111

Advanced Clinical Research Center

Division of Infectious Diseases
感染症分野

Professor
Project Senior Assistant Professor
Assistant Professor
Assistant Professor
Assistant Professor

Hiroshi Yotsuyanagi, M.D., D.M.Sc.
Michiko Koga, M.D., D.M.Sc.
Makoto Saito, M.D., D.Phil.
Aya Ishizaka, Ph.D.
Yoshiaki Kanno, M.D., D.M.Sc.

教 授
特任講師
助 教
助 教
助 教

博士（医学）
博士（医学）
博士（医学）
博士（理学）
博士（医学）

四
古
齋
石
菅

柳
賀
藤
坂
野

道
芳

宏
子
真
彩
明

Our overall goal is medical sciences on infectious diseases in two directions, fromclinic to bench and from bench to clinic. Our main subjects have been the
immunopathogenesis of HIV-1 infection in addition to other viruses, especiallyhepatitis viruses. Since the emergence of SARS-CoV2, we started the basic andclinical research using clinical samples obtained from SARS-CoV2-infected patients
admitted to the IMSUT Hospital, to settle down COVID-19.

1.  Clinical research of COVID-19
Eisuke Adachi1, Amato Ohtani1, Kazuhiko Ikeuchi1,
Yoshiaki Kannno, Makoto Saito, Michiko Koga, Hiroshi Yotsuyanagi
1
Department of Infectious Diseases and Applied Immunology, IMSUT hospital, IMSUT
Since the emergence and spread of SARS-CoV-2 inJapan at the beginning of 2020, numerous COVID-19
patients have been admitted to IMSUT Hospital. To
date, over 800 patients with COVID-19 have been admitted to our hospital. Through the observation ofthese patients, we have encountered numerous clinical questions and conducted investigations into various factors, including patients’ backgrounds, clinicalfindings, and laboratory data. Our research has yielded several novel and compelling findings, which wehave published in international journals. Moreover,
five clinical trials on COVID-19 were conducted at
IMSUT Hospital, generating valuable evidence aimed
at enhancing both national and global health. In 2023,
in Japan, patients with COVID-19 were no longer legally required to be isolated, resulting in a huge reduction in the number of hospitalized patients at ourfacility. However, towards the end of the year, thenumber of patients began to increase once more,
prompting the need for us to prepare for a potential
resurgence or the emergence of a new pandemic.
2.  Basic research for the control of COVID-19
Michiko Koga, Makoto Saito, Amato Ohtani1, Kazuhiko Ikeuchi1, Eisuke Adachi1, Shinya Yamamoto,Takeya Tsutsumi, Aya Ishizaka, Taketoshi Mizutani2, Ai Tachikawa-Kawana3, Ken Ishii4, Yoshihiro
Kawaoka5, Hiroshi Yotsuyanagi
2
Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences,
The University of Tokyo
3
AIDS Research Center, National Institute of Infectious Diseases
4
Division of Vaccine Science, IMSUT
5
Division of Virology, IMSUT
Several laboratories at IMSUT and external institutes have continued COVID-19-related research during 2022, and we have been working in collaboration
with some of these laboratories. Our main mission is
to obtain and share clinical samples from COVID-19

112
patients, but we are also conducting basic research byourselves such as microbiomes in those patients. Additionally, we are attempting to perform high-resolution transcriptomic analysis of blood immune cells
from disease progression to recovery in COVID-19 toenhance a better understanding of the protective andpathogenic immune responses of the disease. Specifically, we are performing gut microbiome analysis as
well as single-cell RNA sequencing (scRNA-seq) toobtain a bias-free and comprehensive imaging of immune responses in peripheral blood mononuclear
cells (PBMCs) from patients with COVID-19. We also
ran an analysis of changes in the nasal microbiome
after COVID-19 vaccination.
3.  Analysis of genetic sequence of hepatitis viruses.
Ayako Sedohara, Kazuaki Takahashi, Yoshiaki
Kanno, Makoto Saito, Kazuhiko Ikeuchi1, Eisuke
Adachi1, Michiko Koga, Takeya Tsutsumi, Hiroshi
Yotsuyanagi
Of the hepatitis viruses, HAV and HEV are transmitted orally, HAV mainly from marine products and
HEV from meat of wild animals such as deer andpork liver. Both HAV and HEV are found in large
quantities in stools, but there have been few cases ofhuman-to-human transmission of HEV in Japan. On
the other hand, HAV can be sexually transmitted,
with epidemics occurring through fecal-oral transmission. Isolation of viral RNA from patient bloodand stool, quantification of copy number, and sequencing to determine genotype and mutation are
extremely important to understand the characteristics
of epidemic strains, such as virulence and drug resistance, and to use them for treatment. In this laboratory, analyses are being conducted using specimensfrom HAV or HEV-infected patients collected fromvarious regions. At the same time, we are verifying
whether HAV or HEV infection is present in specimens of unidentified hepatitis in which infection with
HBV or HCV, which also cause hepatitis, has been
ruled out.
4. Evaluation of the efficacy of HA vaccine for
HIV-MSM and analysis of NAFLD in HIV-infected patients
Michiko Koga, Makoto Saito, Megumi Kubota, Tomoe Senkoji, Eisuke Adachi1, Kazuhiko Ikeuchi1,
Tadashi Kikuchi1, Amato Otani1, Kazuaki Takahashi, Takeya Tsutsumi, Hiroshi Yotsuyanagi
Hepatitis A (HA) is a vaccine-preventable disease.
In regions with good sanitation, men who have sex
with men (MSM) are the key affected populations.
During the 2018–2019 HA outbreak among MSM in
Japan, we actively vaccinated MSM living with hu-

man immunodeficiency virus (MSM-LWHIV) with
Aimmugen®. As previously reported, their antibody
seroconversion rate due to vaccination was lower
than that of healthy individuals. We evaluated attenuation after the one-series vaccination (comprising
three inoculations) and the factors associated with attenuation. We retrospectively examined anti-HA-IgG
titers and other clinical data from our hospital’s medical records. Fifty-one MSM-LWHIV were included.
All were seropositive after the third dose with a median HA-IgG titer of 10.1 (interquartile range: 7.2–12.2)
s/co. In 45 (40–49) months, seropositivity decreased to90% (46/51) and was attenuated to a median of 4.4(2.3–6.5) s/co. Lower baseline B cell counts (p=0.049),
lower anti-HA-IgG levels after the second dose
(p=0.002), and lower anti-HA-IgG levels after thethird dose (p=0.003) were associated with seronegativity. Anti-HA-IgG titers of vaccinated MSM-LWHIV
may be attenuated; thus, additional immunizations
should be considered.
Now, we have started to evaluate NAFLD and
MAFLD of LWHIV. Of the 102 LWHIV, the prevalence of NAFLD was estimated to be 53.9% from theelastography CAP value, and 7.8% were suspected ofprogressing fibrosis and immediate improvement inmetabolic risk factors as desired. We are also conducting research from the perspective of the microbiome.
5. Characteristics of Transmitted Drug-ResistantHIV-1 in Recently Infected Treatment-Naive Patients in Japan.
Michiko Koga, Kazuhiko Ikeuchi1, Eisuke Adachi1,
Tadashi Kikuchi1, Takeya Tsutsumi, Hiroshi Yotsuyanagi
Progress in antiretroviral treatment has led to fewer virological failure cases, but about 10% of treatment-naive HIV/AIDS cases are reported to harbordrug-resistant strains (RS), suggesting transmissionof drug-resistant HIV. We have determined the trend
in the prevalence of transmitted drug-resistant (TDR)
HIV in Japan from 2003.
Drug-resistance tests had been performed on nationwide HIV-1-infected cases newly diagnosed. The
overall prevalence of TDR was about 10.4% in 2022.
6.  Exploratory research of the malignancy with
HIV-infected hemophilia patients
Michiko Koga, Takahiro Tanaka, Aya Ishizaka,
Akari Fukuda, Takashi Hosaka1, Hiroshi Yotsuyanagi,
It is speculated that hemophilia who were infectedwith HIV through contaminated blood products produced in the US before 1986 are at a higher risk ofdeveloping malignancies because of aging and immune dysfunction. Since April 2021, we have initiated113
this research with the following four objectives. 1.
Construction and operation of a system design for ahealth examination. 2. Medical support at the time ofdiagnosis of malignancy and after diagnosis. 3. Mental care associated with malignancy. 4. Public relations regarding support and diseases.
We also reported that HIV-infected patients suffered much stress under the COVID-19 pandemic.
7. Characterization of mutations in HBV isolated
from HBsAg-positive blood donors in Japan.
Ayako Sedohara, Kazuaki Takahashi, Yoshiaki
Kanno, Kazuhiko Ikeuchi1, Eisuke Adachi1, Takeya
Tsutsumi, Hiroshi Yotsuyanagi
In Japan, routine HBV vaccination began in 2016
for children aged 0 years. The HBV vaccine targets thehydrophilic amino acids in the S-region of the HBV
epitope. Mutations in the DNA sequence of this S-region can cause amino acid substitutions. The aminoacid substitution causes a drop in the titer of antibodies to HBV produced by the vaccine, which is called a
vaccine escape mutation. In Japan, the rate of infection with HBV is low and few people over the age of
8 have antibodies against HBV because few people
have been vaccinated against it. However, if the number of people with antibodies against HBV increases
in the future due to vaccination, the number of HBVwith antibodies resistant to HBV may increase. It isvery important to regularly monitor the prevalence of
HBV in Japan. In this study, blood donations that tested positive for HBsAg are collected, HBV DNA is isolated, HBV copy number is examined, and genotypes
and mutations are analyzed by whole genome sequence. As a result, we are detecting vaccine escapemutations and mutations that confer resistance totherapeutic drugs for hepatitis B. Drug resistance mutations are important for the treatment of acute andchronic hepatitis and should continue to be monitored closely. This study provides a baseline for future HBV epidemic strain trends.
8. Identification of HIV-associated neurocognitive disorder (HAND) biomarker from HIV-infected individuals presenting with neuropathy.
Ayako Sedohara, Kotaro Arizono, Hiroshi Yotsuyanagi
Antiviral drugs suppress the growth of HIV, allowing HIV-infected people to live the same life as
healthy people. Because HIV is a retrovirus with reverse transcriptase, the HIV gene is incorporated into
the host genome. Even though antiviral drugs can
suppress viral production, the HIV provirus incorporated into the genome cannot be eliminated, andchronic inflammation is known to persist in HIV patients. Various complications are known to result

from this chronic inflammation, among which
HIV-associated neurocognitive disorder (HAND) significantly affects the quality of life of patients. On theother hand, HAND cannot be detected by common
dementia tests, so a diagnosis requires a combinationof several psychological tests. It is against this background that testing for HAND is not performed unless the physician determines that HAND is suspected or the patient does not want to be tested. A
biomarker that would allow HAND to be diagnosed
with a minimally invasive blood test is desired. In thisstudy, we identified several candidate HAND biomarkers from plasma of HIV patients. In the future,
we will develop a method to test them as HAND biomarkers in clinical tests.
9. Identification of drugs which reactivate latentHIV-1 reservoir
Ayako Sedohara, Michiko Koga, Makoto Saito, Kazuhiko Ikeuchi1, Eisuke Adachi1, Tomohiko Koibuchi1, Hiroshi Yotsuyanagi
The eradication of HIV provirus from HIV-infected patients is a crucial for curing HIV. A populationof HIV-infected CD4 T-cells represents a latent infection, or reservoir. The latently infected cells can bereactivated by treatment with an latency reversing
agent (LRA), allowing eradication by the host immune system, also termed the kick-and-kill strategy.
It has been reported that histone acetyltransferase inhibitor SAHA strongly reactivates latent HIV reservoir. Using CD4 T-cells derived from HIV-infectedindividuals, we tried to identify novel chemical compounds that act as an LRA. Consequently, we identified that valemetostat/DS-3201/(R)-OR-S2, novel enhancer of zeste homolog 1/2 (EZH 1/2) dual inhibitor,
acts as an LRA. EZH2 is a component of polycomb
repressive complex 2 (PRC2) and functions as a methyltransferase. EZH2 methylates lysine 27 on histone
H3 protein (H3K27). Tri-methylated H3K27(H3K27me3) marks the gene silencing region and ismainly observed around the 5’LTR, the transcriptional regulatory region, in latently infected HIV-1 cells.
EZH2 is involved in the maintenance of HIV-1 latency. Treatment of HIV-1 latently infected cells with valemetostat reversed latency in vitro and ex vivo in adose- and duration-dependent manner at levels similar to SAHA. Furthermore, co-administration of
SAHA with valemetostat showed an additive effecton latency reversal.
10. Analysis of the HIV-associated gut microbiome
Aya Ishizaka, Michiko Koga, Taketoshi Mizutani2,
Eisuke Adachi1, Tetsuro Matano3,6, Hiroshi Yotsuyanagi
6
Department of AIDS Vaccine Development, IMSUT Hspital, IMSUT114
Loss of gut mucosal barrier function persists during HIV infection and allows translocation of gut-derived bacteria as well as microbial products into circulation. We reported the relevance between gut
dysbiosis and chronic inflammation in people livingwith HIV infection (PLWH). We are currently analyzing gut microbiota alterations longitudinally to further elucidate the causal relationship between
HIV-specific gut microbiota dysbiosis and the incidence of age-related diseases in PLWH.
11. Clinical epidemiology of malaria in pregnancy
Makoto Saito
Malaria stands as the primary cause of mortality
in tropical regions, with pregnant women being especially vulnerable. Malaria during pregnancy has detrimental effects on both the mother and fetus. As partof a global collaboration with colleagues in sub-Saharan Africa and Asia, we conducted a pooled meta-analysis of clinical data to evaluate the safety of
antimalarials during pregnancy. This research supported the revision of malaria guidelines by theWorld Health Organization and by the US CDC. Currently, we are engaged in new projects focusing on
the pharmacoepidemiology of antimalarials during
pregnancy.
12. Analysis of rifaximin effect on the small intestinal microbiome
Kazuhiko Ikeuchi1, Takeya Tsutsumi, Aya Ishizaka,
Taketoshi Mizutani2, Ayako Sedohara, MichikoKoga, Satoru Tamaoki7, Hiroshi Yotsuyanagi
7
Medical Affairs Department, ASKA Pharmaceutical Co., Ltd.
Rifaximin is a poorly absorbed broad-spectrum
antibiotic used for hepatic encephalopathy, but rifaximin does not alter the stool microbiota. Because theantimicrobial effect of rifaximin increases by micellization with bile acids, we hypothesized that rifaximin
alters the microbiota in the duodenum and jejunum,
where bile acids are abundant. Using CCl4-induced

liver fibrosis mice, we showed that rifaximin decrease
Lactobacillaceae in the duodenum and jejunum,
which is known to increase in patients with hepatic
encephalopathy. Rifaximin may exert its effect by altering the duodenal and jejunal microbiota. Thechanges in the duodenal and small intestinal microbiota were not associated with that of stool, suggestingthat the analysis of stool microbiota is insufficient toevaluate upper intestinal microbiota.
13. Analysis of transmission route of HCV among
HIV patients
Kazuhiko Ikeuchi1, Kazuya Okushin8, Makoto Saito, Eisuke Adachi1, Michiko Koga, Takeya Tsutsumi
Tomoyuki Takura9, Hiroshi Yotsuyanagi
9Department of Healthcare Economics and Health
Policy, Graduate School of Medicine, The University of Tokyo
Hepatitis C virus (HCV) has been mainly transmitted through injection drug use, but recently, sexual transmission among men who have sex with men(MSM), which is also a major route of HIV transmission, is increasing. However, the prevalence of HIV
and the incidence of other sexually transmitted infections (STIs) among HCV patients have been rarely reported. Using a healthcare insurance claim data of
employees and their dependents covering seven-million people in Japan, we evaluated HIV prevalence
among HCV patients. HIV prevalence among young
male HCV patients was very high in Tokyo. HCV/HIV co-infected patients were more likely to acquire
HIV before HCV, which is a known feature of MSM.
They also had a higher incidence of STIs. These findings suggest that HCV might be prevalent as an STI
among MSM particularly in Tokyo.
We also analyzed the long-term incidence of HCVamong people living with HIV (PLWH) in the IMSUT
hospital. In the multivariable analysis, MSM, IDU,
and syphilis infection during study period were associated with HCV incidence, suggesting that HCV
could be transmitted by both injection drug and sexual contact.

Publications
1.		Ishizaka A, Koga M, Mizutani T, Yamayoshi S,
Iwatsuki-Horimoto K, Adachi E, Suzuki Y, Kawaoka Y, Yotsuyanagi H. Association of gut microbiota with the pathogenesis of SARS-CoV-2 Infection in people living with HIV. BMC Microbiol.
24:6. 2024
2.		Adachi E, Saito M, Otani A, Koga M, Yotsuyanagi
H. Favorable virological outcome, characteristics
of injection site reactions, decrease in renal function biomarkers in Asian people with HIV receiv-

ing long-acting cabotegravir plus rilpivirine. AIDSRes Hum Retroviruses. doi: 10.1089/AID.2023.0108.
2024
3.		Kado A, Tsutsumi T, Yotsuyanagi H, Ikeuchi K,
Okushin K, Moriya K, Koike K, Fujishiro M. Differential peripheral memory T cell subsets sensitively indicate the severity of non-alcoholic fatty
liver disease. Hepatol Res. doi: 10.1111/hepr.14009.
2023
4.		Uraki R, Kiso M, Iwatsuki-Horimoto K, Yamay-

115
oshi S, Ito M, Chiba S, Sakai-Tagawa Y, Imai M,
Kashima Y, Koga M, Fuwa N, Okumura N, Hojo
M, Iwamoto N, Kato H, Nakajima H, Ohmagari N,
Yotsuyanagi H, Suzuki Y, Kawaoka Y. Characterization of a SARS-CoV-2 EG.5.1 clinical isolate invitro and in vivo. Cell Rep. 42(12):113580. 2023
5.		Adachi E, Owada R, Sato S, Kono M, Yotsuyanagi
H. Febrile gluteal inflammation evident on imaging findings after long-acting cabotegravir administration. Clin Infect Dis. doi: 10.1093/cid/ciad705.
2023
6.		Ikeuchi K, Saito M, Adachi E, Koga M, Okushin K,
Tsutsumi T, Yotsuyanagi H. Injection drug use andsexually transmitted infections among men who
have sex with men: A retrospective cohort study at
an HIV/AIDS referral hospital in Tokyo, 20132022. Epidemiol Infect. 151:e195. 2023
7.		Takahashi R, Matsubara Y, Takahashi S, Yokoyama
K, Ahyoung LL, Koga M, Sakamoto H, Boku N,
Shida D, Yotsuyanagi H. Refractory Intestinal Behçet-Like Disease Associated with Trisomy 8 Myelodysplastic Syndrome Resolved by Parenteral
Nutrition. Case Rep Gastroenterol. 17(1):287-293.
2023
8.		Koga M, Iwatsuki-Horimoto K, Kikuchi T, Yamayoshi S, Kawaoka Y, Yotsuyanagi H. Previous omicron infection may be protective against reinfection with omicron variant BA.5 for at least 5months.Clin Microbiol Infect. 29(1):120-121, 2023
9.		Kanda T, Sasaki-Tanaka R, Ishii K, Suzuki R, Inoue
J, Tsuchiya A, Nakamoto S, Abe R, Fujiwara K,
Yokosuka O, Li TC, Kunita S, Yotsuyanagi H, Okamoto H; AMED HAV and HEV Study Group. Recent advances in hepatitis A virus research andclinical practice guidelines for hepatitis A virus
infection in Japan. Hepatol Res. doi: 10.1111/
hepr.13983. 2023
10.	Hidaka M, Eguchi S, Hasegawa K, Shimamura T,
Hatano E, Ohdan H, Hibi T, Hasegawa Y, Kaneko
J, Goto R, Egawa H, Eguchi H, Tsukada K, Yotsuyanagi H, Soyama A, Hara T, Takatsuki M. Impact
of sustained viral response for hepatitis C virus on
the outcomes of liver transplantation in hemophilic patients with human immunodeficiency virus/
hepatitis C virus co-infection: A nationwide survey in Japan. Hepatol Res. 53(1):18-25, 2023
11.	Ikeda M, Okugawa S, Kashiwabara K, Moritoyo T,
Kanno Y , Jubishi D, Hashimoto H, Okamoto K,
Tsushima K, Uchida Y, Mitsumura T, Igari H,
Tsutsumi T, Araoka H, Yatera K, Yamamoto Y, Nakamura Y, Otani A, Yamashita M, Wakimoto Y,
Shinohara T, Adachi-Katayama M, Oyabu T,
Kanematsu A, Harada S, Takeshita Y, Nakano Y,
Miyazaki Y, Sakao S, Saito M, Ogura S, Yamasaki
K, Kawasuji H, Hataji O, Inoue JI, Seto Y, Moriya
K. Multicenter, Single-Blind, Randomized Controlled Study of the Efficacy and Safety of Favipiravir and Nafamostat Mesilate in Patients with
COVID-19 Pneumonia. Int J Infect Dis. S1201-

9712(22)00684-1, 2023. Epub ahead of print.
12.	Uraki R, Ito M, Kiso M, Yamayoshi S, IwatsukiHorimoto K, Sakai-Tagawa Y, Imai M, Koga M,
Yamamoto S, Adachi E, Saito M, Tsutsumi T, Otani
A, Fukushi S, Watanabe S, Suzuki T, Kikuchi T,
Yotsuyanagi H, Maeda K, Kawaoka Y. Antiviralefficacy against and replicative fitness of an
XBB.1.9.1 clinical isolate. iScience. 26(11):108147.
2023
13.	Suzuki T, Taniguchi Y, Komiyama J, Kuno T,
Adomi M, Abe T, Inokuchi R, Miyawaki A, Imai S,
Saito M, Ohbe H, Aso S, Kamio T, Tamiya N, Iwagami M. Characteristics and in-hospital mortalityof patients with COVID-19 from the first to fifth
waves of the pandemic in 2020 and 2021 in the Japanese Medical Data Vision database. Heliyon.
9(9):e19490. 2023
14.	Kingstad-Bakke B, Cleven T, Bussan H, Yount BL
Jr, Uraki R, Iwatsuki-Horimoto K, Koga M,
Yamamoto S, Yotsuyanagi H, Park H, Mishra JS,
Kumar S, Baric RS, Halfmann PJ, Kawaoka Y,
Suresh M. Airway surveillance and lung viral control by memory T cells induced by COVID-19
mRNA vaccine. JCI Insight. 8(22):e172510. 2023
15.	Ikeuchi K, Fukushima K, Tanaka M, Yajima K, Saito M, Imamura A. Changes in rapid plasma reagin
titers in patients with syphilis before and after
treatment: A retrospective cohort study in an HIV/AIDS referral hospital in Tokyo. PLoS One. 18(9):e0292044. 2023
16.	Mori N, Mikamo H, Mukae H, Yanagihara K, Kunishima H, Sasaki J, Yotsuyanagi H. Influence of thecoronavirus infectious disease 2019 pandemic on
infectious disease practice and infection control inJapan: A web questionnaire survey. J Infect Chemother. 30(1):1-6. 2024
17.	Minami T, Sato M, Toyoda H, Yasuda S, Yamada
T, Nakatsuka T, Enooku K, Nakagawa H, Fujinaga
H, Izumiya M, Tanaka Y, Otsuka M, Ohki T, Arai
M, Asaoka Y, Tanaka A, Yasuda K, Miura H, Ogata
I, Kamoshida T, Inoue K, Nakagomi R, Akamatsu
M, Mitsui H, Fujie H, Ogura K, Uchino K, Yoshida
H, Hanajiri K, Wada T, Kurai K, Maekawa H, Kondo Y, Obi S, Teratani T, Masaki N, Nagashima K,
Ishikawa T, Kato N, Yotsuyanagi H, Moriya K, Kumada T, Fujishiro M, Koike K, Tateishi R. Machinelearning for individualized prediction of hepatocellular carcinoma development after the eradication of hepatitis C virus with antivirals. J Hepatol.
S0168-8278(23)00424-5. 2023
18.	Kado A, Tsutsumi T, Yotsuyanagi H, Ikeuchi K,
Okushin K, Moriya K, Koike K, Fujishiro M. Noninvasive approach to indicate risk factors of nonalcoholic steatohepatitis overlapping autoimmune
hepatitis based on peripheral lymphocyte pattern.
J Gastroenterol. 58(12):1237-1251. 2023
19.	Saito M, Phyo AP, Chu C, Proux S, Rijken MJ,
Beau C, Win HH, Archasuksan L, Wiladphaingern
J, Phu NH, Hien TT, Day NP, Dondorp AM, White116
NJ, Nosten F, McGready R. Severe falciparum malaria in pregnancy in Southeast Asia: a multi-centre retrospective cohort study. BMC Med. 21(1):320. 2023
20.	Adachi E, Saito M, Kikuchi T, Ikeuchi K, Koga M,
Tsutsumi T, Yotsuyanagi H. Incidence of sexuallytransmitted hepatitis C virus infection among men
who have sex with men in Japan from 2009 to
2023. J Med Virol. 95(8):e29039. 2023
21.	Yasuda M, Takahashi S, Miyazaki J, Wada K,
Kobayashi K, Matsumoto M, Hayami H, Yamamoto S, Kiyota H, Sato J, Matsumoto T, Yotsuyanagi
H, Hanaki H, Masumori N, Hiyama Y, Nishiyama
H, Kimura T, Yamada H, Matsumoto K, Ishikawa
K, Togo Y, Tanaka K, Sadahira T, Inokuchi J,
Hamasuna R, Ito K, Hirayama H, Hayashi K, Kurimura Y, Kadena H, Ito S, Shiono Y, Maruyama T,
Ito M, Hatano K, Chokyu H, Ihara H, Uno S,
Monden K, Yokoyama T, Kano M, Kaji S, Kawahara M, Sumii T, Tojo T, Hosobe T, Naito K, Kawai S,
Nishimura H, Izumitani M, Yoh M, Matsumura
M, Fujita R, Takayama K, Hara M, Nishi S. The
third nationwide surveillance of antimicrobial
susceptibility against Neisseria gonorrhoeae frommale urethritis in Japan, 2016-2017. J Infect Chemother. 29(11):1011-1016. 2023
22.	Adachi E, Saito M, Otani A, Koga M, Yotsuyanagi
H. Transient decrease in T cells and atypical lymphocyte proliferation after the onset of mpox. J
Med Virol. 95(8):e29021. 2023
23.	Yamamoto S, Yamayoshi S, Ito M, Sakai-Tagawa Y,
Nakachi I, Baba R, Kamimoto S, Ogura T, Hagiwara S, Kato H, Nakajima H, Uwamino Y, Yagi K,
Sugaya N, Nagai H, Saito M, Adachi E, Koga M,
Tsutsumi T, Duong C, Okuda M, Murakami J, Furusawa Y, Ujie M, Iwatsuki-Horimoto K, Yotsuyanagi H, Kawaoka Y. Differences among epitopes
recognized by neutralizing antibodies induced by
SARS-CoV-2 infection or COVID-19 vaccination.
iScience. 26(7):107208. 2023
24.	Ishizaka A, Koga M, Mizutani T, Uraki R, Yamayoshi S, Iwatsuki-Horimoto K, Yamamoto S, Imai
M, Tsutsumi T, Suzuki Y, Kawaoka Y, Yotsuyanagi
H. Antibody induction and immune response innasal cavity by third dose of SARS-CoV-2 mRNA
vaccination. Virol J. 20(1):146. 2023
25.	Uraki R, Ito M, Kiso M, Yamayoshi S, IwatsukiHorimoto K, Sakai-Tagawa Y, Imai M, Koga M,
Yamamoto S, Adachi E, Saito M, Tsutsumi T, Otani
A, Kashima Y, Kikuchi T, Theiler J, Yotsuyanagi H,
Suzuki Y, Korber B, Kawaoka Y. Efficacy of antivirals and mRNA vaccination against an XBF clinical isolate. Lancet Reg Health West Pac. 34:100777.
2023
26.	Wiladphaingern CS, Stolbrink M, Stolady D, Saito
M, Beau C, Choun K, Wah TG, Mu N, Htoo K, Nu
B, Keereevijit A, Wiladpaingern J, Carrara V, Phyo
AP, Lwin KM, Luxemburger C, Proux S, Charunwatthana P, McGready R, White NJ, Nosten F. Se-vere Falciparum and Vivax Malaria on the Thailand-Myanmar Border: A Review of 1503 Cases.
Clin Infect Dis. 77(5):721-728. 2023
27.	Miyazaki T, Hosogaya N, Fukushige Y, Takemori
S, Morimoto S, Yamamoto H, Hori M, Ozawa Y,
Shiko Y, Inaba Y, Kurokawa T, Hanaoka H, Iwanami S, Kim K, Iwami S, Watashi K, Miyazawa K,
Umeyama T, Yamagoe S, Miyazaki Y, Wakita T,
Sumiyoshi M, Hirayama T, Izumikawa K, Yanagihara K, Mukae H, Kawasuji H, Yamamoto Y, Tarumoto N, Ishii H, Ohno H, Yatera K, Kakeya H, Kichikawa Y, Kato Y, Matsumoto T, Saito M,
Yotsuyanagi H, Kohno S. A Multicenter Randomized Controlled Trial To Evaluate the Efficacy
and Safety of Nelfinavir in Patients with Mild
COVID-19. Microbiol Spectr. 11(3):e0431122. 2023
28.	Saeki H, Mabuchi T, Asahina A, Abe M, Igarashi
A, Imafuku S, Okubo Y, Komine M, Takahashi K,
Torii H, Morita A, Yotsuyanagi H, Watanabe A,
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29.	Adachi E, Ikeuchi K, Otani A, Saito M, Koga M,
Yotsuyanagi H. Mpox associated with PantonValentin leucocidin-producing methicillin-resistant Staphylococcus aureus among people with
HIV. J Infect Chemother. 29(7):710-712. 2023
30.	Ohnishi T, Watanabe S, Matsumoto T, Yotsuyanagi H, Sato J, Kobayashi I, Iinuma S, Nagayama T,
Shibuya S, Ogawa N, Iozumi K, Nakajima Y, Kurikawa Y, Kobayashi M, Matsuo K, Ishikawa H,
Shimizu T, Tsutsui K, Kawamura T, Okuyama R,
Seishima M, Akita Y, Kasugai C, Yano K, Tamada
Y, Mizutani K, Kabashima K, Yamada N, Ikeda M.
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31.	Ikeuchi K, Tsutsumi T, Ishizaka A, Mizutani T, Sedohara A, Koga M, Tamaoki S, Yotsuyanagi H.
Modulation of duodenal and jejunal microbiota
by rifaximin in mice with CCl(4)-induced liver fibrosis. Gut Pathog. 15(1):14. 2023
32.	Bramer LM, Hontz RD, Eisfeld AJ, Sims AC, Kim
YM, Stratton KG, Nicora CD, Gritsenko MA,
Schepmoes AA, Akasaka O, Koga M, Tsutsumi T,
Nakamura M, Nakachi I, Baba R, Tateno H, Suzuki S, Nakajima H, Kato H, Ishida K, Ishii M,
Uwamino Y, Mitamura K, Paurus VL, Nakayasu
ES, Attah IK, Letizia AG, Waters KM, Metz TO,
Corson K, Kawaoka Y, Gerbasi VR, Yotsuyanagi
H, Iwatsuki-Horimoto K. Multi-omics of NET formation and correlations with CNDP1, PSPB, and117
L-cystine levels in severe and mild COVID-19 infections. Heliyon. 9(3):e13795. 2023
33.	Uraki R, Ito M, Kiso M, Yamayoshi S, IwatsukiHorimoto K, Sakai-Tagawa Y, Furusawa Y, Imai
M, Koga M, Yamamoto S, Adachi E, Saito M, Tsutsumi T, Otani A, Kashima Y, Kikuchi T, Yotsuyanagi H, Suzuki Y, Kawaoka Y. Efficacy of antivirals
and bivalent mRNA vaccines against SARS-CoV-2
isolate CH.1.1. Lancet Infect Dis. 23(5):525-526.
2023
34.	Soga T, Duong C, Pattinson D, Sakai-Tagawa Y,
Tokita A, Izumida N, Nishino T, Hagiwara H,
Wada N, Miyamoto Y, Kuroki H, Hayashi Y, Seki
M, Kasuya N, Koga M, Adachi E, Iwatsuki-Horimoto K, Yotsuyanagi H, Yamayoshi S, Kawaoka Y.
Characterization of Influenza A(H1N1)pdm09 Viruses Isolated in the 2018-2019 and 2019-2020 Influenza Seasons in Japan. Viruses. 15(2):535. 2023
35.	Yotsuyanagi H, Ohmagari N, Doi Y, Imamura T,
Sonoyama T, Ichihashi G, Sanaki T, Tsuge Y, Uehara T, Mukae H. A phase 2/3 study of S-217622 inparticipants with SARS-CoV-2 infection (Phase 3part). Medicine (Baltimore). 102(8):e33024. 2023
36.	Kado A, Inoue Y, Moriya K, Tsutsumi T, Ikeuchi K,
Okushin K, Yotsuyanagi H, Koike K, Fujishiro M.
Triglyceride level and soft drink consumption
predict nonalcoholic fatty liver disease in nonobese male adolescents. Hepatol Res. 53(6):497510. 2023
37.	Uraki R, Ito M, Kiso M, Yamayoshi S, Iwatsuki-Horimoto K, Furusawa Y, Sakai-Tagawa Y,
Imai M, Koga M, Yamamoto S, Adachi E, Saito M,
Tsutsumi T, Otani A, Kikuchi T, Yotsuyanagi H,
Halfmann PJ, Pekosz A, Kawaoka Y. Antiviral andbivalent vaccine efficacy against an omicron
XBB.1.5 isolate. Lancet Infect Dis. 23(4):402-403.
2023
38.	Saeki H, Mabuchi T, Asahina A, Abe M, Igarashi
A, Imafuku S, Okubo Y, Komine M, Sano S, Torii
H, Morita A, Yotsuyanagi H, Watanabe A, Ohtsuki
M; Committee for reviewing the safety of molecularly targeted drugs for psoriasis, Japanese Dermatological Association. English version of Japanese guidance for use of biologics for psoriasis(the 2022 version). J Dermatol. 50(2):e41-e68. 2023
39.	Uraki R, Ito M, Furusawa Y, Yamayoshi S, Iwatsuki-Horimoto K, Adachi E, Saito M, Koga M,
Tsutsumi T, Yamamoto S, Otani A, Kiso M,
Sakai-Tagawa Y, Ueki H, Yotsuyanagi H, Imai M,
Kawaoka Y. Humoral immune evasion of the omicron subvariants BQ.1.1 and XBB. Lancet InfectDis. 23(1):30-32. 2023
40.	Mukae H, Yotsuyanagi H, Ohmagari N, Doi Y,
Sakaguchi H, Sonoyama T, Ichihashi G, Sanaki T,
Baba K, Tsuge Y, Uehara T. Efficacy and Safety of
Ensitrelvir in Patients With Mild-to-Moderate
Coronavirus Disease 2019: The Phase 2b Part of a
Randomized, Placebo-Controlled, Phase 2/3
Study. Clin Infect Dis. 76(8):1403-1411. 2023
41.Michiko Koga Makoto Saito Megumi Kubota, Tomoe Senkoji, Eisuke Adachi, Kazuhiko Ikeuchi, Tadashi Kikuchi, Amato Otani, Kazuaki Takahashi,
Takeya Tsutsumi, Hiroshi Yotsuyanagi, Attenuation of hepatitis A antibody after immunization
with hepatitis A vaccine (Aimmugen®) in people
living with human immunodeficiency virus. Hepatol Res, in press.