Effect of Hyperbilirubinemia on Hepatic Hypertrophy after Portal Vein Embolization and Liver Failure after Hepatectomy in Primary Biliary Malignancy

Clinical question
Does hyperbilirubinemia at the time of portal vein embolization (PVE) have an impact on hypertrophy of the future liver remnant (FLR) and the incidence of post-hepatectomy liver failure in primary biliary malignancy?

Take-away point
Hyperbilirubinemia at the time of PVE does not appear to have an effect on FLR hypertrophy. The incidence of grade 3 post-hepatectomy liver failure is not likely to be influenced, either.

Reference
Yim, Jaehyun et al. Effect of Hyperbilirubinemia on Hepatic Hypertrophy after Portal Vein Embolization and Liver Failure after Hepatectomy in Primary Biliary Malignancy. JVIR, Volume 30 , Issue 1 , 31 - 37

Click here for abstract

Study design:
Retrospective case-control study

Funding source:
Self-funded or unfunded

Setting:
Single tertiary referral center

Summary

Percutaneous transhepatic PVE is considered when extended hepatic resection for hepatobiliary malignancy is required but future liver remnant (FLR) volume is too small (recommended FLR 20-40%). High bilirubin levels at the time of PVE have been associated with poor hepatic hypertrophy and surgical outcomes. Treatment is often delayed to decrease serum bilirubin levels, which in turn risks progression of disease leading to unresectability. By convention, total serum bilirubin < 5mg/dl is recommended prior to PVE but this is not well defined in the literature. The authors divided 87 patients with primary biliary malignancy into a hyperbilirubinemia group (>3mg/dl) and a control group. FLR volumes and % FLR change were compared. Liver failure post-hepatectomy (defined as increasing INR and bilirubin levels on or after postop day 5) was also assessed. FLR volume and %FLR were not significantly different between the 2 groups on both univariable analysis and multivariable analysis (i.e. accounting for other potential factors affecting FLR hypertrophy). 75 patients underwent hepatectomy (n=23 right hepatectomy , n=52 right + seg IV). 63 patients experienced post-hepatectomy liver failure. Patients with hyperbilirubinemia had higher rates of hepatic failure after hepatectomy on univariable analysis but not significantly different on multivariable analysis.

Commentary

This retrospective study correlates total hyperbilirubinemia (5.80 ± 2.44 mg/dL) at time of PVE to FLR hypertrophy. The results suggest that PVE can be safely performed with hyperbilirubinemia without concern for inferior FLR hypertrophy outcomes. The study has the common limitations of a retrospective review and low patient numbers. The authors note that several factors affect FLR hypertrophy and many of these were accounted for in the multivariable analysis. This lends credence to the results of the study. A few factors were unaccounted for (e.g. fatty liver change) however the authors recognize this as a potential weakness. The percentage of liver failure following hepatic resection in this study is unusually high and substantially higher than comparative studies (49% vs 1.2-32%). This is attributed to a large number of patients in this study not achieving an FLR > 20% after PVE and prior to hepatectomy. FLR remnants < 20% following PVE suggest either a substandard PVE technique resulting in lower hypertrophy percentages or un-accounted confounding factors. Additionally, no explanation was provided by the authors for the amplified resection rates in patients without standard adequate FLRs, which in most literature requires at least 20% FLR. There is good merit in this study in that many practitioners performing PVE are likely using an anecdotal bilirubin of < 5mg/dl as a cutoff for PVE, which is based upon surgical literature. Future directions of study could include a subgroup analysis to identify a bilirubin inflection point where hepatic hypertrophy noticeably decreases. Further studies in this area will providence evidence based bilirubin criteria for improved outcomes following PVE and surgical resection.

Post author
Trevor Downing, M.D.
Assistant Professor
Department of Interventional Radiology
Wake Forest University, Baptist Medical Center
Winston Salem, N.C.