INTRODUCTION — Patients with liver disease who require surgery are at greater risk for surgical and anesthesia related complications than those with a healthy liver [1-4]. The magnitude of the risk depends upon the type of liver disease and its severity, the surgical procedure, and the type of anesthesia.
The assessment of surgical risk in patients with liver disease will be reviewed here. Patients with liver disease may have concomitant disorders (such as cardiovascular disease) that influence surgical outcomes; these issues are discussed separately. (See "Preoperative medical evaluation of the healthy patient" and "Estimation of cardiac risk prior to noncardiac surgery".)
SCREENING FOR LIVER DISEASE BEFORE SURGERY — Patients undergoing surgery should undergo a history and physical examination to exclude findings or risk factors for liver disease. This may include asking about prior blood transfusions, tattoos, illicit drug use, sexual promiscuity, a family history of jaundice or liver disease, a history of jaundice or fever following anesthesia, alcohol use (current, prior and quantity), and a complete review of current medications. Clinical features suggestive of liver disease (such as fatigue, pruritus, increased abdominal girth, jaundice, palmar erythema, spider telangiectasias, splenomegaly, and gynecomastia and testicular atrophy in men) should be evaluated.
Whether otherwise healthy surgical candidates should undergo biochemical screening for liver disease is controversial. The vast majority of patients found to have abnormal liver biochemical test results do not have advanced liver disease. Thus, it is unlikely that routinely obtaining a liver biochemical profile in otherwise healthy patients without risk factors for liver disease would lead to improved outcomes; thus, such testing is not recommended. (See "Preoperative medical evaluation of the healthy patient".)
EFFECTS OF ANESTHESIA AND SURGERY ON THE LIVER — The effects of anesthesia and surgery on the liver depend upon the type of anesthesia used, the specific surgical procedures, and the severity of liver disease. In addition, perioperative events, such as hypotension, sepsis, or the administration of hepatotoxic drugs, can compound injury to the liver occurring during the procedure. (See "Effects of anesthesia and surgery on the liver".)
ESTIMATING SURGICAL RISK — Assessment of surgical risk in patients with liver disease includes an appraisal of the severity of liver disease, the urgency of surgery (and alternatives to surgery), and coexisting medical illness. Surgical risk assessment is less relevant if immediate surgery is required to prevent death. On the other hand, the vast majority of decisions are made in the setting of semi-urgent or elective procedures for which there is time for risk assessment, optimization of the patient's medical status, and consideration of alternative approaches.
The majority of studies examining the risk of surgery in patients with liver disease have focused on patients with cirrhosis from which a number of risk factors have been identified (table 1) [5-17]. Much less information has been published on the risk of surgery in patients with milder forms of liver disease. The available evidence is derived mostly from small retrospective studies and clinical experience. Furthermore, many of the studies were published prior to the availability of a number of serologic tests for specific types of liver disease, and modern hepatobiliary imaging. Thus, there is relatively little information on the risk of surgery in patients with specific types of liver disease.
Patients in whom surgery is contraindicated — A number of settings have been identified that are associated with unacceptable surgical mortality. As a result, these conditions are usually considered to be contraindications to elective surgery (table 2).
Acute or fulminant hepatitis — Acute hepatitis is a contraindication to elective surgery. This recommendation is based upon older studies, in which operative mortality rates of 10 to 13 percent were reported among icteric patients who underwent laparotomy as part of a diagnostic evaluation that ultimately led to a diagnosis of acute viral hepatitis [18].
Similarly, patients with fulminant hepatitis are gravely ill and are unlikely to withstand surgery other than liver transplantation. (See "Acute liver failure: Definition and etiology".)
Alcoholic hepatitis — Elective surgery is contraindicated in patients with histologic evidence of alcoholic hepatitis. Mortality rates as high as 55 to 100 percent have been observed in such patients undergoing open liver biopsy [19], portosystemic shunt surgery [20-22], or exploratory laparotomy [23]. (See "Clinical manifestations and diagnosis of alcoholic liver disease".)
However, it is possible that advances in surgical technique and postoperative care may have improved the outcome in such patients compared to the above studies, some of which were conducted more than 20 to 30 years ago. This was illustrated in a report from 1984, in which operative liver biopsy findings were reviewed in 164 patients with alcoholic cirrhosis and bleeding varices who underwent emergency portacaval shunt surgery [24]. Of these patients, 49 (30 percent) had histologic evidence of alcoholic hepatitis, but had survival rates similar to those without alcoholic hepatitis. These results have not been duplicated.
We recommend that elective surgery should be delayed for at least 12 weeks, or that a repeat liver biopsy should be considered to confirm resolution. The severity of underlying liver disease should be reassessed prior to making a final recommendation.
Severe chronic hepatitis — Surgical risk in patients with chronic hepatitis correlates with the clinical, biochemical, and histologic severity of disease. Patients with symptomatic and histologically severe chronic hepatitis have increased surgical risk, particularly in those with impaired hepatic synthetic or excretory function, portal hypertension, or bridging or multilobular necrosis on liver biopsy [25,26].
Patients at variable increased risk — The risk of surgery in patients with cirrhosis depends upon the severity of disease, the clinical setting and type of surgical procedure. For over 30 years, the principal predictor of operative risk in patients with cirrhosis has been the Child's classification, but newer studies suggest that the Model for End-Stage Liver Disease (MELD) score may be superior [27].
Child's classification — A number of retrospective studies have demonstrated that perioperative mortality and morbidity in patients with cirrhosis correlate well with the Child-Turcotte (table 3) [28] or Child-Pugh [17,29] classification of cirrhosis (table 4). In one study in 1984, for example, perioperative mortality rates of 10, 31, and 76 percent were observed in 100 patients with predominantly alcoholic cirrhosis undergoing abdominal surgery who were Child-Pugh class A, B, and C, respectively [16]. On multivariate analysis, the Child-Pugh classification was the best predictor of surgical mortality and morbidity. Nearly identical results were observed in a similarly designed study published in 1997 of 92 patients with cirrhosis (approximately 50 percent alcoholic) undergoing abdominal surgery (mortality rates of 10, 30, and 82 percent in patients with Child-Pugh class A, B, and C, respectively) [30]. A study published in 2010, however, showed lower mortality rates of 2, 12, and 12 percent for patients with Child-Pugh class A, B, and C cirrhosis, respectively, undergoing abdominal surgery. A study of 138 patients undergoing intra-abdominal or abdominal wall surgery published in 2011 showed rates of 10, 17, and 63 percent, respectively [31]. Mortality rates have declined in the 2000s, presumably because of improvements in the overall care of critically ill patients [32].
Patients with Child's class A cirrhosis and portal hypertension are at increased risk of postoperative ascites, jaundice, and encephalopathy [33]. Limited observations suggest that postoperative morbidity may be reduced by preoperative placement of a transjugular intrahepatic portosystemic shunt [34].
Measures of hepatic function and the APACHE score — A number of measures of hepatic function have been proposed as predictors of perioperative morbidity and mortality in patients with cirrhosis. Examples include quantitative assessment of liver function with dynamic tests such as galactose elimination capacity, aminopyrine breath testing, indocyanine green clearance, and the rate of metabolism of lidocaine to monoethylglycinexylidide (MEGX). (See "Tests of the liver's biosynthetic capacity (eg, albumin, coagulation factors, prothrombin time)".) However, none has been shown convincingly to provide additional prognostic information compared to the Child-Pugh classification, and, as a result, they are not used widely [35].
The Acute Physiology, Age, and Chronic Health Evaluation System (APACHE III) score can predict survival in cirrhotic patients admitted to an intensive care unit [36]. However, it has not been studied specifically in cirrhotic patients undergoing surgery. (See "Predictive scoring systems in the intensive care unit".)
MELD score — The MELD score is a statistical model predicting survival in patients with cirrhosis (calculator 1 and calculator 2). It has been evaluated principally for selecting patients for liver transplantation. Use of this model for predicting surgical risk in the nontransplant setting has been promising and thus it may ultimately supplant the Child's classification as the principal method for determining surgical risk [37-42]. However, more studies involving diverse groups of surgical patients with a wide range of MELD scores are needed to understand its performance as a predictive model for surgery. The following summarizes representative studies. (See "Model for End-stage Liver Disease (MELD)".)
It has been suggested that patients with a MELD score below 10 can undergo elective surgery, those with a MELD score of 10 to 15 may undergo elective surgery with caution, and those with a MELD score >15 should not undergo elective surgery [43]. A calculator is available (calculator 3)to calculate the estimated 7-day, 30-day, 90-day, 1-year, and 5-year mortality rates after surgery based on the patient's age, ASA class, INR, serum bilirubin and creatinine. The model is based on the original MELD score, not the one currently being used for organ transplantation.
Obstructive jaundice — Patients with obstructive jaundice are at increased risk for several perioperative complications including infections (which result in part from bacterial colonization of the biliary tree, impaired Kupffer cell function, defective neutrophil function, and a high rate of endotoxemia), stress ulceration, disseminated intravascular coagulation, wound dehiscence, and renal failure [44-47]. Perioperative mortality ranged from 8 to 28 percent in several reports [48-50]. As an example, an overall mortality rate of 9 percent was found in a large retrospective study that included 373 patients undergoing surgery for obstructive jaundice [49]. Multivariate analysis identified three predictors of postoperative mortality:
When all three factors were present, mortality approached 60 percent; when none was present, mortality was only 5 percent. Several other preoperative predictors of poor surgical outcome have been observed in other studies including azotemia, hypoalbuminemia, and cholangitis (table 5) [48-53]. The presence of portal hypertension can also be presumed to increase the surgical risk.
A number of interventions have been attempted to reduce morbidity and mortality in these patients:
Limited evidence suggests that the administration of bile salts or lactulose to patients with obstructive jaundice can prevent both the endotoxemia and the exaggerated renal vasoconstriction [54,71-73]. In one report, for example, 102 patients with obstructive jaundice who had a serum bilirubin concentration >5.8 mg/dL (100 micromoles/liter) were randomly assigned to receive lactulose, sodium deoxycholate (a bile salt) or no specific treatment prior to surgery [72]. Postoperative deterioration in renal function in patients with normal preoperative function was significantly more common in patients who had received no specific treatment.
Another approach that has been attempted to reduce the incidence of renal failure is the postoperative administration of mannitol [54,74]. Despite its theoretical benefit, maintenance of intravascular volume, and the avoidance of nephrotoxic drugs, such as aminoglycosides, are probably more critical elements in management [75-77].
Prophylactic oral antibiotics, such as rifaximin, have also been proposed as a means to reduce adverse effects of endotoxemia but a benefit has not yet been demonstrated. Furthermore, it is possible that oral antibiotics could increase endotoxemia because they may lead to increased release of endotoxin caused by destruction gram-negative organisms. On the other hand, intravenous broad-spectrum antibiotics should generally be given perioperatively to reduce the incidence of postoperative infection, although a benefit on mortality has not been demonstrated [54].
Whether patients with cholestatic liver disease (such as primary biliary cirrhosis and primary sclerosing cholangitis) also have an increased risk of acute tubular necrosis following surgery has not been well studied. An interesting clinical observation is that patients with primary biliary cirrhosis appear to be at decreased risk for developing hepatorenal syndrome after surgery compared to patients with other forms of liver disease [78]. A possible explanation is the natriuretic and renal vasodilator actions of retained bile salts.
Cardiac surgery — Cardiac surgery is associated with increased mortality in patients with cirrhosis compared to other surgical procedures.
A number of risk factors for hepatic decompensation following cardiac surgery have been identified including the total time of cardiopulmonary bypass, use of nonpulsatile as opposed to pulsatile cardiopulmonary bypass, and need for perioperative pressor support [82]. Cardiopulmonary bypass can exacerbate underlying coagulopathy by inducing platelet dysfunction, fibrinolysis, and hypocalcemia [83].
Thus, the least invasive options, such as angioplasty, valvuloplasty, or minimally invasive revascularization techniques, should be considered in patients with advanced cirrhosis who require invasive intervention for cardiac disease [84]. (See "Minimally invasive coronary artery bypass graft surgery: Clinical efficacy of beating heart surgery".) Cardiac surgery followed by liver transplantation has been performed in rare instances [82,85,86]. Even more rarely, liver transplantation has been undertaken before cardiac surgery in patients with left ventricular dysfunction [83]. This approach is hazardous because of the risk of hemodynamic instability resulting from reduced venous return and reperfusion of the graft during liver transplantation [82].
Hepatic resection — Patients with cirrhosis undergoing resection for hepatocellular carcinoma or other liver tumors are at increased risk for hepatic decompensation compared to those undergoing other types of operations [87]. In addition to having severe underlying disease, a significant portion of functional hepatocellular mass may be removed in a setting in which patients already have severely compromised hepatic reserve. In the past, cirrhosis was considered to be a contraindication to resection of hepatic tumors since mortality rates exceeded 50 percent.
More recently, the perioperative mortality rate for hepatic resection has decreased to 3 to 16 percent, although postoperative morbidity rates are still as high as 60 percent [88-96]. The improvement in outcomes has been attributed to better patient selection (including earlier detection of tumors), meticulous preoperative preparation, intensive intra- and postoperative monitoring, and improved surgical techniques. Postresectional liver failure is defined as an INR >1.7 (prothrombin time index <50 percent) and serum bilirubin greater than 2.9 mg/dL (50 micromol/L), the so-called 50-50 criteria, and is associated with a mortality rate of about 60 percent compared with 1.2 percent when the criteria are not met [97]. Options for treating hepatocellular carcinoma, including surgical resection, are discussed elsewhere. (See "Surgical resection for hepatocellular carcinoma".)
Several systems for risk stratification of patients undergoing hepatic resection have been proposed, although none has been validated extensively. A database study of 587 patients who underwent hepatic resection concluded that the Child-Pugh Score and American Society of Anesthesiologists (ASA) physical status classification were better predictors of morbidity and mortality than the MELD score [98]. The ASA score was the only significant predictor of 30-day mortality (area under the receiver operating curve {ROC} of 0.63) while the ASA and Charlson Index of Comorbidity were the only significant predictors of morbidity (ROC of 0.56 and 0.40, respectively). However, the low ROC areas indicate that none of these models was an accurate predictor of outcomes. Moderate to severe hepatic steatosis (>30 percent of liver volume) is a risk factor for postoperative complications after major hepatectomy [99].
Trauma — Trauma patients found to have cirrhosis at laparotomy are at increased risk for morbidity and mortality. In one study, the overall mortality rate was 45 percent, significantly higher than of a matched control population (24 percent) [100]. Mortality and morbidity rates were increased even for patients considered to have relatively minor trauma. The authors recommended that trauma patients found to have cirrhosis at laparotomy be admitted to the intensive care unit for close monitoring and aggressive management irrespective of the severity of their injuries.
Patients with minimally increased risk — Patients with mild to moderate chronic liver disease without cirrhosis usually tolerate surgery well. However, medical therapy should be optimized prior to surgery.
Mild chronic hepatitis — Asymptomatic patients with mild chronic hepatitis are at low risk for complications [101]. In one report, for example, no major complications were noted during 34 surgical procedures in 24 patients with mild to moderate chronic hepatitis [101]. Two patients developed sustained hyperbilirubinemia, both of whom had preoperative bilirubin levels of 2.5 mg/dL (35.91 micromoles/liter) or more.
Fatty liver and nonalcoholic steatohepatitis — Although the histologic appearance of nonalcoholic steatohepatitis (NASH) is similar to alcoholic hepatitis, patients with NASH do not appear to have excessive mortality following elective surgery. However, a trend toward increased mortality following hepatic resection has been observed in those with moderate to severe steatosis (>30 percent of hepatocytes containing fat) [102].
NASH is relatively common in patients with morbid obesity who undergo gastric bypass surgery. Cirrhosis, due presumably to NASH, has been found unexpectedly in up to 6 percent of such patients, in whom a perioperative mortality rate of 4 percent has been observed [15].
It may be difficult to distinguish NASH from alcoholic hepatitis since the histologic features can be identical, and patients do not always admit to alcohol ingestion. (See "Epidemiology, clinical features, and diagnosis of nonalcoholic steatohepatitis" and "Screening for unhealthy use of alcohol and other drugs".) Thus, recommending a period of abstinence from alcohol prior to surgery is advisable for all patients with the histologic appearance of steatohepatitis, or those who are suspected of excessive alcohol consumption, since alcoholics are at increased risk for perioperative complications, such as alcohol withdrawal and hepatotoxicity with therapeutic doses of acetaminophen (often used for analgesia in the postoperative period) [103], even if they do not have liver disease. Furthermore, alcohol may potentiate the toxicity of halothane [104,105].
Autoimmune hepatitis — Elective surgery is usually well-tolerated in patients with autoimmune hepatitis who have compensated liver disease. Perioperative "stress" doses of hydrocortisone should be given to patients taking prednisone.
Hemochromatosis — Patients with hemochromatosis should be evaluated for complications such as diabetes and cardiomyopathy, which could influence perioperative care. (See "Clinical manifestations of hereditary hemochromatosis".) In the past, a relatively poor outcome of liver transplantation in these patients compared to other types of liver disease was attributed to underlying cardiomyopathy [106], but outcomes have improved with careful patient selection.
Wilson disease — Patients with Wilson disease who have neuropsychiatric involvement may not be able to provide informed consent. Furthermore, surgery can precipitate or aggravate neurologic symptoms. (See "Diagnosis of Wilson disease".) D-penicillamine (a copper chelator commonly used for treatment), interferes with the crosslinking of collagen and may impair wound healing [107,108]. As a result, the dose should be decreased prior to surgery and during the first one to two postoperative weeks. (See "Treatment of Wilson disease".)
OPTIMIZING MEDICAL THERAPY — In addition to assessing surgical risk, all patients with known liver disease should be assessed for the presence of jaundice, coagulopathy, ascites, electrolyte abnormalities, renal dysfunction and encephalopathy, all of which may require specific treatment prior to surgery. The basic principles involved in the evaluation of patients with specific forms of liver disease are discussed in detail separately. (See "Diagnostic approach to the patient with cirrhosis".)
Percutaneous gastrostomy (PEG) is contraindicated in patients with ascites, and should usually be avoided in patients with portal hypertension due to the possibility of lacerating an abdominal wall varix during PEG insertion.
Following surgery, patients with liver disease should be observed closely for hepatic decompensation, which often presents with worsening jaundice, encephalopathy, and ascites. The best biochemical measures of liver function are probably the prothrombin time and serum bilirubin concentration. However, the serum bilirubin concentration usually rises, particularly after complicated surgery, multiple blood transfusions, excessive bleeding, hemodynamic instability, or systemic infection. Renal function, serum electrolytes, and glucose should also be monitored carefully.
SUMMARY AND RECOMMENDATIONS — Considering the above data and clinical experience, guidelines for assessing the risk of elective or semi-urgent surgery in patients with liver disease can be suggested:
For other patients, the risk of surgery should be considered individually depending upon the clinical setting and the type of procedure:
Consideration should also be given as to whether surgery can be deferred until after liver transplantation (either orthotopic or live donor) in appropriate candidates.
All topics are updated as new information becomes available. Our peer review process typically takes one to six weeks depending on the issue.