Advertisement

A simple, noninvasively determined index predicting hepatic failure following liver resection for hepatocellular carcinoma

  • Tsuyoshi Ichikawa
  • Takahiro Uenishi
  • Shigekazu Takemura
  • Kazuki Oba
  • Masao Ogawa
  • Shintaro Kodai
  • Hiroji Shinkawa
  • Hiromu Tanaka
  • Takatsugu Yamamoto
  • Shogo Tanaka
  • Satoshi Yamamoto
  • Seikan Hai
  • Taichi Shuto
  • Kazuhiro Hirohashi
  • Shoji Kubo
ORIGINAL ARTICLE

Abstract

Background

A novel index, the serum aspartate aminotransferase activity/platelet count ratio index (APRI), has been identified as a biochemical surrogate for histological fibrogenesis and fibrosis in cirrhosis. We evaluated the ability of preoperative APRI to predict hepatic failure following liver resection for hepatocellular carcinoma.

Methods

Potential preoperative risk factors for postoperative hepatic failure (hepatic coma with hyperbilirubinemia, four patients; intractable pleural effusion or ascites, 30 patients; and variceal bleeding, one patient) as well as APRI were evaluated in 366 patients undergoing liver resection for hepatocellular carcinoma. Prognostic significance was determined by univariate and multivariate analyses.

Results

Hepatic failure developed postoperatively in 30 patients, causing death in four. APRI correlated with histological intensity of hepatitis activity and degree of hepatic fibrosis, and was significantly higher in patients who developed postoperative hepatic failure than in others without failure. Risk of postoperative hepatic failure increased as the serum albumin concentration and platelet count decreased and as indocyanine green retention rate at 15 min, aspartate and alanine aminotransferase activities, and APRI increased. Only APRI was an independent preoperative factor on multivariate analysis. Of the four patients who died of postoperative hepatic failure, three had an APRI of at least 10.

Conclusions

Preoperative APRI independently predicted hepatic failure following liver resection for hepatocellular carcinoma. Patients with an APRI of 10 or more have a high risk of postoperative hepatic failure.

Keywords

Liver resection Hepatocellular carcinoma Liver failure APRI Platelet count 

Abbreviations

HCC

Hepatocellular carcinoma

APRI

Aspartate aminotransferase/platelet count ratio index

Anti-HCV

Anti-hepatitis C virus antibody

HBsAg

Hepatitis B surface antigen

ICGR15

Indocyanine green retention rate at 15 min

AST

Aspartate aminotransferase

ALT

Alanine aminotransferase

AFP

α-Fetoprotein

HAI

Histological activity index

Introduction

Liver resection in patients with hepatocellular carcinoma (HCC) may result in postoperative hepatic failure, since most patients with HCC also have chronic liver disease including cirrhosis [1, 2, 3, 4, 5, 6, 7, 8, 9]. To avoid resection likely to lead to postoperative hepatic failure, various methods have been developed for preoperative assessment of liver function [4, 5, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19]. However, some of these are complex and require calculations involving multiple formulas.

Previous studies have identified hepatic fibrosis and active hepatitis as negative predictive factors for effective liver regeneration and as risk factors for postoperative hepatic failure [3, 9, 20, 21]. Histopathologic examination of liver biopsy specimens presently remains the “gold standard” for assessing degree of active hepatitis and hepatic fibrosis. However, liver biopsy cannot be performed in all candidates for liver surgery because of its cost and risk of complications. Recently, a novel index, the aspartate aminotransferase (AST)/platelet count ratio index (APRI), has been identified as a biochemical marker for histological fibrogenesis and fibrosis in cirrhosis [22, 23]. APRI has been reported to correlate with hepatic fibrosis and magnitude of abnormalities in liver function tests [22, 23]. This simple ratio is calculated from results of routinely available, noninvasive, and inexpensive laboratory tests.

In the present study, we evaluated the relationship between preoperative APRI and postoperative hepatic failure following liver resection, and the ability of the ratio to serve as a marker to identify candidates who cannot safely undergo liver resection for HCC.

Patients and methods

Patients and determination of APRI

From the beginning of 1994 to the end of 2004, liver resection for HCC was performed for 372 patients in our department. Patients excluded from this study included five who underwent concomitant resection of a synchronous second tumor, and one who underwent liver resection combined with right atrial tumor thrombectomy requiring extracorporeal circulation. The 366 patients remaining as subjects in this study included 297 men and 69 women; their ages ranged from 30 to 85 years (mean ± SD, 63.6 ± 8.2). In total, 249 patients were positive for anti-hepatitis C antibody (anti-HCV) alone, 54 patients for hepatitis B surface antigen (HBsAg) alone, four patients for both anti-HCV and HBsAg, and 59 patients were negative for both viral markers. APRI was calculated as AST activity (IU/L)/platelet count (104/μl) [22].

The study was conducted in accordance with the Helsinki Declaration and the guidelines of the Ethics Committee at our institution.

Postoperative hepatic failure

Variables previously shown to predict postoperative hepatic failure included hepatic coma with hyperbilirubinemia (total serum bilirubin concentration >5 mg/dl for more than 5 days); intractable pleural effusion or ascites requiring use of diuretics or thoracocentesis, or abdominal paracentesis on two or more occasions or institution of continuous abdominal drainage; or variceal bleeding [24, 25].

Operative procedure

The operative procedures is outlined below (major hepatectomy; segmentectomy or greater, minor hepatectomy; smaller than segmentectomy, anatomic hepatectomy; subsegmentectomy or greater, nonanatomic hepatectomy; smaller than subsegmentectomy).

Pathologic examination

Surgical specimens were cut serially into tissue blocks 5 mm thick, fixed in 10% formalin, and stained with hematoxylin and eosin. Histologic grade with respect to tumor differentiation was assigned using a modification of the classification by Edmondson and Steiner [26, 27]. The histologic activity index (HAI) was used with some modifications [28, 29] to evaluate severity of active hepatitis (histologic activity grade) and degree of hepatic fibrosis (histologic fibrosis grade). HAI scores consist of four components: component 1, periportal necrosis with or without bridging necrosis; component 2, intralobular degeneration and focal necrosis; component 3, portal inflammation; and component 4, fibrosis. Summed HAI scores of 0 for (components 1–3) indicated no activity (histologic activity score, 0); scores of 1–3, minimal activity (histologic activity score, 1); scores of 4–8, mild activity (histologic activity score, 2); scores of 9–12, moderate activity (histologic activity score, 3); and score of 13 or more indicated severe activity (histologic activity score, 4). The degree of fibrosis (histologic fibrosis score) was determined from component 4 of the HAI score. A histologic fibrosis grade of 1 indicated portal fibrous expansion; a grade of 2 indicated the presence of portal–portal septa without architectural distortion; a grade of 3 indicated portocentral septa with architectural distortion; and a grade of 4 indicated cirrhosis.

Statistics

Student’s t test was used to examine differences in age and tumor size. The Mann–Whitney U test was used to examine differences in laboratory test results. Fisher’s exact test or the χ2 test was used to compare categorical data between groups. Correlations between APRI and results of other laboratory tests were determined using Pearson’s correlation coefficient. The correlation between the APRI and histologic activity score or fibrosis score in noncancerous liver was determined by Spearman’s rank correlation. Odds ratios were used to estimate relative risk for postoperative hepatic failure. Logistic regression was used for univariate analysis, while multiple logistic regression analysis was used for multivariate analysis. For multivariate analysis, variables possibly significant (P < 0.1) on univariate analysis were evaluated. P values less than 0.05 were considered significant.

Results

Preoperative APRI, which ranged from 0.6 to 51.3 (mean ± SD, 5.0 ± 4.4), correlated with serum concentrations of total bilirubin and albumin, indocyanine green retention test results at 15 min (ICGR15), serum activities of AST and alanine aminotransferase (ALT), platelet count, and prothrombin test (Table 1).
Table 1

Correlations between APRI and results of other laboratory tests

Laboratory test

Correlation coefficient

P value

Total bilirubin

0.306

<0.0001

Albumin

−0.248

<0.0001

ICGR15

0.280

<0.0001

AST

0.756

<0.0001

ALT

0.625

<0.0001

Platelet count

−0.555

<0.0001

Prothrombin test (%)

−0.132

0.0119

ICGR 15 Indocyanine green retention rate at 15 min, AST aspartate aminotransferase, ALT alanine aminotransferase

APRI also correlated with both histologic activity score (P = 0.0003) and histologic fibrosis score (P = 0.0247).

Postoperative hepatic failure developed in 30 patients (hepatic coma with hyperbilirubinemia in four patients; intractable pleural effusion or ascites in 30 patients; and variceal bleeding in one patient). Four of these patients died of hepatic failure while still in the hospital. Clinicopathologic findings were compared between the 30 patients with postoperative hepatic failure and the 336 patients without failure (Table 2). These groups were similar in age, gender, percentage of patients with a history of alcohol abuse (defined as an estimated daily intake of 86 g of ethanol for at least 10 years, according to the criteria of the Liver Cancer Study Group of Japan [30]), diabetes mellitus, blood transfusion, and anti-HCV and HBsAg positivity. Although serum total bilirubin concentration, ICGR15, and prothrombin test results did not differ between groups, serum albumin concentration and platelet count were significantly lower in patients with postoperative hepatic failure than in these without it. Serum activities of AST and ALT and also the APRI (Fig. 1) were significantly higher in patients with than without postoperative hepatic failure. Although no difference was noted in tumor size, operative procedure, or operative time was noted between them, intraoperative blood loss was significantly greater in patients who developed postoperative hepatic failure. The percentage of patients with moderate hepatitis activity (histologic activity grade 3) or cirrhosis (histologic fibrosis grade 4) was significantly greater in patients who developed postoperative hepatic failure.
Table 2

Demographic and clinicopathologic features of patients with and without hepatic failure after liver resection

Parameter

Hepatic failure

P value

No, n = 336

Yes, n = 30

Age, years, mean ± SD

63.6 ± 8.4

64.0 ± 6.9

0.8912

Gender, M:F

274:62

23:7

0.5125

Alcohol abuse

115

10

0.9593

History of blood transfusion

75

8

0.5922

Anti-HCV

229

24

0.1784

HBs-Ag

54

4

0.6940

Diabetes mellitus

55

7

0.4562

Total bilirubin (mg/dl)

0.8 (0.5, 1.3)

0.9 (0.5, 1.4)

0.3008

Albumin (g/dl)

3.7 (3.3, 4.2)

3.6 (2.9, 4.1)

0.0309

ICGR15 (%)

15.0 (7.5, 25.2)

17.8 (7.0, 34.5)

0.2434

AST (IU/l)

52 (30, 96)

64 (46, 107)

0.0208

ALT (IU/l)

56 (26, 113)

70 (38, 129)

0.0232

Platelet count (×104/μl)

14.3 (8.4, 22.9)

11.6 (5.6, 20.5)

0.0068

Prothrombin test (%)

94 (73, 135)

94 (76, 131)

0.9798

APRI

3.8 (1.6, 9.0)

5.3 (2.6, 13.3)

0.0039

AFP, >20 ng/ml

180

18

0.5200

Tumor size, cm, mean ± SD

3.8 ± 2.8

4.2 ± 2.8

0.4504

Operative procedure, major:minor

125:211

14:16

0.3061

Operative procedure, anatomic:nonanatomic

170:166

17:13

0.2571

Intraoperative blood loss (g)

725 (196, 2595)

1450 (478, 3662)

0.0002

Time of operation (min)

282 (180, 440)

317 (213, 500)

0.1016

Histologic activity grade

 0–2

300

20

0.0003

 3

34

10

 

Histologic fibrosis grade

 0–3

194

11

0.0247

 4, representing cirrhosis

141

19

 

Most laboratory results, intraoperative blood loss, and time of operation are given as medians (with 10th and 90th percentiles)

Anti-HCV Anti-hepatitis C virus antibody, HBsAg hepatitis B surface antigen, ICGR 15 indocyanine green retention rate at 15 min, AST aspartate aminotransferase, ALT alanine aminotransferase, AFP α-fetoprotein

Fig. 1

APRI in two groups of patients who underwent liver resection for hepatocellular carcinoma. APRI values of patients with and without postoperative hepatic failure ranged from 0.6 to 26 and from 1.1 to 51.3, respectively (mean ± SD, means shown as small squares, 8.3 ± 9.3 and 4.7 ± 3.5). Bars, 10th and 90th percentiles; bottoms and tops of boxes, 25th and 75th percentiles; lines across boxes, medians; circles, outliers; closed circles, patients who died of postoperative hepatic failure

Table 3 shows odds ratios (OR) for the candidate risk factors associated with postoperative hepatic failure as calculated by univariate analysis. Serum albumin concentration (OR = 0.241), ICGR15 (OR = 1.046), AST (OR = 1.008), ALT (OR = 1.008), platelet count (OR = 0.925), APRI (OR = 1.125), histologic activity grade 3 (OR = 4.286), and cirrhosis (OR = 2.377) were risk factors for postoperative hepatic failure. APRI in three of the four patients who died of postoperative hepatic failure was 10 or more. Risk of postoperative hepatic failure increased as serum albumin concentration and platelet count decreased, and as ICGR15, AST, and ALT activities and APRI increased. Risk of postoperative hepatic failure also increased with greater intraoperative blood loss, and was also high in patients with moderately active hepatitis or cirrhosis according to histopathologic examination. Risk of postoperative hepatic failure correlated closely with both severity of active hepatitis and degree of hepatic fibrosis.
Table 3

Risk factors for hepatic failure after liver resection for hepatocellular carcinoma, evaluated by univariate analysis

Variable

Odds ratio

95% CI

P value

Age (per 1 year)

1.003

0.958–1.050

0.8908

Gender

 Female

1.000

  

 Male

0.743

0.305–1.810

0.5138

Alcohol abuse

 (−)

1.000

  

 (+)

0.979

0.441–2.177

0.9593

History of blood transfusion

 (−)

1.000

  

 (+)

1.261

0.539–2.947

0.5929

Anti-HCV

 (−)

1.000

  

 (+)

1.869

0.742–4.707

0.1844

HBsAg

 (−)

1.000

  

 (+)

0.803

0.270–2.395

0.6945

Diabetes mellitus

 (−)

1.000

  

 (+)

1.406

0.572–3.456

0.4580

AFP (ng/ml)

 ≤20

1.000

  

 >20

1.283

0.599–2.748

0.5208

Total bilirubin (per 1 mg/ml)

1.788

0.616–5.184

0.2848

Albumin (per 1 g/dl)

0.241

0.086–0.678

0.0070

ICGR15 (per 1%)

1.046

1.005–1.088

0.0272

AST (per 1 IU/l)

1.008

1.000–1.017

0.0459

ALT (per 1 IU/l)

1.008

1.000–1.016

0.0572

Platelet count (per 1 × 104/μl)

0.925

0.860–0.996

0.0385

Prothrombin test (per 1%)

0.999

0.983–1.016

0.9279

APRI (per 1)

1.125

1.045–1.211

0.0017

Operative procedure

 Minor

1.000

  

 Major

1.477

0.697–3.129

0.3085

Operative procedure

 Non-anatomic

1.000

  

 Anatomic

1.529

0.736–3.175

0.2545

Intraoperative blood loss (per 1 g)

1.000

1.000–1.001

0.0147

Time of operation (per 1 min)

1.003

1.000–1.006

0.0804

Histologic activity grade

 0–2

1.000

  

 3

4.286

1.858–9.888

0.0006

Histologic fibrosis grade

 1–3

1.000

  

 4, representing cirrhosis

2.377

1.096–5.152

0.0283

Anti-HCV Anti-hepatitis C virus antibody, HBsAg hepatitis B surface antigen, ICGR 15 indocyanine green retention rate at 15 min, AST aspartate aminotransferase, ALT alanine aminotransferase, AFP α-fetoprotein

Multivariate analysis was used to estimate the adjusted odds ratio for postoperative hepatic failure based on preoperative data (Table 4). Because the aim of this study was to evaluate the role of the APRI as preoperative prediction of postoperative hepatic failure; significant risk factors on univariate analysis which were acquired postoperatively were eliminated. APRI was the only independent preoperative risk factor for postoperative hepatic failure (adjusted OR = 1.098, 95% CI; 1.018–1.184).
Table 4

Risk factors for hepatic failure after liver resection for hepatocellular carcinoma, evaluated by multivariate analysis

Variable

Odds ratio

95% CI

P value

Albumin (per 1 g/dl)

0.360

0.114–1.140

0.0823

ICGR15 (per 1%)

1.026

0.975–1.081

0.3222

Prothrombin test (per 1%)

1.007

0.990–1.025

0.4052

APRI

1.098

1.018–1.184

0.0149

ICGR 15 Indocyanine green retention rate at 15 min, APRI AST to platelet ratio index

We next compared the 330 patients with a low APRI (<10) with the 33 patients whose APRI was high (≥10) (Table 5). A cut-off line for APRI of 10 yielded the most significant differences in cut off lines (counting number) which we decided. The sensitivity, specificity, and positive predictive value of APRI ≥ 10 for postoperative hepatic failure were 27.3%, 7.8%, and 27.3%, respectively. The prevalence of hepatic coma and intractable pleural effusion or ascites was significantly higher among patients with a high APRI than in those with a low APRI. Variceal bleeding developed in only one patient, who had an elevated APRI (≥10). Although only 1 of the 333 patients with a low APRI died of postoperative hepatic failure, 3 of 33 patients with a high APRI died of this complication (P = 0.0025). APRI was ≥10 in three of four patients who died of postoperative hepatic failure. The serum concentrations of total bilirubin and albumin, ICGR15, and prothrombin test results were distributed over wide ranges in these four patients (Table 6).
Table 5

Features of hepatic failure in patients with high or low APRI

Feature

APRI

P value

≤10

>10

(n = 333)

(n = 33)

Hepatic coma

2

2

0.0422

Intractable pleural effusion or ascites

23

10

<0.0001

Variceal bleeding

0

1

0.0902

Death from hepatic failure

1

3

0.0025

Table 6

Results of laboratory tests and operative methods in four patients who died of postoperative hepatic failure

Patient no.

Age (year)

T-bil (mg/dl)

Albumin (g/dl)

ICGR15 (%)

Prothrombin test (%)

APRI

Operative method

1

72

0.3

3.0

37.4

74

11.0

Partial

2

62

0.9

3.0

13.0

94

12.7

Partial

3

59

1.4

3.8

23.1

100

3.96

Rt. lobectomy

4

55

1.3

2.9

26.9

104

11.5

Partial

T-bil Total bilirubin, ICGR 15 indocyanine green retention rate at 15 min, APRI AST to platelet ratio index

The clinical significance of the APRI in the determination of operative methods was investigated. The APRI was 10 or greater in only 4 of 139 patients who underwent major hepatectomy; it is thus not possible to evaluate the role of APRI in only patients who underwent major hepatectomy. For the 227 patients who underwent minor hepatectomy, APRI was a significant risk factor for postoperative hepatic failure.

Discussion

In this study, we attempted to develop a preoperative risk marker for predicting postoperative hepatic failure in patients with hepatocellular carcinoma who are candidates for hepatic resection using only routine laboratory tests. High APRI was a risk factor for postoperative hepatic failure on univariate analysis and the only independent preoperative risk factor on multivariate analysis.

Cirrhosis is a well-known risk factor for postoperative hepatic failure [3, 10, 13, 20, 31, 32]. Degree of hepatic fibrosis is a negative predictor of liver regeneration and restoration of liver function after liver resection [33] that also influences the risk of postoperative ascites and pleural effusion [34] and duration of postoperative hepatic failure [9]. Active hepatitis has also been reported to be a potential risk factor for hepatic failure following liver resection [9, 31, 35]. We previously reported that active hepatitis and severe hepatic fibrosis are each risk factors for postoperative hepatic failure [25]. However, since biopsy specimens of noncancerous hepatic tissue are not readily obtainable preoperatively from all patients for reasons of safety and other issues, less invasive markers are needed. Recently, the APRI, which is calculated from AST activity and the platelet count, has been reported to correlate with histologic degree of hepatic fibrosis [22, 23]. In the present study we confirmed that APRI correlated with both histologic activity grade and histologic fibrosis grade in patients with HCC. Thus, preoperative determination of the APRI informs the surgeon about severity of active hepatitis and degree of fibrosis, and provides a measure of the risk of postoperative hepatic failure.

The indocyanine green clearance test has been used to develop guidelines for extent of liver resection [3, 5, 7, 18, 21, 36, 37, 38, 39, 40, 41, 42]. In this study, the role of the APRI in decision-making concerning extent of liver resection since remained unclear. In fact, it was not possible to evaluate the role of the APRI, since the APRI was 10 or greater in only 4 of 139 patients who underwent major hepatectomy. The percentage of patients with postoperative hepatic failure was significantly higher among those with a high APRI (≥10) than among those with a low APRI (<10). The percentage of patients who died of hepatic failure also was significantly higher among those with a high APRI than among those with a low APRI. We suggest that APRI ≥ 10 is a more useful marker for postoperative death than any other laboratory tests (total bilirubin, albumin, ICGR15, and prothrombin test). The APRI was thus useful for determining whether liver resection itself is indicated in patients with chronic liver disease. Since patients who have a high APRI have active hepatitis and severe hepatic fibrosis, care is needed to avoid postoperative hepatic failure. Treatments for HCC include locoregional treatment including percutaneous ethanol injection, microwave coagulation therapy, and radiofrequency ablation therapy and transarterial therapy, including transcatheter arterial embolization and hepatic arterial infusion chemotherapy [43]. These alternatives can be considered for patients with a high APRI.

Other reported risk factors for postoperative hepatic failure include patient age [10, 31], diabetes mellitus [13], and excessive intraoperative blood loss [7, 13, 18, 21, 32, 33]. Although excessive intraoperative blood loss was a risk factor on univariate analysis, age and diabetes mellitus were not found to be risk factors in the present study.

In conclusion, preoperative APRI was correlated with postoperative hepatic failure; in particular, APRI of ten or more carries a high risk of postoperative hepatic failure.

References

  1. 1.
    Lai EC, Fan ST, Lo CM, Chu KM, Liu CL, Wong J. Hepatic resection for hepatocellular carcinoma. An audit of 343 patients. Ann Surg. 1995;221:291–8.PubMedCrossRefGoogle Scholar
  2. 2.
    Takenaka K, Kawahara N, Yamamoto K, Kajiyama K, Maeda T, Itasaka H, et al. Results of 280 liver resections for hepatocellular carcinoma. Arch Surg. 1996;131:71–6.PubMedGoogle Scholar
  3. 3.
    Wu CC, Ho WL, Yeh DC, Huang CR, Liu TJ, P’Eng FK. Hepatic resection of hepatocellular carcinoma in cirrhotic livers: is it unjustified in impaired liver function? Surgery. 1996;120:34–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Cohnert TU, Rau HG, Buttler E, Hernandez-Richter T, Sauter G, Reuter C, et al. Preoperative risk assessment of hepatic resection for malignant disease. World J Surg. 1997;21:396–400.PubMedCrossRefGoogle Scholar
  5. 5.
    Lau H, Man K, Fan ST, Yu WC, Lo CM, Wong J. Evaluation of preoperative hepatic function in patients with hepatocellular carcinoma undergoing hepatectomy. Br J Surg. 1997;84:1255–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Lise M, Bacchetti S, Da Pian P, Nitti D, Pilati PL, Pigato P. Prognostic factors affecting long term outcome after liver resection for hepatocellular carcinoma: results in a series of 100 Italian patients. Cancer. 1998;82:1028–36.PubMedCrossRefGoogle Scholar
  7. 7.
    Nonami T, Nakao A, Kurokawa T, Inagaki H, Matsushita Y, Sakamoto J, et al. Blood loss and ICG clearance as best prognostic markers of post-hepatectomy liver failure. Hepatogastroenterology. 1999;46:1669–72.PubMedGoogle Scholar
  8. 8.
    Pol B, Campan P, Hardwigsen J, Botti G, Pons J, Le Treut YP. Morbidity of major hepatic resections: a 100-case prospective study. Eur J Surg. 1999;165:446–53.PubMedCrossRefGoogle Scholar
  9. 9.
    Farges O, Malassagne B, Flejou JF, Balzan S, Sauvanet A, Belghiti J. Risk of major liver resection in patients with underlying chronic liver disease: a reappraisal. Ann Surg. 1999;229:210–5.PubMedCrossRefGoogle Scholar
  10. 10.
    Yamanaka N, Okamoto E, Kuwata K, Tanaka N. A multiple regression equation for prediction of posthepatectomy liver failure. Ann Surg. 1984;200:658–63.PubMedCrossRefGoogle Scholar
  11. 11.
    Didolkar MS, Fitzpatrick JL, Elias EG, Whitley N, Keramati B, Suter CM, et al. Risk factors before hepatectomy, hepatic function after hepatectomy and computed tomographic changes as indicators of mortality from hepatic failure. Surg Gynecol Obstet. 1989;169:17–26.PubMedGoogle Scholar
  12. 12.
    Noguchi T, Imai T, Mizumoto R. Preoperative estimation of surgical risk of hepatectomy in cirrhotic patients. Hepatogastroenterology. 1990;37:165–71.PubMedGoogle Scholar
  13. 13.
    Shimada M, Matsumata T, Akazawa K, Kamakura T, Itasaka H, Sugimachi K, et al. Estimation of risk of major complications after hepatic resection. Am J Surg. 1994;167:399–403.PubMedCrossRefGoogle Scholar
  14. 14.
    Kwon AH, Ha-Kawa SK, Uetsuji S, Kamiyama Y, Tanaka Y. Use of technetium 99 m diethylenetriamine-pentaacetic acid-galactosyl-human serum albumin liver scintigraphy in the evaluation of preoperative and postoperative hepatic functional reserve for hepatectomy. Surgery. 1995;117:429–34.PubMedCrossRefGoogle Scholar
  15. 15.
    Bruix J, Castells A, Bosch J, Feu F, Fuster J, Garcia-Pagan JC, et al. Surgical resection of hepatocellular carcinoma in cirrhotic patients: prognostic value of preoperative portal pressure. Gastroenterology. 1996;111:1018–22.PubMedCrossRefGoogle Scholar
  16. 16.
    Zimmermann H, Reichen J. Hepatectomy: preoperative analysis of hepatic function and postoperative liver failure. Dig Surg. 1998;15:1–11.PubMedCrossRefGoogle Scholar
  17. 17.
    Kubota K, Makuuchi M, Kusaka K, Kobayashi T, Miki K, Hasegawa K, et al. Measurement of liver volume and hepatic functional reserve as a guide to decision-making in resectional surgery for hepatic tumors. Hepatology. 1997;26:1176–81.PubMedGoogle Scholar
  18. 18.
    Miyagawa S, Makuuchi M, Kawasaki S, Kakazu T. Criteria for safe hepatic resection. Am J Surg. 1995;169:589–94.PubMedCrossRefGoogle Scholar
  19. 19.
    Belghiti J, Ogata S. Assessment of hepatic reserve for indication of hepatic resection. J Hepatobiliary Pancreat Surg. 2005;12:1–3.PubMedCrossRefGoogle Scholar
  20. 20.
    Nagasue N, Yukaya H, Ogawa Y, Kohno H, Nakamura T. Human liver regeneration after major hepatic resection. A study of normal liver and livers with chronic hepatitis and cirrhosis. Ann Surg. 1987;206:30–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Das BC, Isaji S, Kawarada Y. Analysis of 100 consecutive hepatectomies: risk factors in patients with liver cirrhosis or obstructive jaundice. World J Surg. 2001;25:266–72. discussion 272–273.PubMedCrossRefGoogle Scholar
  22. 22.
    Wai CT, Greenson JK, Fontana RJ, Kalbfleisch JD, Marrero JA, Conjeevaram HS, et al. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology. 2003;38:518–26.PubMedCrossRefGoogle Scholar
  23. 23.
    Castera L, Vergniol J, Foucher J, Le Bail B, Chanteloup E, Haaser M, et al. Prospective comparison of transient elastography, fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C. Gastroenterology. 2005;128:343–50.PubMedCrossRefGoogle Scholar
  24. 24.
    Horii K, Kubo S, Hirohashi K, Kinoshita H. Changes in erythrocyte deformability after liver resection for hepatocellular carcinoma associated with chronic liver disease. World J Surg. 1999;23:85–90.PubMedCrossRefGoogle Scholar
  25. 25.
    Kubo S, Tsukamoto T, Hirohashi K, Tanaka H, Shuto T, Takemura S, et al. Correlation between preoperative serum concentration of type IV collagen 7 s domain and hepatic failure following resection of hepatocellular carcinoma. Ann Surg. 2004;239:186–93.PubMedCrossRefGoogle Scholar
  26. 26.
    Liver Cancer Study Group of Japan. Classification of primary liver cancer. 1st English ed. Tokyo: Kanehara; 1997.Google Scholar
  27. 27.
    Edmondson HA, Steiner PE. Primary carcinoma of the liver: a study of 100 cases among 48, 900 necropsies. Cancer. 1954;7:462–503.PubMedCrossRefGoogle Scholar
  28. 28.
    Knodell RG, Ishak KG, Black WC, Chen TS, Craig R, Kaplowitz N, et al. Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology. 1981;1:431–5.PubMedCrossRefGoogle Scholar
  29. 29.
    Desmet VJ, Gerber M, Hoofnagle JH, Manns M, Scheuer PJ. Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology. 1994;19:1513–20.PubMedCrossRefGoogle Scholar
  30. 30.
    Liver Cancer Study Group of Japan. Primary liver cancer in Japan: clinicopathological features and results of surgical treatment. Ann Surg. 1990;211:277–87.Google Scholar
  31. 31.
    Nagasue N, Kohno H, Tachibana M, Yamanoi A, Ohmori H, El-Assal ON. Prognostic factors after hepatic resection for hepatocellular carcinoma associated with child-Turcotte class B and C cirrhosis. Ann Surg. 1999;229:84–90.PubMedCrossRefGoogle Scholar
  32. 32.
    Takenaka K, Kanematsu T, Fukuzawa K, Sugimachi K. Can hepatic failure after surgery for hepatocellular carcinoma in cirrhotic patients be prevented? World J Surg. 1990;14:123–7.PubMedCrossRefGoogle Scholar
  33. 33.
    Miyazaki S, Takasaki K, Yamamoto M, Tsugita M, Otsubo T. Liver regeneration and restoration of liver function after partial hepatectomy: the relation of fibrosis of the liver parenchyma. Hepatogastroenterology. 1999;46:2919–24.PubMedGoogle Scholar
  34. 34.
    Tanaka S, Kubo S, Tsukamoto T, Hirohashi K, Tanaka H, Shuto T, et al. Risk factors for intractable pleural effusion after liver resection. Osaka City Med J. 2004;50:9–18.PubMedGoogle Scholar
  35. 35.
    Eguchi H, Umeshita K, Sakon M, Nagano H, Ito Y, Kishimoto SI, et al. Presence of active hepatitis associated with liver cirrhosis is a risk factor for mortality caused by posthepatectomy liver failure. Dig Dis Sci. 2000;45:1383–8.PubMedCrossRefGoogle Scholar
  36. 36.
    Fan ST, Lai EC, Lo CM, Ng IO, Wong J. Hospital mortality of major hepatectomy for hepatocellular carcinoma associated with cirrhosis. Arch Surg. 1995;130:198–203.PubMedGoogle Scholar
  37. 37.
    Matsumata T, Kanematsu T, Yoshida Y, Furuta T, Yanaga K, Sugimachi K. The indocyanine green test enables prediction of postoperative complications after hepatic resection. World J Surg. 1987;11:678–81.PubMedCrossRefGoogle Scholar
  38. 38.
    Fujio N, Sakai K, Kinoshita H, Hirohashi K, Kubo S, Iwasa R, et al. Results of treatment of patients with hepatocellular carcinoma with severe cirrhosis of the liver. World J Surg. 1989;13:211–7. discussion 217–218.PubMedCrossRefGoogle Scholar
  39. 39.
    Hemming AW, Scudamore CH, Shackleton CR, Pudek M, Erb SR. Indocyanine green clearance as a predictor of successful hepatic resection in cirrhotic patients. Am J Surg. 1992;163:515–8.PubMedCrossRefGoogle Scholar
  40. 40.
    Yasui M, Harada A, Torii A, Nakao A, Nonami T, Takagi H. Impaired liver function and long-term prognosis after hepatectomy for hepatocellular carcinoma. World J Surg. 1995;19:439–43.PubMedCrossRefGoogle Scholar
  41. 41.
    Midorikawa Y, Kubota K, Takayama T, Toyoda H, Ijichi M, Torzilli G, et al. A comparative study of postoperative complications after hepatectomy in patients with and without chronic liver disease. Surgery. 1999;126:484–91.PubMedGoogle Scholar
  42. 42.
    Imamura H, Sano K, Sugawara Y, Kokudo N, Makuuchi M. Assessment of hepatic reserve for indication of hepatic resection: decision tree incorporating indocyanine green test. J Hepatobiliary Pancreat Surg. 2005;12:16–22.PubMedCrossRefGoogle Scholar
  43. 43.
    Poon RT, Fan ST, Tsang FH, Wong J. Locoregional therapies for hepatocellular carcinoma: a critical review from the surgeon’s perspective. Ann Surg. 2002;235:466–86.PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2008

Authors and Affiliations

  • Tsuyoshi Ichikawa
    • 1
  • Takahiro Uenishi
    • 2
  • Shigekazu Takemura
    • 1
  • Kazuki Oba
    • 1
  • Masao Ogawa
    • 1
  • Shintaro Kodai
    • 1
  • Hiroji Shinkawa
    • 1
  • Hiromu Tanaka
    • 1
  • Takatsugu Yamamoto
    • 2
  • Shogo Tanaka
    • 2
  • Satoshi Yamamoto
    • 1
  • Seikan Hai
    • 1
  • Taichi Shuto
    • 3
  • Kazuhiro Hirohashi
    • 3
  • Shoji Kubo
    • 1
  1. 1.Department of Hepato-Biliary-Pancreatic SurgeryOsaka City University Graduate School of MedicineOsakaJapan
  2. 2.Department of SurgeryIshikiri-Seiki HospitalOsakaJapan
  3. 3.Department of General PracticeOsaka City University HospitalOsakaJapan

Personalised recommendations