Reply
Authors: Sasan Roayaie, Morris Sherman, Lewis R. Roberts
Journal: Hepatology (2016)

Potential conflict of interest: Dr. Sherman consults for Merck, Gilead, AbbVie, and Bristol‐Myers Squibb. Reply: The expansion of criteria for hepatic resection of hepatocellular carcinoma (HCC) to include patients with clinically relevant portal hypertension (PHTN) and/or less‐than‐ideal liver function has been a topic of debate for quite some time. My co‐authors and I recently published results from analysis of a large, multinational data set that showed that the majority of patients undergoing hepatic resection for HCC did not meet the criteria set forth by guidelines of the American Association for Study of Liver Diseases (AASLD) or European Association for Study of the Liver (EASL) in terms of liver function and/or presence of clinically relevant PHTN.1 We also found that patients with either clinically relevant PHTN or total bilirubin >1 mg/dL achieved survival equivalent to candidates that were considered "ideal" based on AASLD/EASL criteria. However, survival was significantly lower for patients with both clinically relevant PHTN and total bilirubin >1 mg/dL. It is very reassuring to see that Professor Trevisani and his colleagues have validated our findings after their review of an independent, large data set from an Italian multicenter consortium. Their results regarding the expansion of criteria along the lines of PHTN and liver function are essentially identical to ours. They also demonstrated that hepatic resection for HCC in patients with either total bilirubin <2 mg/dL or those with PHTN resulted in survival equivalent to otherwise "ideal" candidates, but not when these two risk factors were combined. However, we must keep in mind that results of resection for HCC depend on the interaction among several variables, and that the extent of hepatic resection was not addressed by either of the above studies. This concept was very nicely demonstrated in the study by Cittero et al. showing that postoperative liver dysfunction was associated with three independent variables: PHTN, extent of resection and Model for End‐Stage Liver Disease (MELD) score.2 The study found that performing "limited" liver resection on patients with PHTN and MELD ≤9 carried a very low (4.9%) risk of postoperative hepatic dysfunction. Another prospectively conducted study by Cucchetti et al. also demonstrated that "limited" hepatic resections in patients with hepatic vein portal gradient (HVPG) ≥10 mm Hg could be performed safely with no mortality and with a low risk of postoperative hepatic dysfunction, particularly among those with MELD ≤10.3 We now have two independent, large, multicenter trials demonstrating that safe hepatic resection in patients with either elevated total bilirubin or clinically relevant PHTN is possible without compromising survival when compared to ideal candidates. The extent of resection has also been established as a critical and independent variable. Finally, we have prospective data demonstrating that "limited" resection in patients with HVPG ≥10 mm Hg can be performed safely. The mounting evidence seems to indicate that the criteria for hepatic resection may be narrowly, but safely, expanded by including patients with either elevated bilirubin or PHTN, but not both and only in the context of a "limited" resection. However, there are likely limits of portal pressure or bilirubin beyond which mortality starts to rise. Unfortunately, none of these studies have explored these limits. These should ideally be assessed in prospective studies. Our findings and those of Dr. Trevisani and his colleagues provide ethical justification for undertaking these studies.