Combined preoperative albumin bilirubin score and hepatectomy percentage for evaluate the liver regeneration after partial hepatectomy

Abstract

Surgical resection is a pivotal therapeutic approach for addressing hepatic space-occupying lesions, with liver volume restoration and hepatic functional recovery being crucial for assessing surgical prognosis. The preoperative albumin-bilirubin (ALBI) score, encompassing serum albumin and bilirubin levels, can be determined via blood analysis, effectively mitigating human error and providing an accurate depiction of liver function. The hepatectomy ratio, which is the proportion of the liver volume removed to the total liver volume, is critical in preserving an adequate liver tissue volume to ensure postoperative hepatic functional compensation, minimize surgical complications, and reduce mortality rates. Incorporating the preoperative ALBI score and hepatectomy ratio aids surgeons in assessing the optimal timing and extent of partial hepatectomy. The introduction of preoperative albumin bilirubin score and hepatectomy percentage is beneficial for the surgeons to evaluate the timing and magnitude of partial liver resection.

Key Words: Liver regeneration; Partial hepatectomy; Preoperative albumin bilirubin score; Hepatectomy percentage

Core Tip: Preoperative albumin bilirubin score can visually indicate the reserve of liver function, which is one of the indexes to evaluate liver volume recovery after partial hepatectomy. Besides, the size of the removed portion of the liver is also critical for the recovery of liver volume. By combining these two methods, the surgeons can determine the size and timing of a partial liver removal.

TO THE EDITOR

We read with interest an observational study by Takahashi et al[1], who enrolled 268 patients who were underwent partial hepatectomy with different hepatectomy types. The regeneration index and late regeneration rate as quantitative indicators and multi-factor analysis showed that preoperative albumin bilirubin (ALBI) score and liver resection rate were independent risk factors for liver volume recovery, which resulted in an instructive advice for surgeons to perform a partial liver resection.

In a normal liver, cell turnover is very slow. However, experimental models of partial hepatectomy or chemical injury have shown that extracellular and intracellular signaling pathways are used to restore the liver to its pre-injury size and weight. Liver is the only solid organ ensure that the liver-to-weight ratio is always 100% in homeostasis by using a regenerative mechanism[2].

ALBI is a useful score for objectively evaluating liver function, the size of liver resection is closely related to liver regeneration[3]. We agree with author’s insight that liver regeneration after partial liver resection was determined by the percentage of liver resection and preoperative ALBI score, while different patterns of liver regeneration after partial liver resection can be evaluated in the same way is unclear.

Due to the adverse consequences of hepatic space occupying disease, partial resection of the liver can achieve a more ideal therapeutic goal. However, post-hepatectomy liver failure (PHLF) is closely related to the regenerative capacity of the remaining liver tissues. Therefore, accurate judgment of liver regeneration after hepatectomy is very important to avoid PHLF[4].

Hepatocyte-driven hepatic regeneration, which involves the proliferation of original hepatocytes, is the main mode of regeneration. On the other hand, hepatic progenitor cell-driven liver regeneration is a secondary mode. When the primary mode does not work effectively, the secondary mode plays an important role in liver regeneration. The liver mass is replaced by a replication of existing hepatocytes without activating progenitor cells in partial hepatectomy. However, in the case of chemical liver injury, activation and replication of progenitor cells does occur. Liver sinusoidal endothelial cells contribute to liver regeneration after partial hepatectomy and are key elements in regulating the liver response to injury and regeneration. Liver macrophages are a heterogeneous population in terms of origin and function. It is known to be involved in coordinating all stages of liver regeneration after partial hepatectomy[5]. Studies have shown that 30% of the residual liver after partial hepatectomy is only through hepatocyte hypertrophy without cell division and regeneration, and 70% of the partial hepatectomy is through hepatocyte hypertrophy and regeneration[6]. Latest research findings that in the classical 2/3 partial hepatectomy model, the spatial coordination mechanism of metabolism and intercellular regulatory networks during liver regeneration were be elucidated[7]. The results showed that the metabolic function of each liver region was down-regulated, although the liver retained its zoning characteristics during regeneration. Liver regeneration is mostly achieved through the IL-6/JAK/STAT3 signaling pathway that promotes hepatocyte proliferation and the PI3K/PDK1/Akt signaling pathway that promotes cell growth[8]. Besides, there were differences in cellular responses in different regions, such as higher activation of Wnt and NF-κB pathways in the central vein, higher activation of IL-6 pathways in the portal vein, and more active ribosome production in the middle region. The process of liver regeneration is mainly facilitated by the dynamic behavior of hepatocytes, in which hepatocytes undergo significant changes, such as reprogramming, in which they lose their original identity and acquire the properties of other cells. This phenomenon of hepatocyte reprogramming, coupled with hepatocyte expansion, plays a central role in liver regeneration[9]. Through spatial gene regulatory network analysis, we identified a series of important transcription factors involved in the maintenance of liver zoning, and elucidated the mechanism of spatial and temporal coordination of gene regulatory network in liver regeneration. Among them, it was found that transcriptional cofactor Tbl1xr1 was activated by inflammatory signals after hepatectomy[10], and knockdown of Tbl1xr1 significantly inhibited hepatocyte proliferation, demonstrating its key regulatory role in liver regeneration[11]. It is interesting to note that, in addition to partial liver resection, histological examination of patients with polycystic liver after unroofing and fenestration procedures showed no dysplasia in the cyst wall and significant increase in liver parenchyma, which may provide research direction for liver regeneration after compression relief. Studies have shown that the neural guiding protein netrin-1 has been reported to promote regeneration after nerve injury[12]. In addition, a study has found that caspase11/gasdermin D (GSDMD) mediated pyroptosis is activated in regenerating liver after 70% partial liver resection. By removing GSDMD to inhibit apoptosis, liver damage can be significantly reduced and liver regeneration can be accelerated[13].

Liver regeneration after partial hepatectomy is very important for the quality of life of patients after hepatectomy. Preoperative ALBI score and percentage of liver resection are important parts to judge liver regeneration. It is of great significance to study the process of liver regeneration by studying the changes of cells and the regulation of major signaling pathways after liver resection[14]. In the future, we should assess the factors that influence liver regeneration after hepatectomy by using more comprehensive global/multi-center studies.

At present, we can conclude that patients with preoperative liver function and ALBI grade 2a or higher may experience reduced postoperative liver regeneration. In addition, the residual liver volume after small liver resection has returned to its original size, but the residual liver volume after large liver resection has not returned to its original volume. So we have reason to believe that by combining these two aspects, liver regeneration after partial liver resection will receive a more authoritative reference.