Assessment of the Patient Before Liver Resection

Grade 0

Unrestricted activity; able to perform all pre-diagnosis activities

Grade 1

Strenuous physical activity is limited, but able to move around freely and engage in less intense physical activity or seated work, including housework and general office work

Grade 2

Able to move around freely and perform self-care, but has lost the ability to work. Active less than half of the day

Grade 3

Can only participate partially in self-care; spends more than half the time during the day in bed or chair

Grade 4

Disabled. Cannot take care of self. Bedridden

However, patients with a Child’s score of A who are undergoing liver resection can have normal preoperative albumin levels. Some scholars believe that prealbumin levels are a more appropriate assessment of nutritional status in patients with cirrhosis.

3.2 Assessment of Cardiovascular Function

Preoperative hypertension should be controlled, with blood pressure maintained with medication at 160/100 mmHg or less. A careful list of medications should be obtained from patients who are taking oral antihypertensive drugs. For patients who take reserpine to control blood pressure, reserpine must be replaced with other antihypertensive drugs preoperatively; elective surgery must be delayed for at least 1 week after stopping reserpine.

Preoperative routine electrocardiogram is necessary. Patients with arrhythmias should have 24 h of Holter monitoring. When necessary, patients with a history of structural heart disease should have an echocardiogram. Patients who are suspected of having severe coronary artery stenosis or occlusion must undergo coronary CT or angiography, when necessary. For these patients, a joint assessment by anesthesia and cardiovascular specialists before surgery could help to improve the perioperative outcomes.

3.3 Assessment of Pulmonary Function

Preoperative routine chest X-rays can identify pulmonary parenchymal disease or pleural abnormalities. In smokers and patients with previous lung disease or who are older than 60 years, preoperative pulmonary function tests should be considered. In patients with severe impairment of lung function, elective surgery should be performed with caution. Smokers should stop smoking before surgery; 1–2 weeks of smoking cessation leads to recovery of mucociliary function and reduced sputum volume. Quitting for 6 weeks can improve lung capacity. For patients with acute respiratory infections, elective surgery is best delayed for 1–2 weeks; in cases of emergency surgery, antibiotics should be used, and inhaled anesthetics should be avoided to the extent possible.

3.4 Coagulation

A thorough preoperative inquiry into the patient’s medical history and family history is very important. In patients with known coagulation disorders or hemophilia, a hematologist’s assistance should be enlisted. Conventional coagulation panels and platelet counts should be obtained. Patients who are taking warfarin should stop taking it preoperatively; warfarin should be replaced with low-molecular-weight heparin, which can be stopped the night before surgery. For patients undergoing emergency surgery, vitamin K can be used to counteract the effects of warfarin. Patients with obstructive jaundice before surgery should receive routine supplements of vitamin K.

3.5 Blood Glucose

Diabetes can increase the risk of postoperative infection, liver failure, and other complications. Also, diabetic patients may have asymptomatic coronary artery disease or renal dysfunction. Patients with diet-controlled diabetes do not require special preoperative care. Oral hypoglycemic agents should be continued until the night before surgery. Long-acting hypoglycemic agents should be discontinued for 2–3 days before surgery, and short-acting insulin should be used to control blood glucose. Patients using insulin should stop taking insulin on the morning of surgery. The target blood glucose value is less than 11.2 mmol/L.

3.6 Assessment of Liver Function and Liver Reserve

The Child-Pugh classification is the most commonly used method for the clinical assessment of liver function and includes the following five parameters: total bilirubin level, albumin level, the presence of ascites, the presence of hepatic encephalopathy, and clotting time (Table 3.2). Each parameter is scored according to severity on a scale of 1–3 points; the five scores are summed for a minimum score of 5 points and a maximum score of 15 points. Patients are then divided into classes A, B, and C (class A – 5–6 points; class B – 7–9 points; and class C – 10–15 points. The Child-Pugh score is a semiquantitative method for determining the prognosis of patients with cirrhosis. Patients with Child class A liver disease have a 1-year rate of liver failure-related mortality of <5 %. Child class B liver disease is associated with a 1-year liver failure-related mortality rate of 20 %. Child class C disease represents severe decompensation of liver function, and the 1-year mortality rate due to liver failure is 55 %. According to the Child-Pugh classification standards [1], hepatic resection is well tolerated in class A patients and can be tolerated in class B patients with adequate preparation. However, there is still some risk in these patients. Class C patients tolerate surgery poorly, contraindicating hepatectomy.

Table 3.2

Child-Pugh classification score criteria

Clinical and biochemical indicators	1	2	3
Hepatic encephalopathy (grade)	None	1–2	3–4
Ascites	None	Mild	Moderate, severe
Total bilirubin (μmol/L)	<34	34–51	>51
Albumin (g/L)	>35	28–35	<28
Coagulation time (s)	<4	4–6	>6

However, the Child-Pugh classification does not accurately reflect the patient’s liver reserve. Impaired liver reserve may still exist in patients with a Child class of A. Therefore, these patients require further quantification of liver function, which can be assessed by measuring the ability of the liver to remove certain exogenous compounds. The main quantitative tests of liver blood flow include the following: the indocyanine green (ICG) excretion test, the galactose clearance test, and the sorbitol clearance test. The main microsomal liver cell function tests include the caffeine clearance test and the antipyrine clearance test. These compounds are only processed by hepatic metabolism; if the liver reserve capacity is decreased, the clearance rate for these compounds is also decreased, and retention rates are increased.

3.6.1 Indocyanine Green Clearance Test

Currently, the most common clinical assessment of a patient’s liver reserve capacity is the ICG excretion test, which measures the 15-min indocyanine green retention rate (ICGR15) and the maximum clearance rate (ICG max) to reflect the patient’s liver function reserve.

Indocyanine green is a photosensitive material that rapidly combines with human serum proteins after injection. It under goes greater than 90 % cell uptake by the liver and is then secreted into bile in its free form; it does not enter the enterohepatic circulation. There is no organized extrahepatic clearance and no toxic side effects. Its clearance rate depends on the amount of hepatic blood flow and bile duct patency hepatocytes. Hepatic blood flow may reflect liver perfusion and hepatocyte metabolism. ICG excretion by the liver is more significantly affected by blood flow velocity; therefore, any factor that affects hepatic blood flow (such as portal vein thrombosis) will affect its clearance rate. Biliary excretion disorders (such as obstructive jaundice) can also obstruct ICG removal. In these circumstances, the ICG excretion test will not accurately reflect the hepatic functional reserve. Generally, in patients with Child class A disease, patients with an ICG R15 <10 % can tolerate resection of up to four hepatic segments. When the ICG R15 is 10–19 %, patients can tolerate resection of two to three liver segments, and when the ICG R15 is 20–29 %, only one segment can be safely resected.

When the ICG R15 is 30–39 %, only a conservative partial liver resection can be tolerated. When the ICG R15 is ≥40 %, only tumor enucleation can be performed [2].

3.6.2 Artery Ketone Body Ratio (AKBR)

The liver is the main site of energy metabolism. The hepatic mitochondrial NAD +/NADH ratio reflects the energy metabolism of the liver. The NAD +/NADH ratio of liver ketone bodies (acetoacetate/β – hydroxybutyrate) and the NAD +/NADH = acetoacetate/β – hydroxybutyrate × β – hydroxybutyrate dehydrogenase equilibrium are constant. When hepatocyte function is impaired, the chain of liver mitochondrial respiration is damaged, and the AKBR value is decreased. It is generally believed that if AKBR is > 0.7, the liver mitochondrial function is normal, and the liver can produce enough ATP to maintain normal reserve function and withstand most types of surgery. If the AKBR is 0.4–0.7, mitochondrial function is impaired, and insufficient ATP is generated; such patients can only tolerate partial hepatic resection or resection of the tumor only.

When AKBR is <0.4, the mitochondrial function is severely impaired, and the liver cannot produce ATP; these patients cannot tolerate any type of liver resection [3].

3.6.3 Oral Glucose Tolerance Test (OGTT)

Glucose metabolism in the liver requires normal structure and function of the liver cells. Hepatic glycogen synthesis is an energy-consuming process, and the OGTT curve type may reflect the hepatic energy reserve. An early-morning OGTT test is performed by measuring fasting blood sugar in approximately 2 ml of venous blood. Then, 75-g anhydrous glucose dissolved in approximately 250 ml of water is consumed within 5 min. Blood glucose levels are subsequently measured at 30, 60, and 120 min (using 2-mL samples for each measurement). Based on these values, an OGTT curve is generated; the OGTT curve can be divided into the following three types:1) Normal/parabolic (P-type) – the OGTT curve peaks at 30 or 60 min after the glucose load, after 120 min, glucose has decreased to normal; 2) Linear (L-type) curve – glucose continues to increase after 60 min, or remains elevated 120 min after the glucose load, reflecting poor glucose tolerance; and 3) the Intermediate (I-type) is somewhere between these two, where the curve peaks at 60 or 90 min, but blood glucose does not return to normal after 120 min. When the liver energy reserve is normal, blood glucose normalizes 2 h after the load, yielding a P-type OGTT curve. In patients with hepatitis or cirrhosis, progressive disease impairs the normal function of the liver cells and decreases glycogen synthase and hepatic mitochondrial cytochrome a + (a3) content, causing decreased production of ATP. In this situation, the liver cannot quickly synthesize glycogen from blood sugar, and the OGTT curve can change to type I or L from a P-type. It is generally believed that P-type OGTT reflects good liver reserve and an ability to tolerate surgery, while an L-type OGTT suggests diminished liver reserve capacity in patients with poor liver function, creating considerable risk with liver resection [4].

3.6.4 Assessment of Liver Volume

Patients undergoing liver resection require complete resection of the tumor and need sufficient remaining liver tissue to prevent postoperative liver failure. Therefore, preoperative assessment of residual liver volume is very important. However, the optimal residual liver volume in patients with baseline postoperative liver failure is controversial and is affected by the presence of underlying liver disease, weight, and other factors. Shirabe et al. [5] found that in patients with a remaining liver volume after hepatectomy of less than 250 ml/m² (m² refers to the patient’s body surface area), the probability of occurrence of postoperative liver failure was as high as 38 %. Therefore, they recommend a minimum residual liver volume of 250 ml/m² for a safe hepatectomy. In patients with liver cirrhosis and chronic liver disease, Schindl et al. [6] showed that a residual liver volume of 26.6% was the critical value predicting for liver failure after hepatectomy. However, studies suggest that a residual liver volume of greater than 25 % is sufficient to prevent postoperative liver failure [7, 8]. Kishi [9] even contends that a residual liver volume of > 20 % permits safe liver resection. However, in patients with impaired liver function cirrhosis, residual liver volume must increase correspondingly. Sudaet al. [10] studied patients with biliary tumors and obstructive jaundice and concluded that these patients require an increased residual liver volume of 40 % in order to avoid postoperative liver failure. For patients with cirrhosis, residual liver volume is generally recommended to be 40–50 % in order to avoid postoperative liver failure [11, 12].

CT volumetric analysis is the main method for performing liver volume measurements. However, this method can only be used to measure liver volume and does not effectively evaluate the function of the remaining liver cells. Especially in patients with cirrhosis, this method may overestimate function because of the poor-quality remnant liver, so patients are at risk of liver failure. Asialoglycoprotein receptor (asialoglycoprotein, ASGP) is only present in mammalian cells and has specific receptors in the liver. The intravenous injection of technetium-labeled asialoglycoprotein receptor and its analogs galactosy l human serum albumin (galactosy l human serum albumin-diethylenetriamine-pentaacetic acid, TcGSA) can quickly allow measurement of hepatic ASGP. GSA clearance rates may reflect hepatic reserves. Kokudo [13] used logistic regression analysis in a study of relevant factors in patients with liver failure after liver resection. The amount of residual liver ASGP was a meaningful indicator; when it was less than 0.05 mmol/L, there was a postoperative liver failure rate of 100 %. This technology can be used in patients with jaundice and in ICG-intolerant patients [14].

3.7 Assessment of Portal Hypertension

Varying degrees of cirrhosis are present in 80–90 % of patients. Surgery is higher risk in patients with liver cirrhosis. Therefore, accurate preoperative assessment of patients with cirrhosis and portal hypertension is necessary to reduce operative risk. At present, the gold standard for the diagnosis of portal hypertension is a measurement of the patient’s hepatic venous pressure gradient (HVPG). The measurement is obtained by threading a catheter into the internal jugular vein or femoral vein, then into the inferior vena cava, and subsequently into the hepatic vein. Then the catheter balloon is inflated, blocking hepatic venous return, and manometry is performed. In this case, the measured parameter is wedge hepatic venous pressure (WHVP). Free hepatic venous pressure (FHVP) is measured again after the balloon is deflated. The following equation expresses the relationship among these values: HVPG=WHVP-FHVP. Under normal circumstances, HVPG is 3–5 mmHg; an HVPG >5 mmHg is considered to indicate the presence of portal hypertension [15]. An elevated HVPG in patients undergoing liver resection is considered to be associated with a higher incidence of postoperative complications and a higher risk of liver failure [16, 17]. However, in many recent studies, portal hypertension was not considered an absolute contraindication to liver resection; Child class A patients with portal hypertension did not have a higher postoperative complication rate than liver cancer patients without portal hypertension [18–20]. Even in patients with significant splenomegaly and hypersplenism, concurrent splenic resection is also safe and can improve the prognosis of patients with hepatocellular carcinoma [18].

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