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Introduction: Isolated abdominal aortic dissection (IAAD) has been reported to account for 1.1%-4.1% of all aortic dissections. If detected late, it is associated with a risk of aortic rupture. We investigated the risk factors and characteristic imaging findings of incidentally discovered IAAD using abdominal ultrasonography (AUS) during health check-up and hereby report our findings., Methods: The study sample included 41 patients with abdominal aortic abnormalities identified by AUS performed during a health check-up at our hospital and who were diagnosed with IAAD by contrast-enhanced computed tomography (CT); in addition, 205 patients were included in the nonevent group. Furthermore, risk factors and characteristic imaging findings of IAAD were examined retrospectively., Results: Compared with the nonevent group, smoking and fatty liver were observed significantly more frequently in the IAAD group. Ultrasound findings indicated an intimal flap in 35 cases (85.4%), whereas CT scan revealed displacement of intimal calcifications in 32 cases (78.0%)., Conclusion: Compared with the nonevent group, there were significantly more cases of fatty liver and smoking habits in the IAAD group. In older patients with risk factors for fatty liver and smoking habits, if IAAD is suspected, it is important to monitor the abdominal aorta using ultrasonography during health check-ups., (© 2024 The Author(s). Journal of Clinical Ultrasound published by Wiley Periodicals LLC.)

Aims: The multisociety consensus nomenclature has introduced steatotic liver disease (SLD) with diverse subclassifications, which are metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol-associated steatotic liver disease (MetALD), alcohol-associated liver disease (ALD), specific etiology, and cryptogenic. We investigated their prevalence, as per the new definition, in individuals undergoing health check-ups. Additionally, we analyzed the distribution of Fibrosis-4 (FIB-4) index and vibration-controlled transient elastography (VCTE)-derived liver stiffness measurement (LSM) for MASLD., Methods: In this cross-sectional study, 6530 subjects undergoing a health check-up in Japan were included. Conventional B-mode ultrasound was carried out on all 6530 subjects, and those with MASLD underwent VCTE., Results: The prevalence of SLD was 39.5%, comprising MASLD 28.7%, MetALD 8.6%, ALD 1.2%, specific etiology SLD 0.3%, and cryptogenic SLD 0.7%. Subjects with VCTE-derived LSM ≥8 kPa constituted 2.1% of MASLD. FIB-4 ≥1.3 showed that the sensitivity, specificity, positive predictive value (PPV), and negative predictive value for diagnosing VCTE-derived LSM ≥8 kPa were 60.6%, 77.0%, 5.3%, and 98.9%, respectively. The referral rate to specialists was 23.8% using FIB-4 ≥1.30. "FIB-4 ≥1.3 in subjects <65 years and FIB-4 ≥2.0 in subjects ≥65 years" showed higher PPV (6.7%) and lower referral rate (17.1%) compared with FIB-4 ≥1.3, but the sensitivity (54.5%) did not show adequate diagnostic capability as a noninvasive test for diagnosing VCTE-derived LSM ≥8 kPa., Conclusions: Acknowledging the selection bias in hepatology centers, we undertook this prospective health check-up study. Although the FIB-4 index proves to be a convenient marker, it might not perform well as a primary screening tool for liver fibrosis in the general population (UMIN Clinical Trials Registry No. UMIN000035188)., (© 2024 Japan Society of Hepatology.)

Background and Aims: The diagnostic performance of the Fibrosis-4 (FIB-4) index and nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS) is poor in patients with type 2 diabetes mellitus (T2DM). We determined the usefulness of the Enhanced Liver Fibrosis (ELF) test in patients with T2DM., Methods: A total of 1228 patients with biopsy-proven NAFLD were enrolled. The diagnostic performance of the ELF test for predicting advanced fibrosis in participants with or without T2DM was evaluated in comparison with the FIB-4 index and NFS., Results: Overall, the area under the curve of the ELF test for predicting advanced fibrosis was greater (0.828) than that of the FIB-4 index (0.727) and NFS (0.733). The diagnostic performance of the ELF test (area under the curve, 0.820) was also superior to that of the FIB-4 index (0.698) and NFS (0.700) in patients with T2DM. With the low cutoff values for each noninvasive test, the ELF test provided an acceptable false negative rate (cutoff value 9.8, 6.7%) in this population, unlike the FIB-4 index (1.30, 14.5%) and NFS (-1.455, 12.4%). After propensity score matching to avoid selection bias including age, sex, body mass index, and the prevalence of advanced fibrosis, the ELF test with a low cutoff value showed a high sensitivity (≥91.4%) and a high negative predictive value (≥96.8%), irrespective of the presence or absence of T2DM., Conclusions: The high diagnostic performance of the ELF test for predicting advanced fibrosis in individuals with or without T2DM could address an unmet medical need for accurate assessment of liver fibrosis in patients with diabetes and NAFLD., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Aim: To compare patient characteristics and outcomes between the overall and Japanese populations of GLIMMER., Methods: GLIMMER was a multicenter, double-blind, randomized, placebo-controlled, Phase IIb study evaluating linerixibat for the treatment of pruritus in patients with primary biliary cholangitis., Results: In total, 147 patients were randomized in the GLIMMER overall population with 38 patients comprising the Japanese population. Demographics and baseline clinical characteristics were similar across treatment groups and between both populations. A reduction in mean worst daily itch score from baseline to week 16 (primary endpoint) was seen in all groups, with the largest reduction observed with linerixibat 40 mg twice daily (BID; -2.92 [95% confidence interval: -5.07, -0.76] and -2.86 [95% confidence interval: -3.76, -1.95] for Japanese and overall populations, respectively). The highest proportion of responders was generally in the 40 mg BID group in both populations regardless of the responder definition applied. Improvements in health-related quality of life were generally consistent in both populations. In the Japanese and overall populations, on-treatment drug-related adverse events were reported in 25% and 19% of patients in the placebo group and 0%-86% and 31%-78% of patients in the linerixibat groups, respectively. Consistent with the mechanism of action, the most common events were gastrointestinal in nature. The effects of linerixibat on pharmacodynamic biomarkers favored BID dosing., Conclusions: Therapeutic responses and safety of linerixibat were consistent between the Japanese and overall populations of GLIMMER. Linerixibat may provide an effective treatment option for cholestatic pruritus in patients with primary biliary cholangitis., Clinical Trial Registration: NCT02966834., (© 2023 The Authors. Hepatology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Hepatology.)

Aim: Agile 3+ and Agile 4 scores, based on liver stiffness measurement (LSM) by transient elastography and clinical parameters, were recently reported to be effective in identifying advanced fibrosis and cirrhosis in nonalcoholic fatty liver disease (NAFLD). This study aimed to validate the utility of these scores in Japanese patients with NAFLD., Methods: Six hundred forty-one patients with biopsy-proven NAFLD were analyzed. The severity of liver fibrosis was pathologically evaluated by one expert pathologist. The LSM, age, sex, diabetes status, platelet count, and aspartate aminotransferase and alanine aminotransferase levels were used to calculate Agile 3+ scores, and the parameters above excluding age were used for Agile 4 scores. The diagnostic performance of the two scores was evaluated using receiver operating characteristic (ROC) curve analysis. Sensitivity, specificity, and predictive values of the original low cut-off (for rule-out) value and high cut-off (for rule-in) value were tested., Results: For diagnosis of fibrosis stage ≥3, the area under the ROC (AUROC) was 0.886, and the sensitivity of the low cut-off value and the specificity of the high cut-off value were 95.3% and 73.4%, respectively. For diagnosis of fibrosis stage 4, AUROC, the sensitivity of the low cut-off value, and the specificity of the high cut-off value were 0.930, 100%, and 86.5%, respectively. Both scores had higher diagnostic performance than the FIB-4 index and the enhanced liver fibrosis score., Conclusions: Agile 3+ and Agile 4 are reliable noninvasive tests to identify advanced fibrosis and cirrhosis in Japanese NAFLD patients with adequate diagnostic performance., (© 2023 Japan Society of Hepatology.)

Aim: The enhanced liver fibrosis (ELF) test is a noninvasive method for diagnosing hepatic fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). This multicenter cohort study aimed to evaluate the accuracy of the ELF test and compare it with other noninvasive tests in Japan., Methods: We analyzed 371 Japanese patients with biopsy-proven NAFLD. We constructed area under the receiver operator characteristic curves (AUROC) to determine the diagnostic accuracies of the ELF test, the Mac-2-binding protein glycosylation isomer (M2BPGi), the Fibrosis-4 (FIB-4) index, and combinations of these indices., Results: In patients with F0/F1/F2/F3/F4 fibrosis, the median values of the ELF test were 8.98/9.56/10.39/10.92/11.41, respectively. The AUROCs of the ELF test for patients with F0 versus F1-4, F0-1 versus F2-4, F0-2 versus F3-4, and F0-3 versus F4 fibrosis were 0.825/0.817/0.802/0.812, respectively. The AUROCs of the ELF test were greater than those of the FIB-4 index and M2BPGi at each fibrosis stage. Respective low and high cut-off values yielded sensitivities and specificities for predicting advanced fibrosis (≥F3) of 91.1% and 50.8%, and 38.5% and 92.8%, respectively. For F3 or F4 fibrosis, the combined values from the ELF test and FIB-4 index showed a sensitivity of 98.5%, and the combined values from the ELF test and M2BPGi assay showed a specificity of 97.5%., Conclusions: In Japan, the ELF test predicts NAFLD-related fibrosis from its early stages. The diagnostic ability of the ELF test was not inferior to that of other indices, and the combined values of ELF plus other indices were more accurate., (© 2022 The Authors. Hepatology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Hepatology.)

Background & Purpose: Protease-free regimens for chronic hepatitis C virus (HCV) infection are safe and effective for persons with either compensated or decompensated cirrhosis. We examined the efficacy and safety of sofosbuvir-velpatasvir in participants with HCV and compensated cirrhosis in Japan., Methods: This was a Phase 3, multi-center, open-label study. At 20 sites, 37 individuals with chronic HCV infection of any genotype and compensated cirrhosis received sofosbuvir-velpatasvir (400 mg/100 mg) daily for 12 weeks. Participants were treatment-naïve or treatment-experienced with interferon-based treatments with or without HCV NS3/4A protease inhibitors. Prior exposure with HCV NS5A or NS5B inhibitors was prohibited. The primary study endpoint was sustained virologic response 12 weeks after treatment (SVR12)., Results: Among participants, 62% had HCV genotype 1 infection, and 38% had HCV genotype 2. More than three quarters (29/37, 78%) were HCV treatment naïve. All participants (37/37, 100%) achieved SVR12. Seventeen participants (46%) and three participants (8%) had pretreatment resistance-associated substitutions to HCV NS5A and NS5B nucleoside inhibitors respectively, yet no on-treatment breakthrough or relapse occurred. Sofosbuvir-velpatasvir for 12 weeks treatment was safe and well tolerated. The most commonly reported adverse events were headache (8%, 3/37) and diarrhea (5%, 2/37). One serious adverse event, patella fracture, occurred and was considered not treatment related. No participants discontinued study treatment due to an adverse event. Three participants (8%) had a Grade 3 laboratory abnormality; all were hyperglycemia., Conclusion: Sofosbuvir-velpatasvir resulted in high SVR rates and was well tolerated among Japanese patients with HCV and compensated cirrhosis. This single-tablet regimen offers a highly effective, protease-inhibitor free regimen for treating HCV., Clinicaltrials: gov Identifier: NCT04112303., (© 2022 Gilead Sciences and The Authors. Hepatology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Hepatology.)

PURPOSE We retrospectively evaluated the efficacy of percutaneous sclerotherapy using a 4 F catheter and 40 mL of 5% ethanolamine oleate (EO) for symptomatic large hepatic cysts. METHODS Twenty-four patients, including 10 with polycystic liver disease (PLD), were eligible. The mean long- and short-axis diameters of the cyst on computed tomography (CT) were 145.0 ± 35.5 mm (range, 72-216 mm) and 110.5 ± 21.4 mm (range, 63-150 mm), respectively. After aspiration of the fluid contents using a 4 F pigtail catheter, 40 mL of 5% EO was injected into the cyst for 30 min. Then, the catheter was withdrawn after EO removal. Symptomatic relief and complications were evaluated. The percentage reductions at the early (1-3 months later) and late (at the final follow-up) responses were evaluated using an estimated cyst volume calculated by using the following formula: volume = π/6 × long-axis diameter × (short-axis diameter)2 on the maximum cross-section image on CT. Spearman's rank correlation coefficient (ρ) was used to evaluate the correlation between the pretreatment estimated cyst volume and percentage reduction of early and late responses and between the percentage reduction of the late response and length of the follow-up period after sclerotherapy. RESULTS The symptoms disappeared in 23 patients and improved in 1 patient with PLD. The mean aspirated fluid volume was 1337.8 ± 845.4 mL (range, 140-3200 mL). In 1 patient, EO injection was postponed until the second procedure was performed 40 days later due to intraperitoneal leakage of contrast material. In another patient, the EO volume was reduced to 20 mL because of a small cyst size. The mean early and late percentage reductions of the treated cyst were 52.3% ± 23.8% and 87.5% ± 20.4% (mean follow-up period: 48.0 ± 42.4 months), respectively. The symptom recurred in 2 patients with PLD and 1 underwent additional sclerotherapy 14 months later due to re-enlargement of the treated cyst. Another patient underwent transarterial embolization 5 years and 4 months later for other enlarged cysts, although the treated cyst markedly shrank. There were significant negative correlations between the pretreatment estimated cyst volume and percentage reduction of early (P = .027, ρ = - 0.46) and late (P= .007, ρ = - 0.52) responses. However, there were no significant correlations between the percentage reduction and length of the follow-up period (P = .19, ρ = 0.31). Transient pain developed in 1 patient and low-grade fever in 3. CONCLUSION Sclerotherapy using a 4 F catheter and 40 mL of 5% EO is safe and effective for symptomatic large hepatic cysts.

The indication of transarterial chemoembolization (TACE) has advanced to hepatocellular carcinoma (HCC) of Barcelona Clinic Liver Cancer (BCLC) stage A when surgical resection (SR), thermal ablation, and bridging to transplantation are contraindicated; however, TACE for small HCC is frequently difficult and ineffective because of less hypervascularity and the presence of tumor portions receiving a dual blood supply. Here, we report outcomes of superselective conventional TACE (cTACE) for 259 patients with HCCs within three lesions smaller than 3 cm using guidance software. Automated tumor feeder detection (AFD) functionality was applied to identify tumor feeders on cone-beam computed tomography during hepatic arteriography (CBCTHA) data. When it failed, the feeder was identified by manual feeder detection functionality and/or selective angiography and CBCTHA. Regarding the technical success in 382 tumors (mean diameter, 17.2 ± 5.9 mm), 310 (81.2%) were completely embolized with a safety margin (5 mm wide for HCC ≤25 mm and 10 mm wide for HCC >25 mm). In 61 (16.0%), the entire tumor was embolized but the safety margin was not uniformly obtained. The entire tumor was not embolized in 11 (2.9%). Regarding the tumor response at 2-3 months after cTACE in 303 tumors excluding those treated with combined radiofrequency ablation (RFA) or SR and lost to follow-up, 287 (94.7%) were classified into complete response, seven (2.3%) into partial response, and nine (3.0%) into stable disease. The mean follow-up period was 44.9 ± 27.6 months (range, 1-109) and the cumulative local tumor progression rates at 1, 3, 5, and 7 years were 17.8, 27.8, 32.0, and 36.0%, respectively. The 1-, 3-, 5-, and 7-year overall and recurrence-free survival rates in 175 patients, excluding those with Child-Pugh C class, who died of other malignancies, or who underwent combined RFA or hepatic resection, were 97.1 and 68.7, 82.8 and 34.9, 64.8 and 20.2, and 45.3 and 17.3%, respectively. Our results indicate the efficacy of superselective cTACE using guidance software for HCC within three lesions smaller than 3 cm.

Frailty including physical inactivity is associated with the survival of patients with hepatocellular carcinoma (HCC). We aimed to investigate the effects of in-hospital exercise on frailty in patients with HCC. This was a multi-center observational study. Patients with HCC were classified into exercise ( n = 114) and non-exercise ( n = 67) groups. The exercise group was treated with a mixture of aerobic and resistance exercises (20-40 min/day, median four days). Frailty was assessed using the liver frailty index (LFI). Factors for changes in LFI were examined by multivariate and decision-tree analyses. The factors were also examined after propensity score matching. During hospitalization, LFI was significantly improved in the exercise group compared to the non-exercise group (ΔLFI -0.17 vs. -0.02, p = 0.0119). In multivariate analysis, exercise (odds ratio (OR) 2.38, 95% confidence interval (CI) 1.240-4.570, p = 0.0091) and females (OR 2.09; 95%CI, 1.062-4.109; p = 0.0328) were identified as independent factors for the improvement of LFI. In the decision-tree analysis, exercise was identified as an initial classifier associated with the improvement of LFI. Similar findings were also seen in the propensity score matching analyses. We demonstrated that in-hospital exercise improved frailty in patients with HCC. Thus, in-hospital exercise may be beneficial for improving physical function in patients with HCC.

We investigated the development of hepatits B virus (HBV) reactivation in patients receiving immunosuppressive therapy or chemotherapy at our hospital for 8 years. Using the automatic checking system for HBV reactivation coded using medical information that has been in operation in our hospital since October 2012, we prospectively observed the occurrence status of HBV reactivation in immunosuppressive/chemotherapy cases for 8 years. HBV reactivation occurred in 31 of 1516 patients with HBV infection. It occurred annually between 1 and 7 cases in multiple clinical departments, and in 8 of 59 patients treated with rituximab, 10 of 653 patients treated with antineoplastic agents, 10 of 399 patients treated with steroids, and 3 of 212 patients treated with direct-acting antivirals. The cumulative incidence of HBV reactivation was 1.2%, 2.3%, and 3.4% at 1, 2, and 3 years, respectively. The results of Cox regression analysis showed that the incidence of HBV reactivation was significantly higher in patients who received rituximab (odds ratio:12.841) or steroid (hazard ratio:4.264) or those who tested positive for HBc antibody alone (hazard ratio:11.005). We observed the occurrence of HBV reactivation in HBV-infected patients treated with immunosuppressive therapy or chemotherapy. HBV reactivation by immunosuppressive therapy or chemotherapy still occurs, and further safety management and caution are required in the hospital.

Type 2 diabetes (T2D) is associated with diabetic nephropathy as well as nonalcoholic steatohepatitis (NASH), which can be called "diabetic hepatopathy or diabetic liver disease". NASH, a severe form of nonalcoholic fatty disease (NAFLD), can sometimes progress to cirrhosis, hepatocellular carcinoma and hepatic failure. T2D patients are at higher risk for liver-related mortality compared with the nondiabetic population. NAFLD is closely associated with chronic kidney disease (CKD) or diabetic nephropathy according to cross-sectional and longitudinal studies. Simultaneous kidney liver transplantation (SKLT) is dramatically increasing in the United States, because NASH-related cirrhosis often complicates end-stage renal disease. Growing evidence suggests that NAFLD and CKD share common pathogenetic mechanisms and potential therapeutic targets. Glucagon-like peptide 1 (GLP-1) receptor agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors are expected to ameliorate NASH and diabetic nephropathy/CKD. There are no approved therapies for NASH, but a variety of drug pipelines are now under development. Several agents of them can also ameliorate diabetic nephropathy/CKD, including peroxisome proliferator-activated receptors agonists, apoptosis signaling kinase 1 inhibitor, nuclear factor-erythroid-2-related factor 2 activator, C-C chemokine receptor types 2/5 antagonist and nonsteroidal mineral corticoid receptor antagonist. This review focuses on common drug pipelines in the treatment of diabetic nephropathy and hepatopathy.

A 78-year-old man was hospitalized because of rapid progression of chronic renal failure and diagnosed with multiple myeloma (MM) IgG-λ type ISS-III R-ISS-II with complex karyotype including t(14;19). Even after receiving bortezomib-based regimens, his renal failure progressed. He became dependent on dialysis, which was required three times a week. After introducing the daratumumab (DARA)-based regimen, his renal function improved, the frequency of dialysis decreased to twice a week, and the free light chain (FLC) ratio also improved. However, his myeloma eventually followed a refractory course; therefore, pomalidomide (POM)-dexamethasone (Pd) regimen was administered. Pd regimen had a marked effect and normalized the FLC ratio after three courses of the treatment. However, his myeloma reprogressed with multiple extramedullary masses and he became del(17p) positive; eventually, he died on the 470th day of disease. MM with t(14;19) is rare and has a poor prognosis with a highly aggressive course; however, early introduction of DARA or POM may provide long-term response.

Objective We started an information technology (IT) system that encodes the medical treatment status of hepatitis B virrus (HBV) with a 9-digit number, automatically checks for inappropriate situations occurring due to immunosuppression and chemotherapy that do not comply with the flowchart of the hepatitis B countermeasure guideline, and promotes correct HBV medical treatment in our hospital. We conducted a prospective study of HBV reactivation using this system. Methods Among 21,607 cases that were managed using this system, 1,206 patients who were HBs antigen-negative, HBc antibody- and/or HBs antibody-positive and in whom HBV DNA quantification was performed two times or more were examined for the occurrence of HBV reactivation. The study population included: malignant lymphoma patients using rituximab (n=40), patients with malignant tumors using anticancer agents (n=546), patients treated with steroids (n=274), rheumatoid arthritis (RA) patients (n=144), patients using immunosuppressants/biologics (n=26), and patients undergoing hepatitis C direct acting antiviral (DAA) treatment (n=176). Results HBV reactivation was observed in 27 cases undergoing treatment with the following agents: rituximab (n=6), anticancer agents (n=8), steroids (n=10), anti-RA agents (n=1), and hepatitis C DAA (n=2). Among the 40 patients who were using rituximab, 6 (18.2%) showed a high rate of reactivation. In 10 in which HBV reactivation occurred at a median of 10 (range, 4-32) months after steroid administration, 6 occurred after the 7th month, and 1 patient showed HBs antigen positivity and severe hepatitis. Conclusion Continuing of the operation of an automatic check system using coded medical information to check for the reactivation enabled this prospective study of HBV reactivation. Careful attention should be paid to patients using steroids, as well as malignant lymphoma patients who are treated with rituximab. The results of the present study suggest that the present IT encoding system would be useful for preventing HBV reactivation.

Background: Chronic hepatitis C virus (HCV) infection with genotypes (GT) 1 and 2 accounts for over 50% of HCV infections globally, including over 97% of all HCV infections in Japan. Here, we report an integrated analysis of efficacy and safety of 8-week treatment with the all-oral, fixed-dose combination of the direct acting antivirals (DAA), glecaprevir and pibrentasvir (G/P), in DAA-naïve Japanese and overseas patients without cirrhosis and with HCV GT1 or GT2 infection., Methods: Data from 899 DAA-naïve patients without cirrhosis and with HCV GT1 or GT2 infection treated with G/P (300/120 mg) for 8 weeks in the six Phase 2 or 3 overseas or Japan-only clinical trials were included. All patients who received ≥ 1 dose of G/P were included in an intent-to-treat (ITT) analysis. The objectives were to evaluate rate of sustained virologic response 12 weeks post-treatment (SVR12) and safety of the 8-week regimen in the ITT population., Results: Overall, SVR12 was achieved by 98.9% (889/899) of DAA-naïve patients without cirrhosis, including 99.2% (597/602) of GT1-infected and 98.3% (292/297) of GT2-infected patients. Less than 1% (2/899) of patients overall and no Japanese patients experienced virologic failure. SVR12 rate was > 97% for patients regardless of baseline characteristics, and common comorbidities or co-medications. Overall, < 1% (2/899) discontinued G/P due to an adverse event (AE) and 1.6% (14/899) of patients experienced a serious AE., Conclusions: 8-week G/P treatment is safe and efficacious in DAA-naive patients without cirrhosis and with HCV GT1 or GT2 infection, demonstrating high SVR12 rates regardless of baseline patient and disease characteristics. CLINICALTRIALS., Gov Identifiers: The trials discussed in this paper were registered with ClinicalTrials.gov as follows: NCT02707952 (CERTAIN-1), NCT02723084 (CERTAIN-2), NCT02243280 (SURVEYOR-I), NCT02243293 (SURVEYOR-II), NCT02604017 (ENDURANCE-1), NCT02738138 (EXPEDITION-2).

To investigate the efficacy of eltrombopag for the treatment of thrombocytopenia in patients with chronic hepatitis C, a phase II, single-arm, open-label study with a 9-week pre-antiviral phase was conducted, followed by a 48-week antiviral phase and a 24-week follow-up phase. The proportion of patients who achieved a platelet count threshold, the proportion of patients who maintained a platelet count >50,000/µl, sustained virological response (SVR) rates and safety parameters were evaluated. Of the 45 enrolled patients (median age, 59 years; median platelet count, 63,000/µl; 98% with Child-Pugh class A), 43 (96%) achieved the platelet count threshold during the pre-antiviral phase. A total of 13 patients (29%) experienced ≥1 adverse event (AE), of which headache and vomiting were the most common, and 41 patients (mostly receiving eltrombopag 12.5 mg or 25 mg) entered the antiviral phase, of which 36 (88%) maintained the platelet count threshold; no patient platelet count decreased below 25,000/µl. Nine patients (22%) achieved an SVR at the 24-week follow-up. Grade ≥3 AEs occurred in 25 patients (61%). A total of 8 serious AEs occurred in five patients (12%). No mortality, thromboembolic events (TEEs), or cataract progression were reported. Eltrombopag increased the platelet count in chronic hepatitis C virus-infected patients with cirrhosis and thrombocytopenia and enabled them to initiate and complete interferon-based antiviral therapy (NCT01636778; first submitted: July 05, 2012).

Aim: To retrospectively evaluate the outcomes of conventional transarterial chemoembolization (cTACE) for hepatocellular carcinoma (HCC) ≥10 cm., Methods: Twenty-five patients with naïve HCC ≥10 cm (mean maximum tumor diameter, 130 ± 27.6 mm; single [n = 12], 2-9 [n = 6], and ≥10 [n = 7]) without extrahepatic spread treated with cTACE were eligible. Five (20%) had vascular invasion. Two to three stepwise cTACE sessions using iodized oil ≤10 mL in one cTACE session were scheduled. When the tumor recurred, additional cTACE was repeated on demand, if possible. Overall survival (OS) rates were calculated using the Kaplan-Meier method. The prognostic factors were evaluated using uni- and multivariate analyses., Results: Stepwise cTACE sessions were completed for 20 (80%) patients, but could not be completed for four (16%). In the remaining (4%) patient, the whole tumor was embolized in one session. Additional treatment, mainly cTACE, was undertaken for 19 (76%) patients. The OS rates at 1, 3, and 5 years were 68, 34.7, and 23.1%, respectively. A tumor number of three was a significant prognostic factor (P = 0.020) and the 1-, 3-, and 4-year OS rates in patients with ≤3 and ≥4 tumors were 81.3 and 33.3, 55.6 and 11.1, and 38.9% and 0%, respectively. Whole tumor embolization and the serum level of protein induced by vitamin K absence or antagonist-II were also significant prognostic factors (P < 0.001 and P = 0.042, respectively). Bile duct complications requiring additional interventions developed in two (8%) patients., Conclusion: Conventional TACE is safe and effective for huge HCCs, but has limited effects in cases with four or more tumors., (© 2019 The Japan Society of Hepatology.)

Background: We reported a cross-sectional study on causes of liver injury in Japanese type 2 diabetes mellitus (T2D) patients (JG 2013). We assessed overall and cause-specific mortality risk during follow-up of patients enrolled in JG 2013., Methods: This was a longitudinal, multicenter cohort study. Of the 5642 Japanese T2D patients who visited T2D clinics of nine hospitals in the original study, 3,999 patients were followed up for an average of 4.5 years. Expected deaths in T2D patients were estimated using age-specific mortality rates in the general population (GP) of Japan. Standardized mortality ratios (SMRs) were calculated to compare mortality between T2D patients and GP., Results: All-cancer mortality was significantly higher in T2D patients than in the GP [SMR 1.58, 95% confidence interval (CI) 1.33-1.87]. Among malignancies, hepatocellular carcinoma (HCC) conferred the highest mortality risk in T2D patients (SMR 3.57, 95% CI 2.41-5.10). HCC-associated mortality risk in T2D patients remained significantly high (SMR 2.56, 95% CI 1.64-3.97) after adjusting for high positivity rates of hepatitis B surface antigen (1.7%) and anti-hepatitis C virus (5.3%). In T2D patients with platelet counts < 200 × 10 3 /μl, SMR of HCC increased from 3.57 to 6.58 (95% CI 4.34-9.58). T2D patients with platelet count > 200 × 10 3 /μl showed no increase in mortality risk (SMR 0.68) of HCC., Conclusions: HCC-associated mortality risk was the highest among all cancers in Japanese T2D patients. Regular follow-up may be important for T2D patients with platelet counts < 200 × 10 3 /μl for early detection of HCC.

Glecaprevir (nonstructural protein 3/4A protease inhibitor) and pibrentasvir (nonstructural protein 5A inhibitor) (G/P), a coformulated once-daily, all oral, ribavirin (RBV)-free, direct-acting antiviral regimen, was evaluated for safety and efficacy in hepatitis C virus genotype 2 (GT2)-infected Japanese patients, including those with compensated cirrhosis. CERTAIN-2 is a phase 3, open-label, multicenter study assessing the safety and efficacy of G/P (300/120 mg) once daily in treatment-naive and interferon ± RBV treatment-experienced Japanese patients without cirrhosis but with GT2 infection. Patients were randomized 2:1 to receive 8 weeks of G/P (arm A) or 12 weeks of sofosbuvir (400 mg once daily) + RBV (600-1000 mg weight-based, twice daily) (arm B). The primary endpoint was noninferiority of G/P compared to sofosbuvir + RBV by assessing sustained virologic response at posttreatment week 12 (SVR12) among patients in the intent-to-treat population. SVR12 was also assessed in treatment-naive and interferon ± RBV treatment-experienced patients with GT2 infection and compensated cirrhosis who received G/P for 12 weeks in the CERTAIN-1 study. A total of 136 patients were enrolled in CERTAIN-2. SVR12 was achieved by 88/90 (97.8%) patients in arm A and 43/46 (93.5%) patients in arm B. No patient in arm A experienced virologic failure, while 2 did in arm B. The primary endpoint was achieved. In CERTAIN-1, 100% (18/18) of GT2-infected patients with compensated cirrhosis achieved SVR12. Treatment-emergent serious adverse events were experienced by 2 patients without cirrhosis in each arm and no patient with cirrhosis. Conclusion: The results demonstrate high efficacy and favorable tolerability of G/P in GT2-infected Japanese patients. (Hepatology 2018;67:505-513)., (© 2017 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.)

Aim: Portal vein thrombosis (PVT) is one of the most critical disorders in liver disease patients. These patients have the imbalance of coagulation and coagulation inhibition resulting from decreased levels of coagulation inhibitory factors, such as protein C, protein S, and antithrombin III (AT-III). We designed this randomized, double-blind, placebo-controlled trial comparing the safety and efficacy of AT-III for PVT in liver disease patients with those who received no treatment., Methods: Eligible patients were diagnosed with the association of thrombus, without tumor thrombus, and thrombus in more than 50% of the cross-sectional lumen of the portal vein. Patients with 70% or less serum level of AT-III were included. The study drug was given up to three times in a 5-day consecutive infusion interval if the thrombus decreased in size. Efficacy was evaluated by contrast enhanced computed tomography using a five-grade scale (complete response, partial response, slight response, no response, and progression). From October 2014 through to March 2016, 36 patients were randomly assigned to the AT-III group and 37 patients to the placebo group., Results: The proportion of patients with complete response or partial response of PVT was significantly higher in the AT-III group (55.6%; 20/36 patients; 95% confidence interval, 38.1-72.1) than in the placebo group (19.4%; 7/36 patients, 95% confidence interval, 8.2-36.0) (P = 0.003). The overall incidence of adverse events and adverse drug reactions did not differ significantly between the two groups., Conclusion: Antithrombin III is one of the essential therapies for patients with PVT in cases with lower concentration levels of AT-III., (© 2017 The Authors. Hepatology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Hepatology.)

Aim: To evaluate the incidence and condition of necrotic tumor excretion into the biliary system in patients with hepatocellular carcinoma (HCC) >5 cm treated with conventional transcatheter arterial chemoembolization (TACE)., Methods: Eighty-three patients who underwent TACE for newly developed HCC >5 cm without an intraductal tumor thrombus and were followed-up by computed tomography for longer than 6 months were eligible. According to the location, the maximum tumors were divided into central (in contact with the left or right hepatic duct, n = 39) or peripheral (not in contact with them, n = 44). When high-density material in the biliary system that was not seen on pretreatment computed tomography was identified, it was determined as excreted necrotic tumor tissue containing iodized oil. The incidence, interval between TACE and occurrence of the necrotic tumor excretion, and clinical course were evaluated., Results: Tumor excretion into the biliary system was identified in nine (10.8%) patients with a central tumor (mean diameter, 85.0 ± 29.6 mm) 28-433 days (mean, 219.3 ± 128.2) after the initial TACE. In one patient, the necrotic tumor cast caused cholangitis 1203 days after the initial TACE, and was endoscopically removed. Infection of the embolized tumor developed in two cases and percutaneous drainage was carried out 105 and 158 days later, respectively., Conclusions: Excretion of necrotic tumors into the biliary system after TACE was not rare in patients with centrally located HCC >5 cm. The detached tumor rarely caused symptoms and the communication between the tumor and bile duct caused the infection of tumors., (© 2017 The Japan Society of Hepatology.)

Unlabelled: Approximately 2 million Japanese individuals are infected with hepatitis C virus and are at risk for cirrhosis, end-stage liver disease, and hepatocellular carcinoma. Patients in whom interferon (IFN)/ribavirin (RBV) therapy has failed remain at risk as effective therapeutic options are limited. This phase 2, randomized, open-label study evaluated an IFN- and RBV-free regimen of once-daily ombitasvir (ABT-267), an NS5A inhibitor, plus paritaprevir (ABT-450), an NS3/4A protease inhibitor dosed with ritonavir (paritaprevir/ritonavir), in pegylated IFN/RBV treatment-experienced Japanese patients with hepatitis C virus subtype 1b or genotype 2 infection. Patients without cirrhosis (aged 18-75 years) with subtype 1b infection received ombitasvir 25 mg plus paritaprevir/ritonavir 100/100 mg or 150/100 mg for 12 or 24 weeks; patients with genotype 2 infection received ombitasvir 25 mg plus paritaprevir/ritonavir 100/100 mg or 150/100 mg for 12 weeks. Sustained virologic response (SVR) at posttreatment week 24 (SVR24 ) was the primary endpoint. Adverse events were collected throughout the study. One hundred ten patients received ≥1 dose of study medication. In the subtype 1b cohort, SVR24 rates were high (88.9%-100%) regardless of paritaprevir dose or treatment duration. In the genotype 2 cohort, SVR24 rates were 57.9% and 72.2% with 100 mg and 150 mg of paritaprevir, respectively. The SVR24 rate was higher in patients with subtype 2a (90%) than 2b (27%). Concordance between SVR12 and SVR24 was 100%. The most common adverse events overall were nasopharyngitis (29%) and headache (14%)., Conclusion: In this difficult-to-treat population of patients in whom prior pegylated IFN/RBV had failed, ombitasvir/paritaprevir/ritonavir demonstrated potent antiviral activity with a favorable safety profile among Japanese patients with hepatitis C virus genotype 1b or 2a infection., (© 2015 The Authors. HEPATOLOGY published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.)

Background: We previously reported that the indicator of glycaemic control, glycated albumin (GA) levels, are low in relation to glycaemia in patients with high alanine aminotransferase (ALT) levels in non-alcoholic fatty liver disease because of chronic inflammation, and that the GA/glycated haemoglobin ratio (G/H ratio) is inversely correlated with hepatic function in patients with chronic liver disease. The severity of liver fibrosis is known to be a good indicator for surveillance, and for determining the prognosis and optimal treatment of non-alcoholic steatohepatitis (NASH). In this study, we aimed to investigate the clinical usefulness of measuring the G/H ratio for predicting the severity of liver fibrosis in patients with NASH., Methods: The study subjects were 36 patients with histologically diagnosed NASH (19 men, 17 women; mean age 54.8±12.2 years, body mass index 28.3±5.0 kg/m2). The relationships of the G/H ratio to hepatic function tests and fibrosis stage in the liver were investigated., Results: The G/H ratio in patients with NASH was inversely correlated with ALT (P<0.001) and platelet count (P<0.0001). Furthermore, the G/H ratio was positively correlated with the fibrosis stage in liver (P=0.003)., Conclusions: These results suggest that the G/H ratio increases along with the fibrosis stage in patients with NASH.

Purpose: To retrospectively evaluate the efficacy of chemoembolization for inoperable hepatocellular carcinoma (HCC) tumors larger than 5 cm in diameter., Materials and Methods: Chemoembolization was performed in 30 patients with HCCs with a largest diameter of more than 5 cm with three or fewer lesions and no portal vein tumor thrombus. The mean maximum tumor diameter was 7.7 cm +/- 2.4. When the tumor was extremely large and had multiple feeding arteries, stepwise chemoembolization sessions at intervals of 3-10 weeks were performed. In addition, extrahepatic collateral supply was identified and embolized. Local therapeutic effects, survival rates, and complications were analyzed., Results: The mean follow-up period was 33.8 months +/- 24.1. One to 13 chemoembolization sessions (mean, 4.0 sessions +/- 3.0) were performed in each patient. Additionally, 62 collateral vessels were embolized in 21 patients, including 22 vessels in 14 patients at the initial procedure. Early tumor response rate 2-3 months after treatment was 43.3% by Response Evaluation Criteria In Solid Tumors. Complete radiologic response was achieved in 19 patients. Eleven patients died between 4 and 61 months after treatment (mean, 27.2 months +/- 21.8), including four deaths unrelated to hepatic causes. Nineteen patients have survived for 6-103 months (mean, 37.5 months +/- 25.2). Overall and progression free-survival rates at 1, 3, and 6 years were 82.3% and 66.0%, 73.9% and 57.6%, and 32.9% and 34.2%, respectively. Three infectious complications developed and were managed by interventions., Conclusions: Chemoembolization was effective for large HCCs, although there is a risk of infectious complications after the procedure., (Copyright (c) 2010 SIR. Published by Elsevier Inc. All rights reserved.)

Aim: To evaluate the histopathologic findings in the surgical specimen of hepatocelluar carcinoma after transcatheter arterial chemoembolization (TACE) at the most distal portion of the sub-subsegmental artery of the liver (ultraselective TACE)., Methods: Histolopathologic findings from nine tumors with a mean diameter of 3.1 cm +/- 1.7 from patients who underwent hepatectomy after ultraselective TACE were evaluated, especially with regard to the relationship between peritumoral liver parenchymal necrosis and portal vein visualization during TACE. Portal vein visualization was classified into three grades by a spot digital radiograph obtained just after TACE: 0, no obvious portal vein visualization; 1, visualization of the portal vein adjacent to the tumor; and 2, visualization in the whole embolized area or extending into the surrounding non-embolized areas. Unenhanced computed tomography (CT) was obtained 1 week later and surgical resection was performed 37 +/- 6.3 days after ultraselective TACE., Results: Portal vein visualization during TACE was classed as grade 1 in 5 tumors and grade 2 in 4. Histopathologically, complete tumor necrosis was observed in 7 tumors (77.8%). In 2 tumors (1 of grade 1, the other grade 2), a small viable portion or viable daughter nodule was seen. Macroscopic parenchymal necrosis adjacent to the tumor was observed in all 4 grade 2 tumors including gas-containing areas on CT obtained 1 week after TACE., Conclusions: Ultraselective TACE induces not only complete tumor necrosis but also peritumoral parenchymal necrosis, similar to that after radiofrequency ablation, when the portal veins are markedly visualized during the TACE procedure.

Centrilobular zonal necrosis (CZN) is not a pattern typically associated with autoimmune hepatitis (AIH). However, it has occasionally been reported that CZN occurs without the classic histologic features of AIH in patients with autoimmune abnormalities. In this study, we examined the clinicopathological features of 5 cases of CZN with autoimmune features not associated with classic AIH. The patients were 1 man and 4 women (24-82 years). Three patients had subjective symptoms (general malaise, arthralgia, and fever). All had antinuclear antibodies (1:40 to 1:1280). Liver biopsy showed CZN without any histologic features of classic AIH. Liver injury was sustained without medication in 4 cases, whereas it was spontaneously improved in 1 case. However, 2 months later, this patient was found to have recurrent liver dysfunction. Liver biopsy at the time of recurrence again showed CZN without the features of classic AIH. All patients were effectively treated with prednisone. Based on a review of a total of 17 cases of CZN with autoimmune features, including previously reported cases, the patients could be classified into 3 groups: cases without recurrence, cases with recurrent CZN, and cases with progression to classic AIH. Patients of the 2 former groups did not develop classic AIH during follow-up. Factors predictive of recurrence were younger age, being male, and high serum bilirubin or transaminase concentrations at first presentation (P < .05). This study suggested that CZN with autoimmune features corresponds to the early stage of classic AIH in some cases and might be a distinct type of autoimmune liver disease in others.

Purpose: To retrospectively evaluate the relationship between local tumor recurrence and iodized oil deposition in the portal vein by using ultraselective transcatheter arterial chemoembolization (TACE) for small hepatocellular carcinoma., Materials and Methods: One-hundred twenty-three tumors smaller than 5 cm in diameter (mean diameter, 1.9 cm; median diameter, 1.6 cm) were treated with TACE by using a 2-F tip microcatheter at a distal portion of the subsegmental artery of the liver. Portal vein visualization at spot radiography during TACE was divided into three grades, as follows: 0 = not visualized, 1 = limited near the tumor, and 2 = whole or extended to the embolized area. Local recurrence rates of each grade group were compared. The recurrent pattern was divided into intratumoral and peritumoral recurrence. Complications were also analyzed., Results: Of the 123 tumors, 53 (43.1%) were classified as grade 2, 52 (42.3%) were classified as grade 1, and 18 (14.6%) tumors were classified as grade 0. Overall local recurrence rates at 12, 24, and 36 months were 25.6%, 34.7%, and 34.7%, respectively. The local recurrence rates for the grades 2, 1, and 0 groups were 7.9%, 24.8%, and 85.7%, respectively, at 12 months and 17.7%, 38.9%, and 85.7% at 24 months. Recurrence rates in the grade 2 group were significantly lower than those in the grades 1 and 0 groups (P = .0485 and P < .0001, respectively). Intratumoral recurrence was observed in 21 tumors, most of which were in the grade 0 group. Peritumoral recurrence was noted in 16 tumors, most of which were in the grade 2 group. There were no major complications., Conclusion: Ultraselective TACE was safe and effective in a significant number of tumors. In particular, local recurrence was significantly lower when a greater degree of portal vein visualization was demonstrated during TACE.

We report that imaging findings of focal hepatic lesion mimicking cavernous hemangioma supplied by the portal vein, which showed delayed enhancement on CT and hyperintensity similar to that of cerebrospinal fluid on T2-weighted MR images. Biopsy specimen showed the dilated portal veins and hyperplastic change in the surrounding liver parenchyma. CT during arterial portography (CTAP), in particular single-level dynamic CTAP, could clearly depict the abnormal dilated portal vein in the lesion and facilitated the diagnosis of this condition.

There is now increasing evidence that IgG4 is closely involved in idiopathic sclerosing lesions, such as sclerosing pancreatitis and sclerosing sialadenitis. In this report, we describe a case of IgG4-related retroperitoneal and mediastinal fibroses. A 52-year-old man presented with dull back pain and was found to have a continuously surrounding paraaortic mass. A biopsy specimen taken from the retroperitoneum showed a diffuse lymphoplasmacytic infiltration intermixed with fibrosis. Many IgG4-positive plasma cells were demonstrated on immunostaining. His serum IgG4 concentration was 392 mg/dL (reference range, <70). We treated this patient with a corticosteroid, which markedly diminished the paraaortic mass along with lowering of his serum IgG4 concentration. The possible involvement of IgG4 was suggested in the pathogeneses of retroperitoneal and mediastinal fibroses in this patient. IgG4 might be useful in the clinical management of retroperitoneal or mediastinal fibrosis to differentiate them from malignant tumors and predict steroid sensitivity.

Purpose: To evaluate the incidence of each extrahepatic collateral pathway to hepatocellular carcinoma (HCC) and to assess technical success rates and complications of transcatheter arterial chemoembolization (TACE) through each collateral., Methods: We retrospective evaluated extrahepatic collateral pathways to HCC on angiography in 386 procedures on 181 consecutive patients. One hundred and seventy patients had previously undergone TACE. TACE through extrahepatic collaterals using iodized oil and gelatin sponge particles was performed when a catheter was advanced into the tumor-feeding branch to avoid nontarget embolization., Results: A single collateral was revealed in 275 TACE procedures, two were revealed in 74, and three or more were revealed in 34. Incidences of collateral source to HCC were 83% from the right inferior phrenic artery (IPA), 24% from the cystic artery, 13% from the omental artery, 12% from the right renal capsular artery (RCA) and left IPA, 8% from the right internal mammary artery (IMA) and right intercostal artery (ICA), and 7% from the right inferior adrenal artery (IAA). Technical success rates of TACE were 53% in the right ICA, 70% in the cystic artery, 74% in the omental artery, 93% in the left IPA, 96% in the right IPA, and 100% in the right RCA, right IMA, and right IAA. Complications included skin necrosis after TACE through the right IMA (n = 1), cholecystitis after TACE through the cystic artery (n = 1), and ulcer formation after TACE through the right gastric artery (n = 1), in addition to pleural effusion and basal atelectasis after TACE through the IPA and IMA., Conclusion: Our study suggests that TACE through extrahepatic collaterals is possible with high success rates, and is also relatively safe.

Purpose: To evaluate reconstructed patterns of occluded inferior phrenic artery (IPA) and determine the technical success rate and complications of transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) fed by the occluded IPA through the anastomosing branch., Materials and Methods: In 19 patients, 24 IPAs, including two that had been previously embolized, were demonstrated through collateral pathways. The incidence of each collateral circulation was evaluated. Thirteen IPAs in 12 patients fed the tumor and TACE was attempted. TACE was performed only if the catheter could be advanced into the anastomosing branch so that the nontarget branches were avoided., Results: A reconstructed unilateral IPA was observed in 14 patients (11 right IPAs and three left IPAs) and two reconstructed IPAs were observed in five. The IPA was demonstrated through the dorsal pancreatic artery (n = 13), inferior or middle adrenal artery (n = 7), left gastric artery (n = 2), contralateral IPA (n = 2), lumbar artery (n = 1), and small branch derived from the celiac trunk (n = 1). Five IPAs (21%) were demonstrated through more than two separate arteries, including two demonstrated through both dorsal pancreatic arteries arising from the celiac and superior mesenteric artery. The IPA opacified through the lumbar artery had been previously embolized. TACE of the reconstructed IPA was possible in 10 of 13 IPAs (77%). Complications related to the procedure were a small amount of pleural effusion (n = 4) and basal atelectasis (n = 2)., Conclusion: The IPA is reconstructed mainly through the retroperitoneal anastomosing branch in the upper abdomen. TACE of the reconstructed IPA can be performed with a high success rate without major complications.

Purpose: To evaluate the safety, technical success rate, and effectiveness of transcatheter arterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (HCC) fed by the cystic artery., Materials and Methods: Treatment of 27 tumors in 25 patients fed by the cystic artery was attempted with TACE. Twenty-two patients had previously undergone one to eight TACE sessions (mean, four sessions), and the duration after initiation of treatment of HCC was 4-69 months (mean, 24). In three patients, parasitization of the cystic artery was revealed at initial angiography. TACE was performed only when the microcatheter could be inserted into the tumor feeding branch and the stain of the gallbladder wall disappeared. The therapeutic effects and complications were retrospectively analyzed., Results: Seventeen tumors were completely fed by the cystic artery and 10 were fed by both the hepatic artery and cystic artery. Attenuation or occlusion of the hepatic artery was observed in 56%. The tumor feeding branch arising from the cystic artery could be successfully embolized in 18 tumors (67%) of 16 patients without severe complications. Adequate iodized oil accumulation was achieved in 14 tumors (52%) of 12 patients. Percutaneous therapy (n = 7), radiation (n = 4), and TACE after cholecystectomy (n = 1) were added for tumors with incomplete or unsuccessful TACE. Local progression was observed in three (21%) of 14 tumors treated by TACE alone during a mean follow-up period of 18 months., Conclusion: TACE via the cystic artery was safe and technically possible in 67% of patients. If adequate iodized oil accumulation is obtained, which was only achieved in 52% of patients, sufficient therapeutic effect may be expected.

The authors report the use of a catheter with a large side hole in the catheterization of the right inferior phrenic artery (IPA) arising from the proximal portion of the celiac trunk. A 5-F catheter with a side hole on either the top or the right side of the superior portion near the tip was used in five patients with hepatocellular carcinoma fed by the right IPA, which could not be selected by a conventional coaxial technique. In all patients, a 3-F microcatheter was successfully advanced into the right IPA through the side hole of this catheter introduced into the celiac artery or the common hepatic artery.

A 34-year-old woman and a 54-year-old woman were treated with interferon-alpha (IFN-alpha) for chronic hepatitis C. Three months after the cessation of the IFN-alpha therapy, each patient developed hypothyroidism with the presence of thyroid-stimulation-blocking antibody (TSBAb) and TSH-binding inhibitor immunoglobulin (TBII). These two patients were treated with thyroxine, and both TSBAb and TBII activities gradually decreased. Although both TSBAb and TBII became negative several months after the start of the replacement therapy, the replacement dosage of L-thyroxine could not be reduced. Thyroid biopsies showed that the follicular epitheliums were flattened in both cases with lymphocytic infiltration. These findings suggest that IFN-alpha may induce hypothyroidism and the transient emergence of TSBAb and TBII.

Serial changes of intrahepatic portal blood flow were studied before and after percutaneous ethanol injection therapy (PEIT) for hepatocellular carcinoma (HCC). In all eight patients examined, wedge-shaped perfusion defects distal to the tumor were clearly demonstrated by dynamic sequential computed tomography during arterial portography (CT-AP). However, no abnormalities of arterial blood flow were detected in the areas of reduced portal blood flow by enhanced computed tomography (CT), indicating that portal blood flow of the liver was selectively decreased by PEIT. Moreover, histopathological finding of two resected liver tissues after PEIT revealed organized thrombi in the portal veins in the non-cancerous liver tissues distal to the tumors. These findings suggest that decreased segmental portal flow is frequent after PEIT and obstructive vasculitis is caused by the drainage of ethanol injected in the tumor.

We report two cases of membranous obstruction of the inferior vena cava (MOIVC) in which we observed patchy calcification in the membrane. The location of the calcification in the membrane was confirmed histologically. This finding was found histologically in four of eight cases of MOIVC, and it is a useful finding in the CT diagnosis of MOIVC.