Clinical outcome of 251 patients with extrahepatic metastasis at initial diagnosis of hepatocellular carcinoma: Does transarterial chemoembolization improve survival in these patients?

Background and Aims: The therapeutic efficacy of transarterial chemoembolization (TACE) has not been evaluated in hepatocellular carcinoma (HCC) patients with extrahepatic metastasis. We investigated the efficacy of TACE with/without systemic chemotherapy (s‐chemo) in these patients. Methods: We performed a survival analysis of consecutive HCC patients with extrahepatic metastasis, diagnosed at initial presentation according to treatment modality after stratification, using the Child–Pugh classification and intrahepatic HCC T stage, retrospectively. Results: Between 2005 and 2007, 251 patients were newly diagnosed with HCC involving extrahepatic metastasis at our institution. Among those, 226 were classified as Child–Pugh A–B and the other 25, Child‐Pugh C. Within the Child–Pugh A–B group, repeated TACE or transarterial chemoinfusion (TACI) was performed with/without s‐chemo in 171 patients. Eight of 226 received s‐chemo alone, and 47, conservative management (CM) alone. The median survival time of patients treated with TACE/TACI with s‐chemo, TACE/TACI alone, and CM was 10, 5, and 2.9 months in patients classified as Child–Pugh A and T3‐stage HCC (TACE/TACI with s‐chemo vs CM, P = 0.0354; TACE/TACI alone vs CM, P = 0.0553) and 7.1, 2.6, and 1.6 months in Child–Pugh B and T3‐stage patients, respectively (TACE/TACI with s‐chemo vs CM, P = 0.0097; TACE/TACI alone vs CM, P < 0.0001). Individual treatment with TACE/TACI or sorafenib showed independent prognostic significance in the multivariate analysis. Conclusion: Repeated TACE could show significant survival benefits in metastatic HCC patients with conserved liver function and intrahepatic HCC T3 stage. The survival data of our study could be used as a historical control for TACE monotherapy in future clinical trials evaluating combination treatments containing TACE in these patients.     

Endoscopic thermal ablation therapies for hepatocellular carcinoma: a multi-center study

Aim:  The differing efficacies of radiofrequency ablation and microwave coagulation for hepatocellular carcinoma (HCC) are unknown. Therefore, we performed a multi-center study to assess the factors contributing to survival and local recurrences of HCC among patients with solitary tumors who underwent endoscopic thermal ablation as their primary treatment.
Methods:  From six institutions, 391 patients with solitary HCC who were first treated by endoscopic thermal ablation were enrolled in this study and assessed retrospectively. We investigated age, gender, location of tumor, longest diameter of tumor, method of anesthesia, type of endoscope, method of thermal ablation, Child–Pugh classification, the Japan Integrated Staging score and the Cancer of the Liver Italian Program score. Statistical analyses were performed using univariate analysis with log–rank test and multivariate analysis with the Cox proportional hazards model.
Results:  On univariate analysis, advanced Child–Pugh score, advanced Italian Program score and local recurrences were significant predictors of poor survival. Young age (≤70), large tumor (>30 mm) and the use of the thoracoscopic approach were significant predictors for the development of local recurrence. On multivariate analysis, local anesthesia and advanced Child–Pugh score were independent predictors of poor survival. Young age, large tumor, local anesthesia and the use of the thoracoscopic approach were independent predictors for the development of local recurrence. The method of thermal ablation did not influence survival or local recurrence.
Conclusions:  Differences in the effect on survival and local recurrence between microwave and radiofrequency were not observed in this retrospective, multi-center study of endoscopic thermal ablation for HCC.     

Combination therapy with transarterial chemoembolization and interferon-α compared with transarterial chemoembolization alone for hepatitis B virus related unresectable hepatocellular carcinoma

Background and Aims:  The present study was carried out to test the hypothesis that interferon-α (IFN-α) treatment would reduce or postpone the recurrence rate and improve the overall survival rate in patients after transarterial chemoembolization (TACE) treatment of hepatitis B virus (HBV) related unresectable hepatocellular carcinoma (HCC).
Methods:  216 patients with unresectable HBV-related HCC were randomized into a TACE group and a TACE-IFN group, each group had 108 patients. In the TACE-IFN group, patients received IFN-α1b at a dose of 3 million units (mu) three times a week by intramuscular injection one week after/before TACE treatment, for 48 weeks.
Results:  The median disease-free survival in the TACE-IFN treatment group was 23.6 months (95% CI: 21.4–25.8) and 20.3 months (95% CI: 15.8–24.8) in the TACE group ( P  = 0.027). The disease free rate at 24 months in the TACE group was lower than in the TACE-IFN group (39.8% vs 59.3%, P  = 0.004). The median overall survival was 29 months (95% CI: 27.5–32.1) in the TACE-IFN group and 26 months (95% CI: 20.1–31.9) in the TACE group ( P  = 0.003). The 2-year overall survival in the TACE-IFN group was higher than in the TACE group (72.2% vs 52.8%, P  = 0.003).
Conclusions:  IFN-α treatment reduced recurrence and improved the survival of patients after TACE treatment of HBV-related HCC, with acceptable toxicities.     

Combination therapy of radiofrequency ablation and transarterial chemoembolization in recurrent hepatocellular carcinoma after hepatectomy compared with single treatment

Aim:  To assess the efficacy and safety of radiofrequency ablation (RFA) combined with transarterial chemoembolization (TACE) in recurrent hepatocellular carcinoma (HCC) after hepatectomy and to compare its outcome with a single modality.
Method:  We retrospectively studied 103 patients with recurrent HCCs after hepatectomy who were excluded from repeat hepatectomy. Of them, 81 patients were male and 22 were female (mean age 55.8 ± 10.7 years; range, 30–80 years). According to treatment modality, these patients were divided into three groups: RFA was used as the sole first-line anticancer treatment in 37 patients (RFA group); TACE was used as the sole first-line anticancer treatment in 35 patients (TACE group). RFA followed by TACE was performed in 31 patients (combination group). There was no significant difference in clinical material between the three groups. Indices including treatment success rate, intrahepatic recurrence rate and survival were obtained for analysis and comparison.
Results:  The treatment success rate of the combination group was significantly higher than that of the TACE group (93.5 vs. 68.6%, P  = 0.011). The intrahepatic recurrence rate of the combination group was significantly lower than that of the TACE group (20.7 vs 57.1%, P  = 0.002) and the RFA group (20.7 vs 43.2%, P  = 0.036). The overall 1-, 3- and 5-year survival rates were 73.9, 51.1 and 28.0% respectively in the RFA group; 65.8, 38.9 and 19.5% respectively in the TACE group; and 88.5, 64.6 and 44.3% respectively in the combination group. There was a significant difference in survival between the combination group and the TACE group ( P  = 0.028).
Conclusion:  RFA combined with TACE was more effective in treating recurrent HCC after hepatectomy compared to single RFA or TACE treatment. This combination therapy can thus be a valuable choice of treatment for recurrent HCC.     

Abnormality of the hepatic vein waveforms in cirrhotic patients with portal hypertension and its prognostic implications

Background and Aim:  We investigated the prognostic significance of changes in the Doppler hepatic vein (HV) waveforms in cirrhotic patients with portal hypertension and the mechanisms of these changes.
Methods:  A total of 103 consecutive patients were included in this study and their HV waveforms were classified into four types: type I, triphasic waveform; type II, biphasic waveform; type III, biphasic waveform with reduced phasic oscillations; and type IV, a flat waveform.
Results:  Type I was observed in 34, type II in 40, type III in 23, and type IV in six patients. The 5-year survival rates were 90%, 89%, 41%, and 0% in type I, II, III, and IV, respectively. Five variables including the Child–Pugh score, albumin, bilirubin, ascites, and HV waveform significantly correlated with the survival in a univariate analysis. A multivariate analysis only identified the HV waveform (type III and IV) to be an independent prognostic value. Even in Child–Pugh class B patients, the 5-year survival rate for type III or IV was as poor as 26% in comparison to 92% for type I or II. In contrast, in Child–Pugh class C patients, the 5-year survival rate for type I or II was as good as 63% in comparison to 25% for type III or IV. Furthermore, the changes in HV waveforms correlated with the extent of hepatic fibrosis, the increase in portal perfusion per liver volume, or the decrease in portal vascular resistance.
Conclusions:  Analyzing the HV waveforms was thus found to be a simple method for accurately assessing the prognosis in cirrhotic patients with portal hypertension.     

Outcome of transarterial chemoembolization monotherapy, and in combination with percutaneous ethanol injection, or radiofrequency ablation therapy for hepatocellular carcinoma

Aim:  Hepatocellular carcinoma (HCC) is one of the most commonly occurring malignances worldwide. Curative therapies such as resection, percutaneous ethanol injection (PEI) and radiofrequency ablation (RFA) have been applied to patients with early-stage HCC. Patients with more advanced cancers require local or systemic therapies. We present the results of our retrospective review conducted to evaluate whether transarterial chemoembolization (TACE) alone and combined TACE with percutaneous ablation for HCC exhibited superior efficacy to palliative treatment.
Methods:  The effects of TACE and of the combined therapies (TACE + PEI or TACE + RFA) on the long-term survival rates were evaluated in 268 untreated HCC patients by various statistical analyses.
Results:  The cumulative survival rates in the TACE alone group were significantly superior to those in the palliative treatment group. Further, the cumulative survival rates in the combined TACE + PEI/RFA group were significantly superior to those in the TACE alone group. When the comparison among the groups was restricted to patients with two or three tumors fulfilling the Milan criteria, significantly greater prolongation of survival was observed in the combined TACE + PEI/RFA group than in the PEI/RFA alone group.
Conclusions:  The aforementioned treatment modalities yielded greater improvements of the survival rate and survival duration as compared to palliative treatment in HCC patients. Furthermore, in terms of the effect on the survival period, combined TACE + PEI/RFA therapy was more effective than TACE monotherapy, and also more effective than PEI or RFA monotherapy in cases with multiple tumors fulfilling the Milan criteria.     

Pathologic response to preoperative transarte-rial chemoembolization for resectable hepato-cellular carcinoma may not predict recurrence after liver resection

BACKGROUND: Pathologic response(PR) predicts survival after preoperative chemotherapy and resection of a malignancy. Occasionally, transarterial chemoembolization(TACE)may be selected for preoperative management of resectable hepatocellular carcinoma(HCC). This study investigated whether PR to preoperative TACE can predict recurrence after resection for resectable HCC.METHODS: We conducted analysis of 106 HCC patients who underwent TACE followed by liver resection with a curative intent. The PR was evaluated as the mean percentage of nonviable tumor area within each tumor. We divided the patients into three groups according to response rate: complete PR(CPR), major response(MJR: PR≥50%) and minor response(MNR: PR50%). The primary endpoint was disease-free survival, and the secondary endpoints were predicting factors for tumor recurrence and MJR+CPR.RESULTS: Among the 121 TACE patients, PR could be measured in 106(87.6%). The mean interval between TACE and liver resection was 33.1 days. The 5-year disease-free survival rates by PR status were as follows: 40.6% CPR, 43.7% MJR, and 49.0% MNR(P=0.815). There were also no significant differences in overall survival between the three groups. Multivariate analyses revealed that microvascular invasion and capsular invasion(hazard ratio [HR]=11.224, P=0.002 and HR=2.220P=0.043) were independent predictors of disease-free survival.Multivariate analysis of the predictors of above 50% PR revealed that only hepatitis B was an independent factor.CONCLUSION: These data could reflect that the PR after TACE for resectable HCC may not be useful for predicting recurrence of HCC after resection.     

Long-term prognosis of cirrhotics with an upper gastrointestinal bleeding episode: Does infection play a role?

Background and Aim:  We evaluated the effect of infection on the short- and long-term outcome of cirrhotic patients with upper gastrointestinal bleeding (UGIB), in a series of patients not submitted to antibiotic prophylaxis.
Methods:  The cirrhotic patients hospitalized for UGIB were prospectively followed up until the last visit, death, or transplantation. A standard screening protocol was used for bacterial infection at admission.
Results:  In total, 205 patients were included in the study. Antibiotics were administered in 79 (38.5%) patients and an infection was documented in 64 (31.4%) patients. In total, 130 (63.4%) patients died after a mean (SD) follow up of 23.8 (30.9) months. Six-week mortality was higher in the infected patients ( P  < 0.0001). The mortality of patients who were alive 6 weeks after admission was not different between the infected and non-infected patients. Antibiotic use or bacterial infection, the Child–Pugh score, hepatocellular carcinoma, and creatinine were the independent predictors of 6-week mortality. Age and the Child–Pugh score were the only predictors of mortality of the patients who had survived for more than 6 weeks after acute bleeding. In total, 51 (24.9%) patients rebled, 37 (18.1%) within 5 days of admission. Rebleeding was more frequent (41.8% vs 14.3%, P  < 0.0001) in infected patients, mostly due to differences in early rebleeding (31.6% vs 9.5%, P  = 0.0001).
Conclusion:  Bacterial infection is associated with failure to control UGIB and early mortality in cirrhotic patients, but does not seem to affect the outcome of patients who overcome the bleeding episode.     

Effect of laparoscopic splenectomy on portal hypertensive gastropathy in cirrhotic patients with portal hypertension

Aim:  This study investigated the relationship between portal hypertensive gastropathy (PHG) and splenomegaly, and the effect of laparoscopic splenectomy on PHG in cirrhotic patients with portal hypertension.
Methods:  Seventy patients with liver cirrhosis and portal hypertension were prospectively studied. Indication for laparoscopic splenectomy was bleeding tendency in 10 patients, induction of interferon in 45, treatment of hepatocellular carcinoma in seven, and treatment for endoscopic injection sclerotherapy-resistant esophagogastric varices in eight. The severity of PHG was classified into none, mild, or severe according to the classification by McCormack et al. The severity of liver disease was classified using the Child–Pugh score. All patients underwent upper gastrointestinal endoscopy before and 1 month after the operation.
Results:  The prevalence of PHG was significantly correlated with the severity of liver disease using the Child–Pugh score. The severity of PHG was significantly correlated with the resected spleen volume. One month after the operation, PHG was improved in 16 of 17 patients with severe PHG and in 12 of 32 with mild PHG. The Child–Pugh score showed a significant improvement (6.8 ± 1.4 to 6.2 ± 1.2) at 3 months after laparoscopic splenectomy ( P  < 0.0001).
Conclusions:  PHG may be associated with splenomegaly, and laparoscopic splenectomy may have a beneficial effect on PHG, at least for a short time.     

Eradication of hepatitis C virus profoundly prolongs survival in hepatocellular carcinoma patients receiving transarterial chemoembolization

Adjuvant pegylated interferon plus ribavirin treatment (PegIFN/RBV) reduces recurrence and prolongs survival in early stage hepatocellular carcinoma (HCC) patients with chronic hepatitis C (CHC) infection receiving resection or ablation. However, the impact of antiviral therapy in intermediate and advanced stage of CHC‐HCC patients is uncertain. This study aimed to investigate the impact PegIFN/RBV treatment on recurrence‐free interval and survival in patients with HCC receiving transarterial chemoembolization (TACE). From 2010 to 2013, 274 CHC patients from a 1073 patient‐based cohort composed of freshly diagnosed HCC and receiving TACE treatment the Chang Gung Memorial Hospital, Linkou Medical Center were recruited. Propensity score matching (PSM) (age, gender, AST to Platelet Ratio Index (APRI), tumour size, tumour number and Child‐Turcotte‐Pugh score) with the ratio 1:2 for patients with and without PegIFN/RBV treatment was performed. Statistics were performed with SPSS V.20 (IBM, USA). After matching, 153 patients were analysed and 27 patients (17.6%) achieved sustained virologic response (SVR). The 2‐year cumulative overall survival rate and recurrence‐free survival rate among patients with SVR, non‐SVR, and untreated were 85.2% vs 58.3% vs 69.6% (P=.001) and 73.3% vs 53.8% vs 58.5% (P=.013). By Cox regression analysis, non‐SVR, untreated, increase CTP score and nonresponder to TACE were independent factors related to mortality. The SVR achieved by PegIFN/RBV treatment markedly improves survival and reduces tumour recurrence in CHC‐HCC patients receiving TACE treatment after complete response.     

Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma: Is the addition of subcutaneous interferon‐α‐2b beneficial?

Aim:  We previously reported the benefits of hepatic arterial infusion chemotherapy (HAIC) using cisplatin (CDDP), 5-fluorouracil (5-FU) [low-dose FP], and leucovorin/isovorin for advanced hepatocellular carcinoma (HCC). In this study, we investigated the efficacy of combination therapy with HAIC and subcutaneous interferon (IFN)- α-2b in patients with advanced HCC.
Methods:  Of the 48 patients, 31 received low-dose FP with leucovorin/isovorin (HAIC group) and 17 received combination therapy comprising low-dose FP with isovorin and subcutaneous IFN-α-2b (combination group). Prognostic factors were evaluated by univariate and multivariate analyses of the patient and the disease characteristics.
Results:  There were no significant differences in the response rate (patients with complete or partial response/all patients; P  = 0.736) and survival ( P  = 0.399) between both groups. Univariate analysis revealed that IFN therapy was not a significant prognostic factor. Multivariate analysis showed 3 variables, namely, Child–Pugh score ( P  = 0.010), α-fetoprotein level ( P  = 0.0047), and additional therapy ( P  = 0.002), to be significant prognostic factors.
Conclusions:  We considered that combination therapy with HAIC and subcutaneous interferon (IFN)-α-2b was not beneficial for advanced HCC.     

Ischemic bile duct injury as a serious complication after transarterial chemoembolization in patients with hepatocellular carcinoma

BACKGROUND: Bile duct injuries after transarterial chemoembolization (TACE) have been reported; however, the exact pathogenic mechanisms and clinical implications of the injuries remain to be clarified. STUDY: A total of 950 consecutive patients with hepatocellular carcinoma (HCC) were studied. Among them, 807 were treated with TACE and the remaining 143 were treated with transarterial chemoinfusion (TACI) of cisplatin. RESULTS: None of 143 patients with HCC treated with TACI were found to have any radiographic evidence of biliary injury. In contrast, of the 807 patients treated with TACE, 17 (2%) developed biliary complications. Of all complications, 12 (71%) were subcapsular bilomas; 3 (17%), focal strictures of the common hepatic duct or common bile duct; and 2 (12%), diffuse mild dilatation of the intrahepatic bile ducts. Interestingly, 2 of the 12 bilomas were found in the lobe that was not embolized with gelatin sponge particles. The median numbers of TACE tended to be greater in the patients with focal stricture than in those with bilomas (6.0 vs. 2.5; p = 0.08). All 3 patients with focal strictures and 4 of the 12 patients with bilomas had associated serious bacterial infections at presentation. CONCLUSIONS: Bilomas seem to be caused by iodized oil rather than gelatin sponge particles; focal strictures of large bile ducts seem to be caused by gelatin sponge particles. We suggest that adjustments in the amounts of iodized oil or gelatin sponge particles and in the sites of embolization may reduce ischemic biliary injuries after TACE.     

Combined hepatectomy and radiofrequency ablation versus TACE in improving survival of patients with unresectable BCLC stage B HCC

BACKGROUND: Combined hepatectomy and radiofrequency ablation(RFA) provides an additional treatment for patients with Barcelona Clinic Liver Cancer(BCLC) stage B hepatocellular carcinoma(HCC) who are conventionally deemed unresectable. This study aimed to analyze the outcome of this combination therapy by comparing it with transarterial chemoembolization(TACE). METHODS: We retrospectively reviewed 51 patients with unresectable BCLC stage B HCC who had received the combination therapy. We compared the survival of these patients with that of 102 patients in the TACE group(control). Prognostic factors associated with worse survival in the combination group were analyzed.RESULTS: No differences in tumor status and liver function were observed between the TACE group and combination group. The median survival time for the combination group and TACE group was 38(6-54) and 17(3-48) months, respectively(P0.001). The combination group required longer hospitalization than the TACE group [8(5-14) days vs 4(2-9) days,P0.001]. More than two ablations decreased the survival rate in the combination group. CONCLUSIONS: Combined hepatectomy and RFA yielded a better long-term outcome than TACE in patients with unresectable BCLC stage B HCC. Patients with a limited ablated size(≤2 cm), a limited number of ablations(≤2), and adequate surgical margin should be considered candidates for combination therapy.     

Clinical features and survival in Chinese patients with hepatitis B e antigen-negative hepatitis B virus-related cirrhosis

Aim:  To compare the clinical features of hepatitis B e antigen (HBeAg)-negative and HBeAg-positive cirrhosis, and to define the survival and prognostic indicators of Chinese HBeAg-negative hepatitis B virus (HBV)-related cirrhosis.
Methods:  Two hundred and seventeen patients with chronic hepatitis B cirrhosis were studied. Survival was calculated using the Kaplan–Meier method. Proportional hazards Cox regression procedure was used to identify independent predictors of survival. The relationship between HBV-DNA viral load and prognosis was also investigated.
Results:  The mean follow-up time was 35 months (3–47 months). HBeAg-negative liver cirrhosis patients comprised the greatest number of cirrhosis patients. Median alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, median total leukocytes (WBC), hemoglobin (Hb), platelet (Plt) and HBV-DNA levels and the proportion of HBV-DNA > 10⁵ copies/mL were lower in HBeAg-negative patients. There were fewer complications in patients treated with lamivudine than in other patients. Survival rates were significantly reduced in patients with HBeAg-negative cirrhosis ( P  = 0.0024). The baseline Child–Pugh scores and more than one decompensation during follow up were independent variables correlated with survival of HBeAg-negative liver cirrhosis patients ( P  = 0.006 and P  = 0.001, respectively). The HBV-DNA viral load did not correlate with any complications or mortality rates of HBeAg-negative patients.
Conclusions:  The clinical features of HBeAg-negative and -positive liver cirrhosis differ. Survival was significantly reduced for Chinese patients with HBeAg-negative than -positive cirrhosis. Factors contributing to the prognosis were baseline Child–Pugh scores and the presence of more than one decompensation during follow up.     

Clinical features and outcomes of cirrhosis due to non-alcoholic steatohepatitis compared with cirrhosis caused by chronic hepatitis C

Background and Aim:  Ethnic differences in non-alcoholic steatohepatitis (NASH) are well-documented, but there has been no study on the prognosis of Japanese NASH patients with cirrhosis. Accordingly, we compared cirrhotic NASH with liver cirrhosis caused by chronic hepatitis C (LC-C) to clarify its clinical features and define the risk factors for death.
Methods:  A prospective evaluation of the outcomes of NASH patients with severe fibrosis was started in 1990. Data on age- and sex-matched patients with biopsy-proven LC-C were collected retrospectively and used as the control.
Results:  There were 68 patients with cirrhotic NASH and 69 with LC-C. The Child–Turcotte–Pugh (CTP) class was similar in these two groups. Although the outcome of the NASH group was better than that of the LC-C group, cirrhotic NASH followed a similar course to that of LC-C; that is, complications of cirrhosis developed, including hepatocellular carcinoma (HCC; the 5-year HCC rate was 11.3% for NASH and 30.5% for HCV) and death (the 5-year survival rates were 75.2% and 73.8%, respectively). HCC was the leading cause of death in both groups (NASH, 47%; HCV, 68%). The occurrence of HCC and the CTP class were significant risk factors for mortality in NASH patients according to a multivariate analysis (HCC: hazard ratio [HR] 7.96, 95% confidence interval [CI] 2.45–25.88, CTP class A: HR 0.17, 95% CI 0.06–0.50).
Conclusion:  In conclusion, the present study confirmed that cirrhotic NASH has a similar course to LC-C. The occurrence of HCC was the strongest predictor of mortality in the NASH groups. These findings may be helpful when deciding on therapeutic interventions for NASH and also for the daily management of these patients.     

Local radiotherapy as a complement to incomplete transcatheter arterial chemoembolization in locally advanced hepatocellular carcinoma.

PURPOSE: In order to determine the effect of additional radiotherapy (RT) after an incomplete transcatheter arterial chemoembolization (TACE) in an unresectable hepatocellular carcinoma (HCC), the treatment results of patients receiving TACE plus RT were analyzed and compared with those treated with TACE alone. MATERIALS AND METHODS: One hundred and five patients with an unresectable HCC were treated with TACE from January 1992 to December 2002. In 73 of these patients, the TACE was incomplete. Among them, TACE was repeatedly performed in 35 patients (TACE group), and the remaining 38 patients were also treated with local RT (TACERT group). The patients were either in stage III or IVa, Eastern Cooperative Oncology Group 2 or less, and Child-Pugh class A or B. The average frequency of TACE prior to RT was 2 and the RT was started within 7-10 days after the TACE. RESULTS: The 2-year survival rate was significantly higher in the TACERT than in the TACE group (36.8 % vs. 14.3%, P=0.001). According to the tumor size, the 2-year survival rates in the TACERT and TACE groups were 63% vs. 42% in 5-7 cm (P=0.22), 50% vs. 0% in 8-10 cm (P=0.03), and 17% vs. 0% in larger than 10 cm (P=0.0002) respectively. CONCLUSION: There was a significantly improved survival rate in the TACERT group of unresectable HCC patients than in the TACE group, particularly in case of tumors > or =8 cm in diameter. Therefore, RT in addition to TACE is strongly recommended for patients with an unresectable HCC.     

Ascitic fluid infection in patients with hepatitis B virus-related liver cirrhosis: Culture-negative neutrocytic ascites versus spontaneous bacterial peritonitis

Background and Aim:  Ascitic fluid infection (AFI) consists of culture-negative neutrocytic ascites (CNNA) and spontaneous bacterial peritonitis (SBP). The present study compared the clinical characteristics and prognosis of CNNA and SBP in hepatitis B virus (HBV)-related cirrhotic patients.
Methods:  We analyzed 130 consecutive patients hospitalized due to the first episode of AFI between January 1998 and December 2007.
Results:  The mean age of the patients was 52.3 years (88 men, 42 women). Ninety-three patients (71.5%) had CNNA and 37 patients (28.5%) had SBP; 117 patients (90.0%) died after a median survival period of 6.4 months. Patients with CNNA and SBP survived for a median period of 6.9 months and 5.4 months, respectively ( P  = 0.417). Patients with SBP showed higher in-hospital mortality than those with CNNA (16.2 vs 4.3%; P  = 0.031). Binary logistic regression analysis showed that culture positivity of ascitic fluid (CNNA vs SBP) was the only independent predictor of in-hospital mortality ( P  = 0.042). In a Cox regression model for the 120 patients (92.3%) who survived the first episode of AFI, only the Child–Pugh score remained significant for survival ( P  = 0.007), whereas no association was observed for culture positivity of ascitic fluid (CNNA vs SBP) during the first episode of AFI ( P  = 0.752).
Conclusions:  Although in-hospital mortality was higher in patients with SBP than CNNA, the clinical course of the two groups was similar after the first episode of AFI. Thus, liver transplantation should be considered, irrespective of culture positivity of ascitic fluid.     

Efficacy of platinum analogue for advanced hepatocellular carcinoma unresponsive to transcatheter arterial chemoembolization with epirubicin

Aim:  Hepatocellular carcinoma (HCC) often shows resistance to transcatheter arterial chemoembolization (TACE). Such patients often have a poor prognosis and are unresponsive to other forms of therapy. The aim of this retrospective study was to determine the response to TACE using platinum analogues in patients deemed resistant to TACE using epirubicin.
Methods:  We studied 152 consecutive patients with advanced HCC resistant to TACE using epirubicin. All cases were treated with platinum analogue using transcatheter arterial chemotherapy with or without embolization.
Results:  Computed tomography at 3 months after therapy showed complete response (CR) in 6 patients (4.0%), partial response (PR) in 28 (18%), stable disease (SD) in 35 (23%), and progressive disease (PD) in 83 (55%). The cumulative survival rates for PR/CR patients who received platinum analogue-transcatheter arterial chemotherapy with or without embolization (81.8% at first year, 53.9% at second year, and 33.1% at third year) were significantly higher than those of SD/PD patients (36.6%, 17.5% and 7.4%, respectively) ( P  < 0.001). The 50% survival period was extended almost 1.4 year in PR/CR patients who received platinum analogue-transcatheter arterial chemotherapy with or without embolization.
Conclusion:  Our retrospective study is the first to report the efficacy of platinum analogues for advanced HCC unresponsive to TACE using epirubicin.     

Correlation of routinely used coagulation parameters and presence of portal vein thrombosis in patients with liver cirrhosis

Aim:  Portal vein thrombosis (PVT) is a serious complication in patients with liver cirrhosis. In patients with advanced stages of liver cirrhosis plasmatic coagulation and platelet count are often reduced. However, patients with normal coagulation status might carry a high risk for developing PVT. A correlation between coagulation status used in clinical routine and the incidence of PVT in patients with liver cirrhosis has been evaluated in the present retrospective analysis.
Methods:  88 patients with liver cirrhosis were identified by screening a database. Of these patients, 23 suffered from PVT. Patients were classified according to the Child–Pugh classification. Patients were subdivided into early stages (Child A) and advanced stages (Child B/C) of liver cirrhosis.
Results:  In patients with Child–Pugh A cirrhosis, there was no difference in activated partial thromboplastin time (apTT), international normalized ratio (INR), and platelet count between the PVT ( n  = 7) and the control group ( n  = 35). In contrast, the median apTT and INR were significantly lower in patients with Child B/C cirrhosis and PVT ( n  = 16) in comparison with patients without PVT (37 s vs 43 s [ P  = 0.017] and 1.25 vs 1.40 [ P  = 0.022]), respectively. Platelet count did not differ significantly in patients with advanced liver cirrhosis and PVT from those without PVT.
Conclusion:  Patients with advanced liver cirrhosis and PVT displayed lower apTT and INR compared with those without PVT. Therefore, patients with advanced liver cirrhosis and almost normal coagulation parameters might be at particular risk of developing PVT. The results suggest that regular monitoring using Doppler-ultrasound should be carried out in these patients, especially when liver transplantation is intended.     

Urinary bile acid sulfate levels in patients with hepatitis C virus-related chronic liver diseases

Aim:  Urinary bile acids are mainly conjugated with sulfuric acid, and urinary sulfated bile acid (USBA) levels in hepatobiliary diseases have been reported. However, the relationship between USBA and fasting serum total bile acid (TBA) has not been studied in hepatobiliary diseases. In the present study, we measured USBA levels in patients with hepatitis C virus-related chronic liver diseases, and the relationship between TBA and various laboratory tests was studied.
Methods:  USBA was measured using an automatic assay kit in 66 patients with chronic hepatitis and 28 patients with liver cirrhosis, and its relationship between TBA and various laboratory tests was studied.
Results:  The median USBA level was 10.7 µmol/g creatinine in patients with chronic hepatitis and 41.1 µmol/g creatinine in liver cirrhosis ( P  = 0.000). More patients with chronic hepatitis had elevated USBA levels (61%) compared to TBA level (39%) ( P  = 0.002). USBA level was well correlated with TBA (r_s = 0.680), and negatively correlated with albumin (r_s = −0.488), prothrombin time (r_s = −0.385) and platelet counts (r_s = −0.394). In patients with liver cirrhosis, USBA was significantly elevated in Child–Pugh class B compared to Child–Pugh class A ( P  = 0.036).
Conclusion:  Although the metabolic pathways of USBA and TBA are different, these levels correlated very well, and USBA is considered to be a useful indicator of hepatic function like TBA in patients with chronic hepatitis C.