Comparison of hepatic arterial infusion chemotherapy versus sorafenib monotherapy in patients with advanced hepatocellular carcinoma.

OBJECTIVES: Sorafenib is the standard treatment for advanced hepatocellular carcinoma (HCC) with distant metastasis, unresectable HCC, and those refractory to transcatheter arterial chemoembolization (TACE) or with macroscopic vascular invasion (MVI). The application of sorafenib has been approved by the Japanese Government-sponsored Medicare for unresectable HCC. In this retrospective cohort study we aimed to compare various aspects of HAIC with sorafenib in the treatment of Child-Pugh A patients with advanced HCC who were otherwise free of extrahepatic metastasis. METHODS: Altogether 177 patients with advanced HCC at Child-Pugh class A who were free of extrahepatic metastasis were retrospectively enrolled. The patients were divided into the HAIC group (n = 136) and the sorafenib group (n = 41), and were followed up until their death or withdrawal of therapy. Responses to treatment and overall survival were determined and compared between the two groups. RESULTS: The proportion of patients with complete response, partial response, stable disease and progressive disease were 5.9%, 25.0%, 40.4% and 21.3% in the HAIC and 2.4%, 2.4%, 43.9% and 41.5% in the sorafenib group, respectively. The response rate was higher in the HAIC group than in the sorafenib group (30.9% vs 4.8%). The median survival time was 10 months in both HAIC and sorafenib groups. In patients with macroscopic vascular invasion (MVI) by the case-control method, the response rate was higher in the HAIC group than in the sorafenib group. Overall survival was longer in the HAIC group than in the sorafenib group (14 months vs 7 months, P = 0.005). Multivariate analysis identified MVI (hazard ratio 2.4, P = 0.018) as an independent prognostic factor of survival in the sorafenib group. CONCLUSIONS: Response rate to HAIC was higher than that to sorafenib monotherapy. Prognosis was favorable in HAIC responders despite MVI. HAIC might be a potential treatment option for advanced HCC without extrahepatic metastasis.

Efficacy and safety of the anticoagulant drug, danaparoid sodium, in the treatment of portal vein thrombosis in patients with liver cirrhosis.

AIM: To assess the efficacy and safety of the anticoagulant drug, danaparoid sodium, in the treatment of portal vein thrombosis (PVT) in patients with liver cirrhosis. METHODS: A consecutive 26 cirrhotic patients with PVT were enrolled in this retrospective cohort study. The etiologies of cirrhosis were hepatitis B virus-related, hepatitis C virus-related, alcoholic and cryptogenic in five, 14, three and four patients, respectively. Child-Pugh grade A, B and C was noted in 13, eight and five patients, respectively. Patients were treated with 2 weeks' administration of danaparoid sodium followed by the evaluation of PVT reduction and adverse events. RESULTS: All patients experienced reduction of PVT through the treatment. The median volume of PVT before and after treatment was 2.40 cm(3) (range, 0.18-16.63) and 0.37 cm(3) (range, 0-5.74), respectively. The median reduction rate of PVT volume was 77.3% (range, 18-100%). According to the reduction rate, complete reduction (CR), partial reduction (PR, ≥50%) and stable disease (SD, <50%) were observed in four (15%), 16 (62%) and six patients (23%), respectively. The median volume of PVT before treatment was significantly different between CR + PR and SD (2.09 vs 4.35 cm(3) , P = 0.045). No severe adverse events such as bleeding symptoms (e.g. gastrointestinal bleeding and cerebral hemorrhage) and thrombocytopenia were encountered. CONCLUSION: Danaparoid sodium for the treatment of PVT in patients with liver cirrhosis was safe and effective. Therefore, anticoagulation therapy with danaparoid sodium could have potential as one of the treatment options in PVT accompanied by cirrhosis.

Role of 3-D conformal radiotherapy for major portal vein tumor thrombosis combined with hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma.

AIM: To evaluate the response, survival and safety on 3-D conformal radiotherapy (3D-CRT) for major portal vein tumor thrombosis (PVTT) combined with hepatic arterial infusion chemotherapy (HAIC) for advanced hepatocellular carcinoma (HCC). METHODS: In this retrospective study, 83 advanced HCC patients treated with HAIC who met the following criteria were enrolled: (i) PVTT of the main trunk or first branch of the portal vein; (ii) no extrahepatic metastasis; (iii) Child-Pugh score of 5-7; (iv) performance status of 0 or 1; and (v) no history of sorafenib treatment. The response, overall survival (OS), time to treatment failure (TTF), post-progression survival (PPS) and safety were compared between HAIC combined with 3D-CRT for PVTT (RT group, n = 41) and HAIC alone (non-RT group, n = 42). RESULTS: The objective response of PVTT was significantly higher in the RT group (56.1%) than in the non-RT group (33.3%), while that of intrahepatic tumor and OS were not significantly different between groups. Median OS, TTF and PPS were significantly longer in the RT group than in the non-RT group (8.6 and 5.0 months, 5.0 and 2.7 months, and 5.3 and 1.5 months, respectively) among intrahepatic tumor non-responders to HAIC, whereas those were not significantly different between groups among intrahepatic tumor responders to HAIC. By multivariate analysis, the combination of 3D-CRT with HAIC was an independent contributing factor for OS (hazard ratio, 3.2; 95% confidence interval, 1.692-6.021; P < 0.001) among intrahepatic HCC non-responders to HAIC. CONCLUSION: 3D-CRT for PVTT combined with HAIC could provide survival benefit to non-responder to HAIC.

Evaluation of early response to hepatic arterial infusion chemotherapy in patients with advanced hepatocellular carcinoma using the combination of response evaluation criteria in solid tumors and tumor markers.

BACKGROUND AND AIM: To assess the early response and outcome of hepatic arterial infusion chemotherapy (HAIC) in patients with advanced hepatocellular carcinoma (HCC). METHODS: One hundred sixty-five HCC patients treated with HAIC were reviewed retrospectively. The early response to one course of HAIC treatment was evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) and changes in α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP). RESULTS: The median survival time (MST) for all patients was 9.5 months. The early imaging response by RECIST was assessed as partial response (PR), stable disease (SD), and progressive disease (PD) in 32 (19.3%), 86 (52.1%), and 47 (28.4%) patients, respectively. Survival correlated with early imaging response (MST in PR, 20.6; SD, 11.4; PD, 5.0 months; P < 0.0001). The MST was also significantly different in patients with AFP ratio of ≤ 1 or > 1 and DCP ratio of ≤ 1 or > 1 (worst MST, 6.5 months in patients with AFP ratio of > 1 and DCP ratio of > 1). Among patients with SD early imaging response, patients with AFP ratio of > 1 and DCP ratio of > 1 had significantly poorer survival than others (MST 7.4 vs. 12.6 months, P = 0.014). The decrease in AFP and DCP in the early stage treatment with HAIC were identified as significant and independent factors associated with survival of not only all patients, but also patients with SD early imaging response. CONCLUSION: The use of the combination of RECIST and tumor marker ratio could be useful for assessment of the early response to HAIC and prognosis of patients with advanced HCC.

Efficacy and safety of sitagliptin for the treatment of nonalcoholic fatty liver disease with type 2 diabetes mellitus.

BACKGROUND/AIMS: Dipeptidyl peptidase-4 inhibitor is useful for the treatment of type 2 diabetes mellitus (DM). However, effects on liver function and glucose metabolism in nonalcoholic fatty liver disease (NAFLD) have not been established. The objective of this study was to evaluate the efficacy and safety of sitagliptin in NAFLD patients with type 2 DM. METHODOLOGY: Forty-four patients with biopsy-proven NAFLD with type 2 DM were evaluated. Patients were administered sitagliptin (50 mg/day) for 12 months. RESULTS: Hemoglobin A1c (HbA1c) decreased by 0.7% after treatment (P < 0.001). While HbA1c levels decreased by 0.4% in the low HbA1c (< 7.5%) group, those decreased by 1.2% in the high HbAlc (> or = 7.5%) group. Liver transaminases did not change significantly during the treatment. Improvement of HbA1c (deltaHbA1c) and that of aspartate aminotransferase (deltaAST), alanine aminotransferase (deltaALT) was positively correlated (r = 0.425, and 0.455, respectively), especially in the high HbA1c (> or = 7.5%) group before treatment (r = 0.568, and 0.501, respectively). CONCLUSIONS: Sitagliptin for the treatment of NAFLD with type2 DM was safe and showed similar antidiabetic effects as reported for type 2 DM, suggesting that tight glycemic control would contribute to the improvement of NAFLD based from the findings of correlation between the changes of HbA1c and transaminases.

Pilot study of stereotactic body radiation therapy combined with transcatheter arterial chemoembolization for small hepatocellular carcinoma.

BACKGROUND/AIMS: We retrospectively evaluated the local tumor control and safety of transcatheter arterial chemoembolization (TACE) followed by stereotactic body radiation therapy (SBRT) for small hepatocellular carcinoma (HCC) in this pilot study. METHODOLOGY: Twenty-eight patients not for the indication of hepatectomy or ablation procedures were enrolled in this study. Eligible criteria was as followed: i) less than 3 hypervascular HCC nodules, each up to 30 mm in diameter; ii) not suitable for the hepatic resection or ablative therapy; iii) Child-Turcotte-Pugh (CTP) score < or = 7. SBRT was performed within 1-2 months after TACE. Treatment efficacy was evaluated, according to the Response Evaluation Criteria in Cancer of the Liver (RECICL). RESULTS: The median local tumor control time was not reached. The 1-year cumulative local tumor control rate was 96.3%. The median disease-free survival time was 18 months. The 1- year cumulative overall survival rate was 92.6%. One patient (3.6%) died due to intrahepatic ectopic multiple recurrence and systemic metastasis and one (3.6%) due to cerebral hemorrhage. No patients experienced severe acute hematologic or physical toxicity or radiation induced liver damage. CONCLUSIONS: Our study demonstrated SBRT combined with TACE is a safe and effective modality of the locoregional therapy for small primary HCC.

Interferon lambda 4 polymorphism affects on outcome of telaprevir, pegylated interferon and ribavirin combination therapy for chronic hepatitis C.

AIM: The predictive value of the recently identified interferon-λ (IFNL)4 polymorphism on the outcome of telaprevir (TVR), pegylated interferon (PEG IFN) plus ribavirin (RBV) combination therapy for chronic hepatitis C is unknown. METHODS: We assessed predictive factors for sustained virological response (SVR) for TVR, PEG IFN plus RBV combination therapy in 283 genotype 1 chronic hepatitis C patients. IFNL4 polymorphism ss469415590 was analyzed by Invader assay. RESULTS: SVR rates for patients with IFNL4 TT/TT genotype were significantly higher than for those with the IFNL4 TT/ΔG or ΔG/ΔG genotypes (93% and 59%, respectively, P < 0.0001). In a multivariate regression analysis, prior treatment history (treatment-naïve patients or patients who relapsed during prior treatment) (odds ratio [OR], 2.385; P = 0.028), rapid virological response (OR, 6.800; P < 0.0001) and ss469415590 TT/TT genotype (OR, 8.064; P < 0.0001) were identified as significant independent predictors for SVR. In patients with IFNL4 TT/ΔG or ΔG/ΔG genotypes, SVR rates for non-RVR patients were significantly lower than RVR patients (22% and 75%, respectively, P < 0.0001). CONCLUSION: Analysis of IFNL4 polymorphism is a valuable predictor in patients receiving TVR triple therapy.

Clinical outcome and prognostic factors of patients with hepatocellular carcinoma and extrahepatic metastasis treated with sorafenib.

AIM: The purpose of this study was to assess the clinical outcome and identify prognostic factors following treatment of patients with advanced hepatocellular carcinoma (HCC) and extrahepatic metastasis with sorafenib. METHODS: Sixty-one HCC patients with extrahepatic metastasis who were treated with sorafenib were enrolled in this retrospective cohort study. RESULTS: The median survival time (MST) of all patients was 11 months. The median time to radiological progression was 4.2 months. The response rates (complete response [CR] + partial response [PR]) by Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST were 3.0% and 8.0%, respectively, while the disease control rates (CR + PR + stable disease) were 49% and 49%, respectively. Multivariate analysis identified T factor (intrahepatic tumor stage, T 0-2), response to disease control and des-γ-carboxy prothrombin (<2600 mAU/mL) as significant and independent determinants of survival. Intrahepatic tumor stage before treatment allows stratification of prognosis of patients treated with sorafenib. Four T0 patients remained alive. The MST of patients with T1 (n = 6), T2 (n = 10), T3 (n = 23) and T4 (n = 18) of intrahepatic tumor stage was 20, 23, 7 and 5 months, respectively. Among the progressive disease group, patients with T0-2 intrahepatic tumor stage had better prognosis than patients with T3-4. CONCLUSION: In HCC patients with extrahepatic metastasis who are treated with sorafenib, intrahepatic tumor stage was a significant and independent prognostic factor.

Percutaneous transvenous embolization for portosystemic shunts associated with encephalopathy: Long-term outcomes in 14 patients.

AIM: To evaluate the clinical outcomes of percutaneous transvenous embolization (PTE) for portosystemic shunt (PSS) associated with encephalopathy METHODS: Fourteen patients with portosystemic encephalopathy (PSE) were enrolled in this retrospective cohort study. We evaluated technical success, clinical success, complication and outcomes. RESULTS: In cases in which PSS was one of main causes of PSE, three also had splenorenal shunts, four gastrorenal shunts, four superior mesenteric vein systemic shunts, one inferior mesenteric vein systemic shunt and two main trunk of portal vein inferior vena cava shunts. We used only ethanolamine oleate (EO) in five; EO and coils in five; EO, coils and n-butyl 2-cyanoacrylate (NBCA) in two; and coils and NBCA in two patients as embolic materials. The rate of primary and secondary technical success was 93% (13/14 patients) and 100%, respectively. No major complications were encountered related to PTE. Follow-up period was a median of 27 months (range, 12-79). All patients had sustained disappearance of PSE. PSE recurred in one patient because of another PSS development. Thus, clinical success was achieved in 93% (13/14 patients). The ammonia levels 1 year after PTE were significantly improved compared with pre-PTE (median, 102 vs 41 µmol/L) and maintained lower levels 2 and 3 years later. Child-Pugh scores did not change significantly. Esophageal varices were aggravated in 29% (4/14 patients). Five patients died, but no death of hepatic failure related to PTE was encountered. CONCLUSION: PTE could be one of the useful treatment options for PSE.

Predictive value of the IFNL4 polymorphism on outcome of telaprevir, peginterferon, and ribavirin therapy for older patients with genotype 1b chronic hepatitis C.

BACKGROUND: Older patients with chronic hepatitis C have a lower virological response to interferon (IFN) treatment compared to younger patients. The efficacy of telaprevir (TVR) and PEG-IFN plus ribavirin combination therapy and the predictive value of recently identified IFN lambda (IFNL) 4 polymorphisms on the outcome of therapy for older patients have not been addressed. METHODS: We assessed predictive factors for sustained virological response (SVR) to triple therapy in 226 younger (≤65 years) and 87 older (>65 years) Japanese patients with chronic genotype 1 hepatitis C. IFNL4 polymorphism ss469415590 was analyzed by Invader assay. RESULTS: The SVR rate for older patients was slightly lower than for younger patients (69 vs. 82%, P = 0.043). In the older group, the SVR rate for patients with the IFNL4 TT/TT genotype was significantly higher than patients with TT/ΔG or ΔG/ΔG genotypes (81.8 and 42.9%, P = 0.003). In multivariate regression analysis, rapid virological response (OR 36.601, P = 0.002) and IFNL4 TT/TT genotype (OR 19.502, P = 0.009) were identified as significant independent predictors for SVR in older patients. Treatment-related decreases in hemoglobin and increases in serum creatinine were higher in older patients than younger patients. Reduction of initial TVR dose to 1,500 mg per day alleviated these adverse events without compromising SVR rate in older patients. CONCLUSIONS: Analysis of IFNL4 polymorphisms is a valuable predictor in older patients receiving TVR triple therapy. 1,500 mg per day is a suitable initial TVR dose for older Japanese patients.

Non-invasive liver fibrosis score calculated by combination of virtual touch tissue quantification and serum liver functional tests in chronic hepatitis C patients.

AIM: Acoustic radiation force impulse (ARFI) technology, involving the shear wave velocity (SWV) with virtual touch tissue quantification (VTTQ), are currently available for the assessment of liver fibrosis, while there is no index derived from the combination of SWV and blood tests. The aim of this study was to develop a new index for assessment of liver fibrosis. METHODS: The subjects were 176 consecutive patients with hepatitis C (training set [n = 120] and validation set [n = 56]) who underwent liver biopsy in our institution. RESULTS: In the training set, SWV, international normalized ratio (INR) and alanine aminotransferase (ALT) correlated independently and significantly with fibrosis. According to this, we developed the VIA index = -1.282 + 0.965 × SWV + 1.785 INR + 0.00185 ALT. The areas under the receiver-operator curve (AUROC) of the VIA index were 0.838 for the diagnosis of significant fibrosis (≥F2), 0.904 for the severe fibrosis (≥F3) and 0.958 for the cirrhosis (F4) in the training set. While in the validation set, AUROC of the VIA index were 0.917 for F2 or higher, 0.906 for F3 or higher and 1.000 for F4, respectively. AUROC of the VIA index was improved compared to SWV alone, equivalent for VIA for the diagnosis of F2 or higher, and superior to that of FIB-4 index and aspartate aminotransferase-to-platelet ratio index for the diagnosis of F3 or higher and F4. CONCLUSION: The VIA index is potentially more useful for assessment of liver fibrosis than SWV alone, and easily and accurately measures liver fibrosis stage.

A second attack of cholestasis associated with erythropoietic protoporphyria was successfully treated by plasma exchange and blood transfusion.

Erythropoietic protoporphyria (EPP) is a rare hereditary disease that can sometimes cause acute liver failure based on cholestasis. Acute liver failure is a fatal complication and is associated with EPP in 1-4 % of patients. Although it is extremely difficult to recover from acute liver failure, we experienced an important case of EPP where the patient recovered from the first attack of cholestasis with antibiotic treatment. The patient recovered from a second attack of cholestasis with blood infusion and plasma transfusion. This case suggests that the supply of heme by blood transfusion and the elimination of excess protoporphyrin production by plasma exchange may be a useful treatment for patients with acute cholestasis associated with EPP.

Long-term outcome of patients with gastric varices treated by balloon-occluded retrograde transvenous obliteration.

BACKGROUND AND AIM: To assess the short- and long-term outcome of patients with gastric varices (GV) after balloon-occluded retrograde transvenous obliteration (B-RTO) by comparing bleeding cases with prophylactic cases. METHODS: Consecutive 100 patients with GV treated by B-RTO were enrolled in this retrospective cohort study. We compared the technical success, complications, and survival rates between bleeding and prophylactic cases. RESULTS: Of 100 patients, 61 patients were bleeding cases and 39 patients were prophylactic cases. Technical success was achieved in 95% of bleeding case and in 100% of prophylactic case, with no significant difference between these groups (overall technical success rate, 97%). The survival rates at 5 and 10 years were 50% and 22% in bleeding case, and 49% and 36% in prophylactic case, respectively. There was also no significant difference (P = 0.420). By multivariate analysis, survival rates correlated significantly with liver function (hazard ratio 2.371, 95% CI 1.457-3.860, P = 0.001) and hepatocellular carcinoma development (HR 4.782, 95% CI 2.331-9.810, P < 0.001). The aggravating rates of esophageal varices (EV) were 21%, 50%, and 54% at 12, 60, and 120 months after B-RTO. By multivariate analysis, aggravating rates significantly correlated with EV existing before B-RTO (HR 18.114, 95% CI 2.463-133.219, P = 0.004). CONCLUSION: B-RTO for GV could provide the high rate of complete obliteration and favorable long-term prognosis even in bleeding cases as well as prophylactic cases. Management of EV after B-RTO, especially in coexisting case of GV and EV, would be warranted.

Clinical outcome of sorafenib treatment in patients with advanced hepatocellular carcinoma refractory to hepatic arterial infusion chemotherapy.

BACKGROUND AND AIM: It has been reported about poor prognosis in patients with advanced hepatocellular carcinoma (HCC) refractory to hepatic arterial infusion chemotherapy (HAIC). We assessed the survival benefits of sorafenib therapy for advanced HCC in HAIC refractory patients. METHODS: The study subjects were 191 patients with advanced HCC who had been treated with HAIC. Sorafenib was used in 27 patients who finally failed to respond to HAIC (HAIC/sorafenib group). Clinical outcome was compared between HAIC/sorafenib and HAIC alone groups. RESULTS: There were no significant differences in clinical characteristics and response rate of HAIC between the two groups (response rate: 25.9%, HAIC/sorafenib group; 30.4%, HAIC alone group). The median survival time (MST) for all patients was 11.0 months. The survival rate was significantly higher in the HAIC/sorafenib group than HAIC alone group (MST 22.2 vs 8.7 months, P = 0.017). From administration sorafenib, the disease control rate was 51.8% with MST of 10.4 months. Among HAIC non-responders, the survival rate was significantly higher in the HAIC/sorafenib group than HAIC alone group. Multivariate analysis identified additional therapy with sorafenib as significant and independent determinant of overall survival in all patients and HAIC non-responders. CONCLUSION: Additional therapy with sorafenib could probably improve the prognosis of HAIC refractory patients.

Utility of controlled attenuation parameter measurement for assessing liver steatosis in Japanese patients with chronic liver diseases.

AIM: Steatosis is a common histological feature of chronic liver disease, especially alcoholic and non-alcoholic fatty liver disease, as well as chronic hepatitis C. A recent study showed that evaluating the controlled attenuation parameter (CAP) with transient elastography was an efficient way of non-invasively determining the severity of hepatic steatosis. The objective of this study was to prospectively evaluate the utility of CAP for diagnosing steatosis in patients with chronic liver disease. METHODS: One hundred and fifty-five consecutive patients with suspected chronic liver disease underwent steatosis diagnosis using CAP, blood sample analyses, computed tomography for assessing the liver/spleen ratio and liver biopsy. Steatosis was graded according to the percentage of fat-containing hepatocytes: S0, less than 5%; S1, 5-33%; S2, 34-66%; and S3: more than 66%. RESULTS: The CAP was significantly correlated with steatosis grade, and there were significant differences between the CAP value of the S0 patients and those of the patients with other grades of steatosis. S0 and S1-3 hepatic steatosis were considered to represent mild and significant steatosis, respectively. The CAP values of the patients with mild and significant steatosis were significantly different (P < 0.0001). The area under the receiver-operator curve (AUROC) value of the CAP for diagnosing significant steatosis was 0.878 (95% confidence interval, 0.818-0.939), and the optimal CAP cut-off value for detecting significant steatosis was 232.5 db/m. In multivariate analysis, the CAP (P = 0.0002) and the liver to spleen ratio (P = 0.004) were found to be significantly associated with significant steatosis. CONCLUSION: The CAP is a promising tool for rapidly and non-invasively diagnosing steatosis.

[A case of clonorchiasis complicated with the expansion of liver cyst].

A 61-year-old man was admitted to our hospital for examination of the cause of rapid growth of a liver cyst. We found a slight dilatation of bile duct in the vicinity of the liver cyst. Then, we underwent ERCP and found a communication between the bile duct and liver cyst. Bile cytodiagnosis revealed a large quantity of clonorchis eggs. The patient like to do eat raw freshwater fish and we suspected that the acute expansion of the cyst was due to clonorchiasis. Following administration of 40mg/kg praziquantel, the blood clonorchis antibody disappeared and the liver cyst also disappeared after 6 months. We encountered a case of clonorchiasis complicated with growth of a liver cyst. Medical interviews should be conducted carefully along with meticulous examinations.

Risk factors for the exacerbation of esophageal varices or portosystemic encephalopathy after sustained virological response with IFN therapy for HCV-related compensated cirrhosis.

BACKGROUND: We aimed to identify risk factors contributing to the exacerbation of esophageal varices (EV) or portosystemic encephalopathy after hepatitis C virus (HCV) eradication with interferon (IFN) therapy in patients with compensated cirrhosis. Also, the prognosis after HCV eradication was analyzed. METHODS: Fifty-two patients with sustained virological response to IFN treatment for HCV-related compensated cirrhosis were enrolled in this retrospective cohort study. RESULTS: At the achievement of HCV eradication, in 31 of the 52 patients (60 %), feeding vessels for EVs (left gastric vein, posterior gastric vein, short gastric vein) were shown, and in 18 patients (35 %) there were extrahepatic portosystemic shunts (paraesophageal vein, paraumbilical vein, and splenorenal shunt). Although the HCV eradication was successful, significant improvements were not observed in portosystemic collateral vessels 1 year after HCV eradication, and EVs were exacerbated in 19 (36 %) patients. The cumulative 1- and 3-year rates of EV exacerbation were 13 % and 49 %, respectively. By multivariate analysis, the existence of feeding vessels for EVs at HCV eradication was an independent predictive factor for the exacerbation of EVs (P = 0.009). Seven patients who had an extrahepatic portosystemic shunt at HCV eradication developed portosystemic encephalopathy during follow up. The 1-, 3-, and 5-year incidences of portosystemic encephalopathy were 6, 21, and 34 %, respectively. The cumulative 5-year survival rate of the cohort was 81 %. Two patients died of hepatocellular carcinoma (HCC). CONCLUSIONS: Our findings suggest that the existence of radical portosystemic collateral vessels at successful HCV eradication increases the risk of the exacerbation of EVs and the incidence of portosystemic encephalopathy in patients with HCV-related cirrhosis.

Stereotactic body radiation therapy combined with transcatheter arterial chemoembolization for small hepatocellular carcinoma.

BACKGROUND AND AIMS: To compare the tumor control and safety of stereotactic body radiation therapy (SBRT) combined with transcatheter arterial chemoembolization (TACE) for small, solitary, and hypervascular hepatocellular carcinoma (HCC) with TACE alone. METHODS: Three hundred and sixty-five HCC patients who had solitary, ≤ 3 cm, and hypervascular nodule were treated with TACE. Among them, 30 patients followed by SBRT (SBRT group) and 38 patients without additional therapy and previous HCC treatment (control group) were enrolled in this retrospective cohort study. Local tumor progression, complication, and disease-free survival were compared between these groups. RESULTS: There was no difference in clinical background between these groups. Complete response to therapy was noted in 29 (96.3%) patients of the SBRT group, and in only one (3.3%) patient of the TACE group (P < 0.001). None of the patients developed acute hematologic toxicity of more than Common Terminology Criteria for Adverse Events Grade 3 during and after the treatment. Furthermore, none of the SBRT group developed radiation-induced liver damage. Disease-free survival of the 12 patients without previous HCC treatments in SBRT group was significantly superior to that in control group (15.7 months vs 4.2 months; P = 0.029). CONCLUSION: The results indicated that SBRT combined with TACE is a safe and effective modality for locoregional treatment of small solitary primary HCC, and could be potentially a suitable option.

Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma according to Child-Pugh classification.

BACKGROUND AND AIM: We compared the treatment response, survival, and safety to hepatic arterial infusion chemotherapy (HAIC) in patients with advanced hepatocellular carcinoma (HCC) according to Child-Pugh (CP) score. METHODS: The study subjects were 249 patients with advanced HCC and CP class A and B who had been treated with HAIC. Patients were grouped according to CP score (5/6, 7 and 8/9) and their tumor response, tolerance, and survival were assessed. RESULTS: The median survival time (MST) was 8.2, 9.7, 6.3, and 3.9 months for the whole group, patients with CP 5/6, 7 and 8/9, respectively (P < 0.0001). Complete response (CR) and partial response (PR) were seen in 11 and 57 patients, respectively, with an overall response rate of 27.3%. The response rate was higher in patients with CP score 5/6 and 7, than CP 8/9 (30.5%, 28.2%, 13.8%). The dropout rate was significantly higher in patients with CP score 8/9 than the other two (8.0%, 12.8%, 33.3%, respectively). The survival rate was significantly better in patients who achieved CR/PR than the others with CP score 5/6, 7. CP score 8/9 was an independent negative factor for response and survival. CONCLUSION: Advanced HCC patients with CP score of 5/6 and 7 showed a better response to HAIC and better prognosis than those with CP score 8/9.

[A case of advanced hepatocellular carcinoma with lung, brain and lymph node metastases recurred 8 years after hepatectomy successfully treated by operation, radiation and systemic chemotherapy using S-1/CDDP].

A 30-year-old man underwent a left lobectomy and S5/6 partial hepatectomy in August 2001 for hepatocellular carcinoma (HCC). A lung tumor was detected by positron emission tomography (PET-CT) 8 years after the surgery. In May 2010, he received pulmonary tumor resection and the histopathological findings revealed metastasis of HCC. However a metastatic brain tumor was detected by computed tomography (CT) in September 2010, therefore surgery and radiation therapy were subsequently performed. Thereafter, metastatic hilar lymph node appeared in December 2010, therefore we performed systemic chemotherapy using S-1/cisplatin combined with radiation therapy for the metastatic tumor. The tumor was markedly decreased and no shadow was detected by PET-CT. He has been followed up in the outpatient clinic with no recurrence.