Publications by authors named "Mitsuhiko Moriyama"

202 Publications

COVID-19 After Treatment With Direct-acting Antivirals for HCV Infection and Decompensated Cirrhosis: A Case Report.

In Vivo 2022 Jul-Aug;36(4):1986-1993

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

Background: Eradication of hepatitis C virus (HCV) from chronic HCV-infected patients could improve liver function and prevent hepatocarcinogenesis in the long term. Eradication of HCV by direct-acting antivirals (DAAs) also leads to dynamic immunological changes. We report a case of recurrent coronavirus disease 2019 (COVID-19) that developed immediately after combination treatment with DAAs for HCV infection and decompensated cirrhosis.

Case Report: A 55-year-old male was started on a 12-week treatment with combination of HCV NS5A inhibitor velpatasvir and HCV NS5B polymerase inhibitor sofosbuvir. HCV RNA became undetectable after six weeks of treatment and was undetectable at the end of the treatment (EOT). Twelve days after the EOT, we diagnosed the patient with COVID-19 pneumonia, admitted him to our hospital and he was discharged two weeks later. One week after his discharge, he visited our hospital again, was diagnosed with recurrent COVID-19 pneumonia readmitted for a second time. Four days after second admission, cardiac arrest occurred, however, he recovered from severe COVID-19 and achieved sustained virological response and his liver function improved.

Conclusion: In the COVID-19 era, while attention should be paid to the occurrence or exacerbation of infection, including COVID-19, interferon-free DAA combination therapy should be performed for HCV-infected individuals.
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http://dx.doi.org/10.21873/invivo.12923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301408PMC
June 2022

Endoscopic biliary drainage using a 4-Fr catheter for biliary obstruction: a pilot study.

Minim Invasive Ther Allied Technol 2022 Jun 22:1-6. Epub 2022 Jun 22.

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

Introduction: Stent or endoscopic nasobiliary drainage (ENBD) catheter placement for a tight, complicated biliary stricture is still technically challenging. A thin, 4-Fr ENBD catheter (4-Fr catheter) has been developed to overcome this difficulty. The study aimed to evaluate the feasibility of the 4-Fr catheter for endoscopic biliary drainage (EBD).

Material And Methods: We performed a retrospective review of 51 patients who underwent EBD with the 4-Fr catheter because placement of a conventional drainage catheter (CDC) had failed.

Results: The success rate of 4-Fr catheter placement was 96.1% (49/51). The median patency period of the catheter was 114 days (95% CI, 53-200). Among the 49 patients with successful placement of the catheter, adverse events occurred in five (10.2%) patients: post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP), two patients; catheter dislocation, one patient; and kinking of the 4-Fr catheter, two patients. Both cases of PEP improved with conservative treatment, but all cases of catheter dislocation and kinking required reintervention with a 4-Fr catheter. Forty-three (87.8%) patients achieved clinical remission after EBD with a 4-Fr catheter.

Conclusions: The newly developed 4-Fr catheter is safe and feasible for EBD in patients in whom CDC placement is difficult due to a tight, complicated biliary stricture.
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http://dx.doi.org/10.1080/13645706.2022.2090004DOI Listing
June 2022

Evaluation of Potential Anti-Hepatitis A Virus 3C Protease Inhibitors Using Molecular Docking.

Int J Mol Sci 2022 May 27;23(11). Epub 2022 May 27.

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

Hepatitis A virus (HAV) infection is a major cause of acute hepatitis worldwide and occasionally causes acute liver failure and can lead to death in the absence of liver transplantation. Although HAV vaccination is available, the prevalence of HAV vaccination is not adequate in some countries. Additionally, the improvements in public health reduced our immunity to HAV infection. These situations motivated us to develop potentially new anti-HAV therapeutic options. We carried out the in silico screening of anti-HAV compounds targeting the 3C protease enzyme using the Schrodinger Modeling software from the antiviral library of 25,000 compounds to evaluate anti-HAV 3C protease inhibitors. Additionally, in vitro studies were introduced to examine the inhibitory effects of HAV subgenomic replicon replication and HAV HA11-1299 genotype IIIA replication in hepatoma cell lines using luciferase assays and real-time RT-PCR. In silico studies enabled us to identify five lead candidates with optimal binding interactions in the active site of the target HAV 3C protease using the Schrodinger Glide program. In vitro studies substantiated our hypothesis from in silico findings. One of our lead compounds, Z10325150, showed 47% inhibitory effects on HAV genotype IB subgenomic replicon replication and 36% inhibitory effects on HAV genotype IIIA HA11-1299 replication in human hepatoma cell lines, with no cytotoxic effects at concentrations of 100 μg/mL. The effects of the combination therapy of Z10325150 and RNA-dependent RNA polymerase inhibitor, favipiravir on HAV genotype IB HM175 subgenomic replicon replication and HAV genotype IIIA HA11-1299 replication showed 64% and 48% inhibitory effects of HAV subgenomic replicon and HAV replication, respectively. We identified the HAV 3C protease inhibitor Z10325150 through in silico screening and confirmed the HAV replication inhibitory activity in human hepatocytes. Z10325150 may offer the potential for a useful HAV inhibitor in severe hepatitis A.
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http://dx.doi.org/10.3390/ijms23116044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9181686PMC
May 2022

Suppressors of Cytokine Signaling and Hepatocellular Carcinoma.

Cancers (Basel) 2022 May 22;14(10). Epub 2022 May 22.

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

Cytokines are secreted soluble glycoproteins that regulate cellular growth, proliferation, and differentiation. Suppressors of cytokine signaling (SOCS) proteins negatively regulate cytokine signaling and form a classical negative feedback loop in the signaling pathways. There are eight members of the SOCS family. The SOCS proteins are all comprised of a loosely conserved N-terminal domain, a central Src homology 2 (SH2) domain, and a highly conserved SOCS box at the C-terminus. The role of SOCS proteins has been implicated in the regulation of cytokines and growth factors in liver diseases. The SOCS1 and SOCS3 proteins are involved in immune response and inhibit protective interferon signaling in viral hepatitis. A decreased expression of SOCS3 is associated with advanced stage and poor prognosis of patients with hepatocellular carcinoma (HCC). DNA methylations of SOCS1 and SOCS3 are found in HCC. Precise regulation of liver regeneration is influenced by stimulatory and inhibitory factors after partial hepatectomy (PH), in particular, SOCS2 and SOCS3 are induced at an early time point after PH. Evidence supporting the important role of SOCS signaling during liver regeneration also supports a role of SOCS signaling in HCC. Immuno-oncology drugs are now the first-line therapy for advanced HCC. The SOCS can be potential targets for HCC in terms of cell proliferation, cell differentiation, and immune response. In this literature review, we summarize recent findings of the SOCS family proteins related to HCC and liver diseases.
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http://dx.doi.org/10.3390/cancers14102549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9139988PMC
May 2022

Contrast-enhanced ultrasonography for blood flow detection in hepatocellular carcinoma during lenvatinib therapy.

J Med Ultrason (2001) 2022 Jul 30;49(3):425-432. Epub 2022 Mar 30.

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

Purpose: Blood flow reduction after initiation of lenvatinib therapy may not always indicate tumor necrosis. This study aimed to compare the blood flow detectability of contrast-enhanced ultrasonography (CEUS), contrast-enhanced computed tomography (CT), and contrast-enhanced magnetic resonance imaging (MRI) in hepatocellular carcinoma (HCC) during lenvatinib therapy.

Methods: A total of 12 cases underwent CEUS and contrast-enhanced CT/MRI within 2 weeks during lenvatinib therapy. Vascularity on CEUS and CT/MRI was compared.

Results: At the time of CEUS examination, the median period from the start of lenvatinib was 227 ± 210 (31-570) days. CEUS showed hyperenhancement in eight cases (66.7%), hypoenhancement in two cases (16.7%), and no enhancement in one case (8.3%), while CT/MRI showed hyperenhancement in one case (8.3%), ring enhancement in three cases (25.0%), and hypoenhancement in eight cases (66.7%) (p = 0.007). Transarterial chemoembolization (n = 3), radiofrequency ablation (n = 2), and stereotactic body radiation therapy (n = 2) were performed after blood flow detection by CEUS.

Conclusions: The viability of the HCC should be confirmed using CEUS when contrast-enhanced CT/MRI reveals lesion hypoenhancement during lenvatinib therapy.
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http://dx.doi.org/10.1007/s10396-022-01204-8DOI Listing
July 2022

Favipiravir Inhibits Hepatitis A Virus Infection in Human Hepatocytes.

Int J Mol Sci 2022 Feb 27;23(5). Epub 2022 Feb 27.

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

Hepatitis A virus (HAV) is a causative agent of acute hepatitis and can occasionally induce acute liver failure. However, specific potent anti-HAV drug is not available on the market currently. Thus, we investigated several novel therapeutic drugs through a drug repositioning approach, targeting ribonucleic acid (RNA)-dependent RNA polymerase and RNA-dependent deoxyribonucleic acid polymerase. In the present study, we examined the anti-HAV activity of 18 drugs by measuring the HAV subgenomic replicon and HAV HA11-1299 genotype IIIA replication in human hepatoma cell lines, using a reporter assay and real-time reverse transcription polymerase chain reaction, respectively. Mutagenesis of the HAV 5' untranslated region was also examined by next-generation sequencing. These specific parameters were explored because lethal mutagenesis has emerged as a novel potential therapeutic approach to treat RNA virus infections. Favipiravir inhibited HAV replication in both Huh7 and PLC/PRF/5 cells, although ribavirin inhibited HAV replication in only Huh7 cells. Next-generation sequencing demonstrated that favipiravir could introduce nucleotide mutations into the HAV genome more than ribavirin. In conclusion, favipiravir could introduce nucleotide mutations into the HAV genome and work as an antiviral against HAV infection. Provided that further in vivo experiments confirm its efficacy, favipiravir would be useful for the treatment of severe HAV infection.
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http://dx.doi.org/10.3390/ijms23052631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8910232PMC
February 2022

Left Gastric Vein Width Is an Important Risk Factor for Exacerbation of Esophageal Varices Post Balloon-Occluded Retrograde Transvenous Obliteration for Gastric Varices in Cirrhotic Patients.

Medicina (Kaunas) 2022 Jan 28;58(2). Epub 2022 Jan 28.

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

: Balloon-occluded retrograde transvenous obliteration (BRTO) could be currently one of the best therapies for patients with gastric varices. This study examined the exacerbation rates for esophageal varices following BRTO for gastric varices in patients with hepatic cirrhosis. : We enrolled 91 cirrhotic patients who underwent BRTO for gastric varices. In total, 50 patients were examined for exacerbation rates of esophageal varices following BRTO. Esophageal varices and their associated exacerbation were evaluated by upper gastrointestinal endoscopy. Patients were allocated into two groups according to the main inflow tract for gastric varices: (1) 37 patients in the left gastric vein (LGV) group with an LGV width of more than 3.55 mm, and (2) 13 patients in the non-LGV group who had short gastric vein or posterior gastric vein. Moreover, treatment outcomes were retrospectively analyzed. : LGV width ( < 0.01) was the major risk factor for the deterioration of esophageal varices post BRTO. In addition, LGV was the most common inflow tract, and the LGV group contained 74% (37/50) of patients. The exacerbation rates of esophageal varices at 1, 2, 3, and 4 years post BRTO were 40%, 62%, 65%, and 68%, respectively. The comparison of the exacerbation rates for esophageal varices following BRTO according to inflow tract showed that the exacerbation rates were significantly higher in the LGV group than those of the non-LGV group ( = 0.03). In more than half of the subjects, LGV was the main inflow tract for gastric varices, and this group experienced more frequent exacerbations of esophageal varices following BRTO compared to patients with different inflow tract sources. : Careful attention should be paid to the LGV width when BRTO is performed for gastric varices.
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http://dx.doi.org/10.3390/medicina58020205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8875323PMC
January 2022

Efficacy and timing of gastrografin administration after ileus tube insertion in patients with adhesive small bowel obstruction.

Arab J Gastroenterol 2022 Feb 1;23(1):45-51. Epub 2022 Feb 1.

Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1, Oyaguchikami-cho, Itabashi-ku, Tokyo 173-8610, Japan. Electronic address:

Background And Study Aims: Gastrografin administration (GA) is performed for adhesive small bowel obstruction (ASBO) in cases when decompression therapy using an ileus tube fails to relieve the obstruction. This study evaluated the efficacy of GA and optimized its timing after ileus tube insertion.

Patients And Methods: In this retrospective study, we evaluated data from patients with ASBO admitted between January 2014 and August 2018 and included patients who underwent ileus tube intubation and GA. The patients were classified as those treated with GA within 48 h after admission (early GA [EGA]) and those treated later with GA (delayed GA [DGA]). Propensity score matching was performed to compensate for differences between the groups. Short-term outcomes were compared between the two groups.

Results: We included 67 and 80 patients in the EGA and DGA groups, respectively, and 55 pairs with similar background characteristics were matched. The rates of successful conservative management were 87.3% (48/55) in the EGA group, 96.4% (53/55) in the DGA group, and 91.8% (101/110) in the entire sample. The median period of ileus tube insertion in the DGA group was significantly lower than that in the EGA group, whereas other outcomes did not significantly differ between the groups. Aspiration pneumonia occurred in one patient in the EGA group.

Conclusions: GA with an ileus tube achieved a high rate of successful conservative management. Follow-up using decompression with an ileus tube for at least 48 h after admission is recommended in patients with ASBO.
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http://dx.doi.org/10.1016/j.ajg.2021.12.004DOI Listing
February 2022

Comparison of local recurrence in transcatheter arterial chemoembolization of hepatocellular carcinoma with or without accumulation of iodized oil beyond corona enhancement area: Short-term results.

Radiol Oncol 2021 12 22;56(1):69-75. Epub 2021 Dec 22.

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

Background: Local tumor recurrence of hepatocellular carcinoma (HCC) often occurs in blood drainage areas. Corona enhancement is determined by computed tomography during hepatic arteriography (CTHA) and is considered to represent the blood drainage area. This study aimed to investigate the relationship between embolization of corona enhancement area and local tumor recurrence of patients with HCC who underwent transcatheter arterial chemoembolization (TACE).

Patients And Methods: The study retrospectively selected 53 patients with 60 HCC nodules that showed corona enhancement area on late-phase CTHA and showed homogenous accumulation of iodized oil throughout the nodule on non-contrast-enhanced CT performed immediately after TACE. We divided the nodules into two groups, according to whether the accumulation of iodized oil covered the entire corona enhancement area (group A) or not (group B). Local tumor recurrence was compared between the two groups.

Results: The cumulative local tumor recurrence rates for group A (n = 36) were 2.8%, 2.8%, 8.3% at 3, 6, and 12 months, respectively, whereas the recurrence rates for group B (n = 24) were 20.8%, 45.8%, 75% at 3, 6, and 12 months, respectively. The cumulative local tumor recurrence rates for group A were significantly lower than those for group B (hazard ratio, 0.079; 95% confidence interval, 0.026-0.24; < 0.001).

Conclusions: The results of the study suggest that the corona enhancement area may be an accurate safety margin in TACE which should be performed until the embolic area covers the entire corona enhancement area.
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http://dx.doi.org/10.2478/raon-2021-0047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8884859PMC
December 2021

Efficacy of Glecaprevir/Pibrentasvir for Real-World HCV Infected Patients in the Northern Part of Tokyo, Japan.

J Clin Med 2021 Nov 26;10(23). Epub 2021 Nov 26.

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

Hepatis virus C (HCV) infection causes liver cirrhosis and hepatocellular carcinoma (HCC) worldwide. The objective of our study was to examine the effects of the HCV nonstructural protein (NS) 3/4A inhibitor glecaprevir/NS5A inhibitor pibrentasvir on real-world HCV patients in the northern part of Tokyo, Japan. Although 106 patients were consecutively included, a total of 102 HCV-infected patients with chronic hepatitis or compensated cirrhosis, who received 8- or 12-week combination treatment with glecaprevir/pibrentasvir and were followed up to week 12 after the end of treatment were analyzed retrospectively. Only three patients discontinued treatment due to adverse events; however, they achieved a sustained virologic response at 12 weeks (SVR12). Finally, SVR rates were 99.0% (101/102). Only one patient without liver cirrhosis was a treatment relapser who received hepatic resection for HCC approximately two years after commencement of the 8-week combination treatment with glecaprevir/pibrentasvir. After the exclusion of patients with HCV genotype 1b and P32 deletion in the HCV NS5A region, a 12-week combination of glecaprevir/pibrentasvir led to SVR12 in all nine direct-acting antiviral-experienced patients. Glecaprevir/pibrentasvir had a high efficacy and an acceptable safety profile for real-world HCV patients in a single hospital in Japan.
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http://dx.doi.org/10.3390/jcm10235529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8658140PMC
November 2021

A proposed model on MR elastography for predicting postoperative major complications in patients with hepatocellular carcinoma.

BJR Open 2021 24;3(1):20210019. Epub 2021 Nov 24.

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

Objective: To develop a model for predicting post-operative major complications in patients with hepatocellular carcinoma (HCC).

Methods: In all, 186 consecutive patients with pre-operative MR elastography were included. Complications were categorised using Clavien‒Dindo classification, with major complications defined as ≥Grade 3. Liver-stiffness measurement (LSM) values were measured on elastogram. The indocyanine green clearance rate of liver remnant (ICG-Krem) was based on the results of CT volumetry, intraoperative data, and ICG-K value. For an easy application to the prediction model, the continuous variables were converted to categories. Moreover, logistic regression analysis and fivefold cross-validation were performed. The prediction model's discriminative performance was evaluated using the area under the receiver operating characteristic curve (AUC), and the calibration of the model was assessed by the Hosmer‒Lemeshow test.

Results: 43 of 186 patients (23.1%) had major complications. The multivariate analysis demonstrated that LSM, albumin-bilirubin (ALBI) score, intraoperative blood loss, and ICG-Krem were significantly associated with major complications. The median AUC of the five validation subsets was 0.878. The Hosmer-Lemeshow test confirmed no evidence of inadequate fit ( = 0.13, 0.19, 0.59, 0.59, and 0.73) on the fivefold cross-validation. The prediction model for major complications was as follows: -2.876 + 2.912 [LSM (>5.3 kPa)]+1.538 [ALBI score (>-2.28)]+0.531 [Intraoperative blood loss (>860 ml)]+0.257 [ICG-Krem (<0.10)].

Conclusion: The proposed prediction model can be used to predict post-operative major complications in patients with HCC.

Advances In Knowledge: The proposed prediction model can be used in routine clinical practice to identify post-operative major complications in patients with HCC and to strategise appropriate treatments of HCC.
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http://dx.doi.org/10.1259/bjro.20210019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8611681PMC
November 2021

Immune Checkpoint Inhibitor as a Therapeutic Choice for Double Cancer: A Case Series.

Anticancer Res 2021 Dec;41(12):6225-6230

Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.

Background: Hepatocellular carcinoma (HCC) occasionally presents with simultaneous or metachronous primary malignancies of other organs. Despite the limited scope of cytocidal anticancer drugs or molecular targeted agents, immune checkpoint inhibitors (ICIs) can still be used for various malignancies. Here, we present cases of double cancers including HCC treated with ICIs.

Case Report: Case 1: A 70-year-old man with lung cancer and 80-mm HCC underwent nivolumab therapy. The sizes of both cancers remained constant for nine months. Case 2: A 58-year-old man with pharyngeal cancer and HCC. Nivolumab was administered, but was withdrawn after one session because of progressive disease. Case 3: A 71-year-old man with a 5 cm HCC invading the inferior vena cava, and early esophageal cancer. HCC showed a significant volume reduction and esophageal cancer demonstrated slight improvement by atezolizumab and bevacizumab therapy.

Conclusion: A combination therapy including ICI is a promising treatment option for HCC with concurrent malignancies.
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http://dx.doi.org/10.21873/anticanres.15442DOI Listing
December 2021

A Case of Pseudoprogression in Hepatocellular Carcinoma Treated With Atezolizumab Plus Bevacizumab.

J Investig Med High Impact Case Rep 2021 Jan-Dec;9:23247096211058489

Nihon University School of Medicine, Tokyo, Japan.

A 74-year-old man was diagnosed with hepatocellular carcinoma. The tumor in the liver showed a complete response after transcatheter arterial chemoembolization, but lung, bone, and lymph node metastases were observed, so treatment with atezolizumab plus bevacizumab was initiated. After administration, the scans showed tumor growth, but after continuous administration of atezolizumab plus bevacizumab, the tumors finally reduced in size and showed a partial response. The transient growth of the tumors was considered to be pseudoprogression. Herein, we report a case of pseudoprogression in hepatocellular carcinoma treated with atezolizumab plus bevacizumab.
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http://dx.doi.org/10.1177/23247096211058489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8637399PMC
December 2021

The Use of Electronic Medical Records-Based Big-Data Informatics to Describe ALT Elevations Higher than 1000 IU/L in Patients with or without Hepatitis B Virus Infection.

Viruses 2021 11 4;13(11). Epub 2021 Nov 4.

Department of Gastroenterology, Yamanashi Central Hospital, 1-1-1 Fujimi, Kofu, Yamanashi 400-8506, Japan.

Hepatitis B virus (HBV) infection is one of the serious health problems in the world as HBV causes severe liver diseases. Moreover, HBV reactivation has occasionally been observed in patients with resolved HBV infection and patients using immunosuppression and anticancer drugs. Large-scale hospital data focused on HBV infection and severe liver function were analyzed at our hospital, located in an urban area adjacent to Tokyo, the capital city of Japan. A total of 99,932 individuals whose blood samples were taken at 7,170,240 opportunities were analyzed. The HBV surface antigen (HBsAg)-positive group had a more frequent prevalence of patients with higher transaminase elevations than the HBsAg-negative group. However, among the HBsAg-negative group, patients who were positive for anti-HBV surface antibody and/or anti-HBV core antibody, had more severe liver conditions and fatal outcomes. More careful attention should be paid to alanine transaminase (ALT) elevations higher than 1000 IU/L in patients who had current and previous HBV infection.
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http://dx.doi.org/10.3390/v13112216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8624674PMC
November 2021

Diagnostic Ability of High-definition Imaging Using Ultraslim Endoscopes in Early Gastric Cancer.

J Gastric Cancer 2021 Sep 6;21(3):246-257. Epub 2021 Aug 6.

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

Purpose: It is unclear whether high-definition (HD) imaging improves visibility and diagnostic ability in early gastric cancer (EGC) compared with standard-definition (SD) imaging. We aimed to compare the diagnostic performance and visibility scores of HD and SD ultraslim endoscopes in EGC.

Materials And Methods: We used HD and SD ultraslim endoscopes to obtain 60 images with similar compositions of gastric environments. Of the 60 images, 30 showed EGC (15 images for each modality) and 30 showed no EGC (15 images for each modality). Seventeen endoscopists evaluated the presence and location of the lesions in each image. Diagnostic ability was compared between modalities. The color difference between a lesion and the surrounding mucosa (ΔE) was measured and compared between the modalities.

Results: The ability of HD to detect EGC was significantly higher than that of SD (accuracy: 80.8% vs. 71.6%, P=0.017; sensitivity: 94.9% vs. 76.5%, P<0.001; positive predictive value, 76.2% vs. 55.3%, P<0.001; and negative predictive value (NPV), 94.1% vs. 73.5%, P<0.001). The ability of HD to determine the horizontal extent of EGC was significantly higher than that of SD (accuracy: 71.0% vs. 57.8%, P=0.004; sensitivity: 75.3% vs. 49.0%, P<0.001; NPV, 72.9% vs. 55.9%, P<0.001; and area under the curve: 0.891 vs. 0.631, P=0.038). The mean ΔE was significantly higher for HD than for SD (10.3 vs. 5.9, P=0.011).

Conclusions: The HD ultraslim endoscope showed a higher diagnostic performance in EGC than the SD endoscope because it provided good color contrast.
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http://dx.doi.org/10.5230/jgc.2021.21.e23DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505118PMC
September 2021

Ileal Dieulafoy lesion arose 15 years after partial small bowel resection for meconium obstruction of the neonate: a case report.

BMC Pediatr 2021 10 7;21(1):437. Epub 2021 Oct 7.

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

Background: Anastomotic or perianastomotic ulcers present with symptoms such as chronic anaemia and occult bleeding as long-term complications of bowel resection performed in infancy.

Case Presentation: Herein, we describe a 15-year-old girl with a history of surgery for meconium obstruction without mucoviscidosis in infancy who was hospitalized with chief complaints of presyncope and convulsions. Seven hours after admission, she developed melena and went into shock. An emergency laparotomy was performed, and a Dieulafoy lesion was detected near the site of ileal anastomosis from the surgery that had been performed during infancy.

Conclusions: Although overt massive lower gastrointestinal bleeding necessitating emergency care is rare in the long term after infant bowel resection, Dieulafoy lesions can cause serious bleeding, requiring rapid life-saving haemostatic procedures.
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http://dx.doi.org/10.1186/s12887-021-02914-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494758PMC
October 2021

Follow-Up of Patients Who Achieved Sustained Virologic Response after Interferon-Free Treatment against Hepatitis C Virus: Focus on Older Patients.

Medicina (Kaunas) 2021 Jul 27;57(8). Epub 2021 Jul 27.

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

: Direct-acting antiviral agents (DAAs) have improved sustained virologic response (SVR) rates in patients with chronic hepatitis C virus (HCV) infection. Our aim was to elucidate the occurrence of hepatocellular carcinoma (HCC) and to compare the outcomes of patients aged 75 years or older (older group) with those of patients younger than 75 years (younger group) after SVR. : Among 441 patients treated with interferon-free DAA combinations, a total of 409 SVR patients were analyzed. We compared the two age groups in terms of HCC incidence and mortality rates. : Older and younger groups consisted of 68 and 341 patients, respectively. Occurrence of HCC after SVR did not differ between the two groups of patients with a history of HCC. Occurrence of HCC after SVR was observed more in younger patients without a history of HCC ( < 0.01). Although older patients without a history of HCC had a higher mortality rate ( < 0.01), their causes of death were not associated with liver diseases. Among younger patients without a history of HCC, none died. : After SVR, liver disease may not be a prognostic factor in older HCV patients without a history of HCC.
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http://dx.doi.org/10.3390/medicina57080761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399286PMC
July 2021

Genome-wide analysis of hepatitis B virus integration in hepatocellular carcinoma: Insights next generation sequencing.

Hepatobiliary Surg Nutr 2021 Aug;10(4):548-552

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

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http://dx.doi.org/10.21037/hbsn-21-228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350990PMC
August 2021

Celiac Disease Diagnosed after Gastrectomy for Gastric Cancer.

Intern Med 2022 Feb 30;61(3):323-328. Epub 2021 Jul 30.

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

Celiac disease is a systemic autoimmune disorder leading to manifestations of malabsorption syndrome. A 47-year-old Japanese man developed severe diarrhea after surgery for gastric cancer. The diarrhea persisted for seven months, leading to a state of malabsorption. Celiac disease was suspected based on small bowel capsule endoscopy findings. The duodenal findings observed during gastric cancer surgery were reassessed, and Marsh-Oberhuber classification type 3c celiac disease was diagnosed. The anti-tissue glutaminase antibody test results were positive. The patient was started on a gluten-free diet, following which the diarrhea resolved, and the nutritional status improved. Adjuvant therapy after gastric cancer surgery was initiated.
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http://dx.doi.org/10.2169/internalmedicine.7901-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8866787PMC
February 2022

Knockdown of Mitogen-Activated Protein Kinase Kinase 3 Negatively Regulates Hepatitis A Virus Replication.

Int J Mol Sci 2021 Jul 10;22(14). Epub 2021 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.

Zinc chloride is known to be effective in combatting hepatitis A virus (HAV) infection, and zinc ions seem to be especially involved in Toll-like receptor (TLR) signaling pathways. In the present study, we examined this involvement in human hepatoma cell lines using a human TLR signaling target RT-PCR array. We also observed that zinc chloride inhibited mitogen-activated protein kinase kinase 3 (MAP2K3) expression, which could downregulate HAV replication in human hepatocytes. It is possible that zinc chloride may inhibit HAV replication in association with its inhibition of MAP2K3. In that regard, this study set out to determine whether MAP2K3 could be considered a modulating factor in the development of the HAV pathogen-associated molecular pattern (PAMP) and its triggering of interferon-β production. Because MAP2K3 seems to play a role in antiviral immunity against HAV infection, it is a promising target for drug development. The inhibition of MAP2K3 may also prevent HAV patients from developing a severe hepatitis A infection.
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http://dx.doi.org/10.3390/ijms22147420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303476PMC
July 2021

Treatment Outcome of Nab-paclitaxel Plus Gemcitabine for Leptomeningeal Carcinomatosis from Pancreatic Ductal Adenocarcinoma: An Autopsy Case Report.

Intern Med 2021 Dec 19;60(23):3743-3748. Epub 2021 Jun 19.

Department of Gastroenterology, Narita Memorial Hospital, Japan.

A 57-year-old woman with a sudden-onset seizure was hospitalized. Brain magnetic resonance imaging findings led to a suspicion of leptomeningeal carcinomatosis (LMC) without a brain parenchymal tumor, and abdominal computed tomography showed a tumor in the pancreatic tail. Endoscopic ultrasonography-guided fine needle aspiration of the pancreatic mass revealed adenocarcinoma. Therefore, LMC from pancreatic ductal adenocarcinoma was strongly suspected. She received three courses of nab-paclitaxel plus gemcitabine and whole-brain radiation. Shortly thereafter, she developed a severe consciousness impediment and died. A pathological autopsy showed adenocarcinoma in a wide area of the leptomeninges.
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http://dx.doi.org/10.2169/internalmedicine.4456-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8710377PMC
December 2021

Ultrasonographic grayscale findings related to fibrosis in patients with non-alcoholic fatty liver disease: comparison with transient elastography and Fib-4 index.

J Med Ultrason (2001) 2021 Jul 16;48(3):323-333. Epub 2021 Jun 16.

Department of Pathology, Nihon University School of Medicine, 30-1 Oyaguchi Kamimachi, Itabashi-ku, Tokyo, 173-8610, Japan.

Purpose: Fibrosis is a predictor of mortality in patients with non-alcoholic fatty liver disease (NAFLD). In our institution, abdominal ultrasonography has been performed based on a unified method consisting of 25 images. We investigated ultrasonographic grayscale findings related to fibrosis in patients with NAFLD.

Methods: This retrospective study comprised 41 cases of pathologically proven fatty liver between January 2015 and September 2020. A total of 26 ultrasonographic findings were subjectively evaluated. These findings, transient elastography (TE) with M probe, and FIB-4 index were compared with fibrosis stage.

Results: The frequency of roughness of the dorsal side of the surface (p < 0.001), heterogenicity of the parenchyma (p = 0.003), narrowing of the hepatic vein (p = 0.004), and splenomegaly (p < 0.001) were strongly correlated with the fibrosis stage. Logistic regression analysis for stage ≥ 3 showed narrowing of the hepatic vein (odds ratio [OR] 5.860, p = 0.031) and splenomegaly (OR 6.290, p = 0.028). Logistic regression analysis for stage 4 showed roughness of the ventral side of the surface (OR 42.0, p = 0.019). The AUROC for stage 3 and stage 4 with the number of positive ultrasonographic findings was 0.856, and 0.940, respectively. The AUROC for F3 and F4 with TE was 0.831 and 0.861, respectively. The AUROC for stage 3 and stage 4 with FIB-4 index was 0.815 and 0.806, respectively.

Conclusions: Narrowing of the hepatic vein, roughness of the dorsal side of the surface, heterogenicity of the parenchyma, and splenomegaly and their combination could predict fibrosis in patients with NAFLD.
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http://dx.doi.org/10.1007/s10396-021-01107-0DOI Listing
July 2021

Occurrence of hepatitis in an elderly woman during the treatment of pembrolizumab for right advanced renal pelvis, ureteral cancer, and bladder cancer.

JGH Open 2021 Jun 6;5(6):722-724. Epub 2021 May 6.

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

Recently, the use of immune checkpoint inhibitors (ICIs) with or without chemotherapeutic agents has been increasing in the treatment for advanced cancer. Here, we report the occurrence of liver failure after the use of pembrolizumab in an 82-year-old woman with metastatic liver disease derived from right advanced renal pelvis, ureteral cancer, and bladder cancer. She was successfully treated with 0.6 mg/kg daily prednisolone. In patients treated with ICIs, ICI-induced hepatitis is occasionally observed. Even if patients are older, it appears important to diagnose and treat ICI-induced hepatitis earlier by multidisciplinary therapies including steroid treatment. This is a first report of pembrolizumab-induced liver failure in elder patient with age over 80 years. Even if patients are older, it appears important to diagnose and treat ICI-induced hepatitis earlier by multidisciplinary therapies including steroid treatment.
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http://dx.doi.org/10.1002/jgh3.12554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171158PMC
June 2021

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

J Med Ultrason (2001) 2021 Jul 9;48(3):315-322. 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
July 2021

Renal vein measurement using ultrasonography in patients with cirrhotic ascites and congestive heart failure.

J Med Ultrason (2001) 2021 Apr 25;48(2):225-234. Epub 2021 Mar 25.

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

Purpose: Ascites can cause compression of the inferior vena cava (IVC), leading to increased renal venous pressure and renal congestion. Previously, the left renal vein diameter in liver cirrhosis patients with ascites was measured using computed tomography, showing that enlargement of the left renal vein diameter affects the prognosis. Herein, the diameter and flow velocity of the renal veins were measured using ultrasonography.

Methods: Abdominal ultrasonography was performed on 186 patients. The patients were divided into four groups: normal liver (n = 102), liver cirrhosis (LC) without ascites (n = 37), LC with ascites (n = 30), and congestive liver (n = 17). Ultrasonographic measurements for diameter and flow velocity of the IVC, left renal vein main trunk, and segmental renal vein were performed.

Results: The left renal vein diameter increased in the following order: normal liver, LC, LC with ascites, and congestive liver groups (P < 0.001). IVC flow velocity was lower and left renal vein diameter was larger in the congestive liver and LC with ascites groups. These results suggest that the two groups have different pathological conditions, but the mechanism of renal congestion is similar. In patients with LC, IVC compression due to ascites might cause blood stagnation and renal congestion.

Conclusion: The left renal vein and IVC can be measured using ultrasonography. It might help in furthering our understanding of the pathophysiology of renal congestion in these patients.
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http://dx.doi.org/10.1007/s10396-021-01088-0DOI Listing
April 2021

Magnetic resonance elastography-based prediction of hepatocellular carcinoma recurrence after curative resection.

Surgery 2021 07 19;170(1):167-172. Epub 2021 Mar 19.

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

Background: Liver stiffness measurement using magnetic resonance elastography can assess the severity of liver fibrosis, which is significantly associated with recurrence after curative resection for hepatocellular carcinoma. The aim of this prospective study was to investigate whether preoperative liver stiffness measurement by magnetic resonance elastograhy can predict recurrence after curative resection for hepatocellular carcinoma.

Methods: Patients who underwent preoperative liver stiffness measurement and curative resection for hepatocellular carcinoma were enrolled in this study. Potential associations between liver stiffness measurement, along with other clinical and pathologic variables, and intrahepatic hepatocellular carcinoma recurrence were analyzed.

Results: In total, 156 patients were included in this study. During a median follow-up period of 25.1 months (range, 6.0-60.5 months), 72 (46.1%) patients with hepatocellular carcinoma had an intrahepatic recurrence. The median disease-free period after resection was 17.9 months (range, 1.0-60.5 months). In the multivariate analysis, liver stiffness measurement (hazard ratio, 1.27; 95% confidence interval, 1.11-1.43; P <.001) and vascular invasion (hazard ratio, 1.96; 95% confidence interval, 1.15-3.25; P = .013) were identified as independent predictors of recurrence. When the optimal cutoff point was set at 4.53 kPa using the minimal P value approach, the disease-free period after curative resection in 71 patients with a liver stiffness measurement value ≥4.53 kPa (11.3 months [range, 2.0-60.5 months]) was significantly shorter than that of 85 patients with a liver stiffness measurement value <4.53 kPa (22.5 months [range, 1.1-60.5 months]; P <.001).

Conclusion: Liver stiffness measurement using magnetic resonance elastography is a useful preoperative predictor of intrahepatic recurrence after curative resection for hepatocellular carcinoma.
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http://dx.doi.org/10.1016/j.surg.2021.02.027DOI Listing
July 2021

Predictive value of combined computed tomography volumetry and magnetic resonance elastography for major complications after liver resection.

Abdom Radiol (NY) 2021 07 8;46(7):3193-3204. Epub 2021 Mar 8.

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

Purpose: To retrospectively compare the predictive value of computed tomography volumetry (CTV), magnetic resonance elastography (MRE) of the liver, and their combination for major complications after liver resection.

Methods: We enrolled 108 consecutive patients who underwent anatomical liver resection for liver tumors and preoperative contrast-enhanced CT and MRE. The future liver remnant (FLR) ratio was calculated by CTV, while the liver stiffness measurement (LSM) was obtained by MRE. FLR ratio alone, LSM alone, and combined FLR ratio and LSM were evaluated to predict major complications (Clavien-Dindo grade ≥ IIIa). Univariate and multivariate analyses of hepatic biochemical parameters and imaging data were performed to identify predictors of major complications. Receiver operating characteristic analyses of FLR ratio, LSM, and their combination were performed, and the sensitivity and specificity were calculated.

Results: Twenty-two (20.4%) of the 108 patients experienced major complications. According to multiple regression analysis, the FLR ratio (odds ratio [OR] 0.96, 95% confidence interval [CI] 0.91-0.99, p = 0.040) and LSM (OR 1.72, 95% CI 1.01-2.94, p = 0.047) were independent predictors of major complications. The combined FLR ratio and LSM were predictive of major complications, with an area under the curve (AUC) of 0.818, sensitivity of 68.2%, and specificity of 84.9%. The AUC and specificity for combined FLR ratio and LSM were larger than those for FLR ratio (AUC: 0.711, specificity: 80.2%) and LSM (AUC: 0.793, specificity: 80.2%).

Conclusion: Combined CTV and MRE analysis can improve the AUC and specificity for predicting major complications after anatomical liver resection.
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http://dx.doi.org/10.1007/s00261-021-02991-3DOI Listing
July 2021

Male-Dominant Hepatitis A Outbreak Observed among Non-HIV-Infected Persons in the Northern Part of Tokyo, Japan.

Viruses 2021 01 29;13(2). Epub 2021 Jan 29.

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

Recently, we experienced an outbreak of acute hepatitis A virus (HAV) infection between 2018 and 2020. Herein, we describe this male-dominant HAV infection outbreak observed among non-human immunodeficiency virus (HIV)-infected persons in the northern part of Tokyo, Japan. Clinical information was collected from patient interviews and from medical record descriptions. In the present study, 21 patients were retrospectively analyzed. A total of 90.4 and 33.3% of patients were males, and men who have sex with men (MSM), respectively. The total bilirubin levels and platelet counts tended to be lower in the MSM group than in the non-MSM group. C-reactive protein (CRP) levels tended to be higher in acute liver failure (ALF) patients than in non-ALF patients. Prolonged cholestasis was observed in one patient (4.8%). We also found that 18 HAV isolates belonged to HAV subgenotype IA/subgroup 13 (S13), which clustered with the HAV isolate (KX151459) that was derived from an outbreak of HAV infection among MSM in Taiwan in 2015. Our results suggest that the application of antivirals against HAV, as well as HAV vaccines, would be useful for the treatment and prevention of severe HAV infection.
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http://dx.doi.org/10.3390/v13020207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910831PMC
January 2021

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

Intern Med 2021 Jul 1;60(13):2061-2066. 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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313908PMC
July 2021
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