Impact of albumin-bilirubin grade on survival in patients with hepatocellular carcinoma who received sorafenib: An analysis using time-dependent receiver operating characteristic.

BACKGROUND AND AIM: Albumin-bilirubin (ALBI) grade was developed as a new method to assess hepatic function. Sorafenib has been confirmed to be effective in improving survival in patients with advanced hepatocellular carcinoma (HCC). In this study, we investigated the impact of ALBI grade versus Child-Pugh classification on survival in HCC patients who received sorafenib. METHODS: A total of 567 patients with advanced HCC who received sorafenib were included. We analyzed survival based on Child-Pugh classification or score and ALBI grade or score. We also compared the ability of ALBI and Child-Pugh scores to predict survival using time-dependent receiver operating characteristic analysis. RESULTS: Cumulative survival rates at 90, 180, 360, and 720 days were 84.1%, 66.6%, 47.0%, and 23.3%, respectively. Median survival was 316 days (95% confidence interval, 279-377). Both Child-Pugh classification and ALBI grade were independently associated with overall survival in multivariate analyses. In addition, overall survival differed significantly between patients with ALBI grades 1 and 2 (hazard ratio, 1.44; 95% confidence interval, 1.09-1.92, P = 0.011) among patients with a Child-Pugh score of 5. Time-dependent receiver operating characteristic analysis showed that ALBI score predicted overall survival better than Child-Pugh score. CONCLUSIONS: Albumin-bilirubin grade is a better predictor of survival in patients with advanced HCC who received sorafenib therapy than Child-Pugh classification.

Hand-Foot Syndrome and Post-Progression Treatment Are the Good Predictors of Better Survival in Advanced Hepatocellular Carcinoma Treated with Sorafenib: A Multicenter Study.

OBJECTIVE: To determine the relationship between treatment outcomes and hand-foot syndrome (HFS), and the relationship between survival rate and post-progression treatment after sorafenib therapy. METHODS: The study assessed 314 patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib at 5 general hospitals in Kagawa Prefecture, Japan. RESULTS: At the start of sorafenib therapy, 23.6% of the patients had HCC of a Child-Pugh class other than A. The initial sorafenib dose was 800 mg in 9.2% of the patients and 400 mg in 64.3%. Time to progression was 129 days (95% CI: 87.3-170.7) and the median overall survival (OS) was 392 days (95% CI: 316.0-468.0). The OS of the patients with Child-Pugh class A HCC was significantly better than that of the patients with Child-Pugh class B HCC (p < 0.0001). The survival curves for Child-Pugh class A-5 points and class A-6 points were significantly different, with that for class A-5 points being better (p < 0.0001). A significant difference was observed between the patients who exhibited HFS and those who did not, with the former exhibiting a better survival rate (p < 0.001). In addition, the survival rate of the patients who received post-progression treatment after sorafenib therapy was significantly better than that of the patients who did not (p < 0.001). CONCLUSION: In sorafenib therapy, patients with HFS and those who received post-progression treatment exhibited good OS.

Hepatic Function during Repeated TACE Procedures and Prognosis after Introducing Sorafenib in Patients with Unresectable Hepatocellular Carcinoma: Multicenter Analysis.

BACKGROUND/AIM: We evaluated the relationship of hepatic function with repeated transarterial catheter chemoembolization (TACE) and prognosis after sorafenib treatment in various patient cohorts. METHODS: Study 1 comprised of 212 Barcelona clinic liver cancer stage-B (BCLC-B) HCC patients classified as Child-Pugh A (CP-A) and who had received repeated TACE treatments (r-TACE) (naïve:recurrence = 66:146). Study 2 comprised of 435 patients with unresectable HCC classified as CP-A in who sorafenib was introduced (naïve:recurrence = 37:398; CP score 5:6 = 282:153; macro-vessel invasion [MVI]+: extrahepatic metastasis [EHM]+ both negative = 124:226:143). Changes in hepatic function along with CP and albumin-bilirubin (ALBI) score/grade during r-TACE in Study 1, and prognosis after introducing sorafenib in Study 2 were evaluated. RESULTS: Hepatic function worsened to CP-B in 9-14% with each TACE procedure, while 18-21% had a change of classification from ALBI-1 to ALBI-2. When the prognosis of patients with the best CP score of 5 was analyzed, those with ALBI-1 (n = 154) had a better outcome than those with ALBI-2 (n = 128) (MST 17.5 vs. 9.9 months; p = 0.01), while ALBI-1 (n = 43) patients also showed a better outcome than ALBI-2 (n = 34) patients with a CP score of 5 without MVI/EHM (MST: 17.5 vs. 10.0 months; p = 0.029). The Akaike's Information criterion for ALBI-grade (MST: grade 1 vs. 2 = 16.9 vs. 10.4 months; p = 0.001) was also better than that for CP (MST: score 5 vs. 6 = 14.4 vs. 10.5 months; p = 0.003) (3195.6 vs. 3197.5) in all 435 patients. CONCLUSION: The rate of patients with downgraded hepatic function during r-TACE, especially with regard to ALBI-grade, was not low. ALBI-grade was shown to be a better hepatic function assessment tool than CP in patients receiving sorafenib treatment. Strict judgment of TACE-refractory status in patients with unresectable HCC is needed to improve prognosis before downgrading the hepatic function.

Efficacy of zinc administration in patients with hepatitis C virus-related chronic liver disease.

OBJECTIVE: Zinc supplementation has been shown to contribute to inhibition of liver fibrosis and improvement in hepatic encephalopathy. However, little is known about the anti-inflammatory effect of zinc on hepatitis C virus (HCV)-related chronic liver disease (CLD). We therefore examined the effects of zinc administration on inflammatory activity and fibrosis in the liver of patients with HCV-related CLD. MATERIAL AND METHODS: Polaprezinc, a complex of zinc and l-carnosine, was administrated at 225 mg/day for 6 months to 14 patients with HCV-related CLD, in addition to their ongoing prescriptions. Peripheral blood cell counts, liver-related biochemical parameters, serological markers for liver fibrosis, HCV-RNA loads, and serum levels of zinc and ferritin were evaluated before and after zinc administration. RESULTS: Serum zinc concentrations were positively correlated with hepatic reserve before zinc supplementation. A significant increase in serum zinc level was observed after zinc supplementation (64+/-15 versus 78+/-26 mg/dl, p=0.0156). Treatment with polaprezinc significantly decreased serum aminotransferase levels (aspartate aminotransferase (AST): 92+/-33 versus 63+/-23 IU/l, p=0.0004; alanine aminotransferase (ALT): 106+/-43 versus 65+/-32 IU/l, p=0.0002), whereas alkaline phosphatase levels were significantly increased (305+/-117 versus 337+/-118 U/l, p=0.0020). Serum ferritin levels were significantly decreased by treatment with polaprezinc (158+/-141 versus 101+/-80 ng/ml, p=0.0117). The reduction rate of ALT levels by polaprezinc was positively correlated with that of ferritin (r(2)=0.536, p=0.0389). There was a tendency toward a decrease in serum type IV collagen 7S levels after treatment with polaprezinc. However, administration of polaprezinc did not affect peripheral blood cell counts, other liver function tests, or HCV-RNA loads. CONCLUSIONS: These findings suggest that polaprezinc exerts an anti-inflammatory effect on the liver in patients with HCV-related CLD by reducing iron overload.

Successful treatment of hypovascular advanced hepatocellular carcinoma with lipiodol-targetting intervention radiology.

We report a case of hypovascular advanced hepa-tocellular carcinoma (HCC) successfully treated with a novel combination therapy of percutaneous ethanol-lipiodol injection (PELI) and intervention radiology (IVR), lipiodol-targetting IVR (Lipi-IVR). The present case had a hypovascular HCC (3 cm in diameter) located in the S6 region of the liver. Although the tumor was not detectable at all by both of early and late phase of helical dynamic computed tomography (CT), it could be detected by ultrasonography (US) as a low echoic space occupying lesion (SOL) beside the gallbladder and right kidney. Serum levels of alpha fetoprotein (AFP) and AFP-L3 were extremely high. Combination therapy of PELI, firstly reported in our department, and IVR (PELI and IVR, lipiodol-targetting IVR) was performed twice for the treatment. PELI could effectively visualize the location of the tumor for IVR treatment and show the presence of a thin blood vessel branching from the right hepatic artery flowing into the lipiodol deposit. After treatment, the serum levels of AFP and AFP-L3 were rapidly decreased to normal and maintained for more than eight months. Thus, this case expressing the tremendous effect might give us insight into the effectiveness of the novel combination therapy of PELI and IVR for the treatment of hypovascular HCC.

Efficacy of combination therapies of percutaneous or laparoscopic ethanol-lipiodol injection and radiofrequency ablation.

Percutaneous radiofrequency ablation (RFA) is able to destroy hepatocellular carcinoma (HCC) in a few sessions without major complications. We have previously shown that not only the combined use of percutaneous ethanol injection and RFA (PEI-RFA) but also injection of mixture of ethanol and lipiodol (PELIT) was useful for the treatment of HCC. In the present study, we further developed the combined use of PELIT and RFA through percutaneous or laparoscopic approach (PELI-RFA or LELI-RFA) and evaluated its usefulness. Nineteen nodules in 18 cases were treated with PELI-RFA or LELI-RFA. In the cases treated with LELI-RFA, no bleeding and no spilling milky fluid containing tumor cells were observed from the surface of ablated tumors. In the cases sufficiently treated with PELI-RFA or LELI-RFA, the mixture of ethanol and lipiodol was accumulated in the entire region of the tumor and low-density area was observed around the lipiodol deposit by computed tomography (CT). These delineations of coagulated area were helpful to evaluate the precise area of safety margin around the tumor treated with PELI-RFA or LELI-RFA. Furthermore, the total volume of coagulated necrosis significantly and positively correlated with the product of energy requirement for ablation and the volume of ethanol injected by PELI-RFA or LELI-RFA. Among the cases treated with PELI-RFA or LELI-RFA, local recurrence emerged only in one case in whom enough safety margin could not be achieved by PELI-RFA. Therefore, it is critical to evaluate whether enough safety margin could be obtained with RFA therapy, and PELI-RFA and LELI-RFA are helpful in visualizing the safety margin area.