Post-hepatectomy liver failure
Rondi Kauffmann and Yuman Fongcorresponding author
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Abstract
Hepatectomies are among some of the most complex operative interventions performed. Mortality rates after major hepatectomy are as high as 30%, with post-hepatic liver failure (PHLF) representing the major source of morbidity and mortality. We present a review of PHLF, including the current definition, predictive factors, pre-operative risk assessment, techniques to prevent PHLF, identification and management. Despite great improvements in morbidity and mortality, liver surgery continues to demand excellent clinical judgement in selecting patients for surgery. Appropriate choice of pre-operative techniques to improve the functional liver remnant (FLR), fastidious surgical technique, and excellent post-operative management are essential to optimize patient outcomes.
Keywords: Post-hepatectomy liver failure (PHLF), prevention of liver failure, predictive factors for liver failure
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Introduction
Hepatic resections are among some of the most complex operative interventions performed, and are fraught with risk and the potential for complications. Mortality rates after major hepatic resection have been reported to be as high as 30% (1,2) with post-hepatectomy liver failure (PHLF) representing the major source of morbidity and mortality after liver resection. Despite great improvements in outcomes after major liver resection due to refinements in operative technique and advances in critical care, PHLF remains one of the most serious complications of major liver resection, and occurs in up to 10% of cases (3,4). Several studies report a lower rate of PHLF in East Asian countries (1-2%), but when present, PHLF represents a significant source of morbidity and mortality (5).
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Definition
The definition of PHLF has varied widely among groups, making comparison of rates between studies challenging. Numerous definitions of PHLF exist in the literature, with variations by country and between hospitals within the same country. Many definitions include complicated formulas or obscure laboratory tests, such as hepaplastin or hyaluronic acid levels, limiting their utility (6). The Model for End-Stage Liver Disease (MELD) score is one such definition that is widely used. The MELD score is calculated using serum creatinine, INR, and bilirubin, but requires a complex mathematical formula computation (7). The ‘50-50 criterion’ (PT 50 µmL/L) have also been proposed as a simple definition for PHLF (8). However, this definition does not account for any clinical parameters, and relies only on two laboratory values. In 2011, the International Study Group of Liver Surgery (ISGLS) proposed a standardized definition and severity of grading of PHLF. After evaluating more than 50 studies on PHLF after hepatic resection, the consensus conference committee defined PHLF as “a post-operatively acquired deterioration in the ability of the liver to maintain its synthetic, excretory, and detoxifying functions, which are characterized by an increased INR and concomitant hyperbilirubinemia on or after postoperative day 5” (2). While other definitions of PHLF utilizing biochemical or clinical parameters are used by some centers, the ease with which the ISGLS definition can be calculated and used for comparison renders it the definition that ought to be standardized and used.
While PHLF is the most feared complication, the severity of its clinical manifestation ranges from temporary hepatic insufficiency to fulminant hepatic failure. The ISGLS group advocated a simple grading system of PHLF, in which laboratory values, clinical symptoms, and need for increasingly invasive treatments define severity of PHLF. The mildest grade of PHLF, grade A, represents a minor, temporary deterioration in liver function that does not require invasive treatment or transfer to the intensive care unit. The most severe, grade C, is characterized by severe liver failure with multisystem failure and the requirement for management of multi-system failure in the intensive care unit (2) (Table 1). The peri-operative mortality of patients with grades A, B, and C PHLF as determined by this grading schema is 0%, 12% and 54%, respectively (9).
Table 1
Table 1
ISGLS definition and grading of PHLF (2)
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Predictive factors
Patient factors
Various patient-related factors are associated with increased risk of PHLF (Table 2). Operative mortality in patients with diabetes undergoing curative-intent hepatic resection for treatment of colorectal metastases has been shown to be higher than comparable patients without diabetes mellitus (6). In that series, operative mortality was 8% in diabetics compared to 2% in non-diabetics (P1,200 mL (19,20), intra-operative transfusion requirement, need for vena caval or other vascular resection (21), operative time >240 minutes (13), resection of >50% of liver volume, major hepatectomy including right lobe (22), and skeletonization of the hepatoduodenal ligament in cases of biliary malignancy (23). In patients for whom 18 seconds) and bilirubin level (>3 mg/dL) (24). In their analysis, 90% of patients undergoing trisegmentectomy with ≤25% of liver remaining developed hepatic dysfunction, compared to none of the patients who had >25% of liver remaining after the same operation (24). Furthermore, the percentage of remaining liver, as determined by volumetric analysis, was more specific in predicting PHLF than the anatomic extent of resection (24).
Careful evaluation of pre-operative CT scan imaging should focus on liver attenuation. Liver attenuation that is lower than that observed in the spleen indicates fatty infiltration indicative of steatohepatitis (11,24,25) (Figure 1). Similarly, splenomegaly, varices, ascites, or consumptive thrombocytopenia should prompt the clinician to suspect underlying cirrhosis (11) (Figure 2A,B).
Figure 1
Figure 1
CT scan image of steatohepatitis, with liver attenuation lower than that of the spleen.
Figure 2
Figure 2
(A) CT scan demonstrating evidence of cirrhosis, with ascites, small liver, and splenomegaly; (B) CT scan demonstrating evidence of cirrhosis, with ascites, small liver, splenic varices, and splenomegaly.
Although ultrasound and 3-dimensional ultrasound has been advocated by some as a means by which to assess the pre-operative volume of the liver, CT or MRI provide more objective data that is less subject to operator-error. Both CT and MRI show excellent accuracy and precise quantification of hepatic volume (26-28), and are particularly useful in estimating the future liver remnant (FLR) (29).
Numerous methods have been developed for calculating liver volume, using either CT or MRI images. The first technique involved manual tracing of the outline of the liver (30), but has been criticized its time-intensity. Most recently, automatic or semi-automatic techniques have been developed that utilize mathematical formulas to measure liver volumes obtained from CT scan images, utilizing commercially-available software programming. These software-based programs have been shown to correlate well with manual volume estimation, but are performed in a fraction of the time (31).
Although pre-operative estimation of functional liver volume after resection remains the most advanced method for estimating hepatic functional reserve, newer techniques, such as indocyanine green (ICG) clearance and ICG retention rate (ICG R15) have been reported. Under normal conditions, nearly all ICG administered is cleared by the liver. Because the ICG reflects intra-hepatic blood flow, it has long been used to assess liver functional reserve in patients with cirrhosis (32). Only recently, however, have investigations begun into the application of ICG and ICG R15 to