Publications by authors named "Shunichi Matsuoka"

42 Publications

Large-volume cell-free and concentrated ascites reinfusion therapy improves venous flow in patients with liver cirrhosis.

J Med Ultrason (2001) 2021 Apr 9. Epub 2021 Apr 9.

Ascites Treatment Center, Kanamecho Hospital, 1-11-13 Kanamecho, Toshima-ku, Tokyo, 171-0043, Japan.

Purpose: Hemodynamic change after total paracentesis was investigated because it might lead to various complications. Although cell-free and concentrated ascites reinfusion therapy (CART) is safer and more effective than total paracentesis in theory, hemodynamic change after CART has been never reported. And previous studies did not mention hemodynamics of the venous system.

Methods: We investigated the hemodynamic change, including that of the venous system, before and after CART using color Doppler ultrasonography and fast Fourier transform analysis. Twenty-eight patients with tensive cirrhotic ascites underwent ultrasonography the day before and after total volume CART. The diameter and velocity of the main, right, and left portal vein; inferior vena cava (IVC); and right renal vein were measured using ultrasonography.

Results: A total of 11.8 ± 4.4 L of ascites (range 3.6-20.9 L) was filtered and concentrated to 0.85 ± 0.40 L (range 0.36-1.50 L). The diameter of the IVC increased from median 13.5 ± 5.4 mm (range 4-25 mm) to 18.5 ± 4.1 mm (range 7-29 mm) (p = 0.007). The diameter of the right segmental renal vein significantly increased after KM-CART [from 5.0 ± 1.0 (4-8) mm to 7.0 ± 2.0 (3-10) mm] (p = 0.011). Hemodynamic change of the portal venous system was not significant. The time to the next CART in patients with an IVC diameter ≥ 20 mm and < 20 mm was 86 days and 20.5 days (p = 0.035), respectively.

Conclusion: Tensive ascites results in venous congestion in patients with cirrhotic ascites. CART improved venous flow, but it did not change the hemodynamics of the portal venous system.
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http://dx.doi.org/10.1007/s10396-021-01094-2DOI Listing
April 2021

Japanese Man with HCV Genotype 4 Infection and Cirrhosis Who was Successfully Treated by the Combination of Glecaprevir and Pibrentasvir.

Intern Med 2021 Feb 1. Epub 2021 Feb 1.

Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Japan.

A 74-year-old man with a history of transfusion at 35 years old in Egypt was referred to our hospital. He was infected with hepatitis C virus (HCV) genotype 4 (GT4), which is a rare HCV GT in Japan, and was also diagnosed with hepatic compensated cirrhosis. We safely treated the patient for 12 weeks with the combination of glecaprevir and pibrentasvir, and a sustained virologic response (SVR) was achieved. This is the first report of HCV GT4 infection in a treatment-naïve Japanese patient with cirrhosis in whom SVR was achieved with the combination treatment of glecaprevir and pibrentasvir.
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http://dx.doi.org/10.2169/internalmedicine.6728-20DOI Listing
February 2021

Noninvasive Assessment of Liver Fibrosis: Current and Future Clinical and Molecular Perspectives.

Int J Mol Sci 2020 Jul 11;21(14). Epub 2020 Jul 11.

Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Itabashi-Ku, Tokyo 173-8610, Japan.

Liver fibrosis is one of the risk factors for hepatocellular carcinoma (HCC) development. The staging of liver fibrosis can be evaluated only via a liver biopsy, which is an invasive procedure. Noninvasive methods for the diagnosis of liver fibrosis can be divided into morphological tests such as elastography and serum biochemical tests. Transient elastography is reported to have excellent performance in the diagnosis of liver fibrosis and has been accepted as a useful tool for the prediction of HCC development and other clinical outcomes. Two-dimensional shear wave elastography is a new technique and provides a real-time stiffness image. Serum fibrosis markers have been studied based on the mechanism of fibrogenesis and fibrolysis. In the healthy liver, homeostasis of the extracellular matrix is maintained directly by enzymes called matrix metalloproteinases (MMPs) and their specific inhibitors, tissue inhibitors of metalloproteinases (TIMPs). MMPs and TIMPs could be useful serum biomarkers for liver fibrosis and promising candidates for the treatment of liver fibrosis. Further studies are required to establish liver fibrosis-specific markers based on further clinical and molecular research. In this review, we summarize noninvasive fibrosis tests and molecular mechanism of liver fibrosis in current daily clinical practice.
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http://dx.doi.org/10.3390/ijms21144906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402287PMC
July 2020

Different Mechanisms of Action of Regorafenib and Lenvatinib on Toll-Like Receptor-Signaling Pathways in Human Hepatoma Cell Lines.

Int J Mol Sci 2020 May 9;21(9). Epub 2020 May 9.

Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan.

Multiple kinase inhibitors are available for patients with advanced hepatocellular carcinoma (HCC). It is largely unknown whether regorafenib or lenvatinib modulates innate immunity including Toll-like receptor (TLR)-signaling pathways in HCC. We performed real-time RT-PCR to investigate 84 TLR-associated gene expression levels and compared these gene expression levels in each hepatoma cells treated with or without regorafenib or lenvatinib. In response to regorafenib, nine and 10 genes were upregulated in Huh7 and HepG2 cells, respectively, and only C-X-C motif chemokine ligand 10 was upregulated in both cell lines. A total of 14 and 12 genes were downregulated in Huh7 and HepG2 cells, respectively, and two genes (Fos proto-oncogene, AP-1 transcription factor subunit, and ubiquitin conjugating enzyme E2 N) were downregulated in both cell lines. In response to lenvatinib, four and 16 genes were upregulated in Huh7 and HepG2 cells, respectively, and two genes (interleukin 1 alpha and TLR4) were upregulated in both cells. Six and one genes were downregulated in Huh7 and HepG2, respectively, and no genes were downregulated in both cell lines. In summary, regorafenib and lenvatinib affect TLR signaling pathways in human hepatoma cell lines. Modulation of TLR signaling pathway may improve the treatment of HCC patients with refractory disease.
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http://dx.doi.org/10.3390/ijms21093349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246870PMC
May 2020

Superinfection of hepatitis A virus in hepatocytes infected with hepatitis B virus.

Int J Med Sci 2019 20;16(10):1366-1370. Epub 2019 Sep 20.

Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173-8610, Japan; (T.K.).

Hepatitis A virus (HAV) infection is a major cause of acute hepatitis including acute liver failure. Hepatitis B infection (HBV) occurs worldwide, with the highest rates in Asian and African countries, and there are several reports that HAV infection may have a more severe clinical course in patients with chronic HBV infection. We previously demonstrated that Japanese miso extracts have inhibitory effects on HAV replication. In the present study, we examined the replication of HAV and HBV in a hepatocyte superinfection model and the inhibitory effects of Japanese miso extracts on both viruses. According to the results, HAV infection inhibited HBV replication in superinfected hepatocytes, and Japanese rice-koji miso extracts had inhibitory effects on HAV replication. Our findings provide useful information for clinicians in managing HAV infection in patients with chronic HBV infection.
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http://dx.doi.org/10.7150/ijms.32795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6818197PMC
April 2020

Prior hepatitis B virus infection as a co-factor of chronic hepatitis C patient survival after resection of hepatocellular carcinoma.

BMC Gastroenterol 2019 Aug 19;19(1):147. Epub 2019 Aug 19.

Department of Gastroenterology and Hepatology, Nihon University School of Medicine, Tokyo, Japan.

Background: Prior hepatitis B virus infection (PBI) may increase the risk of developing hepatocellular carcinoma (HCC), but the impact of PBI on clinical outcomes following treatment for HCC remains unknown. The aim of this study was to clarify whether PBI affects clinical outcomes after liver resection for hepatitis C virus (HCV)-related HCC by retrospective cohort study.

Methods: PBI patients were defined as those negative for hepatitis B surface antigen and positive for anti-hepatitis B core antibody. Surgical outcomes of HCV-related HCC patients with PBI were compared to those without PBI. Survival of patients with non-B non-C HCC with and without PBI were also compared.

Results: In the HCV group, the median overall survival of 165 patients with PBI was 4.7 years (95% confidence interval [CI], 3.9-5.9), and was significantly shorter compared with 263 patients without PBI (6.6 years [5.3-9.8]; p = 0.015). Conversely, there was no significant difference in recurrence-free survival between the two groups (1.8 years [95% CI, 1.4-2.0] vs 2.0 years [1.7-2.3]; p = 0.205). On Cox proportional hazards regression model, independent factors for overall survival were PBI (hazard ratio 1.38 [95% CI, 1.02-1.87]; p = 0.033), multiple tumors (p = 0.007), tumor size (p = 0.002), and liver cirrhosis (p <  0.001). On the other hand, in the non-B non-C HCC group, both the median overall survival (6.5 years [95% CI, 4.8-7.1]) and recurrence-free survival (2.4 years, [95% CI, 1.5-3.3]) in 104 patients with PBI were not significantly different from those (7.5 years [5.5 - NA; p = 0.932]; and 2.2 years [1.7-2.7; p = 0.983]) in 213 patients without PBI.

Conclusions: PBI and HCV in conjunction with each other affect the survival of patients that have undergone resection for HCC.
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http://dx.doi.org/10.1186/s12876-019-1069-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700986PMC
August 2019

Possible association of arrestin domain-containing protein 3 and progression of non-alcoholic fatty liver disease.

Int J Med Sci 2019 2;16(7):909-921. Epub 2019 Jun 2.

Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan.

The prevalence of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) is increasing worldwide. Several effective drugs for these diseases are now in development and under clinical trials. It is important to reveal the mechanism of the development of NAFLD and NASH. We investigated the role of arrestin domain-containing protein 3 (ARRDC3), which is linked to obesity in men and regulates body mass, adiposity and energy expenditure, in the progression of NAFLD and NASH. We performed knockdown of endogenous ARRDC3 in human hepatocytes and examined the inflammasome-associated gene expression by real-time PCR-based array. We also examined the effect of conditioned medium from endogenous ARRDC3-knockdown-hepatocytes on the apoptosis of hepatic stellate cells. We observed that free acids enhanced the expression of ARRDC3 in hepatocytes. Knockdown of ARRDC3 could lead to the inhibition of inflammasome-associated gene expression in hepatocytes. We also observed that conditioned medium from endogenous ARRDC3-knockdown-hepatocytes enhances the apoptosis of hepatic stellate cells. ARRDC3 has a role in the progression of NAFLD and NASH and is one of the targets for the development of the effective treatment of NAFLD and NASH.
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http://dx.doi.org/10.7150/ijms.34245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6643132PMC
February 2020

Follow-up Results of GT2 Patients After Sofosbuvir/Ribavirin Therapy: Careful Attention to Occurrence of HCC.

Anticancer Res 2019 Jul;39(7):3855-3862

Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.

Background: We examined treatment the efficacy and data on long-term outcomes in real-world Japanese patients infected with hepatitis C virus (HCV) genotype 2 treated with 12-week sofosbuvir/ribavirin combination therapy.

Patients And Methods: In a total of 86 patients who were treated with sofosbuvir/ribavirin, sustained virological response (SVR) rates and long-term-outcomes were retrospectively analyzed.

Results: The adherence to this combination therapy was 98.8%. The rates of SVR at week 24 (SVR24) achieved with this treatment according to the 'intention-to-treat' and 'per-protocol' analyses were 89.5% and 96.2%, respectively. Two patients who experienced relapse did not have any previously reported resistance-associated substitutions in the HCV non-structural protein 5B (NS5B) polymerase region. We did not observe any patients who experienced late relapse but did observe that 50% and 1.3% of patients with and without a previous history of hepatocellular carcinoma (HCC), respectively, developed HCC after achieving SVR24 (with a mean follow-up period of 2.7±0.8 years).

Conclusion: Patients with SVR should be carefully followed-up to screen for the occurrence of HCC, although it is infrequent.
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http://dx.doi.org/10.21873/anticanres.13535DOI Listing
July 2019

Exosomes and Hepatocellular Carcinoma: From Bench to Bedside.

Int J Mol Sci 2019 Mar 20;20(6). Epub 2019 Mar 20.

Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan.

As hepatocellular carcinoma (HCC) usually occurs in the background of cirrhosis, which is an end-stage form of liver diseases, treatment options for advanced HCC are limited, due to poor liver function. The exosome is a nanometer-sized membrane vesicle structure that originates from the endosome. Exosome-mediated transfer of proteins, DNAs and various forms of RNA, such as microRNA (miRNA), long noncoding RNA (lncRNA) and messenger RNA (mRNA), contributes to the development of HCC. Exosomes mediate communication between both HCC and non-HCC cells involved in tumor-associated cells, and several molecules are implicated in exosome biogenesis. Exosomes may be potential diagnostic biomarkers for early-stage HCC. Exosomal proteins, miRNAs and lncRNAs could provide new biomarker information for HCC. Exosomes are also potential targets for the treatment of HCC. Notably, further efforts are required in this field. We reviewed recent literature and demonstrated how useful exosomes are for diagnosing patients with HCC, treating patients with HCC and predicting the prognosis of HCC patients.
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http://dx.doi.org/10.3390/ijms20061406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471845PMC
March 2019

Hepatitis C virus genotype 4-infection and interferon-free treatment in Egypt.

Hepatol Int 2018 Jul 10;12(4):291-293. Epub 2018 Jul 10.

Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo, 173-8610, Japan.

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http://dx.doi.org/10.1007/s12072-018-9883-9DOI Listing
July 2018

Apoptosis and non-alcoholic fatty liver diseases.

World J Gastroenterol 2018 Jul;24(25):2661-2672

Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan.

The number of patients with nonalcoholic fatty liver diseases (NAFLD) including nonalcoholic steatohepatitis (NASH), has been increasing. NASH causes cirrhosis and hepatocellular carcinoma (HCC) and is one of the most serious health problems in the world. The mechanism through which NASH progresses is still largely unknown. Activation of caspases, Bcl-2 family proteins, and c-Jun N-terminal kinase-induced hepatocyte apoptosis plays a role in the activation of NAFLD/NASH. Apoptotic hepatocytes stimulate immune cells and hepatic stellate cells toward the progression of fibrosis in the liver through the production of inflammasomes and cytokines. Abnormalities in glucose and lipid metabolism as well as microbiota accelerate these processes. The production of reactive oxygen species, oxidative stress, and endoplasmic reticulum stress is also involved. Cell death, including apoptosis, seems very important in the progression of NAFLD and NASH. Recently, inhibitors of apoptosis have been developed as drugs for the treatment of NASH and may prevent cirrhosis and HCC. Increased hepatocyte apoptosis may distinguish NASH from NAFLD, and the improvement of apoptosis could play a role in controlling the development of NASH. In this review, the association between apoptosis and NAFLD/NASH are discussed. This review could provide their knowledge, which plays a role in seeing the patients with NAFLD/NASH in daily clinical practice.
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http://dx.doi.org/10.3748/wjg.v24.i25.2661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6034146PMC
July 2018

Association of mRNA expression of iron metabolism-associated genes and progression of non-alcoholic steatohepatitis in rats.

Oncotarget 2018 May 25;9(40):26183-26194. Epub 2018 May 25.

Division of Nephrology, Hypertension and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, Itabashi-Ku, Tokyo 173-8610, Japan.

Background: Excess iron is associated with non-alcoholic steatohepatitis (NASH).

Results: mRNA expression of duodenal cytochrome b, divalent metal transporter 1, ferroportin 1, hepcidin, hephaestin and transferrin receptor 1 in liver were higher in high fat, high cholesterol-containing diet (HFCD) group than in normal diet (ND) group. mRNA levels of divalent metal transporter 1 and transferrin receptor 1, which stimulate iron absorption and excretion, were enhanced in small intestine. Epithelial mucosa of small intestine in HFCD group was characterized by plasma cell and eosinophil infiltration and increased vacuoles. Iron absorption was enhanced in this NASH model in the context of chronic inflammation of small intestinal epithelial cells, consequences of intestinal epithelial cell impairment caused by HFCD. Iron is transported to hepatocytes via portal blood, and abnormalities in iron absorption and excretion occur in small intestine from changes in iron transporter expression, which also occurs in NASH liver. Knockdown of hepcidin antimicrobial peptide led to enhanced heavy chain of ferritin expression in human hepatocytes, indicating association between hepcidin production and iron storage in hepatocytes.

Conclusions: Iron-related transporters in liver and lower/upper portions of small intestine play critical roles in NASH development.

Methods: Expression of iron metabolism-related genes in liver and small intestine was analyzed in stroke-prone spontaneously hypertensive rats (SHR-SP), which develop NASH. Five-week-old SHR-SP fed ND or HFCD were examined. mRNA and protein levels of iron metabolism-related genes in liver and small intestine from 12- and 19-week-old rats were evaluated by real-time RT-PCR and immunohistochemistry or Western blot.
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http://dx.doi.org/10.18632/oncotarget.25488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5995254PMC
May 2018

Early occurrence and recurrence of hepatocellular carcinoma in hepatitis C virus-infected patients after sustained virological response.

Hepatol Int 2018 Mar 4;12(2):90-93. Epub 2018 Apr 4.

Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo, 173-8610, Japan.

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http://dx.doi.org/10.1007/s12072-018-9862-1DOI Listing
March 2018

Persistent Hepatic Inflammation Plays a Role in Hepatocellular Carcinoma After Sustained Virological Response in Patients with HCV Infection.

Int J Med Sci 2018 8;15(5):466-474. Epub 2018 Mar 8.

Division of Gastroenterology and Hepatology, Department of Internal Medicine.

Hepatitis C virus (HCV) infection has long been treated with interferon therapy (IFN). Currently, more than 90% of IFN-treated patients show a sustained virological response (SVR) when also treated with ribavirin and/or a protease inhibitor. Histological inflammation and fibrosis improve in IFN-treated patients, which indicates HCV clearance. IFN also reduces the incidence of hepatocellular carcinoma (HCC). However, a small proportion of patients with SVR develop HCC. To investigate the causes of hepatic carcinogenesis after SVR, we compared the liver histological findings before IFN to those after the development of HCC. In total, 602 patients infected with type C chronic hepatitis or with liver cirrhosis who received IFN therapy during the period from 1992 through 2015 were included in this study. We assessed 14 of the 287 patients who achieved an SVR. HCC was diagnosed by computed tomography, angiography or liver biopsy. The longest time from the SVR until HCC detection was 16.5 years, and the mean was 7.2±4.6 years. Nine of the 14 patients underwent surgery and one radiofrequency ablation. The histological findings of 10 patients were available for comparison. The comparison of the histological findings before treatment with those after the HCC diagnosis revealed an amelioration of liver fibrosis and other inflammatory changes. All ten patients showed improvements in fibrosis and steatosis. However, we observed that mild inflammatory change persisted from 1.8 years to 16.5 years after the confirmation of SVR in all cases. We suspect that persistent histological inflammation is one of the factors contributing to hepatocarcinogenesis (i.e., HCC development) even after successful treatment.
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http://dx.doi.org/10.7150/ijms.23147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5859769PMC
August 2018

Portal-systemic Encephalopathy due to Complicated Spleno-renal Shunt Successfully Treated with Balloon-occluded Retrograde Transvenous Obliteration Using a Double Coaxial Balloon Catheter System and Shape-memory Coils.

Intern Med 2018 Jul 28;57(13):1861-1866. Epub 2018 Feb 28.

Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Japan.

A 70-year-old woman with hepatitis C cirrhosis underwent balloon-occluded retrograde transvenous obliteration for hepatic encephalopathy due to spleno-renal shunt. Because the shunt was thick, long, and winding, we used a coaxial and double interruption system, which enables the effective occlusion of the drainage route, and shape-memory coils, which are more physically stable than conventional metallic coils because they form three-dimensional loops. The patient was successfully treated with the combined usage of these devices, resulting in a normal serum ammonia level. Thereafter, the patient was treated with direct-acting antivirals, and a sustained virological response was achieved.
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http://dx.doi.org/10.2169/internalmedicine.0247-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6064694PMC
July 2018

Retreatment of patients with treatment failure of direct-acting antivirals: Focus on hepatitis C virus genotype 1b.

World J Gastroenterol 2017 Dec;23(46):8120-8127

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nihon University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan.

The recent development of direct-acting antiviral agents (DAAs) against hepatitis C virus (HCV) infection could lead to higher sustained virological response (SVR) rates, with shorter treatment durations and fewer adverse events compared with regimens that include interferon. However, a relatively small proportion of patients cannot achieve SVR in the first treatment, including DAAs with or without peginterferon and/or ribavirin. Although retreatment with a combination of DAAs should be conducted for these patients, it is more difficult to achieve SVR when retreating these patients because of resistance-associated substitutions (RASs) or treatment-emergent substitutions. In Japan, HCV genotype 1b (GT1b) is founded in 70% of HCV-infected individuals. In this minireview, we summarize the retreatment regimens and their SVR rates for HCV GT1b. It is important to avoid drugs that target the regions targeted by initial drugs, but next-generation combinations of DAAs, such as sofosbuvir/velpatasvir/voxilaprevir for 12 wk or glecaprevir/pibrentasvir for 12 wk, are proposed to be potential solution for the HCV GT1b-infected patients with treatment failure, mainly on a basis of targeting distinctive regions. Clinicians should follow the new information and resources for DAAs and select the proper combination of DAAs for the retreatment of HCV GT1b-infected patients with treatment failure.
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http://dx.doi.org/10.3748/wjg.v23.i46.8120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5739919PMC
December 2017

Involvement of Ornithine Carbamoyltransferase in the Progression of Chronic Hepatitis C and Liver Cirrhosis.

Int J Med Sci 2017 14;14(7):629-638. Epub 2017 Jun 14.

Yamasa Corporation, Yamasa Corporation, 2-10-1 Araoi-cho, Choshi, Chiba 288-0056, Japan.

: The involvement of serum ornithine carbamoyltransferase (OCT) in the progression of chronic hepatitis and liver cirrhosis is unclear. : A total 256 patients with chronic hepatitis C and 5 healthy controls were examined. Serum OCT concentrations were measured by enzyme-linked immunosorbent assay. Serum OCT concentrations were compared with serum cytokine and chemokine levels, and with disease severity and development of hepatocellular carcinoma (HCC). : The median OCT concentrations were 21.8 ng/ml for healthy controls, 36.7 ng/ml for F0 stage disease, 48.7 ng/ml for F1 stage, 77.9 ng/ml for F2 stage, 104.8 ng/ml for F3 stage, and 121.4 ng/ml for F4 stage. OCT concentrations were correlated with aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transpeptidase, platelet counts, indocyanine green retention rate at 15 min, prothrombin times, the molar ratio of branched chain amino acids to tyrosine, and tyrosine. Furthermore, there were significant correlations among OCT concentrations and IP10 and IL18 levels. There were weak correlations between serum OCT concentrations and liver histology. The cumulative incidence of HCC in the high-OCT concentration group (≥75.3 ng/ml) was higher than that in the low-OCT concentration group. The measurement of serum OCT concentration may provide a useful marker of disease severity, and thus could be a useful marker for a high risk of HCC occurrence.
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http://dx.doi.org/10.7150/ijms.17641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5562113PMC
May 2018

Renal vein dilation predicts poor outcome in patients with refractory cirrhotic ascites.

Hepatol Res 2018 Feb 16;48(3):E117-E125. Epub 2017 Aug 16.

Department of Gastroenterology, Japan Community Health Care Organization Yokohama Chuo Hospital, Yokohama City, Japan.

Aim: Renal venous hypertension is known to be associated with worsening of renal function in patients with decompensated heart failure. Intra-abdominal hypertension including cirrhotic ascites also leads to renal venous hypertension. We aimed to clarify the effect of renal venous hypertension on cirrhotic ascites.

Methods: Two hepatologists measured the left renal vein diameter in 142 consecutive patients with refractory cirrhotic ascites using non-contrast computed tomography. The renal vein diameter was measured at the renal vein main trunk and upstream of the confluence of collateral veins.

Results: The inter-observer agreements were high for the measurements of the left renal vein (r = 0.918, P < 0.001). The median overall survival for patients with renal vein diameter ≥11 mm was less than that for patients with renal vein diameter <11 mm (P < 0.001; 2.5 vs. 32.0 months). One-year survival rates were 15.3% versus 66.4%. Multivariate analysis revealed renal vein diameter ≥11 mm (hazard ratio, 2.94; P < 0.001; 95% confidence interval, 1.67-5.20) and a high Model for End-stage Liver Disease score combined with serum sodium level (MELD-Na) (hazard ratio, 3.39; P < 0.001; 95% confidence interval, 2.00-5.74) were significant independent predictors of mortality.

Conclusions: Renal vein dilation is a risk factor of mortality in patients with refractory cirrhotic ascites, independent of the MELD-Na score.
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http://dx.doi.org/10.1111/hepr.12935DOI Listing
February 2018

Clinical correspondence to hepatocellular carcinoma-related lesions with atypical radiological pattern.

Biosci Trends 2017 Jul 18;11(3):340-345. Epub 2017 Jun 18.

Department of Digestive Surgery, Nihon University School of Medicine.

In patients at risk of hepatocarcinogenesis, tumors are frequently detected with atypical radiological patterns related to hepatocellular carcinoma (HCC) on imaging studies. Despite their high potential for malignancy, whether to resect such lesions immediately is controversial. Based on histological findings, patients with non-enhanced tumors or enhanced tumors without washout were divided into two groups: those with tumors that should be treated containing well, moderately, and poorly differentiated HCC (Group 1), and those that can be observed containing early HCC, hepatocellular adenoma, focal nodular hyperplasia, dysplastic nodules, and regenerative nodules (Group 2), and we elucidated the clinical correspondence to these tumors. Seventy-two patients had a single tumor with atypical radiological pattern: 39 patients had HCC (Group 1), while 33 patients had benign tumors or early HCC (Group 2). Among nine baseline variables, serum α-fetoprotein (AFP) level in Group 1 (median, 13.2 ng/mL; range, 0.6-5881.6) was significantly higher than that in Group 2 (5.6 ng/mL; 0.8-86.3, P = 0.003). The cut-off value of AFP was 36.4 ng/mL for prediction of Group 1, and the median overall and recurrence-free survival periods of 23 patients in the high-AFP (≥ 36.4 ng/mL) group (5.3 years; 95%CI, 2.1 - N.A. and 1.6 years; 0.5-2.2) were significantly shorter than those of the 49 patients in the low-AFP (< 36.4) group (7.5 years; 7.5 - N.A., P = 0.047, and 2.8 years; 1.9-3.3, P = 0.001). Taken together, HCC-related tumors with an atypical radiological pattern could be observed unless serum AFP level is elevated.
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http://dx.doi.org/10.5582/bst.2017.01110DOI Listing
July 2017

Ventricular Tachycardia as a Complication of Ledipasvir and Sofosbuvir Treatment for HCV Infection.

Intern Med 2017 1;56(7):787-790. Epub 2017 Apr 1.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nihon University School of Medicine, Japan.

We experienced two patients with serious arrhythmias associated with the administration of ledipasvir (LDV) and sofosbuvir (SOF). Neither patient took amiodarone, an agent for which concomitant use is prohibited. One patient was 82 years old and hypertensive; the other was 72 years old and had no cardiovascular risk factors such as hypertension or diabetes mellitus. The arrhythmias were both serious ventricular tachycardia (VT) that converted spontaneously to sinus rhythm, without treatment, and both patients had good outcomes. These cases suggest that LDV/SOF may be associated with an increased risk of heart-related events.
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http://dx.doi.org/10.2169/internalmedicine.56.7948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5457921PMC
June 2017

Diabetes mellitus not an unfavorable factor on the prognosis of hepatitis C virus-related hepatocellular carcinoma.

Hepatol Res 2018 Jan 1;48(1):28-35. Epub 2017 Apr 1.

Departments of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan.

Aim: Diabetes mellitus (DM) is a potential risk factor for hepatocarcinogenesis, especially in patients with hepatitis C virus (HCV) infection. We aimed to elucidate whether DM influences the surgical outcomes of patients with hepatocellular carcinoma (HCC).

Methods: Our patients were routinely controlled to keep urinary glucose excretion to less than 3.0 g/day before surgery, and the serum glucose level under 200 mg/dL after surgery. The surgical outcomes and postoperative complications of 112 patients with HCV-related HCC with DM (DM group) were compared to those of 112 propensity-matched patients without DM (non-DM group).

Results: After a median follow-up of 3.2 years (range, 0.2-11.3 years), the median overall (5.2 years; 95% confidence interval, 3.8-6.5 years) and recurrence-free survival (2.2 years; 1.7-2.9 years) in the DM group were not significantly different from those (6.3 years; 5.4-7.1 years, P = 0.337; and 2.2 years; 1.7-3.6 years, P = 0.613) in the non-DM group. The independent factors related to overall survival were the background liver (hazard ratio, 2.06; 95% confidence interval, 1.27-3.39, P = 0.014) and tumor differentiation grade (2.07; 1.14-4.05, P = 0.015). Thirty-two patients (28.5%) in the DM group and 32 patients (28.5%) in the non-DM group had morbidities after operation, with no significant difference between the groups (P = 1.000). Furthermore, postoperative control status of DM did not affect the prognostic outcome.

Conclusion: Diabetes mellitus does not affect the surgical outcomes of patients with HCV-related HCC, and it is not an unfavorable factor when selecting candidates for liver resection of HCC.
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http://dx.doi.org/10.1111/hepr.12888DOI Listing
January 2018

Steatosis influences the clinical profiles and long-term outcomes of interferon-treated chronic hepatitis C and liver cirrhosis patients.

Int J Med Sci 2017 1;14(1):45-52. Epub 2017 Jan 1.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan 30-1 Oyaguchi Kamicho, Itabashiku, Tokyo 173-8610, Japan.

This study aimed to assess the relationship between steatosis and long-term outcomes of patients with chronic hepatitis C (CH) and liver cirrhosis (LC). The study population included 282 subjects with CH or LC who underwent liver biopsy at our institute. All patients achieved a sustained virological response (SVR) to interferon (IFN). Clinical characteristics, including age, gender and body mass index (BMI), were compared. The liver biopsy specimens of all patients were examined and scores were assigned to indicate the severity of each of the following features: inflammatory cell infiltration in the periportal, parenchymal and portal areas; F (fibrosis) stage; portal sclerotic change; perivenular fibrosis; pericellular fibrosis; bile duct damage; hepatic steatosis. Of the 282 patients, 112 (39.7%) were free of steatosis. The other 170 patients (60.3%) had steatosis. The blood biochemical parameters of the patients with hepatic steatosis were significantly poorer than those of patients free of steatosis. Inflammatory cell infiltration and F stage were both significantly more severe in patients with than in those without steatosis. The incidences of hepatocellular carcinoma differed significantly between the two groups. However, the incidences of hepatocellular carcinoma did not differ significantly between the groups with BMI above and below 25. We consider hepatic steatosis to potentially affect the blood biochemical parameters and clinical profiles of Japanese patients with CH due to hepatitis virus type C. Patients with this form of CH showed favorable clinical responses to IFN. Furthermore, fibrosis and steatosis appear to affect the long-term outcomes of these patients. However, BMI alone cannot be used to predict HCC development.
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http://dx.doi.org/10.7150/ijms.17202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5278658PMC
May 2017

Contrast-enhanced ultrasonographic findings of serum amyloid A-positive hepatocellular neoplasm: Does hepatocellular adenoma arise in cirrhotic liver?

World J Hepatol 2016 Sep;8(26):1110-5

Mariko Kumagawa, Naoki Matsumoto, Yukinobu Watanabe, Midori Hirayama, Takao Miura, Hiroshi Nakagawara, Masahiro Ogawa, Shunichi Matsuoka, Mitsuhiko Moriyama, Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo 173-8610, Japan.

Hepatocellular adenoma (HCA) was recently classified into four pathological subtypes. There have been few studies describing the findings of contrast-enhanced ultrasonography (CEUS) of each type. Our case concerns a 78-year-old man who had undergone routine medical check-ups for hepatitis C for 11 years. Abdominal ultrasonography showed a 28 mm, hypo-echoic mass in the segment 4 of the liver. His integrating amount of drinking was 670 kg convert into ethanol. CEUS with Sonazoid demonstrated mild uniform hypo-enhancement with inflow of microbubbles from the periphery of the tumor in the arterial phase, and heterogeneously hypo-enhancement in the post vascular phase. Because the mass increased in size within 3 mo, a well differentiated hepatocellular carcinoma was suspected, and hepatic resection was performed. Microscopic findings showed homogeneous cell proliferation with low grade atypia, infiltration of inflammatory cells, ductular reactions, fatty deposit in part, and sinusoidal dilation. Immunohistochemistry revealed geographic positive for serum amyloid A (SAA), focal positive for glutamine synthetase, diffuse and strong positive for C-reactive protein, and positive for liver-type fatty acid binding protein. These pathological features corresponded to that of an inflammatory HCA. However, we could not make a clear diagnosis, because HCAs were defined as not to arise in cirrhotic liver. Finally, this tumor was diagnosed as a SAA positive hepatocellular neoplasm.
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http://dx.doi.org/10.4254/wjh.v8.i26.1110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5026994PMC
September 2016

Onset of Tuberculosis from a Pulmonary Latent Tuberculosis Infection during Antiviral Triple Therapy for Chronic Hepatitis C.

Intern Med 2016 1;55(15):2011-7. Epub 2016 Aug 1.

Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Japan.

A 62-year-old man was diagnosed with the onset of tuberculosis (Tb) from a pulmonary latent tuberculosis infection (LTBI) during triple therapy with pegylated interferon α2a, ribavirin, and telaprevir for a chronic hepatitis C infection in 2013 before interferon (IFN)-free anti-viral therapy was introduced in Japan. A liver biopsy before IFN treatment revealed the presence of epithelioid cell granulomas (ECGs). IFN may also be employed for chronic hepatitis B infection and malignant tumors, thus, special attention must be paid to the development of Tb from a LTBI when ECGs are observed before treatment. It is also necessary to review the significance of the liver biopsy.
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http://dx.doi.org/10.2169/internalmedicine.55.6448DOI Listing
March 2017

Prevalence and Risk Factors of Diabetes Mellitus in Patients with Autoimmune Hepatitis.

Intern Med 2016 15;55(8):879-85. Epub 2016 Apr 15.

Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Japan.

Objective: The administration of corticosteroids is a standard treatment for autoimmune hepatitis (AIH), but it can occasionally induce various adverse effects. Diabetes mellitus (DM) is a major complication of chronic liver diseases. We investigated the prevalence and risk factors of DM in patients with AIH.

Methods: We retrospectively analyzed 118 Japanese patients diagnosed with AIH from 1990 to 2014 at our institution. The prognosis of patients with and without DM was also compared.

Results: Twenty-nine (24.5%) patients had DM and 21 (72.4%) received corticosteroids. The annual cumulative incidence rate of newly diagnosed DM was 1.2%. Multivariate analysis showed that DM occurred in older patients [OR=6.290; 95% confidence interval (CI)=1.230-32.100; p=0.018] with higher serum immunoglobulin G levels (OR=12.400; 95% CI=2.560-60.400; p=0.002). A Cox hazard regression analysis revealed that predictive factors for DM were absence of other autoimmune diseases (OR=0.171; 95% CI=0.036-0.805; p=0.025), use of corticosteroids (OR=6.693; 95% CI=1.391-32.210; p=0.049) and lower platelet counts (OR=3.873; 95% CI=1.021-14.690; p=0.046). The 10 year survival rates of the DM and non-DM groups were 94.1% and 94.6%, respectively. There was no significant difference between these groups (p=0.293).

Conclusion: DM occurred in 24.5% of patients with AIH; older age, absence of other autoimmune diseases and higher serum immunoglobulin G levels are risk factors. Taking corticosteroids and a lower platelet count are risk factors for a new onset of DM. DM did not influence the prognosis of AIH patients.
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http://dx.doi.org/10.2169/internalmedicine.55.4957DOI Listing
October 2016

Utility of Partial Splenic Embolization for Hypersplenism using Guglielmi Detachable Coils.

Hepatogastroenterology 2015 May;62(139):683-7

Background/aims: We examined the utility of partial splenic embolization (PSE) using a Guglielmi Detachable Coil (GDC) comparing its safety and therapeutic efficacy with those of conventional metallic coils (IDC).

Methodology: The GDC group comprised 8 patients who were subjected to embolization using a GDC in combination with an IDC, and the IDC group comprised 13 patients. Treatment factors were evaluated by the total number of coils used. We assessed the mean C-reactive protein (CRP) and the increased rate of platelet counts, 2 weeks after treatment.

Results: The rate of increase in platelet counts at 2 weeks after PSE was 2.47 in the GDC group and 3.18 in the IDC group (p = 0.076). The mean CRP levels were 3.0 in the GDC group and 5.9 in the IDC group (p = 0.14). The mean number of coils were 5.3 in the GDC group and 15.3 in the IDC group and this difference was statistically significant (p = 0.0008).

Conclusion: A GDC is excellent in terms of stability and allows the operator to conduct embolization of hypersplenism in an accurate and reliable manner. In summary, use of a GDC for hypersplenism reduced the total number of coils required for successful treatment.
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May 2015

Technique of Transbrachial Angiography and Treatment for Abdominal Diseases: A Study of 6262 Patients.

Hepatogastroenterology 2015 May;62(139):673-6

For over 20 years, we have been using the transbrachial approach as the first-line option for abdominal angiography and transcatheter arterial chemoembolization (TACE). The present study involving 6262 patients (success rate of 99.8%) showed that the transbrachial approach could be used for superselective angiography or computed tomography during angiography (angio-CT) and was effective for hemostasis of abdominal aneurysmal hemorrhage, diverticular hemorrhage and partial splenic embolization. The approach was highly safe with no association with serious complications. Bleeding from the puncture site was reported in 225 cases (0.36%), numbness due to nerve damage at the puncture site. was reported in 376 cases (0.6%), and arteriovenous fistula in the puncture site was reported in 84 cases (0.13%). In the treatment of hepatic disease, the guiding catheter could be inserted deeper into the hepatic artery, and hemostasis after sheath removal required shorter time compared with the transfemoral approach. Based on its safety and usefulness, transbrachial angiography and intervention therapy is a first-line treatment for abdominal diseases.
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May 2015

[Prevention of hepatitis E virus].

Nihon Rinsho 2015 Dec;73 Suppl 9:636-8

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December 2015

[A case of acute progressive primary inflammatory fibrosarcoma of the retroperitoneum].

Nihon Shokakibyo Gakkai Zasshi 2015 Dec;112(12):2160-7

Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine.

A 70-year-old man with liver cirrhosis presented to us with abdominal distention. Computed tomography revealed a giant retroperitoneal tumor. Examination of a biopsy specimen led to a diagnosis of primary inflammatory fibrosarcoma of the retroperitoneum. However, disease progression was rapid, and the patient died 6 weeks after the onset of the disease. Autopsy revealed that the tumor arose from the retroperitoneum and infiltrated the omentum and mesentery. Prognosis of inflammatory fibrosarcoma is poor if resection is incomplete. Establishment of treatment for unresectable cases is necessary.
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http://dx.doi.org/10.11405/nisshoshi.112.2160DOI Listing
December 2015

Hypersplenism Treated by Partial Splenic Embolization Using Guglielmi Detachable Coils.

Intern Med 2015 1;54(17):2179-83. Epub 2015 Sep 1.

Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Japan.

A 52-year-old man underwent partial splenic embolization (PSE) for hypersplenism. The intrasplenic artery targeted for the embolization was large, and the distance between its trifurcated branches was short; therefore, Guglielmi detachable coils (GDC) 360° Complex Shape were used, as well as conventional metal coils, to prevent coil migration. GDC are equipped with a shape-memory function and are more physically stable than conventional metallic coils because they form three-dimensional loops. In this case, an ideal extent of the splenic infarction was successfully achieved using a small number of coils. This is the first report of the use of GDC in PSE for hypersplenism.
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http://dx.doi.org/10.2169/internalmedicine.54.4704DOI Listing
May 2016