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1.
Hepatol Res ; 48(3): E98-E106, 2018 Feb.
Article in English | MEDLINE | ID: mdl-28656607

ABSTRACT

AIM: Transcatheter arterial chemoembolization (TACE) has been recognized as a treatment option for patients with intermediate hepatocellular carcinoma (HCC). This randomized, controlled study compared the local control efficacy of TACE with miriplatin (platinum monohydrate) or with epirubicin. METHODS: The study group consisted of 200 Japanese patients with unresectable HCC treated at the Kitasato University East Hospital (Sagamihara, Japan) between July 2010 and June 2013. The primary end-point of the study was time to tumor progression (TTP). RESULTS: We analyzed 198 patients (99 in the miriplatin group and 99 in the epirubicin group) treated with TACE. The median TTP in the epirubicin group was 5.9 months (95% confidence interval [CI], 4.8-7.0) and 7.6 months (95% CI, 5.8-9.4) in the miriplatin group. There was a significant difference between the two groups (P = 0.021; risk ratio, 1.488; 95% CI: 1.061-2.086). In the epirubicin group, 53 patients (53%) had complete response, 24 patients (24%) had partial response, 12 patients (12%) had stable disease, and 10 patients (10%) had progressive disease. In the miriplatin group, 38 patients (38%) had complete response, 41 patients (41%) had partial response, 2 patients (2%) had stable disease, and 18 patients (18%) had progressive disease. There was no significant difference in the response rate (P = 0.862). Overall incidences of adverse events and adverse drug reactions did not differ significantly between the two groups. CONCLUSION: Miriplatin proved more effective than epirubicin in TACE for unresectable HCC. The trial described in this work has been registered under the trial number: UMIN000004790.

2.
Hepatol Res ; 47(11): 1118-1126, 2017 Oct.
Article in English | MEDLINE | ID: mdl-27943555

ABSTRACT

AIM: To examine whether superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging (MRI) can be used to assess the malignant potential of hepatic hypovascular nodules showing hypointensity during the hepatobiliary phase (HBP) on gadoxetic acid (Gd-EOB-DTPA)-enhanced MRI. METHODS: The study included 42 patients with chronic liver disease who had small hypovascular nodules (5-15 mm) showing hypointensity during the HBP on Gd-EOB-DTPA-enhanced MRI. The SPIO-enhanced T2-weighted MRI analyzed whether the signal intensity of each nodule was high. Nodules were prospectively followed up until hypervascularization by periodic Gd-EOB-DTPA-enhanced MRI. Initial MRI findings and clinical variables were used to analyze predictive factors for hypervascularization. RESULTS: We analyzed 77 nodules, of which 19 (25%) showed hypervascularization during the observation period. The cumulative rates for hypervascularization were 11% and 22% at 1 and 2 years, respectively. Hyperintensity was observed in 12 nodules (16%) on SPIO-enhanced T2-weighted MRI; among these, 7 (58%) showed hypervascularization, whereas 12 (18%) of the remaining 65 nodules without hyperintensity showed hypervascularization (P = 0.007). A Cox model revealed that independent predictors of hypervascularization included hyperintense nodules on SPIO-enhanced MRI (P < 0.001). The cumulative rates for hypervascularization in hyperintense nodules on SPIO-enhanced MRI were 52% at 1 year, whereas these rates were 3% for non-hyperintense nodules. CONCLUSION: Superparamagnetic iron oxide-enhanced MRI is useful for predicting the malignant potential of vascular transformation of hypovascular nodules with hypointensity observed in the HBP on Gd-EOB-DTPA-enhanced MRI.

3.
Hepatol Res ; 46(6): 559-64, 2016 May.
Article in English | MEDLINE | ID: mdl-26355776

ABSTRACT

AIM: Portopulmonary venous anastomoses (PPVA) are shunts between esophageal varices and pulmonary veins. Because PPVA can cause serious complications at the time of sclerotherapy for esophageal varices, it is essential to confirm the existence of any PPVA before treatment. METHODS: The study group comprised 101 patients in whom hemodynamics were evaluated on three-dimensional computed tomography (3D-CT) before either elective or prophylactic treatment of esophageal varices at Kitasato University East Hospital from October 2007 through August 2013. The presence or absence of PPVA, laboratory test results and 3D-CT findings were retrospectively examined in these patients. RESULTS: Nine patients had PPVA, and 92 patients did not. The underlying diseases in the PPVA group were: hepatitis C liver cirrhosis in three; non-B, non-C liver cirrhosis in three; non-alcoholic steatohepatitis in one; primary biliary cirrhosis in one; and autoimmune hepatitis in one. The distribution of underlying diseases did not differ between the PPVA group and the non-PPVA group. When the study variables were statistically compared between the groups, the incidence of large, coil-shaped esophageal varices (grade F3) differed significantly between the groups (P = 0.001). Multivariate analyses of factors related to PPVA revealed that only the grade F3 type of esophageal varices differed significantly between the groups (P = 0.005; hazard ratio, 5.21; 95% confidence interval, 3.1-16.4). CONCLUSION: In patients with grade F3 esophageal varices, the treatment method should be selected on the basis of an accurate hemodynamic analysis using 3D-CT before therapy.

4.
Hepatol Res ; 45(9): 976-985, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25336196

ABSTRACT

AIM: Early evaluation of the response to sorafenib for patients with hepatocellular carcinoma (HCC) remains unclear. This prospective study investigated the early evaluation of the efficacy of sorafenib in patients with advanced HCC using duplex Doppler ultrasonography (DDU). METHODS: Thirty-seven Child-Pugh class-A advanced HCC patients treated with sorafenib 400 mg b.i.d. were enrolled. Changes in portal venous area (PVA) and portal venous flow velocity (PVV) revealed by DDU before and after 2 weeks of sorafenib treatment were evaluated. The relation between the congestion index (PVA/PVV), which reflects the pathophysiological hemodynamics of the portal venous system and the tumor response, according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST), was also assessed. RESULTS: The median progression-free survival and overall survival of all the patients was 2.8 months (95% confidence interval [CI], 2.6-3.2) and 12.8 months (95% CI, 8.7-17.0), respectively. Overall, three patients (8%) had a partial response (PR), 15 (41%) stable disease (SD) and 17 (46%) progressive disease, according to the mRECIST, and two patients (6%) could not be evaluated because of worsened conditions. The decrease in the congestion index was significantly larger in the disease control group (PR/SD) after the sorafenib treatment (P = 0.035); furthermore, the congestion index was the only significant independent predictor of disease control (P = 0.033; hazard ratio, 8.456; 95% CI, 1.182-60.484). CONCLUSION: A decrease in the congestion index revealed by DDU provides an early evaluation of response in patients taking sorafenib for advanced HCC.

5.
Hepatol Res ; 45(3): 279-87, 2015 Mar.
Article in English | MEDLINE | ID: mdl-24802232

ABSTRACT

AIM: Patients with hepatocellular carcinoma (HCC) who receive an initial full dose of sorafenib (800 mg/day) often require a decreased dose (400 mg/day) or discontinuation of therapy because of severe adverse events. We conducted a retrospective analysis of patients with HCC to compare the safety and efficacy of full- to half-dose sorafenib. METHODS: We reviewed the medical records of 218 consecutive patients with intermediate or advanced stage HCC who received half (n = 73) or full-dose sorafenib (n = 145) between 2009 and 2012 at four institutions. A propensity score-matching analysis was used to adjust for potential bias. RESULTS: Multivariate logistic regression analysis showed that increased age was an independent factor for the selection of initial half-dose sorafenib (odds ratio, 1.10; 95% confidence interval, 1.05-1.15; P < 0.001). Fifty-eight patients each in the half-dose and full-dose groups were selected for propensity score matching. The incidence of grade 3-4 severe adverse effects was lower in the half-dose group (47.4% vs 66.7%, P = 0.037). In contrast, the median progression-free survival (PFS) and overall survival (OS) rates were not significantly different (half-dose group, 3.8 and 10.2 months; full-dose group, 2.5 and 8.8 months; P = 0.143 and 0.911, respectively). CONCLUSION: Propensity score-matched analyses indicate that initial half-dose sorafenib treatment led to fewer severe adverse effects and a comparable survival benefit compared with a full dose in select patients with HCC, particularly for those of advanced age.

6.
BMC Gastroenterol ; 14: 84, 2014 May 03.
Article in English | MEDLINE | ID: mdl-24886354

ABSTRACT

BACKGROUND: This study investigated the survival benefits of sorafenib vs. radiotherapy (RT) in patients with unresectable hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT) in the main trunk or the first branch. METHODS: Ninety-seven patients were retrospectively reviewed. Forty patients were enrolled by the Kanagawa Liver Study Group and received sorafenib, and 57 consecutive patients received RT in our hospital. Overall survival was compared between the two groups with PVTT by propensity score (PS) analysis. Factors associated with survival were evaluated by multivariate analysis. RESULTS: The median treatment period with sorafenib was 45 days, while the median total radiation dose was 50 Gy. The Child-Pugh class and the level of invasion into hepatic large vessels were significantly more advanced in the RT group than in the sorafenib group. Median survival did not differ significantly between the sorafenib group (4.3 months) and the RT group (5.9 months; P = 0.115). After PS matching (n = 28 per group), better survival was noted in the RT group than in the sorafenib group (median survival, 10.9 vs. 4.8 months; P = 0.025). A Cox model showed that des-γ-carboxy prothrombin <1000 mAU/mL at enrollment and RT were significant independent predictors of survival in the PS model (P = 0.024, HR, 0.508; 95% CI, 0.282 to 0.915; and P = 0.007, HR, 0.434; 95% CI, 0.235 to 0.779; respectively). CONCLUSIONS: RT is a better first-line therapy than sorafenib in patients who have advanced unresectable HCC with PVTT.


Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Hepatocellular/therapy , Liver Neoplasms/therapy , Niacinamide/analogs & derivatives , Phenylurea Compounds/therapeutic use , Portal Vein , Radiotherapy/methods , Venous Thrombosis/pathology , Aged , Carcinoma, Hepatocellular/complications , Carcinoma, Hepatocellular/pathology , Cohort Studies , Female , Humans , Kaplan-Meier Estimate , Liver Neoplasms/complications , Liver Neoplasms/pathology , Middle Aged , Multivariate Analysis , Niacinamide/therapeutic use , Prognosis , Propensity Score , Proportional Hazards Models , Retrospective Studies , Sorafenib , Survival Rate , Treatment Outcome , Venous Thrombosis/etiology
7.
J Gastroenterol Hepatol ; 29(2): 352-7, 2014 Feb.
Article in English | MEDLINE | ID: mdl-23869689

ABSTRACT

BACKGROUND AND AIM: To examine the efficacy and outcomes of radiotherapy (RT) in patients who have hepatocellular carcinoma with invasion to intrahepatic large vessels (IHLVs). METHODS: Sixty-seven patients who had advanced hepatocellular carcinoma with invasion to IHLVs received three-dimensional conformal RT. IHLV invasion was associated with portal venous tumor thrombosis in 40 patients, tumor thrombosis involving the hepatic vein in 17, and both findings in 10. A daily radiation dose of 1.8-2 Gy was administered using 6 or 10 MV X-rays to deliver a total dose of 30-56 Gy. RESULTS: The overall objective response rate (complete response plus partial response) was 45% (n = 30). The median survival time was 13.7 months in the responder group and 5.9 months in the nonresponder group. An objective response was observed in 28 (56%) of 50 patients with Child-Pugh (C-P) class A and in 2 (12%) of 17 patients with C-P class B. Hepatic function of C-P class A was an independent factor for both RT responder and overall survival on Cox regression analysis (hazard ratio = 9.5, 95% confidence interval = 1.97-46.2, P = 0.005; and hazard ratio = 0.39, 95% confidence interval = 0.2-0.77, P = 0.007, respectively). CONCLUSION: RT is an effective treatment option without serious adverse events. RT should be considered for the patients with better hepatic function who have invasion to IHLVs.


Subject(s)
Carcinoma, Hepatocellular/blood supply , Carcinoma, Hepatocellular/radiotherapy , Hepatic Veins/pathology , Liver Neoplasms/blood supply , Liver Neoplasms/radiotherapy , Portal Vein/pathology , Radiotherapy, Conformal/methods , Aged , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Female , Humans , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Middle Aged , Neoplasm Invasiveness , Neoplastic Cells, Circulating/pathology , Proportional Hazards Models , Radiotherapy Dosage , Survival Rate
8.
Eur J Gastroenterol Hepatol ; 25(6): 683-9, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23395995

ABSTRACT

BACKGROUND: To determine the value of early alterations of the tumor markers α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) for predicting the outcomes of patients with advanced hepatocellular carcinoma (HCC) who receive sorafenib. MATERIALS AND METHODS: Tumor response, overall survival (OS), and progression-free survival (PFS) were retrospectively analyzed in 59 patients with advanced HCC. Serum AFP and DCP were examined for early elevation within 4 weeks after the initiation of sorafenib. An increase in AFP was defined as AFP of more than 20%, and an increase in DCP was defined as more than two-fold higher level than the baseline. The relationship of the clinical characteristics, laboratory data at baseline, and early elevations of AFP and DCP with disease progression was analyzed. RESULTS: The median OS and PFS were 11 and 3.3 months, respectively. The rate of progressive disease (PD) was 54%, and an early increase in AFP was significantly related to PD (P=0.006) and was a significant independent predictor of both poorer OS and PFS (P<0.001, hazard ratio, 4.14; 95% confidence interval, 1.946-8.811; and P=0.001, hazard ratio, 2.852; 95% confidence interval, 1.524-5.337, respectively). There was no association between early increase in DCP and clinical outcomes. CONCLUSION: Early increase in AFP predicted PD and poorer survival and may thus be a useful biomarker in patients with advanced HCC who receive sorafenib.


Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/drug therapy , Niacinamide/analogs & derivatives , Phenylurea Compounds/therapeutic use , alpha-Fetoproteins/metabolism , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/adverse effects , Biomarkers/blood , Biomarkers, Tumor/blood , Carcinoma, Hepatocellular/blood , Disease Progression , Female , Humans , Liver Neoplasms/blood , Male , Middle Aged , Niacinamide/adverse effects , Niacinamide/therapeutic use , Phenylurea Compounds/adverse effects , Prognosis , Protein Precursors/blood , Prothrombin , Retrospective Studies , Sorafenib , Survival Analysis , Time Factors , Treatment Outcome
9.
J Gastroenterol ; 48(2): 269-76, 2013 Feb.
Article in English | MEDLINE | ID: mdl-22825550

ABSTRACT

BACKGROUND: Nocturnal administration of branched-chain amino acid (BCAA) granules improves serum albumin levels in patients with cirrhosis. However, it is unclear whether or not this administration method can improve the patients' quality of life (QOL). In this study, we aimed to investigate the efficacy of BCAA granules, given nocturnally, in improving QOL in these patients. METHODS: We performed a multicenter, randomized controlled trial examining the comparative effects of BCAA granules given orally for 3 months with daytime or nocturnal administration in patients with compensated cirrhosis. Health-related QOL was measured by a Japanese version of the questionnaire on subjective and objective symptoms, and the Short Form-8 (SF-8) questionnaire. RESULTS: Twenty-one patients received BCAA granules three times a day (one sachet after each meal: the daytime group), and 16 patients received the granules twice a day (one sachet after breakfast, and two sachets before bedtime: the nocturnal group). Baseline characteristics did not differ between the groups (whole cohort: Child-Pugh grade A/B, 21/16; mean age, 68.2 years). There was no significant difference in any of the subjects revealed by the questionnaire regarding subjective or objective symptoms, or by the SF-8 between the daytime group and the nocturnal group after 3 months of treatment. The daytime group showed a significant effect on general health, vitality, social functioning, mental health, and role emotional as revealed on the SF-8. Conversely, the nocturnal group exhibited a significant decrease in the occurrence of muscle cramps in the legs (P = 0.014) and significantly improved Fisher's ratio after 3 months (P = 0.04). CONCLUSIONS: Nocturnal administration of BCAA granules in patients with cirrhosis reduced the occurrence of muscle cramps in the leg but did not improve the patients' QOL.


Subject(s)
Amino Acids, Branched-Chain/administration & dosage , Liver Cirrhosis/drug therapy , Quality of Life , Administration, Oral , Adult , Aged , Aged, 80 and over , Amino Acids, Branched-Chain/adverse effects , Amino Acids, Branched-Chain/therapeutic use , Biomarkers/blood , Carcinoma, Hepatocellular/etiology , Drug Administration Schedule , Esophageal and Gastric Varices/etiology , Female , Follow-Up Studies , Humans , Liver Cirrhosis/blood , Liver Cirrhosis/complications , Liver Cirrhosis/rehabilitation , Liver Neoplasms/etiology , Male , Medication Adherence , Middle Aged , Psychometrics , Treatment Outcome
10.
Gan To Kagaku Ryoho ; 39(7): 1065-70, 2012 Jul.
Article in Japanese | MEDLINE | ID: mdl-22790040

ABSTRACT

UNLABELLED: Some clinical studies confirmed the efficacy and safety of sorafenib in advanced hepatocellular carcinoma(HCC), for which the standard initial dose is 400 mg twice daily. However, it is unclear whether this dosage is tolerable for patients with a low body surface area(BSA). We retrospectively analyzed the difference in efficacy and safety of sorafenib between patients with low BSA and high BSA. METHOD: From July 2009 to June 2010, 64 patients with Child-Pugh grade A cirrhosis receiving sorafenib at 4 institutions were enrolled, and divided into two groups(BSA<1. 6m2 and ≥1. 6m2). RESULTS: In BSA<1. 6m2 and BSA≥1. 6m2 groups, grade 3-4 adverse events were observed in 64. 3% and 55. 3% of patients, respectively, and subsequent discontinuation was 38. 5% and 24. 2%, respectively indicating poor compliance in the former group. The disease control rate was 33. 3% and 37. 8%, the median time-to-radiological progression(TTRP)was 2. 1 months and 3. 6 months(p=0. 003), and median survival time was 6. 6 months and 11. 2 months in low BSA and high BSA groups(p=0. 10), respectively. Multi-variate analysis showed that poor prognostic factors for TTRP were ECOG performance status of ≥1 and BSA<1. 6m2. CONCLUSION: Standard dosage seems intolerable for patients with low BSA, and results in poor prognosis.


Subject(s)
Antineoplastic Agents/therapeutic use , Benzenesulfonates/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/drug therapy , Pyridines/therapeutic use , Aged , Antineoplastic Agents/adverse effects , Benzenesulfonates/adverse effects , Carcinoma, Hepatocellular/diagnosis , Female , Humans , Liver Neoplasms/diagnosis , Male , Middle Aged , Neoplasm Staging , Niacinamide/analogs & derivatives , Phenylurea Compounds , Prognosis , Pyridines/adverse effects , Sorafenib
11.
J Gastroenterol ; 47(9): 1030-5, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22402773

ABSTRACT

BACKGROUND AND AIMS: Sorafenib is currently in clinical use as an oral multikinase inhibitor that blocks tumor growth and cell proliferation in advanced hepatocellular carcinoma (HCC). It has been demonstrated in a translating study that sorafenib had a beneficial effect on portocollateral circulation in cirrhotic animals with portal hypertension. This study was prospectively performed to evaluate the portal hemodynamic effect of sorafenib in patients with advanced HCC using duplex Doppler ultrasonography (DDU). METHODS: Twenty-five Child-Pugh class-A patients with advanced HCC had received sorafenib at a dose of 400 mg twice daily. Primary outcomes were changes in portal venous area (PVA; cm(2)) as seen by using DDU before and after a 2-week administration of sorafenib. Secondary outcomes included the changes of laboratory data and other flow data revealed on DDU. RESULTS: PVA was significantly decreased after a 2-week administration (0.78 ± 0.23 vs. 0.64 ± 0.25, P = 0.023), while the portal venous flow velocity (PVV; cm/s) was not significantly changed (0.22 ± 0.06 vs. 0.24 ± 0.07, P = 0.17). Therefore, the congestion index (PVA/PVV), which reflects the pathophysiological hemodynamics of portal venous system, was significantly decreased (3.9 ± 1.7 vs. 3.0 ± 1.4, P = 0.042). CONCLUSIONS: We demonstrated the portal hemodynamic effect of sorafenib in patients with advanced HCC. Considering that this was a short-term study, because sorafenib could be a potential beneficial therapeutic agent for portal hypertension, it will be necessary to verify its clinical benefits for portal hypertension in future studies.


Subject(s)
Antineoplastic Agents/therapeutic use , Benzenesulfonates/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/drug therapy , Pyridines/therapeutic use , Aged , Antineoplastic Agents/adverse effects , Benzenesulfonates/adverse effects , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/physiopathology , Cohort Studies , Female , Hemodynamics/physiology , Humans , Liver/physiology , Liver Function Tests , Liver Neoplasms/mortality , Liver Neoplasms/physiopathology , Male , Middle Aged , Niacinamide/analogs & derivatives , Phenylurea Compounds , Portal Vein/physiology , Prospective Studies , Pyridines/adverse effects , Sorafenib , Treatment Outcome , Ultrasonography, Doppler, Duplex
12.
J Med Case Rep ; 6: 38, 2012 Jan 26.
Article in English | MEDLINE | ID: mdl-22280970

ABSTRACT

INTRODUCTION: In the past, no effective systemic therapy has existed for patients with advanced hepatocellular carcinoma. Sorafenib, an oral multikinase inhibitor, has recently been shown to improve overall survival in patients with advanced hepatocellular carcinoma in two randomized, double-blinded, placebo-controlled trials. This drug has been approved as the first-line therapy for advanced hepatocellular carcinoma patients. We report an intriguing case of advanced hepatocellular carcinoma in which the patient achieved late- onset partial response by prolonged administration of sorafenib in spite of progressive disease. CASE PRESENTATION: A 54-year-old Japanese man was treated with sorafenib for multiple lung metastases after surgical resection for advanced hepatocellular carcinoma accompanied by vascular invasion of the left branch of the portal vein. Although the effective diagnosis was progressive disease, almost all sites began to reduce or disappear eight months after the diagnosis of progressive disease. A dramatic reduction in alpha-fetoprotein and des-gamma-carboxy prothrombin levels was observed. The patient finally achieved partial response and his status remains unchanged. CONCLUSIONS: If tolerated, prolonged sorafenib treatment may be beneficial.

13.
J Gastroenterol ; 47(2): 118-26, 2012 Feb.
Article in English | MEDLINE | ID: mdl-21947706

ABSTRACT

BACKGROUND AND PURPOSE: Elective esophageal variceal ligation (EVL) is performed to decrease the risk of variceal hemorrhage. EVL is associated with adverse effects, including post-ligated bleeding, chest pain, and dysphagia. Proton pump inhibitors (PPIs) are the most potent pharmacological agents for inhibition of gastric acid secretion. However, the long-term effect of PPIs after EVL remains unclear. The aim of this study was to assess the efficacy of rabeprazole, a PPI, after variceal eradication by EVL. METHODS: We performed a randomized, controlled trial in Kitasato University East Hospital. The primary endpoint was treatment failure, defined as variceal hemorrhage or severe medical complications. Between July 2007 and September 2010, 43 patients were randomized into this study and followed up until September 2010. RESULTS: Twenty-one patients in the rabeprazole arm received 10 mg rabeprazole daily after EVL, and 22 patients in the control received no antisecretory treatment from the same stage. Baseline characteristics did not differ between the groups (median Child-Pugh score, 6; median age, 62 years; median follow-up, 18.7 months). The trial was stopped early after an interim analysis showed that the risk of bleeding and failure of rabeprazole treatment was lower than that of no antisecretory treatment with the log-rank test showing a significant difference between the groups (P = 0.007) and a hazard ratio of 0.098 [95% confidence interval, 0.012-0.79 (P = 0.029)]. CONCLUSIONS: Long-term administration of PPIs reduced the risk of treatment failure after EVL. Acid suppression therapy should also be considered as a treatment option after EVL.


Subject(s)
2-Pyridinylmethylsulfinylbenzimidazoles/administration & dosage , Esophageal and Gastric Varices/surgery , Proton Pump Inhibitors/administration & dosage , Aged , Combined Modality Therapy , Female , Humans , Intention to Treat Analysis , Ligation , Male , Middle Aged , Postoperative Period , Rabeprazole , Treatment Failure
14.
Cutan Ocul Toxicol ; 31(3): 253-7, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22172047

ABSTRACT

A 62-year-old male treated with pegylated interferon α-2b plus ribavirin for chronic hepatitis C complained of sudden painless decreased visual acuity. This patient was diagnosed as having simultaneous occlusions of the branch retinal artery and central retinal vein, although he had no history of major risk factors for retinal vessel (artery and vein) occlusion. Unfortunately, visual acuity did not completely recover. Furthermore, the patient was heterozygous for interleukin (IL) 28B genetic polymorphisms. The etiology of interferon-associated retinal vessel occlusion is not yet clear. However, a review based on previous case reports suggested that some factors including ribavirin might act as a risk or cause of retinal vessel occlusion.


Subject(s)
Hepatitis C, Chronic/drug therapy , Interferon-alpha/adverse effects , Polyethylene Glycols/adverse effects , Retinal Artery Occlusion/chemically induced , Retinal Vein Occlusion/chemically induced , Ribavirin/adverse effects , Adult , Humans , Interferon alpha-2 , Interferon-alpha/therapeutic use , Interferons , Interleukins/genetics , Male , Middle Aged , Polyethylene Glycols/therapeutic use , Polymorphism, Genetic , Recombinant Proteins/adverse effects , Recombinant Proteins/therapeutic use , Retinal Artery Occlusion/physiopathology , Retinal Vein Occlusion/physiopathology , Ribavirin/therapeutic use , Visual Acuity
15.
J Gastroenterol ; 46(11): 1316-23, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21850387

ABSTRACT

BACKGROUND: The renin-angiotensin system plays an important role in hepatic fibrosis and portal hypertension. We evaluated the long-term effects of olmesartan, an angiotensin type 1 (AT1) receptor blocker, on hemodynamics and liver fibrosis. METHODS: Forty-eight selected patients with cirrhosis were randomly divided into two groups of 24 patients each, those who received and those who did not receive olmesartan treatment for 1 year. Hepatic hemodynamic studies, and measurements of transforming growth factor-beta1 (TGF-beta1) and blood markers of hepatic fibrosis, including serum hyaluronic acid (HA), type IV collagen, and procollagen III N-terminal propeptide levels, were also performed at the beginning and end of the study. RESULTS: The median dose of the final drug administration was 20 mg (range 10-40 mg). Olmesartan reduced the hepatic venous pressure gradient (HVPG) by -12.9 ± 9.1% (p = 0.035) after 1 year. No significant changes were seen in controls. Six of the 24 patients (25%) in the olmesartan group showed a >20% reduction of HVPG from baseline values. TGF-beta1 was significantly decreased in patients who received olmesartan (7.0 ± 8.2 vs. 3.1 ± 1.6 ng/mL, p = 0.046) but there was no decrease in the controls. A significant trend was shown by correlating HA and TGF-beta1 variations in cirrhosis patients (p = 0.018, r = 0.377). Fibrosis markers were unchanged at the end of the study in both groups. CONCLUSIONS: Olmesartan induced a mild reduction of portal pressure and TGF-beta1 for 1 year, but did not suppress hepatic fibrosis markers.


Subject(s)
Angiotensin II Type 1 Receptor Blockers/administration & dosage , Imidazoles/administration & dosage , Liver Cirrhosis/drug therapy , Portal Pressure/drug effects , Tetrazoles/administration & dosage , Transforming Growth Factor beta1/metabolism , Aged , Biomarkers , Collagen Type IV/blood , Collagen Type IV/drug effects , Esophageal and Gastric Varices/pathology , Female , Humans , Hyaluronic Acid/blood , Liver Cirrhosis/metabolism , Male , Middle Aged , Peptide Fragments/blood , Peptide Fragments/drug effects , Procollagen/blood , Procollagen/drug effects , Prospective Studies
16.
Liver Int ; 31(3): 340-7, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21134110

ABSTRACT

BACKGROUND AND AIM: De novo hepatitis B virus (HBV)-related hepatitis is a well-known fatal complication following chemo-immunosuppressive therapy in patients with past HBV infection (HB surface antigen and serum HBV DNA negative, but HB core antibody and/or HB surface antibody positive). This research was conducted to evaluate the incidence of and clinical features associated with re-appearance of serum HBV DNA following chemo-immunosuppressive therapy in Japanese patients with past HBV infection. METHODS: This is a retrospective review. Forty-five patients with past HBV infection who had received chemo-immunosuppressive therapy for haematological disease were followed up for >6 months, to determine whether the serum test for HBV changed from negative to positive (i.e. re-appearance of serum HBV DNA following chemo-immunosuppressive therapy). RESULTS: Re-appearance of serum HBV DNA was confirmed in five (20.8%) of the 24 patients who had received treatment regimens containing rituximab, but in none of the 21 patients who had not received treatment regimens containing rituximab (P=0.035). The HBV genotype could be determined in four of the five aforementioned patients, and in all four, HBV genotype C, which is the most prevalent genotype in Japan, was identified. CONCLUSION: This research showed that re-appearance of serum HBV DNA is not rare in Japanese patients treated with chemotherapy regimens containing rituximab, and no other factors related to such re-appearance of serum HBV DNA could be identified. Well-designed clinical studies, including immunological and genetic analyses of the host and of the HBV, are required for further elucidation.


Subject(s)
Antibodies, Monoclonal, Murine-Derived/adverse effects , Antineoplastic Agents/adverse effects , Hepatitis B virus/isolation & purification , Hepatitis B, Chronic/virology , Lymphoma/drug therapy , Virus Activation/drug effects , Adult , Aged , Aged, 80 and over , DNA, Viral/blood , Female , Hepatitis B virus/drug effects , Hepatitis B virus/genetics , Hepatitis B, Chronic/epidemiology , Hepatitis B, Chronic/immunology , Humans , Immunocompromised Host , Lymphoma/complications , Male , Middle Aged , Retrospective Studies , Rituximab , Virus Activation/immunology
17.
Hepatol Res ; 40(10): 979-88, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20887333

ABSTRACT

AIM: We prospectively evaluated the reliability and validity of splenic volume with 3-D ultrasound measurement and clarified its clinical usefulness. METHODS: Thirty healthy volunteers and 30 patients with cirrhosis were included in this study. All 3-D ultrasound examinations of splenic volumes were performed twice by two experienced sonographers with transabdominal ultrasound using virtual organ computer-aided analysis (VOCAL). Reliability was confirmed among all subjects by evaluating within-observer repeatability and between-observer reproducibility using intraclass correlation coefficients (ICC) and Bland-Altman plots. Overall between-instrument agreement of the measurements and computed tomography (CT) volumetry among cirrhotic patients were performed to determine validity. RESULTS: For all 240 examinations, 3-D ultrasound visualization and measurement of the spleen volume was possible. Mean spleen volume was 104.0 mL for the volunteers and 283.5 mL for the cirrhotic patients. The repeatability was high, with ICC (95% confidence interval) of 0.996 (0.993-0.997) for observer A and 0.997 (0.994-0.998) for observer B. Moreover, the interobserver ICC was 0.996, indicating high reproducibility. Despite the difference in volume between the volunteers and cirrhotic patients, sensitivity analyses indicated consistent results for both groups. Regarding the validity of the 3-D ultrasound measurement, it also showed moderate to high agreement with CT volumetry, with mean ICC of 0.922 and 0.924 for observers A and B, respectively. The reliability and validity results from the Bland-Altman plots were similar to those from the ICC, with limits of agreement consistently narrow from a clinically practical view. CONCLUSION: 3-D ultrasound measurements using VOCAL are valid and reliable in spleen volume examinations.

18.
Eur J Intern Med ; 21(4): 333-7, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20603047

ABSTRACT

BACKGROUND: Hepatitis B virus (HBV) reactivation is a fatal complication in patients who receive chemotherapy or immunosuppressive therapy. We examined the effect of preventive entecavir (ETV), a new nucleoside analogue on HBV reactivation during chemotherapy or immunosuppressive therapy. METHODS: Between February 2007 and September 2009, sixteen nucleoside analogue treatment-naive patients with chronic HBV infection (HB surface antigen [HBsAg] positive) who required chemotherapy or immunosuppressive therapy were enrolled. Referring to some guidelines, the patients received preventive ETV to reduce incidence of HBV reactivation, and were closely monitored for HBV markers. RESULTS: HBV reactivation did not occur in any of the 16 patients and the indispensable treatments for their underlying diseases could be continued. However, HBV relapsed after preventive ETV was discontinued in 2 patients. CONCLUSIONS: This study suggests that ETV is a useful option for preventing HBV reactivation in patients with chronic HBV infection.


Subject(s)
Antiviral Agents/therapeutic use , Guanine/analogs & derivatives , Hepatitis B virus/drug effects , Hepatitis B/drug therapy , Virus Activation/drug effects , Adult , Aged , Female , Guanine/therapeutic use , Hepatitis B/complications , Hepatitis B/prevention & control , Hepatitis B virus/physiology , Humans , Immunocompromised Host/drug effects , Immunosuppressive Agents/adverse effects , Male , Middle Aged , Secondary Prevention , Treatment Outcome
19.
Am J Gastroenterol ; 104(11): 2747-53, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19603009

ABSTRACT

OBJECTIVES: Intrahepatic distant recurrence (IDR) of hepatocellular carcinoma (HCC) after curative treatment occurs frequently and influences the prognoses. The aim of this study was to determine prognostic factors affecting survival after IDR and the optimum therapy for IDR. METHODS: A total of 115 patients with a single small primary HCC who had complete radiofrequency (RF) ablation were enrolled in this study. The prognostic factors and the optimum therapy affecting survival were statistically analyzed among patients with IDRs. RESULTS: IDRs were observed in 59 (51.3%) patients with the median observation period of 19.6 months. The cumulative rates of IDRs were 11.8, 53.9, and 75.8% at 1, 3, and 5 years, respectively. IDR nodules were present as a single nodule in 38 patients and as multiple nodules in 21 patients. In all, 23 patients died during the follow-up. A total of 30 patients were treated with RF ablation, and 27 were treated with transcatheter arterial chemoembolization (TACE). The overall cumulative survival rates after IDRs were 92.7, 55.4, and 43.7% at 1, 3, and 5 years, respectively. A multivariate analysis showed that treatment with RF ablation for IDR was a significant favorable prognostic factor after IDR (hazard ratio: 0.167, 95% confidence interval: 0.048-0.584, P=0.005). In a comparison of survival after IDR between patients treated with RF ablation and TACE, who were comparable with clinical and tumoral characteristics, the cumulative survival rate of patients treated with RF ablation was significantly higher than that of those treated with TACE (77.2 vs 28.5% at 3 years). The cumulative survival rates obtained from the initial RF ablation of the patients with IDRs treated with repeat RF ablation were similar to those of recurrence-free patients. CONCLUSIONS: Repeat RF ablation should be attempted for IDR as much as possible despite tumor multiplicity for survival benefit; by reducing the need, it will help solve the problem of the current shortage of donors for liver transplantations.


Subject(s)
Carcinoma, Hepatocellular/pathology , Catheter Ablation/methods , Liver Neoplasms/pathology , Neoplasm Invasiveness/pathology , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/surgery , Age Factors , Aged , Biopsy, Needle , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/surgery , Cause of Death , Cohort Studies , Female , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Liver Neoplasms/mortality , Liver Neoplasms/surgery , Lymph Nodes/pathology , Male , Middle Aged , Multivariate Analysis , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Postoperative Complications/mortality , Probability , Prognosis , Proportional Hazards Models , Retrospective Studies , Risk Assessment , Sex Factors , Statistics, Nonparametric , Survival Analysis , Time Factors , Treatment Outcome
20.
Hepatol Res ; 39(8): 772-8, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19473438

ABSTRACT

AIM: Partial splenic embolization (PSE) is a non-surgical procedure developed to treat hypersplenism. The purpose of this study is to evaluate therapeutic benefits of PSE with follow-up radiofrequency ablation (RFA) treatment in hepatocellular carcinoma (HCC) patients with thrombocytopenia. METHODS: Between September 1999 and January 2007, a total of 20 patients with HCC who had a few lesions, each 3 cm or less in diameter, and liver function of Child-Pugh class A or B were enrolled into our study. The patients were diagnosed with marked thrombocytopenia (<50 x 10(3)/mm(3)), or mild thrombocytopenia (<80 x 10(3)/mm(3)) with decreased prothrombin activity. They were treated once or twice with PSE. RFA was given as a follow-up treatment 2 weeks after final PSE. The primary endpoint was a platelet-count increase and improvement of prothrombin activity, and the secondary endpoint was the initiation of RFA. RESULTS: PSE was performed successfully in 19 patients (95%). Two weeks after final PSE, platelet counts increased significantly (38 +/- 14 x 10(3)/mm(3) vs. 97 +/- 43 x 10(3)/mm(3); P < 0.0001), and prothrombin activity improved significantly (59.3 +/- 19.8% vs. 65.2 +/- 17.9%; P < 0.0001). No patients had major complications during the PSE procedure. The secondary endpoint was achieved in 18 of 19 patients (94.7%). The mean overall survival was 2257 days (95% confidence interval; range, 1659-2855 days). The Kaplan-Meier cumulative survival rate was estimated to be 61.9% at 5 years. CONCLUSIONS: PSE is a safe and effective treatment for thrombocytopenia and has adjuvant therapeutic benefits for the therapy of HCC.

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