Hypertrophy and Liver Function in ALPPS: Correlation with Morbidity and Mortality

Abstract

Background: ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) was introduced with the promise to reduce posthepatectomy liver failure (PHLF) in extended hepatectomies but has higher morbidity and mortality rates compared to conventional methods of volume enhancement. There are few studies of the incidence of PHLF after ALPPS and little information on how to avoid PHLF by functional testing. It remains unclear what causes the compromise in liver function despite rapid volume gain and if any of the modifications proposed reduce the incidence of PHLF. This review summarizes published data on this topic. Methods: This is a systematic review that studies literature on the incidence of liver failure and assessment of liver function following ALPPS as well as modifications of the existing technique. Articles were searched in PubMed, evaluated, selected, and tabulated. Results: The literature search revealed 326 articles that met the selection criteria. PHLF criteria as defined by the International Study Group of Liver Surgery (ISGLS) were the most commonly used criteria, but PHLF was frequently not defined. PHLF occurred most frequently after stage 2 of ALPPS at around 30% in most larger studies. Hepatobiliary scintigraphy showed a discrepancy between volume and functional growth of the liver. Function increase was only 50% compared to volume increase. Mechanistic explanations using histologic analyses have been given to explain the immaturity of the liver after rapid hypertrophy. Modifications of ALPPS showed a comparable volumetric gain when compared to classic ALPPS, but data were lacking to assess PHLF. Conclusion: ALPPS has relatively high rates of PHLF, morbidity, and mortality. This may be explained by data demonstrating functional growth when compared to volume growth. ALPPS should not be performed without functional assessment and with caution.

Mitochondrial function after associating liver partition and portal vein ligation for staged hepatectomy in an experimental model

“…Although ALPPS forces more hepatocytes into proliferation, causing significantly greater volumetric regeneration of the FLR, recent studies have reported significantly lagging functional recovery. As the maintenance of liver function is highly energy‐dependent, hepatocyte bioenergy impairment presumably underlies this slower functional regeneration.…”

“…Accordingly, ALPPS-induced accelerated weight gain is not the manifestation of passive congestion or oedema; it is indicative of cellular proliferation, consistent with the clinical findings of Eshmuminov and colleagues 22 . Although ALPPS forces more hepatocytes into proliferation, causing significantly greater volumetric regeneration of the FLR, recent studies 23,24 have reported significantly lagging functional recovery. As the maintenance of liver function is highly energy-dependent, hepatocyte bioenergy impairment presumably underlies this slower functional regeneration.…”

The role of proportionate kinetic growth rate fraction in future remnant liver function over volume determined by 99mTc-Mebrofenin hepatobiliary scintigraphy including SPECT and computed tomography in the risk prediction of postoperative mortality in ALPPS

“…[13][14][15][16] The "disproportionate" increase of the remnant liver volume compared to fRLF might be the cause of the greater morbidity and mortality reported in ALPPS. 7 In addition, recent pathologic studies of the remnant liver showing a higher density but smaller hepatocytes in the remnant liver seem to support the dysfunctional vol-ume theory. These hepatocytes also contain fewer organelles and are thus less metabolic active.…”

“…[3][4][5][6] Individually, the standard analysis of these preoperative assessments have shown shortcomings in predicting PHLF in the interstage of ALPPS. [7][8][9][10] But, by using the results in combination, we suggest a new integrated parameter: the relative proportion kinetic growth rate (KGR) fraction of functional over volume increase that might prove to be better at predicting PHLF at the interstage of ALPPS.…”

Frontiers of Liver Surgery

“…These recounts may provide us with hints for overcoming the unresolved challenges. Additionally, we asked an expert radiologist of PVE as well as two driving forces of the ALPPS procedure in the world to contribute articles on the state-of-the-art technique of PVE to obtain an optimal hypertrophy of the liver [3], on the relationship between hypertrophy and liver function in ALPPS [4], and on the pitfalls in PVE and ALPPS [5]. Moreover, since the modalities of assessing the functional reserve of the liver differ between Western and Eastern countries, we asked two experts in the field from each area to delineate the currently most reliable methods [6,7].…”