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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.
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.
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.
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%).
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.
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.
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.
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.
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.
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
Expanding consensus in portal hypertension: report of the Baveno VI Consensus Workshop: stratifying risk and individualizing care for portal hypertension.
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.
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 Score
Components
1
Child Turcotte Pugh Score
Bilirubin, Ascites, Hepatic encephalopathy, Prothrombin time, Serum Albumin
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
The presence of clinical significant portal hypertension, high liver stiffness (>22kpa) and >30% liver steatosis are risk factors for post resection liver failure.
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.
Hepatic resection of hepatocellular carcinoma in patients with cirrhosis: model of end-stage liver disease (MELD) score predicts perioperative mortality.
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.
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.
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.
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.
The use of blood products to manage bleeding or coagulopathy correction should be guided by viscoelastic tests like Thromboelastography (TEG) or rotational thromboelastometry (ROTEM).
Usefulness of international normalized ratio to predict bleeding complications in patients with end-stage liver disease who undergo cardiac catheterization.
In advance cirrhosis, minimally invasive alternatives like angioplasty, valvuloplasty, and transcatheter aortic valve replacement should be preferred whenever possible.
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.
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.
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.
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.
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.
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.
Emergency hernia repair due to complications like rupture or incarceration has high mortality. Ascites should be controlled aggressively in post-operative period.
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.
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.
Laparoscopic cholecystectomy is preferable and safer approach over open cholecystectomy although it also has higher complications in cirrhosis than patients without cirrhosis.
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.
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.
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.
All patients with CLD should undergo detailed preoperative clinical and laboratory assessment and optimization before elective or semi-elective surgery.
(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
Patients with cirrhosis commonly have thrombocytopenia and increased prothrombin time. Despite having raised prothrombin time, cirrhosis is a state of rebalanced hemostasis.
The prophylactic transfusion of blood products is not recommended and viscoelastic tests for global measure of clot formation provide better assessment.
In patients with severe thrombocytopenia, the use of newer oral thrombopoietin agonists Avatrombopag and Lusutrombopag before planned invasive procedures has been approved by FDA.
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.
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.
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.
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.
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.
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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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.
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.
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Hepatic resection of hepatocellular carcinoma in patients with cirrhosis: model of end-stage liver disease (MELD) score predicts perioperative mortality.
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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.
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