Liver Function Assessment for Perioperative Outcome (PDF)

# Chapter 4: Assessment of Hepatic Function: Implications for Perioperative Outcome and Recovery ## Sean Bennett and Paul J. Karanicolas The limits of hepatic resectability are constantly expanding with our increased understanding of hepatic anatomy and refinements in surgical technique (see Chapt...

# Chapter 4: Assessment of Hepatic Function: Implications for Perioperative Outcome and Recovery ## Sean Bennett and Paul J. Karanicolas The limits of hepatic resectability are constantly expanding with our increased understanding of hepatic anatomy and refinements in surgical technique (see Chapters 2, 102, and 118B). In past years, partial hepatectomy was limited to anatomic resection and small-wedge resections, with a general consensus that two contiguous segments of hepatic parenchyma having adequate vascular inflow/outflow and biliary drainage was the minimum threshold for safe resection. This conventional definition served the surgical community well but has required refinement for two reasons. First, a variety of techniques have been developed that allow more extensive resection than this definition suggests, including induced hypertrophy of the future liver remnant (FLR; e.g., two-stage hepatectomy, portal vein embolization [PVE], associating liver partition and portal vein ligation for staged hepatectomy [ALPPS]), and nonanatomic parenchymal-sparing resections (see Chapter 102). Indeed, through these and other techniques, it may be possible to safely resect tumors from all segments of the liver while maintaining adequate postoperative liver function. Second, patients selected for partial hepatectomy are increasingly treated with preoperative chemotherapy or have other risk factors for background liver injury; in these patients, the minimal requirement of two contiguous segments of liver is likely too liberal and puts patients at an unacceptable risk for posthepatectomy liver failure (see Chapters 69, 89, 90, 98, 101, and 102). Given the trend toward more aggressive liver resections in patients at risk for background liver disease, thorough assessment of hepatic function is crucial. Liver function after hepatic resection is dependent on the quantity and quality of the FLR. Thus optimal assessment of fitness for liver resection would ideally incorporate some measure of FLR volume and function. This is particularly important in patients at risk for or documented evidence of background liver disease, including heavy alcohol consumption, hepatitis, cirrhosis, nonalcoholic steatohepatitis, and chemotherapy-associated liver injury, such as sinusoidal obstruction syndrome, steatosis, and chemotherapy-associated steatohepatitis (see Chapters 69 and 98). Surgeons contemplating major liver resection in patients with any of these risk factors should ensure that some measure of liver function, in addition to FLR volume, is considered. This chapter reviews these two critical components of FLR assessment in detail. ## Assessment of Liver Remnant Volume Extent of liver resection (i.e., the number of segments resected) is strongly correlated with risk of postoperative liver insufficiency. Although this is intuitive and easily assessed, it is actually the volume of liver remaining (i.e., the FLR) that is more predictive of outcome and thus critical to accurately measure. Furthermore, assessment of number of segments remaining is not sufficient because of substantial variability among patients in segmental anatomy and liver volume. In most patients, the right side of the liver represents more than half of the total liver volume (TLV); however, there is a broad range, from 49% to 82%, with the left side of the liver conversely ranging from 17% to 49%. Thus formal radiologic assessment of volumetrics is required to accurately assess the FLR for anticipated major (i.e., 4 segments) liver resection (see Chapter 102). ### Techniques of Volumetry Formal measurement of liver volumes is most commonly accomplished by using computed tomography (CT) or magnetic resonance imaging (MRI). Other imaging modalities may also be used, but CT and MRI are commonly obtained in patient care for characterization of lesions and operative planning, and therefore additional tests are typically not needed. Cross-sectional images obtained from either of these modalities are sequentially marked with the planned resection line, following which the surface area is derived and multiplied by the slice thickness (Figure 4.1). Excellent correlation has been demonstrated between the planned FLR and the actual FLR radiologically, as well as between the calculated resected liver volume and the surgical specimen. Because of the variability in total liver size based on patient body habitus, the FLR volume is typically expressed as a ratio of FLR to TLV. Although the measurement of the FLR is fairly standard, there are several variations to calculate the TLV. The simplest and most intuitive technique involves manually tracing the borders of the liver in a variety of planes and using software to calculate the total volume in the same manner as the FLR calculation. There are several limitations to this technique. Most notably, because resection is usually considered on the basis of hepatic tumors, the volume of the tumors is implicitly included in the measurement of the TLV. This is problematic because the tumor volume does not contribute to hepatic function and so provides a falsely elevated value of the TLV and hence a falsely diminished anticipated FLR ratio. Manually measuring the volume of each tumor and subtracting it from the TLV to yield the total functioning liver volume can correct this but can be labor intensive and prone to measurement error. Some software packages can perform automated subtraction of the tumor volume. The direct measurement technique of TLV is further limited by the fact that the parenchyma beyond tumors may be abnormal because of biliary or vascular obstruction. These limitations typically do not apply to the assessment of the FLR, which usually does not contain tumors. An alternative method referred to as the total estimated liver volume (TELV) was first proposed by Urata and colleagues in Japan for use in liver transplantation. Rather than measuring the TLV directly and subtracting the volume of liver tumors, this technique estimates the TLV based on body surface area (BSA). The formula was subsequently modified to apply to Western patients, based on the observation that Urata's formula underestimated TELV by an average of 323 cm³. The resulting equation (TELV = -794 + 1267 × BSA) has been extensively studied and found to yield a precise estimate of TLV across institutions with different CT scanners and three-dimensional reconstruction techniques. When the TELV is used as the denominator to calculate the FLR ratio (i.e., FLR/TELV), the resultant ratio is referred to as the standardized FLR (SFLR). The measured TLV was compared with the TELV in a study of 243 patients who underwent major liver resection (three or more segments). There was a strong correlation between the two measures across the population; however, in overweight patients (body mass index [BMI] > 25), TELV was significantly higher, yielding a lower sFLR in these patients. Based on the surgeons' thresholds, 47 patients were deemed to have insufficient liver volume for resection using TLV compared with 73 patients using TELV. According to institutional practices at the time, patients who had sufficient liver volume based on TLV underwent resection. The subset of patients who had insufficient volume based on TELV had significantly higher rates of post-hepatectomy liver failure (PHLF) and mortality than did the patients who had sufficient volume based on both calculations. Therefore the authors concluded that TELV (i.e., sFLR) is a better measure of postoperative hepatic insufficiency risk. Increasingly sophisticated software packages are being developed that incorporate semi-automated and fully automated segmentation for both CT and MRI. A number of studies have shown these to be very accurate and time-efficient when compared with the gold standard of manual volumetry for TLV and individual liver segment volumes. These automated software packages have also been shown to be accurate and time-saving for living donor liver transplant patients and for planning a standard right trisectionectomy. Measuring the FLR for a resection not following a standard anatomic plane still requires manual volumetry. ### Volumetric Thresholds Despite the refinement in methods to measure the FLR, the clinical application of the information gathered remains controversial. It has long been clear that patients with lower FLR are at increased risk for hepatic dysfunction, but the exact threshold below which resection should not be performed is debated. Several studies have attempted to address this fundamental question, yielding different conclusions. The variable results may be attributable to the heterogeneity of included patients (some having background liver disease and others healthy livers), methods used to calculate the FLR (TLV vs. TELV), indications for PVE, and definitions of hepatic dysfunction. Furthermore, only two studies analyzed their results using a formal receiving operator characteristic (ROC) curve to determine the optimal FLR threshold, and both studies were limited by small sample sizes. Allowing for these admittedly crucial differences, the optimal cutoff for patients with a normal background liver appears to be between 20% and 30%. A 2006 expert consensus statement recommended a minimum of 20% FLR for major hepatic resection in a patient with a healthy liver and to consider PVE for any FLR less than that. Patients who have received preoperative chemotherapy are at risk for background liver injury that impairs regeneration after partial hepatectomy (see Chapters 69, 98, and 102). There is general consensus that patients treated with extensive preoperative chemotherapy or who have evidence of background liver injury require a larger FLR to allow safe hepatectomy, although the exact threshold is again controversial. Two studies examined this question and performed formal ROC curve analyses, reporting optimal thresholds of 31% and 48.5%, respectively. The largest study includes 194 patients undergoing extended hepatectomy on the right side, stratified by extent of preoperative chemotherapy, with long-duration chemotherapy defined as greater than 12 weeks (86 patients). Using a minimum P-value approach, the authors concluded that the optimal cutoff value of FLR for preventing postoperative liver insufficiency in these patients was 30%. Patients who have received extensive chemotherapy and have an sFLR between 30% and 40% should be investigated closely for any suggestion of underlying liver dysfunction and could be considered for PVE. The optimal FLR threshold in patients with documented underlying liver disease is even less certain, given the additional variability of defining the extent of background liver injury. Some authors advocate for PVE in all patients with chronic liver disease before right side hepatectomy, and others apply a conservative threshold as high as 40%. Given the importance of background liver function, additional functional tests to assess the liver remnant should be considered before embarking on major hepatectomy in the setting of significant background liver disease. ### Volumetry After Hypertrophy In patients at increased risk for PHLF, hypertrophy of the FLR may be induced by preoperative ipsilateral PVE (see Chapter 102C). Other techniques to achieve hypertrophy, such as the ALPPS procedure (see Chapter 102D) or radioembolization with yttrium-90 (see Chapter 94), are discussed in other chapters. Cross-sectional imaging is typically repeated 2 to 6 weeks after PVE, and the FLR (or sFLR) may be recalculated. The post-PVE FLR can be interpreted with the same thresholds previously discussed, although the degree of hypertrophy (DH), defined as absolute difference between FLR before and after PVE, appears to be more informative. The authors of this study recommended that patients without cirrhosis undergoing PVE should have both an sFLR of at least 20% and a DH of at least 5% to undergo safe hepatectomy. In addition to its therapeutic intent, PVE functions as a diagnostic test analogous to a cardiac stress test; patients who do not experience substantial growth in the FLR after PVE should be suspected of harboring background liver disease and approached with caution. Recognizing that the DH is contingent on the duration from PVE to reimaging, surgeons have proposed incorporating some measure of growth rate into consideration. The kinetic growth rate (KGR) may be calculated by dividing the DH by the number of weeks elapsed since PVE. In one study of 107 patients who underwent liver resection for colorectal liver metastases with an sFLR volume of greater than 20%, KGR was a more accurate predictor of postoperative hepatic insufficiency than absolute sFLR or DH (area under the curve [AUC] 0.830). In this study, patients with a KGR less than 2% per week suffered a 21.6% hepatic insufficiency rate and an 8.1% 90-day mortality rate compared with no hepatic insufficiency or 90-day mortality in patients with a KGR greater than 2% per week. In a similar study of 153 patients who underwent major hepatectomy after PVE, post-PVE absolute FLR correlated poorly with liver failure. Both DH and KGR were good predictors of liver failure (AUC 0.80 and 0.79, respectively). Notably, posthepatectomy liver failure did not develop in any patients with a KGR greater than 2.66% per week. In summary, for patients with insufficient FLR (or sFLR) to safely undergo hepatectomy, response to PVE provides a good measure of the remnant liver's ability to hypertrophy. Post-PVE FLR should be interpreted in combination with some measure of extent of hypertrophy (either DH or KGR) to optimally predict a patient's risk for post-hepatectomy liver insufficiency. ## Assessment of Liver Remnant Function Although a thorough assessment of the anticipated FLR volume is required before embarking on major hepatectomy, a complete assessment should ideally also account for the quality of the background liver that will be preserved. The optimal method to assess hepatic function would be accurate, noninvasive, inexpensive, specific to the remnant portion of the liver, and widely reproducible. Unfortunately, none of the techniques currently available fulfill all of these criteria, and therefore none are frequently used in routine assessment. Nevertheless, several newer techniques show promise and with further investigation may find a role in routine assessment of liver function (Table 4.1). ### Clinical Scoring Systems The simplest, most widely available method to assess liver function relies on laboratory investigations either in isolation or combined into clinical scoring systems. Clinicians are familiar with conventional liver laboratory tests routinely used in clinical practice, including enzymatic measures of hepatocyte injury (alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase), and markers of hepatic metabolism bilirubin and synthetic function (albumin and international normalized ratio [INR]). Aberrations in any of these laboratory measures should prompt further investigation of background liver dysfunction, although none of them are sensitive or specific enough for surgeons to rely on exclusively. The Child-Turcotte-Pugh scoring system was developed to predict the risk of death in patients undergoing surgical management of portal hypertension. The Child's score is easily calculated from three readily available laboratory tests (bilirubin, albumin, and INR) and two clinical findings (ascites and encephalopathy). The Child's score is a good marker of global liver function in a patient with cirrhosis and may help in the selection of patients appropriate for resection, particularly in the setting of hepatocellular carcinoma. In general, surgery is reasonable to consider in patients with class A cirrhosis, should be approached cautiously in patients with class B cirrhosis, and should be avoided in patients with class C cirrhosis. In patients without cirrhosis, the Child's score will almost always be normal even when there is substantial background liver dysfunction; in this setting, it does not predict postoperative liver dysfunction, and other tests are needed. Furthermore, it is important to recognize that significant portal hypertension may exist even in Child's A cirrhosis. The Model for End-Stage Liver Disease (MELD) score is a mathematical equation frequently used in liver transplantation to allocate organs. The MELD score is similar to the Child-Pugh score in that it incorporates simple laboratory investigations, including serum bilirubin, creatinine, and INR, although it is more cumbersome to calculate. It was initially validated for the prediction of short-term survival in patients with cirrhosis and has subsequently been validated for long-term survival as well. In patients with cirrhosis undergoing partial hepatectomy, a MELD score greater than 8 is a strong predictor of perioperative mortality and decreased long-term survival. In contrast, in patients without documented background liver injury, a MELD score is not strongly associated with inferior outcomes. First described in 2015, the albumin-bilirubin (ALBI) score categorizes patients into three risk groups based only on their serum albumin and bilirubin. The calculation of the score requires a complex equation; however, a simple nomogram has been created to determine into which group a patient falls: A1, A2, or A3 (from best to worst). This model was developed from 1313 patients with hepatocellular carcinoma (HCC) in Japan and was validated in patients from other geographic regions, patients undergoing hepatectomy, and unresectable patients treated with sorafenib. In patients undergoing resection, the ALBI was better able to predict survival than the Child-Pugh score and could better discriminate between Child-Pugh A patients. Further studies showed ALBI better able to predict both PHLF and survival after hepatectomy when compared with Child-Pugh and MELD Thus, in patients with cirrhosis being considered for partial hepatectomy, Child-Pugh and MELD scores provide good measures of global liver function. Surgeons should approach patients with Child-Pugh class B/C or MELD score greater than 8 with caution and consider alternative treatment approaches. Within the group of Child-Pugh A patients, use of the ALBI score can add further precision in predicting the risk for PHLF. Clinical scoring systems are not sensitive enough to detect background liver injury and subsequent risk of postoperative liver dysfunction in patients without cirrhosis; other methods of functional liver assessment are needed in these patients. ### Measurement of Hepatic Uptake, Metabolism, and Elimination #### Indocyanine Green Clearance Indocyanine green (ICG) clearance is the quantitative measure of hepatic function most used worldwide. ICG is a water-soluble tricarbocyanine dye that binds to albumin and distributes rapidly and uniformly in the blood after intravenous (IV) injection. ICG is exclusively cleared from the bloodstream by the liver in a similar manner to bilirubin and toxins and then excreted unchanged into bile. Thus ICG clearance tests reflect blood flow-dependent clearance, hepatocyte uptake, and biliary excretion. The conventional measurement of ICG clearance involves IV injection of ICG, followed by serial collection of venous blood at 5-minute intervals for 15 minutes. ICG clearance can also be measured noninvasively by pulse-spectrophotometry, which allows for real-time monitoring of liver function. The results of ICG tests may be expressed as the percentage of ICG retained in the circulation 15 minutes after injection (ICG-R15), the plasma disappearance rate (ICG-PDR), and the elimination rate constant (ICG-k). Several studies have identified an association between elevated ICG-R15 and post-hepatectomy complications, with proposed threshold values of ICG-R15 ranging from 14% to 20%. Despite the theoretical attractiveness of ICG clearance as a simple measure of hepatic function, several limitations have hampered enthusiasm for its widespread use. The results of ICG clearance tests are not reliable in patients with hyperbilirubinemia or in patients with intrahepatic shunting or sinusoidal capillarization. Further, ICG clearance testing is a measure of global liver function, so if there is heterogeneous uptake in the liver (e.g., the portion being resected does not function as well because of tumor, biliary obstruction, etc.), the results may be misleading. Finally, ICG testing does not incorporate the extent of resection, or conversely, the volume of the remnant that will remain. Researchers have attempted to mitigate some of these limitations by creating scoring systems and decision trees that incorporate ICG. In one study of patients with cirrhosis, a combination of sFLR greater than 25% and an sFLR/ICG-R15 ratio greater than 1.9 predicted safety to undergo hepatectomy. #### Nuclear Imaging Techniques Theoretically, nuclear imaging represents an attractive preoperative hepatic assessment, combining anatomic considerations (FLR volume) with both total and regional liver functional assessment. Several scintigraphic tests have been developed over the past few decades, but the most widely used radiopharmaceutical imaging methods for liver functional assessment are technetium-99m (99mTc)-labeled galactosyl serum albumin (GSA) scintigraphy and hepatobiliary scintigraphy (HBS) with 99mTc-labeled iminodiacetic acid (IDA) derivatives. Both of these methods provide quantitative data on the total and regional hepatic function, although they are based on different principles and therefore interpretation varies. 99mTc-GSA is an analogue of a glycoprotein (ascites sialo-glycoprotein) that binds to receptors on the hepatocyte cell membrane and is taken up by the hepatocytes. Chronic liver disease results in diminished hepatocyte glycoprotein receptors and subsequent accumulation of plasma glycoproteins. To perform dynamic scintigraphy, an IV bolus of 99mTc-GSA is administered, and images are obtained by using a gamma camera positioned over the heart and liver. Several parameters may be calculated to document the extent of hepatic 99mTc-GSA uptake, including the hepatic uptake ratio (LHL15 [receptor index: uptake ratio of the liver to the liver plus heart at 15 min]) and the blood clearance ratio (HH15 [blood clearance index: uptake ratio of the heart at 15 min to that at 3 min]). In patients with cirrhosis, 99mTc-GSA uptake corresponds well with other conventional liver function tests, including ICG clearance, and predicts histologic severity of disease better than ICG clearance in a substantial proportion of patients. Several small studies have demonstrated an association between poor 99mTc-GSA uptake and postoperative complications after liver resection. 99mTc-GSA uptake is limited by inter-operator and inter-institutional differences and does not provide a measure of regional liver function. To address this limitation, 99mTc-GSA scintigraphy may be combined with static single-photon emission computed tomography-CT (SPECT-CT) to allow a three-dimensional measurement of 99mTc-GSA uptake. Results of dynamic SPECT-CT may help to predict postoperative liver failure; however, this method suffers from the same interobserver variability and environmental factors as dynamic 99mTc-GSA scintigraphy. A single-arm prospective trial of 185 consecutive patients undergoing hepatectomy evaluated the predictive value of 99mTc-GSA SPECT-CT on PHLF and mortality. SPECT-CT was used to calculate the ICG clearance specific to the predicted FLR and demonstrated very good correlation with postoperative bilirubin and INR levels, with a PHLF rate of 8% and 90-day mortality of 0.5%. Furthermore, 7 patients who would not have met their criteria for resection based on the overall ICG-R15 x FLR underwent hepatectomy without PHLF. This demonstrates the heterogeneity of liver function and the importance of measuring the function of the FLR rather than the TLV. 99mTc-mebrofenin is an organic IDA derivative with similar properties to ICG: It has high hepatic uptake, low displacement by bilirubin, and low urinary excretion. The test is administered in an identical manner to 99mTc-GSA scintigraphy, using a gamma camera and calculating similar parameters and ratios. The uptake ratio, however, is divided by the patient's BSA to compensate for differences in metabolic requirements. 99mTc-mebrofenin HBS correlates well with ICG clearance and appears to be a good marker of post-resection liver function. HBS may also be combined with SPECT-CT to allow for the calculation of both the function and volume of the FLR. An FLR function cutoff value of 2.7%/min/m² was shown to have a negative predictive value (NPV) of 97.6% and a positive predictive value (PPV) of 57.1% for PHLF. The main limitation of HBS is, again, inter-observer and inter-institution variability. Although these techniques offer great advantages compared with more conventional methods, further research is needed to ensure that results are reproducible across different settings before wider application. #### Other Measures of Metabolic Function In addition to ICG, several other compounds are metabolized almost exclusively by the liver cytochrome P450 system and have been investigated as potential markers of hepatic function. For example, lidocaine is metabolized to monoethylglycinexylidide (MEGX) primarily in the liver. The MEGX test has been studied in transplantation and critical care medicine and appears to correlate with other measures of hepatic metabolism. A small study demonstrated higher rates of postoperative liver insufficiency among Child-Pugh A patients who had a low MEGX value. Unfortunately, the test is limited by poor reliability and the need for frequent monitoring; therefore its present application in preoperative assessment of liver function is investigational only. Galactose elimination capacity also accurately reflects metabolic function of the liver but is similarly limited by practical constraints and alterations due to environmental conditions. #### Magnetic Resonance Imaging Hepatic Agents MRI with contrast enhancement offers high-resolution cross-sectional assessment of background liver anatomy and accurate characterization of hepatic tumors. MRI is more sensitive and specific than CT for the detection of primary and metastatic liver neoplasms and is used routinely at most centers before embarking on liver resection. Gadolinium ethoxybenzyl dimeglumine (Gd-EOB-DTPA) is a liver-specific contrast agent that has as much as 50% hepatobiliary excretion in a normal liver. Gd-EOB-DTPA improves the detection and characterization of focal liver lesions and diffuse liver disease. Given the hepatic uptake and elimination of Gd-EOB-DTPA, contrast-enhanced MRI may also provide functional assessment of the background liver (Figure 4.2). Several small studies have demonstrated correlation between Gd-EOB-DTPA uptake on MRI and conventional measures of liver function, and with 99mTc-mebrofenin HBS. Postoperative ICG-R15 can also be predicted well using pre-resection MRI. There are several theoretical and practical advantages to using Gd-EOB-DTPA-enhanced MRI to assess liver function. First, MRI is routinely available and frequently used in the preoperative assessment of these patients, so no additional testing is required. Second, functional assessment may be focused on the planned FLR in cases of heterogeneous uptake, rather than calculating uptake for the whole liver as is the case in most other functional quantitative tests. Finally, MRI provides visual assessment of background liver injury, including steatosis and fibrosis, which may further assist in preoperative decision making. MRI has been shown to be superior to sFLR volume and ICG-R15 at predicting PHLF. The most precise predictors for PHLF seem to use a combination of relative liver enhancement (RLE, difference in signal intensity between the unenhanced and hepatobiliary phases) or hepatocellular uptake index (HUI, difference in signal intensity between liver parenchyma and the spleen) specific to the FLR and patient weight. For example, Asenbaum et al. calculated an AUC of 0.9 for predicting PHLF for their outcome of functional FLR, which equals (FLR × remnant RLE)/weight. Similar to using KGR as a measure of liver function after PVE, contrast-enhanced MRI can compare RLE and HUI before and after PVE. Studies performing MRI pre-PVE, post-PVE days 14 and 28, and 10 days post hepatectomy have shown that the increase in RLE from baseline to 14 days post-PVE is an excellent predictor of PHLF, and that beyond 14 days there is minimal improvements in FLR, KGR, and RLE. The availability and common use of MRI, combined with its ability to provide information on both the volume and the function of the FLR, give it the potential to be an extremely useful tool for the assessment of patients being considered for major hepatic resection. Early prospective studies demonstrate a relationship between Gd-EOB-DTPA uptake and clinical outcome postresection. Larger trials demonstrating its NPV and PPV for PHLF and mortality are needed. #### Transient Elastography Ultrasound transient elastography (TE) has been reported as a test to estimate the extent of liver fibrosis. Ultrasound TE has the clear advantages of being noninvasive and fast but is limited by significant inter-observer variability and anatomic variations. Two studies of patients with HCC undergoing hepatectomy found ultrasound TE to have a high NPV of 98% but relatively poor PPV. Therefore ultrasound TE may have a role in screening patients at low risk for PHLF, but a positive test should prompt further investigations and not necessarily preclude resection. #### CT Texture Analysis Texture analysis is an established technique that characterizes regions of interest in an image based on spatial variations in pixel intensity. On CT imaging, texture analysis can potentially quantify regional variations in enhancement that cannot be assessed by inspection. Several studies have shown potential utility of this technique for tumor diagnosis, characterization, and prognostication. Texture variables of preoperative CT scans show promise for predicting postoperative hepatic failure in single-institution and multi-institution studies and may represent a new means of preoperative risk stratification. ## Conclusion Hepatobiliary surgeons now have a variety of tools at their disposal to assist with preoperative assessment of hepatic function. The gold standard remains volumetric-based assessment of the FLR with cross-sectional imaging (CT or MRI). In patients in whom there is concern about insufficient liver volume or background liver injury, response to PVE provides a functional assessment of the FLR in addition to its therapeutic role. Quantitative measures of hepatic uptake, metabolism, and elimination, including ICG clearance, nuclear scintigraphy, and MRI hepatic-specific contrast agents, may have a role in assessment of patients with borderline FLR volume or background liver disease. MRI in particular seems poised to emerge as a complete package to diagnose occult metastases, assess FLR volumetry and FLR-specific function, and assess both the volumetric and functional response to PVE. Further refinement of these techniques may allow for the development of algorithms or decision aids that provide more precise prediction of postoperative hepatic insufficiency, ultimately decreasing postoperative morbidity and mortality. The references for this chapter can be found online by accessing the accompanying Expert Consult website.