The Impact of Posthepatectomy Liver Failure on the Recurrence of Hepatocellular Carcinoma

Iguchi, Kohta; Hatano, Etsuro; Yamanaka, Kenya; Tanaka, Shiro; Taura, Kojiro; Üemoto, Shinji

doi:10.1007/s00268-013-2247-7

Cited by 18 publications

(18 citation statements)

References 48 publications

(63 reference statements)

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“…This results in liver dysfunction and failure, which can even lead to death via multiorgan system failure. Furthermore, tissue damage of the liver parenchyma induced by ischemia/reperfusion (I/R) can potentially lead to postoperative cancer recurrence …”

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confidence: 99%

CAAT/enhancer binding protein–homologous protein deficiency attenuates liver ischemia/reperfusion injury in mice

et al. 2018

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Ischemia/reperfusion injury (IRI) is one of the main causes of liver dysfunction after liver surgery. Involvement of endoplasmic reticulum (ER) stress in various diseases has been demonstrated, and CAAT/enhancer binding protein-homologous protein (CHOP) is a transcriptional regulator that is induced by ER stress. It is also a key regulator of ER stress-mediated apoptosis. The aim of this study was to investigate the role of CHOP in liver IRI. Wild type (WT) and CAAT/enhancer binding protein-homologous protein knockout (CHOP-/-) mice were subjected to 70% liver warm ischemia/reperfusion for 60 minutes. At different times after reperfusion, liver tissues and blood samples were collected for evaluation. Induction of ER stress including CHOP expression was ascertained. Liver damage was evaluated based on serum liver enzymes, liver histology, and neutrophil infiltration. Hepatocyte death including apoptosis was assessed. Liver warm IRI induced ER stress in both WT and CHOP-/- mice. In addition, CHOP expression was up-regulated in WT mice. At 6 hours after reperfusion, liver damage was attenuated in CHOP-/- mice. On the basis of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling staining, apoptotic and necrotic cells were significantly reduced in CHOP-/- mice. CHOP deficiency also reduced the cleavage of caspase 3 and expression of the proapoptotic protein B cell lymphoma 2-associated X protein. Liver IRI induces CHOP expression, and CHOP deficiency attenuates liver IRI by inhibiting apoptosis. Elucidation of the function of CHOP in liver IRI may contribute to further investigation for a therapy against liver IRI associated with the ER stress pathway. Liver Transplantation 24 645-654 2018 AASLD.

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CAAT/enhancer binding protein–homologous protein deficiency attenuates liver ischemia/reperfusion injury in mice

et al. 2018

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“…After ISGLS defined PHLF, Iguchi et al [12] reported significant differences in the duration of surgery (>300 min) and blood loss (>800 mL) between grade A and grades B/C PHLF [Iguchi, 2014]. Fukushima et al [5] reported major hepatectomy, intraoperative blood loss (>1,000 mL) and stage 3 fibrosis as independent risk factors for PHLF, according to the ISGLS definition [5].…”

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confidence: 99%

“…Some groups have investigated the independent risk factors for PHLF using the classification criteria by ISGLS. For example, Fukushima et al [5] reported extent of resection, intraoperative blood loss and fibrosis stage as independent risk factors for the development of PHLF; whereas Iguchi et al [12] showed significant differences in blood loss and duration of surgery between grade A and grade B/C patients.…”

Section: Introductionmentioning

confidence: 99%

“…Major liver resection is frequently contraindicated in many patients with HCC because of the increased risk of PHLF [9-11]. Some studies have shown that PHLF was associated with postoperative HCC recurrence and overall survival [5-12]. Previously, the definition of PHLF varied among studies and institutions; however, the term was recently defined by the International Study Group of Liver Surgery (ISGLS) as an increase in the international normalized ratio (INR) of prothrombin time and concomitant hyperbilirubinemia (according to the normal limits of the local laboratory) on or after postoperative day 5 [13].…”

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confidence: 99%

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Impaired Value of 99m Tc-GSA Scintigraphy as an Independent Risk Factor for Posthepatectomy Liver Failure in Patients with Hepatocellular Carcinoma

et al. 2018

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Background: Posthepatectomy liver failure (PHLF) was recently defined with the corresponding recommendations as follows: grade A, no change in clinical management; grade B, clinical management with noninvasive treatment; and grade C, clinical management with invasive treatment. In this study, we identified the risk factors for grade B and C PHLF in patients with hepatocellular carcinoma (HCC). Methods: Of 339 HCC patients who underwent curative hepatic resection, 218 were included for analysis. The LHL15 index (uptake ratio of the liver to that of the liver and heart at 15 min) was measured by 99m Tc-GSA (99m technetium-labelled galactosyl human serum albumin); remnant LHL15 was calculated as LHL15 × [1 − (resected liver weight − tumor volume)/whole liver volume without tumor]. Results: A total of 163 patients were classified as having no PHLF, whereas 17, 37, and 1 patient had PHLF grade A, B, and C, respectively. There were significant differences in indocyanine green R15, serum albumin, prothrombin time, Child-Pugh classification, LHL15 and remnant LHL15 between patients with grades B/C PHLF and patients with grade A or no PHLF. Only remnant LHL15 was identified as an independent risk factor for grades B/C PHLF (p = 0.023), with a cut-off value of 0.755. Conclusions: Remnant LHL15 was an independent risk factor for grades B/C PHLF. Patients with impaired remnant LHL15 value of <0.755 should be carefully monitored for PHLF.

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“…In establishing new criteria, we accepted the occurrence of grade A PHLF and grade B PHLF with a probability of approximately 20% ( table 4 ). Although PHLF has a negative impact on DFS and OS in patients with HCC [33,34] , no treatments (with the exception of hepatectomy) provide a longer survival benefit for patients with a high risk of PHLF after hepatectomy. A patient with grade A or B PHLF is able to recover from PHLF and rehabilitate within a few months after hepatectomy.…”

Section: Discussionmentioning

confidence: 99%

Validation of the Conventional Resection Criteria in Patients with Hepatocellular Carcinoma in Terms of the Incidence of Posthepatectomy Liver Failure and Long-Term Prognosis

Iguchi

Hatano²,

Yamanaka³

et al. 2015

Dig Surg

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Background/Aims: Resection criteria in hepatocellular carcinoma (HCC) should be established based on the risk of posthepatectomy liver failure (PHLF) and the survival benefit from hepatectomy. This study aimed at verifying the validity of the conventional criteria regarding the incidence of PHLF and the long-term prognosis of HCC patients. Methods: A retrospective study was performed on 265 patients who underwent major hepatectomy. Makuuchi's criteria and the future liver remnant plasma clearance rate of indocyanine green (ICGK-rem) ≥0.05 criterion were evaluated. Results: A total of 107 and 158 patients were within and beyond Makuuchi's criteria, respectively. Makuuchi's criteria were associated with the incidence of PHLF (p = 0.03) but not with its severity (p = 0.12). No differences in disease-free survival (DFS) or overall survival (OS) were observed between the groups (p = 0.75 and p = 0.94, respectively). Using the ICGK-rem ≥0.05 criterion, 223 and 42 patients were within and beyond the criterion, respectively. ICGK-rem was correlated with both the incidence of PHLF (p = 0.002) and its severity (p = 0.03). No differences in DFS or OS were observed between the groups (p = 0.75 and p = 0.29, respectively). Conclusions: Strict criteria are likely to preclude some patients from obtaining the greater survival benefits of hepatectomy. New criteria that consider patient prognosis are needed.

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The Impact of Posthepatectomy Liver Failure on the Recurrence of Hepatocellular Carcinoma

Abstract: EPLF was associated with postoperative HCC recurrence. The prevention of EPLF might improve the prognosis of patients with HCC.

Cited by 18 publications

References 48 publications

CAAT/enhancer binding protein–homologous protein deficiency attenuates liver ischemia/reperfusion injury in mice

CAAT/enhancer binding protein–homologous protein deficiency attenuates liver ischemia/reperfusion injury in mice

Impaired Value of 99m Tc-GSA Scintigraphy as an Independent Risk Factor for Posthepatectomy Liver Failure in Patients with Hepatocellular Carcinoma

Validation of the Conventional Resection Criteria in Patients with Hepatocellular Carcinoma in Terms of the Incidence of Posthepatectomy Liver Failure and Long-Term Prognosis

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