Current standard values of health utility scores for evaluating cost-effectiveness in liver disease: A meta-analysis.

BACKGROUND: Health utility assessments have been developed for various conditions, including chronic liver disease. Health utility scores are required for socio-economic evaluations, which can aid the distribution of national budgets. However, the standard health utility assessment scores for specific health conditions are largely unknown. AIM: To summarize the health utility scores, including the EuroQOL 5-dimensions 5-levels (EQ-5D-5L), EuroQol-visual analogue scale, short from-36 (SF-36), RAND-36, and Health Utilities Index (HUI)-Mark2/Mark3 scores, for the normal population and chronic liver disease patients. METHODS: A systematic literature search of PubMed and MEDLINE, including the Cochrane Library, was performed. Meta-analysis was performed using the RevMan software. Multiple means and standard deviations were combined using the StatsToDo online web program. RESULTS: The EQ-5D-5L and SF-36 can be used for health utility evaluations during antiviral therapy for hepatitis C. HUI-Mark2/Mark3 indicated that the health utility scores of hepatitis B patients are roughly 30% better than those of hepatitis C patients. CONCLUSION: The EQ-5D-5L is the most popular questionnaire for health utility assessments. Health assessments that allow free registration would be useful for evaluating health utility in patients with liver disease.

Identification of Characteristic Genomic Markers in Human Hepatoma HuH-7 and Huh7.5.1-8 Cell Lines.

The human hepatoma-derived HuH-7 cell line and its derivatives (Huh7.5 and Huh7.5.1) have been widely used as a convenient experimental substitute for primary hepatocytes. In particular, these cell lines represent host cells suitable for propagating the hepatitis C virus (HCV) in vitro. The Huh7.5.1-8 cell line, a subline of Huh7.5.1, can propagate HCV more efficiently than its parental cells. To provide genomic information for cells' quality control, we performed whole-genome sequencing of HuH-7 and Huh7.5.1-8 and identified their characteristic genomic deletions, some of which are applicable to an in-house test for cell authentication. Among the genes related to HCV infection and replication, 53 genes were found to carry missense or loss-of-function mutations likely specific to the HuH-7 and/or Huh7.5.1-8. Eight genes, including DDX58 (RIG-I), BAX, EP300, and SPP1 (osteopontin), contained mutations observed only in Huh7.5.1-8 or mutations with higher frequency in Huh7.5.1-8. These mutations might be relevant to phenotypic differences between the two cell lines and may also serve as genetic markers to distinguish Huh7.5.1-8 cells from the ancestral HuH-7 cells.

Clinical comparison of laparoscopic and open liver resection after propensity matching selection.

BACKGROUND: This study aimed to compare the radicality for and clinical advantages of laparoscopic liver resection, which is increasingly used, and the corresponding open procedure by propensity score matching analysis. METHODS: We analyzed 260 hepatocellular carcinoma patients who underwent initial liver resection at our department between January 2003 and June 2011, including 60 laparoscopic (the Lap group) and 200 open cases (the Open group). Propensity scores were calculated for each patient via the use of various clinicopathologic features as covariates, and patients' survival was compared. RESULTS: The Lap group had more women and patients of advanced age (n = 60) than the Open group (n = 200). Tumor size (2.3 cm vs 3.5 cm median), multiple tumors (18.3% vs 41.0%), vascular invasion (15.0% vs 36.5%), poor differentiation status (11.2% vs 24.5%), intraoperative bleeding (110 mL vs 420 mL; median), and operative time (277 minutes vs 312 minutes; median) were significantly more favorable in the Lap group than in the Open group because of a selection bias of the patients (Lap vs Open). The postoperative recurrence-free and overall survival rates were greater in the Lap group than in the Open group; however, when 35 patients from each group were analyzed after propensity score matching of clinicopathologic characteristics of the patients, intraoperative bleeding was lesser in the Lap group. The recurrence-free survival rates at 1, 3, and 5 years were 75.0%, 43.8%, and 43.8%, respectively, in the Lap group and 73.6%, 49.3%, and 37.2%, respectively, in the Open group, which indicated no significant differences (P = .954). Similarly, the overall survival rates at 1, 3, and 5 years were 93.9%, 82.1%, and 82.1%, respectively, in the Lap group and 94.3%, 85.2%, and 61.8%, respectively, in the Open group, indicating no significant differences between the 2 groups (P = .672). CONCLUSION: Our results indicate that laparoscopic liver resection is comparable with the corresponding open procedure in clinical safety and prognostic efficacy.

New technique of extracorporeal hepatic inflow control for pure laparoscopic liver resection.

We have developed a new technique of the Pringle maneuver by clamping outside the abdominal wall for pure laparoscopic liver resection (pure Lap). Our technique successfully controls bleeding and enables pure Lap to be completed without any events, even for a large tumor. Between 2008 and 2010, we compared consecutive patients who received pure Lap with (n=11) and without (n=7) this Pringle maneuver. Although tumor size in the Pringle group was significantly larger than in the no-Pringle group (3.35±1.64 vs. 1.11±0.29 cm, respectively), intraoperative bleeding was not significantly different (165.5±188.5 vs. 177.9±364.4 mL, respectively). In contrast, operation time in the Pringle group was significantly longer than in the no-Pringle group (343.1±99.5 vs. 199.6±63.2 min, respectively). Pure Lap for large tumors is feasible when employing a new Pringle maneuver outside the abdominal wall.

Impact of aging on morbidity and mortality after liver resection: a systematic review and meta-analysis.

Surgery involving elderly patients is becoming increasingly common due to the rapid aging of societies all over the world. The objective of this study was to elucidate the prognostic differences between elderly and young patients who undergo liver resection. A systematic review based on the PRISMA flow diagram was conducted. Ovid Medline and PubMed were used to search for relevant literature published between January 2000 and March 2013, and the modified MINORS score was used to assess the methodological quality. In cases of hepatocellular carcinoma and miscellaneous liver tumors, the morbidity and mortality rate did not differ significantly between the elderly and young patients. For patients with colorectal metastatic liver cancer, the mortality of the young patients was 2.7 times lower than that of elderly patients. Our review of high-quality retrospective studies was able to elucidate the clinical risks of age on the outcomes after liver surgery in specific patient populations.

Preoperative hepatocyte transplantation improves the survival of rats with nonalcoholic steatohepatitis-related cirrhosis after partial hepatectomy.

Liver failure after liver resection for cirrhosis is a critical problem, and no effective therapy except liver transplantation is currently available. The objective of this study was to examine whether hepatocyte transplantation (HT) reduces the poststandard liver resection mortality rate of rats with nonalcoholic steatohepatitis (NASH)-related cirrhosis. Liver resection for hepatocellular carcinoma (HCC) combined with NASH-related cirrhosis has become increasingly common. We developed a rat model of acute liver failure after two-thirds partial hepatectomy (PH) for NASH-related cirrhosis. The mechanism by which HT improved the survival of the model rats was examined in short- and long-term investigations. Female DPPIV(-) recipient F344 rats were fed the choline-deficient l-amino acid (CDAA)-defined diet for 12 weeks. Some of the rats were transplanted with male F344 DPPIV(+) rat hepatocytes 24 h before undergoing PH. The overall post-PH survival of each group was evaluated, and short- and long-term pathological and molecular biological evaluations were also performed. Overall survival was significantly longer in the HT group than the non-HT group (7-day survival rates: 46.7% and 7.7%, respectively). Compared with the recipient livers of the non-HT group, numerous Ki-67(+) hepatocytes and few TUNEL(+) hepatocytes were observed in the livers of the HT group. At 6 months after the HT, the DPPIV(+) hepatocytes had partially replaced the recipient liver and formed hepatocyte clusters in the spleen. Preoperative HT might improve the survival of rats with NASH-related cirrhosis after PH by preventing the host hepatocytes from accelerating their growth and falling into apoptosis.

Propensity score analysis demonstrated the prognostic advantage of anatomical liver resection in hepatocellular carcinoma.

AIM: To compare the prognoses of hepatocellular carcinoma (HCC) patients that underwent anatomic liver resection (AR) or non-anatomic liver resection (NAR) using propensity score-matched populations. METHODS: Between January 2002 and December 2010, 268 consecutive HCC patients, including 110 and 158 patients that underwent AR and NAR, respectively, were retrospectively enrolled in this study. Forty-four patients from each group were selected and matched using logistic multivariate analysis followed by propensity score analysis. RESULTS: In the whole analysis set, the histological background of the liver, liver function, and tumor marker levels differed significantly among the groups. Although the overall survival (OS) and recurrence-free survival rates of the two groups did not differ significantly in the whole analysis set, the OS of the AR group was significantly longer than that of the NAR group after propensity matching (76.2 ± 6.3 mo vs 58.9 ± 6.3 mo; P = 0.0039). Although AR (HR = 0.456, P = 0.039) was found to be a prognostic factor in the univariate analysis, only vascular invasion (HR = 0.228, P = 0.002) and the hepatocyte growth factor level (HR = 52.366, P = 0.035) were subsequently found to be independent prognostic factors. CONCLUSION: AR conveys a survival advantage over NAR in specific subpopulations of HCC patients with tumors of less than 5 cm in diameter, single tumor, and good liver function.

Highest intraoperative lactate level could predict postoperative infectious complications after hepatectomy, reflecting the Pringle maneuver especially in chronic liver disease.

BACKGROUND: The Pringle maneuver is used to minimize blood loss during liver transection; however, it may cause reperfusion injury, which can cause increased intraoperative lactate levels and an immune compromised state. This may further lead to infectious complications. METHODS: Here, we divided 77 patients who underwent hepatectomy between December 2007 and August 2010 into two groups: the chronic hepatitis and liver cirrhosis (CH + LC) group and normal liver (NL) group. We investigated the effect of the highest intraoperative lactate level on occurrence of infectious complications after hepatectomy by assessing the correlations of the highest intraoperative lactate level with total Pringle time, operative factors, and various parameters in serum after surgery. Parameters showing significant correlations with postoperative complications of Clavien-Dindo grade III or higher, with a wound or intra-abdominal infection, were analyzed by using interactive dot diagrams to determine cut-off values with the highest sensitivity and specificity. RESULTS: We noted that, to prevent postoperative infectious complications, the highest lactate level during liver resection should be maintained at <44.0 mg/dL in the NL group and <29.0 mg/dL in the CH + LC group. CONCLUSIONS: Minimizing the highest intraoperative lactate level may be important to prevent increase in postoperative infectious complications after hepatectomy, reflecting the Pringle maneuver especially in chronic liver disease.

Preoperative liver function assessments to estimate the prognosis and safety of liver resections.

Liver function assessment is important to ensure safe surgical procedures in patients with hepatocellular disease. Because the liver influences a wide variety of functions, including protein synthesis and metabolic, immune and storage functions, no single parameter is sufficient to adequately address all of these functions. We reviewed the relevant literature concerning the scoring systems, functional tests, plasma parameters and imaging modalities currently used to evaluate the liver function in an attempt to determine which parameters provide the most comprehensive and useful results. While the Child-Pugh scoring system is the gold standard for liver disease assessment, the liver damage grading system recommended by the Liver Cancer Study Group of Japan is also useful. Various models for end-stage liver disease scoring are used for organ allocation. While the indocyanine green clearance test is widely accepted throughout the world, other assessments have not been used routinely for clinical evaluations. The levels of plasma proteins, including albumin, prealbumin, retinol binding protein, apolipoprotein, coagulation factors and antithrombin III, represent the liver productivity. Liver fibrotic markers also correlate with liver function. Imaging modalities such as (99m)Tc-galactosyl serum albumin scintigraphy, (99m)Tc-mebrofenin hepatobiliary scintigraphy and transient elastography are also available, but future studies are needed to validate their clinical efficacy.

Pancreaticoduodenectomy for biliary tract carcinoma with situs inversus totalis: difficulties and technical notes based on two cases.

Situs inversus totalis (SIT) denotes complete right-left inversion of the thoracic and abdominal viscera. Diagnosis and surgical procedures for abdominal pathology in patients with SIT are technically more complicated because of mirror-image transposition of the visceral organs. Moreover, SIT is commonly associated with cardiovascular and hepatobiliary malformations, which make hepatobiliary-pancreatic surgery difficult. Two cases of pancreaticoduodenectomy for biliary tract carcinoma in patients with SIT are presented. Both patients had an anomaly of the hepatic artery. Advanced diagnostic imaging techniques were very important for careful preoperative planning and to prevent misunderstanding of the arrangement of the abdominal viscera. This facilitated the surgical team's adaptation to the mirror image of the standard procedure and helped avoid intraoperative complications due to cardiovascular and hepatobiliary malformations associated with SIT. Pancreaticoduodenectomy in patients with SIT can be performed successfully with detailed preoperative assessment, use of effective techniques by the surgeon, and appropriate support by assistants.

Continuous monitoring of central venous oxygen saturation predicts postoperative liver dysfunction after liver resection.

BACKGROUND: We examined whether the data obtained by monitoring central venous oxygen saturation (ScvO2) and/or stroke volume variation (SVV) during hepatectomy, as measured with the FloTrac/Vigileo system, can predict postoperative liver dysfunction. METHODS: This study included 33 patients with normal liver function who underwent hepatectomy between December 2007 and August 2010. Baseline ScvO2 and baseline SVV, as control values, were defined as the mean of ScvO2 and SVV, respectively, measured with the FloTrac/Vigileo system before hepatectomy. ScvO2 decrease (ΔScvO2) was defined as the difference between the baseline ScvO2 and the lowest intraoperative ScvO2 and SVV increase (ΔSVV) was defined as the difference between the baseline SVV and the highest intraoperative SVV. Moreover, mean ScvO2 and mean SVV were defined as the means of all ScvO2 and SVV values measured during surgery, respectively. We examined correlations of the new parameters with the highest postoperative values of total bilirubin (T. Bil). RESULTS: The cutoff values for ΔScvO2 and mean SVV for predicting the highest postoperative T. Bil level to be ≥ 3.0 mg/dL with the highest sensitivity and specificity were found to be 10.2% and 13.6%, respectively. The areas under curve in receiver-operating-characteristic analysis of ΔScvO2 and mean SVV were 0.797 and 0.757, respectively, showing significant differences. CONCLUSION: Our results suggest that ΔScvO2 and mean SVV can predict postoperative liver dysfunction. When ΔScvO2 and mean SVV exceed 10.2% and 13.6%, respectively, we advocate that adequate attention be paid to postoperative liver dysfunction, and that early intraoperative general circulatory management measures be implemented as needed.

Prognosis and predictors of surgical complications in hepatocellular carcinoma patients with or without cirrhosis after hepatectomy.

BACKGROUND: Although poor liver function is associated with a high morbidity rate and poor prognosis in hepatocellular carcinoma (HCC) patients, the exact effects of liver pathology on the surgical outcomes of HCC patients are poorly understood. The purpose of this study was to assess how the liver pathology of HCC patients affects their prognosis and complications rate after liver resection. METHODS: Between January 2006 and November 2010, 149 consecutive hepatocellular carcinoma patients, including 79 noncirrhosis patients and 70 cirrhosis patients, were enrolled in this study. RESULTS: Among the noncirrhotic patients, operative time, fresh frozen plasma (FFP) transfusion requirement, tumor size, and serum retinol binding protein (RBP) levels were significantly higher in the complications group than in the complications-free groups. On the other hand, in the cirrhotic patients the prothrombin time (PT) and indocyanine green retention value at 15 min (ICGR15) of the complications group were significantly lower and higher, respectively, than those of the complications-free group. In the noncirrhotic patients, recurrence-free survival and overall survival did not differ between the complications and complications-free groups. On the other hand, in the cirrhotic patients, the recurrence-free survival and overall survival of the complications-free group were significantly longer than those of the complications group. CONCLUSIONS: In the noncirrhotic patients, surgical complications had no prognostic effect, whereas they had a significant survival impact in the cirrhotic patients. The surgical strategy for HCC should be based on the patient's pathological background.

Low-dose steroid pretreatment ameliorates the transient impairment of liver regeneration.

AIM: To determine if liver regeneration (LR) could be disturbed following radiofrequency (RF) ablation and whether modification of LR by steroid administration occurs. METHODS: Sham operation, partial hepatectomy (PH), and partial hepatectomy with radiofrequency ablation (PHA) were performed on adult Fisher 344 rats. We investigated the recovery of liver volume, DNA synthetic activities, serum cytokine/chemokine levels and signal transducers and activators of transcription 3 DNA-binding activities in the nucleus after the operations. Additionally, the effects of steroid (dexamethasone) pretreatment in the PH group (S-PH) and the PHA group (S-PHA) were compared. RESULTS: The LR after PHA was impaired, with high serum cytokine/chemokine induction compared to PH, although the ratio of the residual liver weight to body weight was not significantly different. Steroid pretreatment disturbed LR in the S-PH group. On the other hand, low-dose steroid pretreatment improved LR and suppressed tumor necrosis factor (TNF)-α elevation in the S-PHA group, with recovery of STAT3 DNA-binding activity. On the other hand, low-dose steroid pretreatment improved LR and suppressed TNF-α elevation in the S-PHA group, with recovery of STAT3 DNA-binding activity. CONCLUSION: LR is disturbed after RF ablation, with high serum cytokine/chemokine induction. Low-dose steroid administration can improve LR after RF ablation with TNF-α suppression.

Serum antithrombin III level is well correlated with multiple indicators for assessment of liver function and diagnostic accuracy for predicting postoperative liver failure in hepatocellular carcinoma patients.

BACKGROUND/AIMS: Evaluation of preoperative hepatic reserve is critical to avoid a fatal clinical course such as liver failure. We retrospectively evaluated 158 consecutive hepatocellular carcinoma (HCC) patients who underwent initial hepatectomy. The aim of this study was to determine the correlations of multiple indicators for assessment of liver function before hepatectomy. Furthermore, diagnostic probability for the pathological background and prediction of postoperative liver failure/dysfunction was compared between the antithrombin (AT) III level and indocyanine green retention rate at 15 minutes (ICGR15). METHODOLOGY: Between January 2001 and March 2008, 158 HCC patients who underwent initial hepatectomy were enrolled in this study. Spearman's correlation coefficients (r values) were obtained for 15 clinical laboratory tests including ATIII and ICGR15. Receiver operating characteristic (ROC) curve analysis was used for calculating the probability and predictive ability of the tests. RESULTS: All 158 consecutive HCC patients were eligible for hepatectomy based on the Japanese guideline. ATIII is correlated with 13 of 14 other clinical tests, including albumin, bilirubin, prothrombin time, rapid turnover proteins, HGF, ICGR15 and others. The diagnostic probabilities to distinguish between normal liver and other pathological backgrounds of ATIII and ICGR15 were significantly different. The specificity of ATIII to predict postoperative liver failure/dysfunction was higher than that of ICGR15. CONCLUSIONS: The serum ATIII level before hepatectomy is valuable to estimate the pathological background and predict postoperative liver failure/ dysfunction. It should be possible to use ATIII as an additional indicator for liver function and substitute for ICGR15 in the future.

Area between the hepatic and heart curves of (99m)Tc-galactosyl-human serum albumin scintigraphy represents liver function and disease progression for preoperative evaluation in hepatocellular carcinoma patients.

BACKGROUND/PURPOSE: We developed software to calculate the pixels of interest in the area between the hepatic and heart curves (ABC) of (99m)Tc-galactosyl human serum albumin (GSA) scintigraphy. The aim of this study was to examine the accuracy of the ABC to evaluate liver function before hepatectomy. METHODS: Between January 2005 and December 2010, 205 consecutive patients who underwent initial hepatectomy were enrolled in this study. The ABC was calculated using original computer software. The area under the receiver operating characteristic curve (AUC) was calculated for evaluation of Child-Pugh score grade B (Child B), pathological chronic hepatitis (CH), and liver cirrhosis (LC). RESULTS: The AUC of any indicator for Child B was more than 0.900 except bilirubin. The AUC of ABC for CH and LC (AUC 0.734 each) was comparable to those of HH15 (clearance index; AUC 0.704 and 0.700, respectively) and LHL15 (receptor index; AUC 0.703 and 0.706, respectively) in multiple receiver operating characteristic comparison. CONCLUSIONS: We have developed a novel liver function indicator, the ABC, to count radioactivity in sequence. The ABC reflects liver function according to pathological deterioration of the liver. Although the ABC gave no significant advantage compared to HH15 and LHL15, it improved the AUC evaluation by 0.028-0.034.

The molecular pathogenesis and clinical implications of hepatocellular carcinoma.

The prognosis of hepatocellular carcinoma (HCC) is affected by tumoral factors and liver functions; therefore it is often difficult to select the appropriate therapeutic methods for HCC. Recently, two global phase III trials showed that sorafenib, which is a tyrosine kinase inhibitor, improved the prognosis of patients with advanced HCC. As a new therapeutic strategy for HCC, sorafenib is expected to expand the indication for HCC in the future. However, it alone is insufficient for the molecular-targeted treatment of HCC because the signaling pathway exists not only in cancer cells but also in normal cells. Recently, cancer stem cells (CSCs) have attracted attention as a novel therapeutic target for HCC. There is now much evidence that stem cell properties such as self-renewal, unlimited proliferation, and differentiation are highly relevant to cancer recurrence and the drug resistance of HCC. In this review, we describe the molecular pathogenesis and the current state and future development of molecular- and CSC-therapeutic targeted agents for HCC, citing various reports.

Inhibitor-bound structures of human pyruvate dehydrogenase kinase 4.

The mitochondrial pyruvate dehydrogenase complex (PDC) catalyzes the oxidative decarboxylation of pyruvate to acetyl-CoA. PDC activity is tightly regulated by four members of a family of pyruvate dehydrogenase kinase isoforms (PDK1-4), which phosphorylate and inactivate PDC. Recently, the development of specific inhibitors of PDK4 has become an especially important focus for the pharmaceutical management of diabetes and obesity. In this study, crystal structures of human PDK4 complexed with either AMPPNP, ADP or the inhibitor M77976 were determined. ADP-bound PDK4 has a slightly wider active-site cleft and a more disordered ATP lid compared with AMPPNP-bound PDK4, although both forms of PDK4 assume open conformations with a wider active-site cleft than that in the closed conformation of the previously reported ADP-bound PDK2 structure. M77976 binds to the ATP-binding pocket of PDK4 and causes local conformational changes with complete disordering of the ATP lid. M77976 binding also leads to a large domain rearrangement that further expands the active-site cleft of PDK4 compared with the ADP- and AMPPNP-bound forms. Biochemical analyses revealed that M77976 inhibits PDK4 with increased potency compared with the previously characterized PDK inhibitor radicicol. Thus, the present structures demonstrate for the first time the flexible and dynamic aspects of PDK4 in the open conformation and provide a basis for the development of novel inhibitors targeting the nucleotide-binding pocket of PDK4.

Cluster analysis of indicators of liver functional and preoperative low branched-chain amino acid tyrosine ration indicate a high risk of early recurrence in analysis of 165 hepatocellular carcinoma patients after initial hepatectomy.

BACKGROUND: Cluster analysis is used for dividing many prognostic indicators, including liver function, tumor progression, and operative variables, into specific clusters. The albumin (ALB), hepatocyte growth factor (HGF), and branched chain amino-acid to tyrosine ratio (BTR) may represent the severity of liver disease and function of the hepatic reserve. We developed the ALB-BTR and HGF-BTR classifications depending on each level to find specific unique subgroups. Our aim was to identify specific subgroups destined for favorable and poor prognoses after initial hepatectomy. METHODS: Between 2002 and 2008, 165 patients were analyzed retrospectively. Liver function indicators, including BTR, tumor-related factors, and operative variables, were evaluated by cluster analysis with Ward's criterion. The ALB-BTR classification was divided into 4 groups depending on ALB (cutoff value, 4.0 g/dL) and BTR (cutoff value, 6.0). The HGF-BTR classification was also divided into 4 groups depending on HGF (cutoff value, 0.35 ng/mL) and BTR (cutoff value, 6.0). The prognoses of the subgroups were compared by the log-rank test. RESULTS: Cluster analysis divided multiple indicators into 5 different clusters. In each cluster, we further analyzed subgroups using the ALB-BTR and HGF-BTR classification. Mean recurrence-free survival times in ALB-GI (19.1 ± 2.4 months) and HGF-GIII (29.4 ± 3.8 months) were less than their mean overall survival times. CONCLUSION: Cluster analysis is useful to find similar and different indicators. Even though liver function was well preserved, low BTR could identify early recurrence in hepatocellular carcinoma patients after resection.

Prognostic impact of preoperative the branched-chain amino acid to the tyrosine ratio in hepatocellular carcinoma patients after initial hepatectomy.

INTRODUCTION: The branched-chain amino acid/tyrosine ratio (BTR) reflects the amino acid balance and the severity of liver disease. The aim of the present study was to determine the relationship between BTR and liver function in patients with hepatocellular carcinoma (HCC). Furthermore, we evaluated the clinical usefulness of BTR as a prognostic indicator of disease-free and overall patient survival after initial hepatectomy. METHODS: Between January 2004 and December 2008, 105 consecutive HCC patients who underwent initial hepatectomy were enrolled in this study. The correlation between BTR and preoperative liver functional indicators was evaluated. The cutoff levels of BTR for 2-year survival prediction were evaluated using a dot blot diagram. The patients were divided into high BTR (4.5 or higher) and low BTR (4.4 or lower) groups and these were compared in terms of clinical variables such as liver functional indicators, operative variables, and tumor characteristics. RESULTS: The preoperative BTR level decreased according to the severity of liver disease. BTR was correlated with the albumin, bilirubin, and prealbumin levels, as well as the prothrombin time. Although the preoperative liver function was significantly different between the high BTR and low BTR groups, the operative variables and tumor-related variables were not found to be significantly different. Postoperative complications in the high BTR group were significantly less frequent than in the low BTR group (p = 0.003). Disease-free and overall patient survival in the high BTR group were significantly longer than in the low BTR group (p < 0.001 and p = 0.021, respectively). CONCLUSIONS: BTR reflected the pathological liver background with a high correlation to the other liver functional indicators. BTR is thus considered to be a useful marker to predict postoperative complications, disease-free survival, and overall survival of HCC patients after initial hepatectomy. It is, therefore, a useful indicator of liver function and a predictor for the risk of cancer recurrence and overall survival in HCC patients.