well tolerated. VOCAL-Penn score is a new promising tool and can be the better alternative of CTP, MELD, and Mayo risk score models but more prospective studies with large patients' population are warranted. Certain surgeries like Hepatic resection, intraabdominal, and cardiothoracic have higher risk than abdominal wall hernia repair and orthopedic surgery. Laparoscopic approaches have better outcomes and less risk of liver failure than open surgery. Minimally invasive alternatives like colonic stent placement in case of obstruction can be considered in high-risk cases. Perioperative optimization and management of ascites, HE, bleeding, liver decompensation, and nutrition should be done with multidisciplinary approach. Patients with cirrhosis undergoing high risk elective surgery can develop liver failure in post-operative period and should be evaluated and counseled for liver transplantation if not contraindicated.

      Keywords

      Abbreviations:

      ASA (American Society of Anaesthesiologists), CLD (Chronic liver disease), CTP (Child-Turcotte-Pugh), HCC (Hepatocellular carcinoma), HVPG (hepatic venous pressure gradient), MELD (Model for end stage liver disease), NASH (Non-alcoholic steatohepatitis), ROTEM (rotational thromboelastometry), TEG (Thromboelastography), VOCAL-Penn score (Veterans Outcomes and Costs Associated with Liver Disease-Penn score)
      Chronic liver disease (CLD) is one of the leading global causes of morbidity and mortality. In the last few decades, advances in medical management have led to increased life expectancy of patients with cirrhosis. With rising prevalence of non-alcoholic steatohepatitis (NASH), incidences of metabolic syndrome, cardiovascular diseases and bariatric procedures have also increased in cirrhotic patients. Patients with cirrhosis also have high incidence of umbilical hernias, gall stones, hepatocellular carcinoma, and cholangiocarcinoma.
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      Liver cirrhosis mortality in 187 countries between 1980 and 2010: a systematic analysis.
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      The prognostic role of hepatic venous pressure gradient in cirrhotic patients undergoing elective extrahepatic surgery.
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      • et al.
      Risk of liver and other types of cancer in patients with cirrhosis: a nationwide cohort study in Denmark.
      All these factors have led to an overall increased incidence of various surgical procedures in patients with CLD.
      • Northup P.G.
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      • Kamath P.S.
      AGA clinical practice update on surgical risk assessment and perioperative management in cirrhosis: expert review.
      Surgeries in patients with CLD have been associated with various complications like bleeding, liver decompensation, prolonged hospital stay, and delayed wound healing. Although improved surgical and medical care has led to better survival still post-operative mortality remains high (10–30%).
      • Reverter E.
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      • Albillos A.
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      The prognostic role of hepatic venous pressure gradient in cirrhotic patients undergoing elective extrahepatic surgery.
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      Patients with liver diseases need careful assessment and prognostication before any surgery. In this article, we intend to review the available literature and recent advances in the risk assessment and optimization of patients with CLD undergoing surgery.

      Pre-surgery Evaluation in a Patient Without History of Liver Disease

      A good medical history and thorough medical examination should be conducted for all patients as part of preoperative evaluation before surgery. Any past or family history of liver diseases, alcohol intake, blood transfusion, and high risk behavior are useful clues of possible liver disease. Physical examination should be conducted to look for signs of liver disease. Routine liver function test in healthy individual in the absence of risk factors for liver disease is not recommended. Persons with incidental finding of abnormal liver biochemistry usually do not have advanced liver disease and it is unlikely to affect the outcomes.
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      Committee on Standards and Practice ParametersAmerican Society of Anesthesiologists Task Force on Preanesthesia Evaluation
      Practice advisory for preanesthesia evaluation: an updated report by the American society of anesthesiologists task force on preanesthesia evaluation.

      Effects of Liver Disease on Surgery and Anesthesia

      Because of various pathophysiologic changes in CLD perioperative management and optimization is challenging in these patients.
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      • Ganger D.
      Risk stratification and preoperative evaluation of the patient with known or suspected liver disease: evaluation of Known or Suspected Liver Disease.
      Liver is affected by surgery in multiple ways depending on the type of anesthesia, surgery type, and degree of liver dysfunction. Hemodynamic alterations in cirrhosis make the liver more susceptible for hypotension and hypoxia. Drugs metabolism also get affected in CLDs because of altered cytochrome P450 metabolism, decreased plasma binding proteins, and decreased biliary excretion. Certain anesthetic agents like halothane and longer acting benzodiazepines like diazepam should be avoided while isoflurane and shorter acting lorazepam are preferable. These patients are vulnerable for poor wound healing because of hypoalbuminemia, sarcopenia, and malnutrition. The presence of thrombocytopenia and coagulopathy increase the risk of bleeding and thromboembolic complications.
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      The coagulopathy of chronic liver disease.
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      Perioperative fluid management is also difficult due to presence of edema, hyponatremia, and renal dysfunction.

      Risk Assessment

      The estimation of risk depends on degree or severity of liver disease, nature and timing of surgery, type of anesthesia, and any coexisting medical disease. The timing of surgery should be the first consideration. Risk assessment is needed for routine elective or semi-urgent surgeries. For emergency surgeries as a life saving measure risk assessment is irrelevant and not needed. However, medical caregiver and patient should have an understanding that surgery in such scenario has poor outcomes.
      • Prenner S.
      • Ganger D.
      Risk stratification and preoperative evaluation of the patient with known or suspected liver disease: evaluation of Known or Suspected Liver Disease.
      Another important step in risk assessment is to identify the presence or absence of cirrhosis. Patients with CLD and without cirrhosis usually have low or minimal risk for non-hepatic surgeries.
      • Prenner S.
      • Ganger D.
      Risk stratification and preoperative evaluation of the patient with known or suspected liver disease: evaluation of Known or Suspected Liver Disease.
      ,
      • Runyon B.A.
      Surgical procedures are well tolerated by patients with asymptomatic chronic hepatitis.
      Cirrhosis represents an advanced and irreversible stage of severe fibrosis with liver architectural distortion and regenerative nodules formation. Diagnosis of cirrhosis can be made by clinical examination for signs of decompensation, laboratory parameters, and abdominal imaging. In cirrhosis, the presence of clinically significant portal hypertension indicates altered hemodynamics and these patients have poor surgical outcomes. Markers of clinically significant portal hypertension are hepatic venous pressure gradient (HVPG) 10 or more, presence of esophageal varices, abdominal collaterals on imaging, platelet counts <1.5 lacs per mm3, splenomegaly and ascites
      • de Franchis R.
      Expanding consensus in portal hypertension: report of the Baveno VI Consensus Workshop: stratifying risk and individualizing care for portal hypertension.
      (Figure 1).
      Figure 1
      Figure 1Algorithm for surgical risk assessment in patients with chronic liver disease. CBC, Complete blood count; KFT, Kidney function test; LFT, Liver function test; PT-INR, Prothrombin Time-International normalization ratio; TEG, Thromboelastography; CSPH, clinically significant portal hypertension; CTP, Child Turcotte Pugh; MELD, Model for end stage for liver disease.

      Contraindications for Elective Surgery in Patients With Liver Disease

      Acute liver failure, alcoholic steatohepatitis, acute viral hepatitis, Child class C cirrhosis are considered absolute contraindications for routine surgeries. Along with theses, the presence of severe comorbidities like cardiomyopathy, severe left ventricular dysfunction, Hypoxemia, severe persistent coagulopathy, and American Society of Anaesthesiologists (ASA) class V are also considered as contraindication because of high morbidity and mortality.
      • Prenner S.
      • Ganger D.
      Risk stratification and preoperative evaluation of the patient with known or suspected liver disease: evaluation of Known or Suspected Liver Disease.
      ,
      • Friedman L.S.
      The risk of surgery in patients with liver disease.
      (Table 1).
      Table 1Absolute Contraindications for Elective Surgery.
      1. Acute liver failure
      2. Acute viral hepatitis
      3. Severe Alcoholic hepatitis
      4. Child-Pugh class C cirrhosis
      5. Severe coagulopathy (despite treatment)
      6. Severe comorbidities
      • Cardiomyopathy
      • Severe left ventricular dysfunction
      • Hypoxemia
      • ASA class V
      Adapted from Prenner S clinical liver disease 2016,
      • Prenner S.
      • Ganger D.
      Risk stratification and preoperative evaluation of the patient with known or suspected liver disease: evaluation of Known or Suspected Liver Disease.
      Friedman LS Hepatology 1999.
      • Friedman L.S.
      The risk of surgery in patients with liver disease.

      Risk Predictor Tools

      In cirrhosis, post-operative outcomes are mainly driven by degree of liver dysfunction. Various score models used for cirrhosis staging and prognostication are also useful to predict mortality after surgery. In the past, Child-Turcotte-Pugh (CTP) score has been the main method of risk assessment in patients with CLD. However, recent studies have shown that newer methods like Model for end stage liver disease (MELD) score, Mayo risk score, and recently added VOCAL-Penn model may be better predictors of risk associated with surgery. Other recently added tools are measures for the degree of portal hypertension like liver stiffness measurements and HVPG measurements (Table 2).
      Table 2Surgical Risk Assessment Scores in Patients With CLD.
      Risk ScoreComponents
      1Child Turcotte Pugh ScoreBilirubin, Ascites, Hepatic encephalopathy, Prothrombin time, Serum Albumin
      2MELD ScoreProthrombin time/INR, Creatinine, Bilirubin
      3Mayo Surgical Risk ScoreMELD score, Age, Etiology of cirrhosis, ASA class
      4VOCAL-Penn ScoreAge, Serum albumin, Platelet count, Bilirubin, Surgery category, Emergency indication, Fatty liver disease, ASA Class, Obesity
      ASA class, American Society of Anesthesiologists class; CTP, Child Turcotte Pugh; MELD, Model for end stage liver disease.

      CTP Score

      Various studies have shown in the past that Child classification is one of the best predictors of mortality in patients with cirrhosis. It has been the main tool used before the advent of MELD score.
      • Neeff H.
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      • Spangenberg H.-C.
      • Hopt U.T.
      • Makowiec F.
      Perioperative mortality after non-hepatic general surgery in patients with liver cirrhosis: an analysis of 138 operations in the 2000s using Child and MELD scores.
      In a study of 90 patients with cirrhosis who underwent abdominal surgery, mortality in Child's class A patients was 10%, 30% in class B, and 82% in class C patients.
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      • Watson W.
      • Shayani V.
      • Pickleman J.
      Abdominal operations in patients with cirrhosis: still a major surgical challenge.
      Almost similar mortality was reported in another study of 100 patients.
      • Garrison R.N.
      • Cryer H.M.
      • Howard D.A.
      • Polk H.C.
      Clarification of risk factors for abdominal operations in patients with hepatic cirrhosis.
      Based on these studies patients in Child A group usually cleared for surgery while for those in Child C class elective surgery is contraindicated. However, newer studies point to less correlation between Child class and surgery outcomes.
      • Telem D.A.
      • Schiano T.
      • Goldstone R.
      • et al.
      Factors that predict outcome of abdominal operations in patients with advanced cirrhosis.
      Ascites and hepatic encephalopathy (HE) components of CTP score are more subjective in nature making risk assessment prone to errors. MELD has replaced CTP score as a preferred method for surgical risk assessment in patients with liver cirrhosis. However, in patients with severe portal hypertension and relatively preserved synthetic functions of liver CTP score may be a better marker than MELD.
      • Northup P.G.
      • Friedman L.S.
      • Kamath P.S.
      AGA clinical practice update on surgical risk assessment and perioperative management in cirrhosis: expert review.
      The presence of severe ascites alone even with relatively low MELD score also portends poor surgical outcomes in cirrhosis.
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      Morbidity and mortality in cirrhotic patients undergoing anesthesia and surgery.
      (Table 3).
      Table 3Postoperative Mortality After Non-Hepatic Surgery.
      Child Turcotte Pugh ClassPost operative mortality
      A10%
      B17–31%
      C63–82%
      Adapted from Neeff H et al, journal of gastrointestinal surgery 2011,
      • Neeff H.
      • Mariaskin D.
      • Spangenberg H.-C.
      • Hopt U.T.
      • Makowiec F.
      Perioperative mortality after non-hepatic general surgery in patients with liver cirrhosis: an analysis of 138 operations in the 2000s using Child and MELD scores.
      Mansour A et al, Surgery 1997,
      • Mansour A.
      • Watson W.
      • Shayani V.
      • Pickleman J.
      Abdominal operations in patients with cirrhosis: still a major surgical challenge.
      Garrison RN et al, Ann Surg 1984.
      • Garrison R.N.
      • Cryer H.M.
      • Howard D.A.
      • Polk H.C.
      Clarification of risk factors for abdominal operations in patients with hepatic cirrhosis.

      MELD Score

      MELD score is computed by using serum bilirubin, international normalization ratio (INR), and serum creatinine level. Although initially developed to predict survival in patients undergoing trans jugular intrahepatic portosystemic shunt (TIPSS), MELD score now primarily being used for organ allocation in liver transplant and predicting the prognosis of patients with cirrhosis in general.
      • Kamath P.S.
      • Kim W.R.
      The model for end-stage liver disease (MELD).
      ,
      • Malinchoc M.
      • Kamath P.S.
      • Gordon F.D.
      • Peine C.J.
      • Rank J.
      • ter Borg P.C.
      A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts.
      MELD score is also excellent for risk prediction in patients undergoing non-transplant surgeries. MELD has replaced CTP score as preferred method for risk assessment based on many studies showing MELD on par with or better then CTP score.
      • Befeler A.S.
      • Palmer D.E.
      • Hoffman M.
      • Longo W.
      • Solomon H.
      • Di Bisceglie A.M.
      The safety of intra-abdominal surgery in patients with cirrhosis: model for end-stage liver disease score is superior to child-turcotte-pugh classification in predicting outcome.
      In patients with CLD undergoing surgery MELD score was superior to CTP score in outcome prediction in a small study of 53 patients. A MELD score of >14 was predictor of very high risk for abdominal surgery.
      • Befeler A.S.
      • Palmer D.E.
      • Hoffman M.
      • Longo W.
      • Solomon H.
      • Di Bisceglie A.M.
      The safety of intra-abdominal surgery in patients with cirrhosis: model for end-stage liver disease score is superior to child-turcotte-pugh classification in predicting outcome.
      Many other studies have reported MELD as a better marker than Child Pugh class.
      • Telem D.A.
      • Schiano T.
      • Goldstone R.
      • et al.
      Factors that predict outcome of abdominal operations in patients with advanced cirrhosis.
      ,
      • Perkins L.
      • Jeffries M.
      • Patel T.
      Utility of preoperative scores for predicting morbidity after cholecystectomy in patients with cirrhosis.
      • Farnsworth N.
      • Fagan S.P.
      • Berger D.H.
      • Awad S.S.
      Child-Turcotte-Pugh versus MELD score as a predictor of outcome after elective and emergent surgery in cirrhotic patients.
      • Cucchetti A.
      • Ercolani G.
      • Vivarelli M.
      • et al.
      Impact of model for end-stage liver disease (MELD) score on prognosis after hepatectomy for hepatocellular carcinoma on cirrhosis.
      Based on these studies, in a patient with CLD undergoing elective surgery MELD score of <10 seems safe and score of >15 is a contraindication, while for a patient with MELD 10–15, elective surgery can be consider with caution.
      • Hickman L.
      • Tanner L.
      • Christein J.
      • Vickers S.
      Non-hepatic abdominal surgery in patients with cirrhotic liver disease.
      ,
      • Hanje A.J.
      • Patel T.
      Preoperative evaluation of patients with liver disease.
      Relatively newer MELD-Na score has not been studied much and risk threshold for post operative mortality is not well defined currently.
      • Godfrey E.L.
      • Kueht M.L.
      • Rana A.
      • Awad S.
      MELD-Na (the new MELD) and peri-operative outcomes in emergency surgery.
      (Table 4).
      Table 4Mortality in Cirrhosis at 1 month and 3 months Post-surgery- Comparison of CTP and MELD Scores.
      Scores1 month mortality (%)3 months mortality (%)
      Child Class A1515
      Child Class B932
      Child Class C6060
      MELD ≤888
      MELD 9-161033
      MELD ≥175757
      MELD ≥269090
      CTP Score - Child Turcotte Pugh score, MELD Score- Model for end stage liver disease score.
      Adapted from N. Fransworth et al, American journal of surgery 2004,
      • Farnsworth N.
      • Fagan S.P.
      • Berger D.H.
      • Awad S.S.
      Child-Turcotte-Pugh versus MELD score as a predictor of outcome after elective and emergent surgery in cirrhotic patients.
      Teh SH et al gastroenterology 2007.
      • Teh S.H.
      • Nagorney D.M.
      • Stevens S.R.
      • et al.
      Risk factors for mortality after surgery in patients with cirrhosis.

      Mayo Post-operative Surgical Risk Score

      Mayo risk score is based on MELD score, age, etiology of cirrhosis and ASA class.
      • Teh S.H.
      • Nagorney D.M.
      • Stevens S.R.
      • et al.
      Risk factors for mortality after surgery in patients with cirrhosis.
      Mayo risk score was the best predictor of mortality at 1 month and 3 months in a large study involving patients with cirrhosis who underwent major cardiac and abdominal surgeries. In this study, mortality increased with increasing MELD score, age, and ASA class. Based on this study results, Mayo risk score was developed.
      • Teh S.H.
      • Nagorney D.M.
      • Stevens S.R.
      • et al.
      Risk factors for mortality after surgery in patients with cirrhosis.
      The addition of age and ASA class increases its predictive value and accuracy.
      • Northup P.G.
      • Friedman L.S.
      • Kamath P.S.
      AGA clinical practice update on surgical risk assessment and perioperative management in cirrhosis: expert review.
      The score calculation and estimation of post-surgery mortality can be easily done by online available calculator.

      Post-operative Mortality Risk in Patients with Cirrhosis - Medical Professionals - Mayo Clinic [Internet]. [cited 2021 Oct 7]. Available from: https://www.mayoclinic.org/medical-professionals/transplant-medicine/calculators/post-operative-mortality-risk-in-patients-with-cirrhosis/itt-20434721.

      Although initial studies reported good corelation with post-operative mortality, recent evidences suggest that it may overestimate the surgical risk in patients with cirrhosis, as advancement in medical and surgical management have led to an overall improved outcome.
      • Mahmud N.
      • Fricker Z.
      • Hubbard R.A.
      • et al.
      Risk prediction models for post-operative mortality in patients with cirrhosis.

      VOCAL-Penn Score

      CTP, MELD, and Mayo risk scores although good tools but do not include type of surgery and can overestimate risk in patients undergoing minor or minimally invasive surgeries. Veterans Outcomes and Costs Associated with Liver Disease (VOCAL)-Penn score is the most recent scoring method for preoperative risk assessment in patients with cirrhosis. VOCAL-Penn score model was derived in a multicentre retrospective cohort study of 3785 cirrhosis patients. This online available risk calculator includes nine variables like age, serum albumin, platelet count, serum bilirubin, surgery category, emergency indication, fatty liver disease, ASA classification, and obesity. Interestingly obesity was protective against death following surgery in this study which may be due to the better nutritional reserve. Score predicts risk of death at 1-, 3- and 6-months post-surgery. Authors reported that VOCAL-Penn model was superior to other risk scores like MELD, MELD-Na, CTP, and Mayo post-operative surgical risk score at all timepoints.
      • Mahmud N.
      • Fricker Z.
      • Hubbard R.A.
      • et al.
      Risk prediction models for post-operative mortality in patients with cirrhosis.
      One of the drawbacks of study was that patient's population mainly include early cirrhosis patients with >80% cases belonging to Child Pugh class A. VOCAL-Penn model has also been validated recently in external independent cohorts. VOCAL-Penn model had the highest discrimination for 90 days post-operative mortality and best predictive performance compare to MELD, MELD-Na and Mayo risk score.
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      • Fricker Z.
      • Panchal S.
      • Lewis J.D.
      • Goldberg D.S.
      • Kaplan D.E.
      External validation of the VOCAL-penn cirrhosis surgical risk score in 2 large, independent health systems.
      This new model seems promising and can potentially replace older models like MELD, CTP, and Mayo score for surgical risk assessment in cirrhosis.

      HVPG Measurement

      In a recently published study of 140 patients with cirrhosis who underwent major extrahepatic surgery HVPG, ASA class and high risk surgery were prognostic factor for mortality at 1 year. A value of >16 HVPG was the independent risk factor for mortality, while HVPG >20 was associated with very high mortality. Patients with HVPG <10 did not have decompensation in post-operative period. Study involved the patients undergoing elective surgeries only. HVPG measurement before surgery although cumbersome can be considered for prognostication in selected patients who do not have obvious clinical signs of portal hypertension.

      Risk in Various Surgeries

      Type of surgery cirrhosis patient undergo also affect the post-operative outcomes. Abdominal wall surgeries, minimally invasive surgeries have less mortality compared to intraabdominal and cardiothoracic surgeries. In a retrospective study, major intrabdominal surgeries and cardiovascular surgeries had eight and four times increased mortality respectively in comparison to orthopedic surgeries.
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      • Serper M.
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      • Rothstein K.D.
      • Goldberg D.S.
      In-Hospital mortality varies by procedure type among cirrhosis surgery admissions.

      Hepatic Resection Surgeries

      Liver resection is usually considered in patients with primary hepatic malignancies. The risk of liver decompensation is especially high following liver resection in cirrhosis because functioning liver volume is further reduced in an already compromised liver.
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      • Graf R.
      Strategies for safer liver surgery and partial liver transplantation.
      Liver resection in patients with cirrhosis used to be a contraindication but in recent times mortality has reduced significantly (3–16%) mainly because of improved perioperative medical management and surgical techniques.
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      • et al.
      Liver failure after partial hepatic resection: definition, pathophysiology, risk factors and treatment.
      ,
      Safe cut-off for remanent liver is considered 40% and 20% for cirrhotic and noncirrhotic patients, respectively.
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      • Aloia T.A.
      Surgical resection for hepatocellular carcinoma.
      Liver failure after surgical resection is associated with poor outcomes and high mortality (60%).
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      • et al.
      Liver failure after partial hepatic resection: definition, pathophysiology, risk factors and treatment.
      The presence of clinical significant portal hypertension, high liver stiffness (>22kpa) and >30% liver steatosis are risk factors for post resection liver failure.
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      • Coilly A.
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      ,
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      • Furrer K.
      • Clavien P.-A.
      Hepatic steatosis is a risk factor for postoperative complications after major hepatectomy: a matched case-control study.
      MELD and CTP score although not considered very accurate, can be used for risk prediction. A MELD score of <9 indicate a very low risk of decompensation after surgical resection.
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      • Donohue J.
      • et al.
      Hepatic resection of hepatocellular carcinoma in patients with cirrhosis: model of end-stage liver disease (MELD) score predicts perioperative mortality.
      In a study of 587 patients, CTP and ASA score were better predictors of mortality than MELD score.
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      Predictive indices of morbidity and mortality after liver resection.

      Cardiac Surgery

      Cardiovascular diseases are common in patients with cirrhosis due to the increasing prevalence of metabolic syndrome and NASH. Major cardiac surgeries have a high risk of post-operative liver failure with mortality reaching up to 70% in Child class C.
      • Modi A.
      • Vohra H.A.
      • Barlow C.W.
      Do patients with liver cirrhosis undergoing cardiac surgery have acceptable outcomes?.
      CTP score has been used for risk stratification in these patients and Child class A patients usually have acceptable outcomes (5% mortality). Reported overall mortality is about 17% in major cardiac surgery.
      • Modi A.
      • Vohra H.A.
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      Do patients with liver cirrhosis undergoing cardiac surgery have acceptable outcomes?.
      A modified MELD (MELD XI) score excluding INR has been used in these patients as INR can be elevated due to anticoagulants use. MELD score of 13.5 or more or Child class B and C usually considered a contraindication for major cardiac surgeries.
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      The use of nonpulsatile cardiopulmonary bypass, total time of cardiopulmonary bypass, and need for vasopressor medicines increases the risk of liver decompensation after cardiac surgery. The need of anticoagulants in post-operative periods further complicates the clinical scenario.
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      Case 3-1995. Three patients requiring both coronary artery bypass surgery and orthotopic liver transplantation.
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      The use of blood products to manage bleeding or coagulopathy correction should be guided by viscoelastic tests like Thromboelastography (TEG) or rotational thromboelastometry (ROTEM).
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      • Reuben A.
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      In advance cirrhosis, minimally invasive alternatives like angioplasty, valvuloplasty, and transcatheter aortic valve replacement should be preferred whenever possible.
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      In carefully selected patients, cardiac surgery followed by liver transplantation or rarely liver transplant before cardiac surgery has been reported but experience is very limited.
      • Morris J.J.
      • Hellman C.L.
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      • et al.
      Case 3-1995. Three patients requiring both coronary artery bypass surgery and orthotopic liver transplantation.
      ,
      • Peeraphatdit T.B.
      • Nkomo V.T.
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      • et al.
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      ,
      • Gaudino M.
      • Santarelli P.
      • Bruno P.
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      Coronary angiography and cardiac catheterization appear safe in patients with cirrhosis.
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      AGA clinical practice update on surgical risk assessment and perioperative management in cirrhosis: expert review.

      Bariatric Surgeries

      Before consideration for bariatric surgery, patients should be evaluated for the presence of clinically significant portal hypertension by imaging and endoscopy for varices. Elastography and HVPG measurement are also useful.
      • Northup P.G.
      • Friedman L.S.
      • Kamath P.S.
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      ,
      • Patton H.
      • Heimbach J.
      • McCullough A.
      AGA clinical practice update on bariatric surgery in cirrhosis: expert review.
      There is lack of studies regarding risk stratification in these patients. Although, sleeve gastrectomy is well tolerated in compensated cirrhosis patients but should be avoided in the presence of clinical significant portal hypertension or decompensated cirrhosis.
      • Hanipah Z.N.
      • Punchai S.
      • McCullough A.
      • et al.
      Bariatric surgery in patients with cirrhosis and portal hypertension.
      Cirrhosis detected incidentally during bariatric surgery has about 3.2% mortality.
      • Brolin R.E.
      • Bradley L.J.
      • Taliwal R.V.
      Unsuspected cirrhosis discovered during elective obesity operations.
      Liver transplantation combined with bariatric surgery has also been done in advanced cirrhosis and experience is although limited but encouraging. This combined approach can be consider in selected patients at a centre with experience and may be helpful in preventing the recurrence of NASH in liver allograft organ.
      • Diwan T.S.
      • Rice T.C.
      • Heimbach J.K.
      • Schauer D.P.
      Liver transplantation and bariatric surgery: timing and outcomes.
      • Heimbach J.K.
      • Watt K.D.S.
      • Poterucha J.J.
      • et al.
      Combined liver transplantation and gastric sleeve resection for patients with medically complicated obesity and end-stage liver disease.
      • Zamora-Valdes D.
      • Watt K.D.
      • Kellogg T.A.
      • et al.
      Long-term outcomes of patients undergoing simultaneous liver transplantation and sleeve gastrectomy.
      Combining Roux-en-Y gastric bypass with sleeve gastrectomy may cause significant malabsorption and erratic absorption of immunosuppressive medicines, also doing ERCP in these patients will be difficult if need arises.
      • Northup P.G.
      • Friedman L.S.
      • Kamath P.S.
      AGA clinical practice update on surgical risk assessment and perioperative management in cirrhosis: expert review.
      Endoscopic bariatric procedures in the presence of clinically significant portal hypertension should be avoided.
      • Patton H.
      • Heimbach J.
      • McCullough A.
      AGA clinical practice update on bariatric surgery in cirrhosis: expert review.

      Intraabdominal and Abdominal Wall Surgeries

      Colorectal surgeries are associated with high morbidity with reported mortality up to 26% in patients with cirrhosis.
      • Bhangui P.
      • Laurent A.
      • Amathieu R.
      • Azoulay D.
      Assessment of risk for non-hepatic surgery in cirrhotic patients.
      ,
      • Meunier K.
      • Mucci S.
      • Quentin V.
      • Azoulay R.
      • Arnaud J.P.
      • Hamy A.
      Colorectal surgery in cirrhotic patients: assessment of operative morbidity and mortality.
      Laparoscopic approaches have better outcomes and less risk of liver failure than open surgery.
      • Hickman L.
      • Tanner L.
      • Christein J.
      • Vickers S.
      Non-hepatic abdominal surgery in patients with cirrhotic liver disease.
      ,
      • Kazi A.
      • Finco T.B.
      • Zakhary B.
      • et al.
      Acute colonic diverticulitis and cirrhosis: outcomes of laparoscopic colectomy compared with an open approach.
      Minimally invasive alternatives like colonic stent placement in case of obstruction can be considered in high risk cases.
      On the contrary, elective abdominal wall surgeries like umbilical hernia repair is safer with acceptable risk even in Child class C patients.
      • Eker H.H.
      • van Ramshorst G.H.
      • de Goede B.
      • et al.
      A prospective study on elective umbilical hernia repair in patients with liver cirrhosis and ascites.
      One study reported advance age (>65), Higher MELD (>15), low serum albumin (<3 gm/dl), massive ascites, and presence of esophageal varices as predictors of poor outcome.
      • Cho S.W.
      • Bhayani N.
      • Newell P.
      • et al.
      Umbilical hernia repair in patients with signs of portal hypertension: surgical outcome and predictors of mortality.
      Emergency hernia repair due to complications like rupture or incarceration has high mortality. Ascites should be controlled aggressively in post-operative period.
      • Prenner S.
      • Ganger D.
      Risk stratification and preoperative evaluation of the patient with known or suspected liver disease: evaluation of Known or Suspected Liver Disease.
      In a small study, patients who presented with hernia rupture, preoperative TIPSS placement followed by surgery lead to better control of ascites and improved post-operative outcome.
      • Telem D.A.
      • Schiano T.
      • Divino C.M.
      Complicated hernia presentation in patients with advanced cirrhosis and refractory ascites: management and outcome.
      However, the use of TIPSS before abdominal surgeries other than hernia repair has not been proved useful.
      • Vinet E.
      • Perreault P.
      • Bouchard L.
      • et al.
      Transjugular intrahepatic portosystemic shunt before abdominal surgery in cirrhotic patients: a retrospective, comparative study.

      Cholecystectomy

      The prevalence of gall stone disease is higher in cirrhosis patients and increases with severity of disease.
      • Mallick B.
      • Anand A.C.
      Gallstone disease in cirrhosis—pathogenesis and management.
      Elective cholecystectomy should be avoided in patients with cirrhosis if they are candidate for liver transplantation. Cholecystectomy has high risk of mortality in Child class C patients especially with refractory ascites and these patients should preferably manage conservatively. Per cutaneous cholecystostomy also associated with complications in the presence of massive ascites and coagulopathy. Less invasive procedure like trans papillary gall bladder drainage can be consider if expertise is available.
      • Itoi T.
      • Coelho-Prabhu N.
      • Baron T.H.
      Endoscopic gallbladder drainage for management of acute cholecystitis.
      Laparoscopic cholecystectomy is preferable and safer approach over open cholecystectomy although it also has higher complications in cirrhosis than patients without cirrhosis.
      • Chmielecki D.K.
      • Hagopian E.J.
      • Kuo Y.
      • Kuo Y.
      • Davis J.M.
      Laparoscopic cholecystectomy is the preferred approach in cirrhosis: a nationwide, population-based study.
      • Poggio J.L.
      • Rowland C.M.
      • Gores G.J.
      • Nagorney D.M.
      • Donohue J.H.
      A comparison of laparoscopic and open cholecystectomy in patients with compensated cirrhosis and symptomatic gallstone disease.
      • de Goede B.
      • Klitsie P.J.
      • Hagen S.M.
      • et al.
      Meta-analysis of laparoscopic versus open cholecystectomy for patients with liver cirrhosis and symptomatic cholecystolithiasis.
      • Laurence J.M.
      • Tran P.D.
      • Richardson A.J.
      • Pleass H.C.C.
      • Lam V.W.T.
      Laparoscopic or open cholecystectomy in cirrhosis: a systematic review of outcomes and meta-analysis of randomized trials.
      MELD and CTP score are useful for post-operative mortality prediction in these patients but corelate poorly with the risk of surgical complications.
      • Bingener J.
      • Cox D.
      • Michalek J.
      • Mejia A.
      Can the MELD score predict perioperative morbidity for patients with liver cirrhosis undergoing laparoscopic cholecystectomy?.

      Patients with Chronic Liver Disease Who Have Low or Minimal Risk

      Patients with asymptomatic CLD and without clinically significant portal hypertension or cirrhosis in general tolerate surgeries well. Extrahepatic surgery in these patients usually do not have major complications.
      • Runyon B.A.
      Surgical procedures are well tolerated by patients with asymptomatic chronic hepatitis.
      Patients with NASH with moderate to severe steatosis have high mortality post hepatic resection but do not have increased mortality in non-hepatic surgeries. In a retrospective study involving 102 patients with steatohepatitis and 72 patients with simple steatosis (>33%), post-operative morbidity and mortality was seen only in patient with NASH but not in patients with only steatosis.
      • McCormack L.
      • Petrowsky H.
      • Jochum W.
      • Furrer K.
      • Clavien P.-A.
      Hepatic steatosis is a risk factor for postoperative complications after major hepatectomy: a matched case-control study.
      ,
      • Reddy S.K.
      • Marsh J.W.
      • Varley P.R.
      • et al.
      Underlying steatohepatitis, but not simple hepatic steatosis, increases morbidity after liver resection: a case-control study.
      In contrast, patients with alcoholic steatohepatitis (ASH) have high perioperative mortality and surgery is contraindicated unless lifesaving.
      Alcoholic liver disease: morphological manifestations. Review by an international group.
      Autoimmune hepatitis patients and without any decompensation can undergo elective surgeries with acceptable outcomes. Patients on oral steroid should be given hydrocortisone in perioperative period. Patients with hemochromatosis in the absence of significant cardiac dysfunction or liver decompensation have low post-surgery mortality.
      • Farrell F.J.
      • Nguyen M.
      • Woodley S.
      • et al.
      Outcome of liver transplantation in patients with hemochromatosis.

      Preoperative Optimization

      All patients with CLD should undergo detailed preoperative clinical and laboratory assessment and optimization before elective or semi-elective surgery.
      • Im G.Y.
      • Lubezky N.
      • Facciuto M.E.
      • Schiano T.D.
      Surgery in patients with portal hypertension: a preoperative checklist and strategies for attenuating risk.
      (Table 5) A multidisciplinary approach should be adopted with involvement of medical, surgical, and anesthesia teams from the beginning. Various issues like ascites, coagulopathy, variceal bleeding risk, hepatic encephalopathy, and dyselectrolytemia should be treated and optimized before the planned surgery. The evaluation and management of non-hepatic comorbidities like renal dysfunction, cardiovascular disease should also be done. Elective and semi-elective surgeries can be delayed till these issues are managed or optimized.
      Table 5Check List for Preoperative Assessment in Cirrhosis.
      1. Surgery Indication—Emergency/Elective
      2. Type of Surgery—Cardiac/colorectal/abdominal wall/Orthopedic
      3. Liver disease—Etiology, duration, severity, cirrhosis
      4. Clinically significant portal hypertension—Present/absent
      5. Hepatic decompensation—Past and present
      6. Co-morbid conditions—Present/Absent
      7. Nutrition- Malnutrition/Sarcopenia
      8. Blood investigations—LFT, INR, platelet count, creatinine
      9. Liver imaging—Cirrhosis, Ascites, Portosystemic collaterals
      10. UGIE for varices-Prophylactic Banding if high risk varices and post-surgery anticoagulation needed
      11. Calculate risk score CTP, MELD, Mayo risk score/VOCAL Penn score

      Coagulopathy

      Patients with cirrhosis commonly have thrombocytopenia and increased prothrombin time. Despite having raised prothrombin time, cirrhosis is a state of rebalanced hemostasis.
      • Tripodi A.
      • Mannucci P.M.
      The coagulopathy of chronic liver disease.
      ,
      • Seaman C.D.
      • Ragni M.V.
      Coagulopathy in cirrhosis.
      The prophylactic transfusion of blood products is not recommended and viscoelastic tests for global measure of clot formation provide better assessment.
      • O'Leary J.G.
      • Greenberg C.S.
      • Patton H.M.
      • Caldwell S.H.
      AGA clinical practice update: coagulation in cirrhosis.
      ,
      • De Pietri L.
      • Bianchini M.
      • Montalti R.
      • et al.
      Thrombelastography-guided blood product use before invasive procedures in cirrhosis with severe coagulopathy: a randomized, controlled trial.
      In patients with severe thrombocytopenia, the use of newer oral thrombopoietin agonists Avatrombopag and Lusutrombopag before planned invasive procedures has been approved by FDA.
      • O'Leary J.G.
      • Greenberg C.S.
      • Patton H.M.
      • Caldwell S.H.
      AGA clinical practice update: coagulation in cirrhosis.
      ,
      • Samama C.M.
      • Djoudi R.
      • Lecompte T.
      • Nathan-Denizot N.
      • Schved J.-F.
      Agence Française de Sécurité Sanitaire des Produits de Santé expert group. Perioperative platelet transfusion: recommendations of the Agence Française de Sécurité Sanitaire des Produits de Santé (AFSSaPS) 2003.
      ,
      • Terrault N.
      • Chen Y.-C.
      • Izumi N.
      • et al.
      Avatrombopag before procedures reduces need for platelet transfusion in patients with chronic liver disease and thrombocytopenia.

      Portal Hypertension and Variceal Bleed

      Volume overload should be avoided in patients with varices and central venous pressure should be kept on lower site to decrease the risk of bleeding. Patients who are likely to be put on anticoagulant therapy post-surgery as in cardiovascular surgeries, should undergo prophylactic variceal banding weeks before surgery.
      • Li Z.
      • Sun Y.-M.
      • Wu F.-X.
      • Yang L.-Q.
      • Lu Z.-J.
      • Yu W.-F.
      Controlled low central venous pressure reduces blood loss and transfusion requirements in hepatectomy.
      The placement of TIPSS before surgery has been done in patients with severe portal hypertension. By improving the portal hypertension TIPSS may decrease the post-operative complications and mortality. In a study involving 25 patients with cirrhosis with Mean MELD 15(SD ± 7.6) and 1/4th patients in Child class C, preoperative TIPSS placement was done about 3 weeks before surgery. Actuarial 1 year survival was 74% and early in-hospital mortality only occurred in patients who had MELD > 25 and underwent emergency surgery.
      • Vinet E.
      • Perreault P.
      • Bouchard L.
      • et al.
      Transjugular intrahepatic portosystemic shunt before abdominal surgery in cirrhotic patients: a retrospective, comparative study.
      TIPSS placement can make feasible an otherwise contraindicated surgery in advanced cirrhosis and can be considered in selected patients with refractory ascites, severe portal hypertension and high risk of variceal bleeding.

      Ascites

      Ascites can lead to compromised lung function and raised risk of aspiration. The presence of ascites also increases the risk of abdominal wall hernia and wound dehiscence and should be treated aggressively before surgery. TIPSS can also be considered in selected cases.
      • Northup P.G.
      • Friedman L.S.
      • Kamath P.S.
      AGA clinical practice update on surgical risk assessment and perioperative management in cirrhosis: expert review.
      ,
      • Prenner S.
      • Ganger D.
      Risk stratification and preoperative evaluation of the patient with known or suspected liver disease: evaluation of Known or Suspected Liver Disease.
      ,
      • Telem D.A.
      • Schiano T.
      • Divino C.M.
      Complicated hernia presentation in patients with advanced cirrhosis and refractory ascites: management and outcome.

      Liver Transplantation

      Patients with cirrhosis undergoing surgery with anticipated substantial risk must be counseled regarding need for rescue liver transplantation in post-operative period. Ideally all patients with cirrhosis should undergo preoperative liver transplant evaluation if MELD is > 15 or >15% post-surgery mortality risk unless liver transplantation is contraindicated.
      • Northup P.G.
      • Friedman L.S.
      • Kamath P.S.
      AGA clinical practice update on surgical risk assessment and perioperative management in cirrhosis: expert review.
      ,
      • Northup P.G.
      • Wanamaker R.C.
      • Lee V.D.
      • Adams R.B.
      • Berg C.L.
      Model for end-stage liver disease (MELD) predicts nontransplant surgical mortality in patients with cirrhosis.
      In conclusion, patients with advanced CLD have high risk of morbidity and mortality after surgery. CTP score, MELD, Mayo risk score, and VOCAL-Penn score are helpful in mortality risk assessment. A comprehensive, individualized, and multidisciplinary approach should be adopted for preoperative risk assessment as well as perioperative management. Recently introduced VOCAL-Penn score can be the better alternative of older risk scores models but more prospective studies with larger study population are needed.

      Credit authorship contribution statement

      Shekhar S. Jadaun, Writing – original draft; Sanjiv Saigal, Writing – review & editing.

      Conflicts of interest

      None of the authors have any financial, professional or personal conflicts that are relevant to the manuscript.

      Acknowledgment

      The authors would like to thank Ms Nishu Pundir for help in figures and tables.

      Funding

      No grant or financial support was taken for this research.

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