Prognostic impact of worsening of esophageal varices after balloon-occluded retrograde transvenous obliteration.

BACKGROUND AND AIM: Balloon-occluded retrograde transvenous obliteration (BRTO) is widely performed for treating gastric varices (GVs). However, worsening of esophageal varices (EVs) can be observed after BRTO. This study aimed to investigate the impact of EV worsening on prognosis after BRTO. METHODS: Overall, 258 patients who underwent initial BRTO for GV treatment between January 2004 and May 2019 at 12 institutions were retrospectively registered. RESULTS: Technical success was achieved in 235 patients (91.1%). Based on the exclusion criteria, 37 patients were excluded, and 198 were evaluated. The cumulative worsening rates of EVs at 1, 2, and 3 years were 39.0%, 59.4%, and 68.4%, respectively. In the univariate Cox proportional hazards model, sex, EV size, history of EV treatment, left gastric vein dilatation, platelet count, aspartate transaminase (AST), alanine aminotransferase (ALT), total bilirubin, albumin, albumin-bilirubin score, prothrombin time-international normalized ratio, fibrosis-4 index, AST to platelet ratio index, and spleen width were significantly associated with worsening of EV after BRTO. Multivariate analysis showed that sex (adjusted hazard ratio [aHR] 1.72; 95% confidence interval [CI] 1.03-2.86; P = 0.04), left gastric vein dilatation (aHR 1.90; 95% CI 1.17-3.10; P = 0.01), ALT (aHR 1.01; 95% CI 1.00-1.03; P = 0.02), albumin (aHR 0.61; 95% CI 0.43-0.87; P < 0.01), and spleen width (aHR 1.02; 95% CI 1.01-1.03; P < 0.01) were independent risk factors for worsening of EV after BRTO. Patients with EV worsening within 1 year after BRTO had a significantly worse prognosis than the other patients (P = 0.007). CONCLUSIONS: Early worsening of EV after BRTO was associated with poor prognosis after BRTO.

Primary adenosquamous carcinoma of the liver detected during cancer surveillance in a patient with primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is associated with significant risk for hepatobiliary cancers. Primary hepatic adenosquamous carcinoma (ASC), a rare subtype of cholangiocarcinoma, is composed of both adenocarcinoma and squamous cell carcinoma components. We herein report the case of a patient with PSC who was diagnosed with ASC of the liver during cancer surveillance. A 74-year-old male patient was diagnosed with PSC based on blood chemistry and magnetic resonance cholangiopancreatography findings, and regular surveillance for hepatobiliary cancers was initiated. Four years later, the level of carbohydrate antigen 19-9 rapidly increased, and abdominal imaging studies revealed a cystic mass, 40 mm in diameter, containing a solid component in the right liver lobe. Right lobectomy was performed with a pre-operative diagnosis of cholangiocarcinoma; however, the definitive diagnosis was ASC based on the presence of adenocarcinoma and squamous cell carcinoma components in the resected tumor. The patient did not receive post-operative chemotherapy, but was alive for more than 4 years without recurrence at last follow-up. The present case illustrates that regular surveillance and curative resection might achieve long-term survival in hepatic ASC, which has a poor prognosis.

Non-Hypervascular Hypointense Hepatic Nodules during the Hepatobiliary Phase of Gadolinium-Ethoxybenzyl-Diethylenetriamine Pentaacetic Acid-Enhanced MRI as a Risk Factor of Intrahepatic Distant Recurrence after Radiofrequency Ablation of Hepatocellular Carcinoma.

BACKGROUND: Non-hypervascular hypointense hepatic nodules during the hepatobiliary phase of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI have been reported to be associated with intrahepatic distant recurrence (IDR) after hepatectomy or radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). IDR is categorized into hypervascular transformation of non-hypervascular hypointense hepatic nodules and new intrahepatic recurrence. The aim of this study was to evaluate the relationship between non-hypervascular hypointense hepatic nodules on Gd-EOB-DTPA-enhanced MRI and IDR after RFA, focusing on new intrahepatic recurrence. METHODS: Ninety-one consecutive patients with 115 HCCs undergoing pretreatment Gd-EOB-DTPA-enhanced MRI and RFA for treatment of HCC were enrolled. RESULTS: Of the 91 patients who underwent RFA for HCC, 24 had non-hypervascular hypointense hepatic nodules on pretreatment Gd-EOB-DTPA-enhanced MRI. Recurrences were observed in 15 and 19 patients with and without non-hypervascular hypointense hepatic nodules, respectively. Of the 15 recurrences in patients with non-hypervascular hypointense hepatic nodules, 10 patients had new intrahepatic recurrences. The cumulative incidence of new intrahepatic recurrence was significantly higher in patients with non-hypervascular hypointense hepatic nodules than in those without non-hypervascular hypointense hepatic nodules (p < 0.0001). Multivariate analysis revealed that the presence of non-hypervascular hypointense hepatic nodules and Child-Pugh score were independent risk factors for new intrahepatic recurrence. CONCLUSIONS: Non-hypervascular hypointense hepatic nodules during the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI were a useful predictive factor for IDR, particularly for new intrahepatic recurrence, after RFA.

Feasibility of Extracted-Overlay Fusion Imaging for Intraoperative Treatment Evaluation of Radiofrequency Ablation for Hepatocellular Carcinoma.

BACKGROUND AND AIMS: Extracted-overlay fusion imaging is a novel computed tomography/magnetic resonance-ultrasonography (CT/MR-US) imaging technique in which a target tumor with a virtual ablative margin is extracted from CT/MR volume data and synchronously overlaid on US images. We investigated the applicability of the technique to intraoperative evaluation of radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). METHODS: This retrospective study analyzed 85 HCCs treated with RFA using extracted-overlay fusion imaging for guidance and evaluation. To perform RFA, an electrode was inserted targeting the tumor and a virtual 5-mm ablative margin overlaid on the US image. Following ablation, contrast-enhanced US (CEUS) was performed to assess the ablative margin, and the minimal ablative margins were categorized into three groups: (I) margin <0 mm (protrusion), (II) margin 0 to <5 mm, and (III) margin ≥5 mm. Margin assessment was based on the positional relationship between the overlaid tumor plus margin and the perfusion defect of the ablation zone. Tumors in group I underwent repeat ablation until they were in groups II or III. The final classifications were compared with those obtained by retrospectively created fusion images of pre- and post-RFA CT or MR imaging (CT-CT/MR-MR fusion imaging). RESULTS: Treatment evaluation was impossible using CEUS in six HCCs because the tumors were located far below the body surface. Of the remaining 79 HCCs, the categorizations of minimal ablative margins between CEUS extracted-overlay fusion imaging and CT-CT/MR-MR fusion imaging were in agreement for 72 tumors (91.1%) (Cohen's quadratic-weighted kappa coefficient 0.66, good agreement, p<0.01). CONCLUSIONS: Extracted-overlay fusion imaging combined with CEUS is feasible for the evaluation of RFA and enables intraoperative treatment evaluation without the need to perform contrast-enhanced CT.

Comparison of Contrast-Enhanced Ultrasound and Gadolinium-Ethoxybenzyl-Diethylenetriamine Pentaacetic Acid-Enhanced MRI for the Diagnosis of Macroscopic Type of Hepatocellular Carcinoma.

OBJECTIVE: We compared the efficacy of contrast-enhanced ultrasound sonography (CEUS) with sonazoid and gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI for the assessment of macroscopic classification of nodular hepatocellular carcinoma (HCC). METHODS: Seventy-seven consecutive patients with 79 surgically resected HCCs who underwent both preoperative CEUS and Gd-EOB-DTPA-enhanced MRI were enrolled in this retrospective study. Based on the macroscopic diagnosis of resected specimens, nodules were categorized into the simple nodular (SN) and non-SN type HCC. Two hepatologists independently assessed image datasets of the post-vascular phase of CEUS and hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI to compare their diagnostic performance. RESULTS: Gd-EOB-DTPA-enhanced MRI enabled the evaluation of macroscopic classification in a significantly larger number of nodules than CEUS (78/79 (98.7%) vs. 70/79 (88.6%), p < 0.05). Of 70 nodules that could be evaluated by both modalities, 41 and 29 nodules were pathologically categorized as SN and non-SN, respectively. The areas under the receiver operating characteristic curve (AUC) for non-SN did not differ between CEUS and Gd-EOB-DTPA-enhanced MRI (reader 1: 0.748 for CEUS, 0.808 for MRI; reader 2: 0.759 for CEUS, 0.787 for MRI). The AUC of combined CEUS and Gd-EOB-DTPA-enhanced MRI for SN HCC was 0.855 (reader 1) and 0.824 (reader 2), indicating higher AUC values for the combined modalities. CONCLUSIONS: The diagnostic performance for macroscopic classification of nodular HCC of CEUS was comparable with that of Gd-EOB-DTPA-enhanced MRI, although some HCCs could not be evaluated by CEUS owing to lower detectability. The combination of the 2 modalities had a more accurate diagnostic performance.

Usefulness of ultrasonographic estimation of preperitoneal and subcutaneous fat thickness in the diagnosis of nonalcoholic fatty liver disease in diabetic patients.

PURPOSE: Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) have been regarded as the hepatic manifestation of metabolic syndrome. Abdominal wall fat index (AFI), defined as the ratio of preperitoneal and subcutaneous fat thickness in the abdomen estimated by ultrasonography (US), has been shown to be useful in screening for disorders related to metabolic syndrome. We investigated the relation between AFI and NAFLD/NASH in diabetic patients. METHODS: The degree of fat accumulation in the liver and the thickness of preperitoneal and subcutaneous fat were determined by US in 340 diabetic patients. An NAFLD fibrosis score (NAFLD-FS) was used to assess the advancement of hepatic fibrosis in NAFLD patients. RESULTS: Of all 340 subjects, 209 (61 %) were diagnosed with NAFLD by US. AFI of NAFLD subjects was significantly higher than that of non-NAFLD subjects. Of the 209 subjects with NAFLD, 31 (15 %) were shown to have advanced NASH fibrosis according to NAFLD-FS. Multivariate analysis identified AFI as a significant predictor of advanced fibrosis. CONCLUSION: AFI easily obtained by US was significantly related to the presence of NAFLD and/or advanced hepatic fibrosis in diabetic patients.

Comparative evaluation of three-dimensional Gd-EOB-DTPA-enhanced MR fusion imaging with CT fusion imaging in the assessment of treatment effect of radiofrequency ablation of hepatocellular carcinoma.

PURPOSE: To assess the feasibility of fusion of pre- and post-ablation gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA-MRI) to evaluate the effects of radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC), compared with similarly fused CT images PATIENTS AND METHODS: This retrospective study included 67 patients with 92 HCCs treated with RFA. Fusion images of pre- and post-RFA dynamic CT, and pre- and post-RFA Gd-EOB-DTPA-MRI were created, using a rigid registration method. The minimal ablative margin measured on fusion imaging was categorized into three groups: (1) tumor protruding outside the ablation zone boundary, (2) ablative margin 0-<5.0 mm beyond the tumor boundary, and (3) ablative margin ≥5.0 mm beyond the tumor boundary. The categorization of minimal ablative margins was compared between CT and MR fusion images. RESULTS: In 57 (62.0%) HCCs, treatment evaluation was possible both on CT and MR fusion images, and the overall agreement between them for the categorization of minimal ablative margin was good (κ coefficient = 0.676, P < 0.01). MR fusion imaging enabled treatment evaluation in a significantly larger number of HCCs than CT fusion imaging (86/92 [93.5%] vs. 62/92 [67.4%], P < 0.05). CONCLUSIONS: Fusion of pre- and post-ablation Gd-EOB-DTPA-MRI is feasible for treatment evaluation after RFA. It may enable accurate treatment evaluation in cases where CT fusion imaging is not helpful.

Images of Sonazoid-enhanced ultrasonography in multistep hepatocarcinogenesis: comparison with Gd-EOB-DTPA-enhanced MRI.

BACKGROUND: Little is known about the difference in enhancement patterns of hepatocellular carcinoma (HCC) during multistep hepatocarcinogenesis between the post-vascular phase of Sonazoid-enhanced ultrasonography (SEUS) and hepatobiliary phase of gadolinium ethoxybenzyl diethylenetriamine (Gd-EOB-DTPA)-enhanced MRI, as well as uptakes of Sonazoid and Gd-EOB-DTPA by HCC. METHODS: Seventy patients with 73 histologically proven HCCs (33 hypovascular well-differentiated HCCs and 40 progressed HCCs) and 9 dysplastic nodules (DNs) were enrolled. Enhancement patterns of the lesions on the post-vascular phase of SEUS and hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI were evaluated. Uptakes of Sonazoid and Gd-EOB-DTPA were assessed by Sonazoid enhancement index and EOB enhancement ratio in relation to immunohistochemistry of CD68 and organic anion transporting polypeptide 8 (OATP8), respectively. RESULTS: On the post-vascular phase of SEUS, none of the 9 DNs and 3 of 33 hypovascular well-differentiated HCCs (9 %) were hypoechoic, whereas 3 of 9 DNs (33 %) and 31 of 33 hypovascular well-differentiated HCCs (94 %) showed hypointensity on the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI. Of 31 progressed HCCs, 95 and 93 % were hypoechoic and hypointense on the post-vascular phase of SEUS and hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI, respectively. Sonazoid enhancement indexes decreased in progressed HCCs, correlating with lower Kupffer cell numbers (P < 0.001). EOB enhancement ratios decreased in hypovascular well-differentiated and progressed HCCs, as OATP8 expression declined (P < 0.001). CONCLUSIONS: In stepwise hepatocarcinogenesis, uptake of Sonazoid starts decreasing later than that of Gd-EOB-DTPA. Although signal reductions on the post-vascular phase of SEUS or hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI suggest HCC, hypoechoic appearance on the post-vascular phase of SEUS might be HCC-specific, particularly progressed HCC.

Renal impairment during the treatment of telaprevir with peginterferon and ribavirin in patients with chronic hepatitis C.

AIM: Renal damage has been reported as an important complication during combination treatment of peginterferon (PEG IFN), ribavirin (RBV) and telaprevir (TVR) for chronic hepatitis C. However, very little is known about this complication. We investigated the role TVR plays in renal damage during this triple therapy. METHODS: Twenty-five chronic hepatitis C patients with genotype 1 and high viral load received TVR in combination with PEG IFN and RBV for 12 weeks followed by treatment with PEG IFN and RBV. Renal function of these patients was prospectively evaluated for 16 weeks. RESULTS: Creatinine clearance decreased significantly during PEG IFN/RBV/TVR treatment. Consequently, serum creatinine and cystatin C significantly rose during PEG IFN/RBV/TVR treatment. Serum creatinine returned to pretreatment levels after the termination of TVR. The increase of serum creatinine and cystatin C from baseline significantly correlated with serum TVR level at day 7, which was determined by starting dose of TVR per bodyweight . When the patients were classified according to the starting dose of TVR per bodyweight, renal impairment was observed only in the high-dose (TVR ≥33 mg/kg per day) group, not in the low-dose (TVR <33 mg/kg per day) group. CONCLUSION: These results suggest that TVR dose per bodyweight is important for the occurrence of renal impairment in PEG IFN/RBV/TVR treatment.

Usefulness of the extracted-overlay function in CT/MR-ultrasonography fusion imaging for radiofrequency ablation of hepatocellular carcinoma.

OBJECTIVES: We developed a novel technique of the extracted-overlay function in CT/MR-ultrasonography (US) fusion imaging for radiofrequency ablation (RFA), in which only a tumor extracted from CT/MR images with a virtual ablative margin of arbitrary thickness is overlaid on US. The usefulness of this function is investigated in this preliminary report. METHODS: The volume data of the extracted tumor with a virtual ablative margin were created on an image-processing workstation, and transported into a US unit equipped with a CT/MR-US fusion imaging system. After the positional registration of US and transported images, the extracted tumor with an ablative margin could be overlaid on US. In RFA, using this function, an electrode was inserted targeting the overlaid tumor with an ablative safety margin of 5 mm on US, and the treatment effect was evaluated by dynamic CT. Treatment results of 23 consecutive hepatocellular carcinomas (HCCs) that underwent RFA using this function were retrospectively analyzed. RESULTS: Complete tumor ablation was achieved in 22 (95.7%) and 1 (4.3%) HCCs in 1 and 2 treatment sessions, respectively. CONCLUSIONS: Due to the visualization of an extracted tumor with an ablative safety margin on a US image, even during and after ablation, this function is useful for treatment planning and guidance of RFA.

Ultrasonography fusion imaging system increases the chance of radiofrequency ablation for hepatocellular carcinoma with poor conspicuity on conventional ultrasonography.

OBJECTIVES: To investigate the usefulness of the ultrasonography (US) fusion imaging system for radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). METHODS: Since the US fusion imaging system became available in 2010, we have conducted RFA with this system in all cases. The characteristics of 75 patients with 120 HCCs and 89 patients with 123 HCCs who underwent RFA before the introduction of this system (period A) and after it (period B), respectively, were retrospectively compared. RESULTS: Significant difference in the characteristics of the patients and HCCs between the two periods was found only in the proportion of HCCs with poor conspicuity on grayscale US treated with RFA (1.7%, 2/120 for period A vs. 15.4%, 19/123 for period B, p < 0.01). Among the 19 HCCs with poor conspicuity on grayscale US for period B, 5 and 9 HCCs were identified on grayscale US and contrast-enhanced US, respectively, by the use of the US fusion imaging system, whereas the 5 remaining undetectable HCCs were treated by using the system in conjunction with reference images displayed side-by-side with grayscale US. CONCLUSION: Since the introduction of the US fusion imaging system, it has become possible to perform RFA for HCCs with poor conspicuity on grayscale US.

Utility of computed tomography fusion imaging for the evaluation of the ablative margin of radiofrequency ablation for hepatocellular carcinoma and the correlation to local tumor progression.

AIM: To demonstrate the usefulness of the computed tomography (CT) fusion imaging for the evaluation of treatment effect of radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). METHODS: Eighty-five patients with 94 HCC with complete ablation judged on conventional side-by-side interpretation of pre-RFA and post-RFA CT at the time of RFA were included in this retrospective study. CT data was retrospectively used to create fusion images of pre-RFA and post-RFA CT using automatic rigid registration and manual correction referring to intrahepatic structures and hepatic contours around a tumor. Clinical factors including a minimal ablative margin (MAM) measured on fusion images were examined to prove risk factors for local tumor progression (LTP). RESULTS: LTP was observed in 13 (13.8%) tumors with a median follow up of 21.0 months (range, 2-75). The mean MAM on the fusion image was 1.4 ± 3.1 mm and 23 tumors (24.5%) were judged to be protruding from the ablation zone. Multivariate analysis revealed that protruding from the ablation zone was the only significant factor for LTP (hazard ratio, 7.09; 95% confidential interval, 2.26-22.3; P < 0.001). CONCLUSION: Some HCC were assessed as incomplete ablation on the CT fusion images, although considered completely ablated on side-by-side images at the time of treatment, and incomplete ablation was revealed to be the only independent risk factor for LTP. The CT fusion imaging enables quantitative and accurate evaluation of treatment effect of RFA.

Usefulness of the multimodality fusion imaging for the diagnosis and treatment of hepatocellular carcinoma.

A multimodality fusion imaging system has been introduced for the clinical practice of diagnosis and treatment of hepatocellular carcinoma (HCC), especially for loco-regional treatment. An ultrasonography (US) fusion imaging system can provide a side-by-side display of real-time US images and any cross-sectional images of multiplanar reconstruction of CT or MRI that synchronize real-time US. The US fusion imaging system enables us to perform radiofrequency ablation (RFA) for HCCs difficult to detect on conventional US safely. Besides, we can evaluate the treatment effects of RFA easily at the bedside by combining the contrast-enhanced US and the US fusion imaging system. Fusion images of pre- and post-RFA CT have been utilized for the assessment of the treatment effects of RFA. Although the treatment effects of RFA have been conventionally evaluated, comparing pre- and post-RFA CT side-by-side, the evaluation tends to be inaccurate. On CT fusion images, the tumor and the ablation zone are overlaid and we can grasp the positional relation easily, leading to quantitative and more accurate evaluation. The multimodality fusion imaging system has become quite an important tool for loco-regional treatment of HCC because of its usefulness for both the guidance during the RFA procedure and the evaluation of its treatment effects.

[Progression of hepatic fibrosis observed by repeated liver biopsies in an adult case of COACH syndrome].

A 30-year-old man was admitted to Osaka University Hospital for the treatment of gastric varices and assessment of indication for liver transplant. When he was 6 years old, liver dysfunction was pointed out and diagnosed as chronic inactive hepatitis by liver biopsy. At 13 years of age, the second liver biopsy proved congenital hepatic fibrosis (CHF). The third liver biopsy was performed when he was 30 years old, and the progression of hepatic fibrosis was confirmed. Besides CHF, we recognized oligophrenia, cerebellar ataxia, hypoplasia of cerebellar vermis and coloboma, leading to the diagnosis of COACH syndrome. COACH syndrome is quite rare, and our case is especially valuable because he was diagnosed as an adult case and the progression of hepatic fibrosis could be followed through several liver biopsies. We should be aware of COACH syndrome in mind when we encounter CHF patients.

Overlap syndrome of autoimmune hepatitis and primary sclerosing cholangitis complicated with hepatocellular carcinoma.

Development of hepatocellular carcinoma (HCC) in patients with autoimmune liver disease is less common than in those with other types of chronic liver disease. Here we report a rare case of overlap syndrome consisting of autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC) that was subsequently complicated with HCC. A 72-year-old man was initially diagnosed as being in the cirrhotic stage of AIH on the basis of blood chemistry tests and histological examinations. Computed tomography and magnetic resonance cholangiography 20 months later showed diffuse stricturing of the intrahepatic bile duct with dilatation of the areas between the strictures, compatible with the findings of PSC, which resulted in a diagnosis of AIH/PSC overlap syndrome. The level of serum protein induced by vitamin K absence or antagonist II increased 22 months later, and HCC was diagnosed by radiological examinations. Four cycles of transarterial infusion therapy with cisplatin were performed, but the patient died one year later. Sequential overlap of PSC may have played a part in accelerating AIH disease progression, leading to the development of HCC in this patient. Therefore, HCC surveillance may be important in advanced stages of autoimmune disease, especially in the cirrhotic stage.

Sonazoid-enhanced ultrasonography for the diagnosis of an intrapancreatic accessory spleen: a case report.

We report a case of an intrapancreatic accessory spleen in 59-year-old man, in which contrast-enhanced sonography (US) using Sonazoid, a second-generation contrast agent, was useful for the diagnosis. Sonazoid-enhanced US could prove both hypervascularity and the existence of reticuloendothelial cell systems in the mass, which is the key to the diagnosis of an accessory spleen. Sonazoid-enhanced US might become a standard imaging technique for the diagnosis of an accessory spleen.

Amino acid substitution in the core protein has no impact on relapse in hepatitis C genotype 1 patients treated with peginterferon and ribavirin.

Previous reports demonstrated that amino acid (aa) substitutions in the hepatitis C virus (HCV) core protein are predictors of non-virological responses to pegylated interferon (Peg-IFN) and ribavirin combination therapy. The aim of this study was to investigate the impact of core aa substitutions on viral kinetics during the treatment and relapse after the treatment. The 187 patients with HCV genotype 1 enrolled in this study were categorized into four groups according to core aa substitution patterns: double-wild group (n=92), Arg70/Leu91; 70-mutant group (n=42), Gln70/Leu91; 91-mutant group (n=31), Arg70/Met91; and double-mutant group (n=22), Gln70/Met91. The relationship between the core aa substitutions and the virological response was examined. Multivariate logistic regression analyses showed that substitution at aa 70 was significantly associated with a poor virological response during the first 12 weeks (decline of <1 log from baseline at week 4, <2 log at week 12), and substitution at aa 91 was significantly associated with detectable HCV RNA at week 24. With respect to relapse, only the ribavirin exposure (odds ratio (OR), 0.77; 95% confidence interval (CI), 0.60-0.98) and HCV RNA disappearance between weeks 13 and 24 (OR, 23.69; 95% CI, 5.44-103.08) were associated independently with relapse, with no correlation being found with the core aa substitutions and relapse. In conclusion, the results showed that core aa substitutions can be strong predictive factors at pretreatment of the non-response, but not for relapse, for virological responders with HCV RNA disappearance during treatment.

Comparison of enhancement patterns of histologically confirmed hepatocellular carcinoma between gadoxetate- and ferucarbotran-enhanced magnetic resonance imaging.

PURPOSE: To compare enhancenent patterns of hepatocellular carcinoma (HCC) and dysplastic nodule (DN) between gadoxetate- and ferucarbotran-enhanced MRI. MATERIALS AND METHODS: Patients recruited from ultrasound surveillance for HCC in chronic liver diseases were enrolled in this prospective study approved by institutional review board. Thirty-six patients with 37 histologically proven HCC, including 22 well-differentiated HCCs (wHCC), 15 moderately to poorly differentiated HCCs (mpHCCs), and 4 DNs, underwent gadoxetate-enhanced and ferucarbotran-enhanced MRI. We compared hepatobiliary phase image of gadoxetate-enhanced MRI with ferucarbotran-enhanced MR image regarding signal intensity of HCC and DN relative to surrounding liver parenchyma. We calculated contrast ratios between tumor and liver on pre-enhancement, hepatobiliary phase of gadoxetate-enhanced MRI and ferucarbotran-enhanced MRI. RESULTS: On ferucarbotran-enhanced MRI, all mpHCCs showed hyper-intensity, while 14 wHCCs (14/22;63%) showed iso-intensity. On hepatobiliary phase of gadoxetate-enhanced MRI, 13 mpHCCs (13/15;86%) and 20 wHCCs (20/22;91%) showed hypo-intensity. Two DNs and the other two showed iso- and hypo-intensity, respectively, on gadoxetate-enhanced MRI, whereas all DNs revealed iso-intensity on ferucarbotran-enhanced MRI. Gadoxetate-postcontrast ratio was significantly lower than ferucarbotran-postcontrast ratio in wHCC (P = 0.015). CONCLUSION: The uptake function of hepatocytes that are targeted by gadoxetate is more sensitive than that of Kupffer cells targeted by ferucarbotran in stepwise hepatocarcinogenesis.

Secondary structure of the amino-terminal region of HCV NS3 and virological response to pegylated interferon plus ribavirin therapy for chronic hepatitis C.

The aim of the study was to identify a predictive marker for the virological response in hepatitis C virus 1b (HCV-1b)-infected patients treated with pegylated interferon plus ribavirin therapy. A total of 139 patients with chronic hepatitis C who received therapy for 48 weeks were enrolled. The secondary structure of the 120 residues of the amino-terminal HCV-1b non-structural region 3 (NS3) deduced from the amino acid sequence was classified into two major groups: A and B. The association between HCV NS3 protein polymorphism and virological response was analyzed in patients infected with group A (n = 28) and B (n = 40) isolates who had good adherence to both pegylated interferon and ribavirin administration (>95% of the scheduled dosage) for 48 weeks. A sustained virological response (SVR) representing successful HCV eradication occurred in 33 (49%) in the 68 patients. Of the 28 patients infected with the group A isolate, 18 (64%) were SVR, whereas of the 40 patients infected with the group B isolate only 15 (38%) were SVR. The proportion of virological responses differed significantly between the two groups (P < 0.05). These results suggest that polymorphism in the secondary structure of the HCV-1b NS3 amino-terminal region influences the virological response to pegylated interferon plus ribavirin therapy, and that virus grouping based on this polymorphism can contribute to prediction of the outcome of this therapy.