Attenuation of hepatitis A antibody after immunization with hepatitis A vaccine (Aimmugen) in people living with HIV.

AIM: 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 HIV (MSM-LWHIV) with Aimmugen. As previously reported, their antibody seroconversion rate due to vaccination was lower than that of healthy individuals. However, the durability of Aimmugen in people living with HIV has not yet been reported. We evaluated attenuation after the one-series vaccination (comprising three inoculations) and the factors associated with attenuation. METHODS: We retrospectively examined anti-HA immunoglobulin G (anti-HA-IgG) titers and other clinical data from our hospital's medical records. Patients with no history of vaccination or HA infection (i.e., negative HA-IgG titers) who received one series of Aimmugen, achieved seropositivity, and anti-HA-IgG antibodies were tested ≥2 years after three doses were included. Fisher's exact test and the Mann-Whitney U-test were performed. p < 0.05 was considered statistically significant. RESULTS: 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) (sample/cut-off values [s/co]). In 45 (40-49) months, seropositivity decreased to 90% (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 the third dose (p = 0.003) were associated with seronegativity. CONCLUSIONS: Anti-HA-IgG titers of vaccinated MSM-LWHIV may be attenuated; thus, additional immunizations should be considered.

Development of a partnership between academia, community, and government in response to the 2022 mpox outbreak in Japan.

Objectives　In response to the steady rise in the number of cases of mpox in nonendemic countries, starting with an outbreak in the United Kingdom in May 2022, the World Health Organization declared a public health emergency of international concern on July 23, 2022. As of November 13, 2022, seven cases of mpox have been reported in Japan.Methods　A community engagement approach was applied to prevent the spread of mpox in Japan.Results　A tripartite partnership between academia, community, and government (ACG) was established to promote multisectoral communication between vulnerable communities, medical personnel involved in diagnosis and treatment, public health specialists at public health centers, epidemiologists at the National Institute of Infectious Diseases (NIID), and government and public administration. Through information sharing, this ACG partnership can translate accurate information into effective infection control measures.Conclusion　By developing and maintaining the ACG partnership, an environment will be created that allows an immediate response to future public health crises affecting vulnerable communities. This Practice Report describes the process of establishing an ACG partnership.

Virological outcomes of various first-line ART regimens in patients harbouring HIV-1 E157Q integrase polymorphism: a multicentre retrospective study.

BACKGROUND: Integrase strand transfer inhibitors (INSTIs) are recommended as first-line ART for people living with HIV (PLWH) in most guidelines. The INSTI-resistance-associated mutation E157Q, a highly prevalent (2%-5%) polymorphism of the HIV-1 (human immunodeficiency virus type 1) integrase gene, has limited data on optimal first-line ART regimens. We assessed the virological outcomes of various first-line ART regimens in PLWH with E157Q in real-world settings. METHODS: A multicentre retrospective observational study was conducted on PLWH who underwent integrase genotypic drug-resistance testing before ART initiation between 2008 and 2019 and were found to have E157Q. Viral suppression (<50 copies/mL) rate at 24 and 48 weeks, time to viral suppression and time to viral rebound (≥100 copies/mL) were compared among the first-line ART regimens. RESULTS: E157Q was detected in 167 (4.1%) of 4043 ART-naïve PLWH. Among them, 144 had available clinical data after ART initiation with a median follow-up of 1888 days. Forty-five started protease inhibitors + 2 NRTIs (PI group), 33 started first-generation INSTI (raltegravir or elvitegravir/cobicistat) + 2 NRTIs (INSTI-1 group), 58 started once-daily second-generation INSTI (dolutegravir or bictegravir) + 2 NRTIs (INSTI-2 group) and eight started other regimens. In the multivariate analysis, the INSTI-2 group showed similar or favourable outcomes compared with the PI group for viral suppression rates, time to viral suppression and time to viral rebound. Two cases in the INSTI-1 group experienced virological failure. CONCLUSIONS: The general guideline recommendation of second-generation INSTI-based first-line ART for most PLWH is also applicable to PLWH harbouring E157Q.

Incidence of sexually transmitted hepatitis C virus infection among men who have sex with men in Japan from 2009 to 2023.

Although the prevalence of hepatitis C virus (HCV) infection has decreased significantly with the advent of direct-acting antiviral agents, HCV is known to spread as a sexually transmitted disease among men who have sex with men (MSM), and this study aims to provide a perspective on the future prevalence of HCV in Japan. We examined incidence in two groups of MSM with HIV attending our institution in this retrospective cohort study, from 2009 to 2019 and from 2020 to May 2023 and investigated their background factors. Twenty-two cases were newly confirmed to be HCV infection in 2009-2019 and a total of 9 cases in 2020-2023, with an incidence rate of 5.04 per 1000 person-years in 2009-2019 and 5.55 per 1000 person-years in 2020-2023. All of them were diagnosed at routine outpatient visits for HIV, and few cases were considered to have symptoms of suspected hepatitis that led to a visit to the hospital and a diagnosis of HCV. Although HCV is still prevalent among MSM in Japan, it is possible that it would not have been diagnosed without testing at regular visits as in the case of people with HIV, and that the true prevalence rate among MSM, including non-HIV-infected persons, may be much higher.

Association of demographics, HCV co-infection, HIV-1 subtypes and genetic clustering with late HIV diagnosis: a retrospective analysis from the Japanese Drug Resistance HIV-1 Surveillance Network.

INTRODUCTION: Late diagnosis of the human immunodeficiency virus (HIV) is a major concern epidemiologically, socially and for national healthcare systems. Although the association of certain demographics with late HIV diagnosis has been reported in several studies, the association of other factors, including clinical and phylogenetic factors, remains unclear. In the present study, we conducted a nationwide analysis to explore the association of demographics, clinical factors, HIV-1 subtypes/circulating recombinant form (CRFs) and genetic clustering with late HIV diagnosis in Japan, where new infections mainly occur among young men who have sex with men (MSM) in urban areas. METHODS: Anonymized data on demographics, clinical factors and HIV genetic sequences from 39.8% of people newly diagnosed with HIV in Japan were collected by the Japanese Drug Resistance HIV-1 Surveillance Network from 2003 to 2019. Factors associated with late HIV diagnosis (defined as HIV diagnosis with a CD4 count <350 cells/µl) were identified using logistic regression. Clusters were identified by HIV-TRACE with a genetic distance threshold of 1.5%. RESULTS: Of the 9422 people newly diagnosed with HIV enrolled in the surveillance network between 2003 and 2019, 7752 individuals with available CD4 count at diagnosis were included. Late HIV diagnosis was observed in 5522 (71.2%) participants. The overall median CD4 count at diagnosis was 221 (IQR: 62-373) cells/µl. Variables independently associated with late HIV diagnosis included age (adjusted odds ratio [aOR] 2.21, 95% CI 1.88-2.59, ≥45 vs. ≤29 years), heterosexual transmission (aOR 1.34, 95% CI 1.11-1.62, vs. MSM), living outside of Tokyo (aOR 1.18, 95% CI 1.05-1.32), hepatitis C virus (HCV) co-infection (aOR 1.42, 95% CI 1.01-1.98) and not belonging to a cluster (aOR 1.30, 95% CI 1.12-1.51). CRF07_BC (aOR 0.34, 95% CI 0.18-0.65, vs. subtype B) was negatively associated with late HIV diagnosis. CONCLUSIONS: In addition to demographic factors, HCV co-infection, HIV-1 subtypes/CRFs and not belonging to a cluster were independently associated with late HIV diagnosis in Japan. These results imply the need for public health programmes aimed at the general population, including but not limited to key populations, to encourage HIV testing.

High-level resistance to non-nucleos(t)ide reverse transcriptase inhibitor based first-line antiretroviral therapy in Ghana; A 2017 study.

Expanding access to effective antiretroviral therapy (ART) is a major tool for management of Human Immunodeficiency Virus (HIV) infection. However, rising levels of HIV drug-resistance have significantly hampered the anticipated success of ART in persons living with HIV (PLWH), particularly those from Africa. Though great strides have been made in Ghana toward achieving the UNAIDS "95-95-95" target, a substantial number of PLWH receiving ART have not attained viral suppression. This study investigated patterns of drug resistance mutations in ART naïve as well as ART-experienced PLWH receiving first-line regimen drugs from Ghana. In a cross-sectional study, blood samples were collected from HIV-1 infected adults (≥18 years) attending HIV/AIDS clinic at the Eastern Regional Hospital, Koforidua, Ghana from September to October 2017. Viral RNA isolated from plasma were subjected to genotypic drug resistance testing for Protease Inhibitors (PI), Reverse Transcriptase Inhibitors (RTI), and Integrase Strand Transfer Inhibitors (INSTI). A total of 95 (84 ART experienced, 11 ART naïve) HIV-1 infected participants were sampled in this study. Sixty percent (50/84) of the ART-experienced participants were controlling viremia (viral load < 1,000 copies/ml). Of the 95 patient samples, 32, 34, and 33 were successfully sequenced for protease, reverse-transcriptase, and integrase regions, respectively. The dominant HIV-1 subtypes detected were CRF02_AG (70%), and A3 (10%). Major drug resistance associated mutations were only detected for reverse transcriptase inhibitors. The predominant drug resistance mutations were against nucleos(t)ide reverse transcriptase inhibitors (NRTI)-M184V/I and non-nucleos(t)ide reverse transcriptase inhibitors (NNRTI)-K103N. In the ART-experienced group, M184V/I and K103N were detected in 54% (15/28) and 46% (13/28) of individuals, respectively. Both mutations were each detected in 33% (2/6) of ART naïve individuals. Multiclass resistance to NRTI and NNRTI was detected in 57% of ART-experienced individuals and two ART naïve individuals. This study reports high-level resistance to NNRTI-based antiretroviral therapy in PLWH in Ghana. However, the absence of major PI and INSTI associated-mutations is a good signal that the current WHO recommendation of Dolutegravir in combination with an NRTI backbone will yield maximum benefits as first-line regimen for PLWH in Ghana.

Evaluation of the Geenius HIV 1/2 confirmatory assay for HIV-2 samples isolated in Japan.

BACKGROUND: Although the number of HIV-2-infected individuals is quite low in Japan, at least three groups of HIV-2 (A, B and CRF01_AB) have been detected thus far. In particular, CRF01_AB HIV-2 cases have been found only in limited areas, Cote d'Ivoire and Japan. Here, we demonstrate that Geenius HIV 1/2 Confirmatory Assay (Geenius, Bio-Rad Laboratories) is able to detect HIV-2 samples, including groups A, B and CRF01_AB, isolated in Japan. STUDY DESIGN: A total of 57 plasma samples, including three panels (Ⅰ: HIV-2-positive samples [n=9], Ⅱ: HIV-1 infection with HIV-2 antibody cross-reactivity samples [n=37], and Ⅲ: HIV negative with biological false-positive HIV-2 samples [n=11]) were tested by Geenius. RESULTS: Geenius determined Panel I to be "HIV-2 positive with/without HIV-1 cross-reactivity (n=4, respectively)", including HIV-2 group A and CRF01_AB. In the case with HIV-2 group B, all bands were detected, resulting in a Geenius interpretation of "HIV positive untypable". Geenius classified Panels II and III as "HIV-1 positive (n=37)" or "HIV negative (n=9)", "HIV indeterminate (n=1)" and "HIV-2 indeterminate (n=1)", suggesting 95.8% HIV-2 differentiation by Geenius. CONCLUSIONS: With Geenius, there were fewer false-positives for HIV-1/-2 negativity and fewer cross-reactions with HIV-2 among HIV-1-positive samples. Additionally, the assay could detect HIV-2 genetic group CRF01_AB. Geenius can be expected to be a useful diagnostic tool that is an alternative to conventional Western blotting.

Immunological Correlates of Prevention of the Onset of Seasonal H3N2 Influenza.

On influenza virus infection or vaccination, immune responses occur, including the production of antibodies with various functions that contribute to protection from seasonal influenza virus infection. In the current study, we attempted to identify the antibody functions that play a central role in preventing the onset of seasonal influenza by comparing the levels of several antibody titers for different antibody functions between 5 subclinically infected individuals and 16 patients infected with seasonal H3N2 virus. For antibody titers before influenza virus exposure, we found that the nAb titers and enzyme-linked immunosorbent assay titers against hemagglutinin and neuraminidase (NA) proteins in the subclinically infected individuals were significantly higher than those in the patients, whereas the NA inhibition titers and antibody-dependent cellular cytotoxicity activities did not significantly differ between subclinically infected individuals and infected patients. These results suggest that nAb and enzyme-linked immunosorbent assay titers against hemagglutinin and NA serve as correlates of symptomatic influenza infection.

Predictors associated with a better response to the Japanese aluminum-free hepatitis A vaccine, Aimmugen® , for people living with HIV.

AIM: After the hepatitis A virus (HAV) outbreak among men who have sex with men (MSM) around 2018, the importance of HAV vaccination was emphasized, especially for MSM-living with human immunodeficiency virus (MSM-LWHIV). Aimmugen® is licensed and distributed exclusively in Japan. While administration of three doses is recommended, 85% of recipients in the general population were reported to acquire seroprotection after the second dose. In this study, we evaluated the efficacy of two or three vaccine doses along with predictors associated with the response to Aimmugen® in MSM-LWHIV. METHODS: We retrospectively examined anti-HA-IgG titers of MSM-LWHIV vaccinated with Aimmugen® in our hospital. Patients' data were collected from medical records. RESULTS: Between January 2018 and October 2019, 141 subjects whose median age was 46 years old, were examined. All the subjects were on antiretroviral therapy (ART) and the median CD4 count was 615/µL. The acquisition rate of protectable anti-HA-IgG titers after the second and third dose was 71.1% and 98.6%, respectively. In 114 subjects whose anti-HA-IgG titers were tested after the second-dose, factors significantly associated with better response were prolonged ART duration and higher CD4 count. The titers of anti-HA-IgG after the third dose were higher in those who became seropositive after the second-dose than those who did not. CONCLUSIONS: Three-dose of Aimmugen® for MSM-LWHIV was effective while two-dose was less effective compared to non-HIV-infected people. People-LWHIV with shorter duration of ART and lesser CD4 cell count achieved lower titers of anti-HA-IgG and might require an additional vaccination.

Unique Gut Microbiome in HIV Patients on Antiretroviral Therapy (ART) Suggests Association with Chronic Inflammation.

Chronic inflammation is a hallmark of human immunodeficiency virus (HIV) infection and a risk factor for the development and progression of age-related comorbidities. Although HIV-associated gut dysbiosis has been suggested to be involved in sustained chronic inflammation, there remains a limited understanding of the association between gut dysbiosis and chronic inflammation during HIV infection. Here, we investigated compositional changes in the gut microbiome and its role in chronic inflammation in patients infected with HIV. We observed that the gut microbiomes of patients with low CD4 counts had reduced alpha diversity compared to those in uninfected controls. Following CD4 recovery, alpha diversity was restored, but intergroup dissimilarity of bacterial composition remained unchanged between patients and uninfected controls. Patients with HIV had higher abundance of the classes Negativicutes, Bacilli, and Coriobacteriia, as well as depletion of the class Clostridia. These relative abundances positively correlated with inflammatory cytokines and negatively correlated with anti-inflammatory cytokines. We found that gut dysbiosis accompanying HIV infection was characterized by a depletion of obligate anaerobic Clostridia and enrichment of facultative anaerobic bacteria, reflecting increased intestinal oxygen levels and intestinal permeability. Furthermore, it is likely that HIV-associated dysbiosis shifts the immunological balance toward inflammatory Th1 responses and encourages proinflammatory cytokine production. Our results suggest that gut dysbiosis contributes to sustaining chronic inflammation in patients with HIV infection despite effective antiretroviral therapy and that correcting gut dysbiosis will be effective in improving long-term outcomes in patients. IMPORTANCE Chronic inflammation is a hallmark of HIV infection and is associated with the development and progression of age-related comorbidities. Although the gastrointestinal tract is a major site of HIV replication and CD4+ T-cell depletion, the role of HIV-associated imbalance of gut microbiome in chronic inflammation is unclear. Here, we aimed to understand the causal relationship between abnormalities in the gut microbiome and chronic inflammation in patients with HIV. Our results suggest HIV-associated gut dysbiosis presents a more aerobic environment than that of healthy individuals, despite prolonged viral suppression. This dysbiosis likely results from a sustained increase in intestinal permeability, which supports sustained bacterial translocation in HIV patients, despite effective therapy. Additionally, we observed that several bacterial taxa enriched in HIV patients were associated with increased expression of inflammatory cytokines. Collectively, these results suggest that gut dysbiosis plays an important role in chronic inflammation in HIV patients.

Phylodynamic analysis reveals changing transmission dynamics of HIV-1 CRF01_AE in Japan from heterosexuals to men who have sex with men.

BACKGROUND: HIV-1 circulating recombinant form (CRF) 01_AE is the second major subtype in Japan. Our previous study indicated that CRF01_AE was predominantly circulating in heterosexuals/injecting drug users (IDUs). With implications of increased CRF01_AE infections among men who have sex with men (MSM), this study sought to investigate whether the transmission dynamics of CRF01_AE infections in Japan have changed. METHODS: Sequences from 8032 newly diagnosed HIV-1-infected individuals were analysed. For 614 (7.6%) of CRF01_AE cases, clusters were identified and categorised by transmission risks. Median times to the most recent common ancestors (tMRCA) were estimated. RESULTS: The individuals were predominantly Japanese (64%) and male (72%). MSM became the predominant transmission risk from 2014. Thirty transmission clusters (TCs) and 48 pairs, including 40% of individuals, were identified. MSM were approximately five times more likely to be in a TC compared to heterosexuals, and were the major contributors to TCs. tMRCA data suggest that MSM TCs emerged from 1996 and became predominant around 2000. CONCLUSIONS: CRF01_AE has spread among MSM, with frequent and continuous cluster formations, and MSM has become the predominant transmission risk. Our study suggested that CRF01_AE transmission has shifted from heterosexuals/IDUs to MSM. Prevention measures targeting key populations should be considered for controlling CRF01_AE spread.

Changes in survival and causes of death among people living with HIV: Three decades of surveys from Tokyo, one of the Asian metropolitan cities.

INTRODUCTION: Survival among people living with HIV (PLWH) has dramatically improved in the antiretroviral therapy (ART) era. This is the first study in Asia to describe three decades of surveys on survival and causes of death among PLWH. METHODS: We included 1121 HIV-infected patients, categorized into three period groups according to date of first visit: 1986-1996 (Pre-ART); 1997-2007 (Early-ART); and 2008-2018 (Late-ART). RESULTS: Ten-year all-cause mortality has reduced from Pre-ART (49.6/1000 person-years) to Late-ART (6.3/1000 person-years). Mortality for AIDS-defining illnesses (ADIs) has also reduced from Pre-ART (34.4/1000 person-years) to Late-ART (2.9/1000 person-years), and mortality for non-ADIs has reduced from Pre-ART (11.7/1000 person-years) to Late-ART (2.9/1000 person-years). In the ART-era, deaths from non-AIDS-defining malignancies and unnatural events including suicide represented the majority of non-ADI-related deaths and mortality rates of non-AIDS defining malignancies and unnatural cause event were not different between each group (3.4, 1.9 and 2.5/1000 person-years). Crude cumulative survival improved over the study period, and 10-year survival ratios of HIV-infected patients to the general Japanese population approached 1.00, from Pre-ART (0.66) to Late-ART (0.99). Even in the Late-ART period, survival remained lower in patients with a history of ADIs than in those without, but the difference in 5-year mortality between these groups has shrunk in the Late-ART compared to the Pre-ART. CONCLUSIONS: Mortality for ADIs and non-ADIs in PLWH has reduced in the Early-ART and Late-ART. To improve survival for PLWH further, early HIV detection and treatment and good management of non-AIDS-defining malignancies and mental disorders are needed. (248/250).

Primaquine plus clindamycin as a promising salvage therapy for Pneumocystis jirovecii pneumonia: A retrospective analysis in Japanese patients.

Treatment of intractable Pneumocystis jirovecii pneumonia (PCP) patients with primaquine (PQ) in combination with clindamycin (CLDM) was conducted by the Research Group on Chemotherapy of Tropical Diseases (RG-CTD), as a kind of compassionate use. Primaquine was not nationally licensed at the time but imported by RG-CTD for the use in a clinical research to investigate safety and efficacy in malaria treatment. Eighteen Japanese adult patients thus treated were analyzed. Prior to the treatment with PQ-CLDM, most of the patients had been treated with trimethoprim-sulfamethoxazole first, all of which being followed by pentamidine and/or atovaquone treatment. This combination regimen of PQ-CLDM was effective in 16 (89%) patients and developed adverse events (AEs) in five (28%) patients. AEs included skin lesions, methemoglobinemia, and hepatic dysfunction, though none of them were serious. As a second-line or salvage treatment for PCP, PQ-CLDM appears to be a better option than pentamidine or atovaquone. Currently in Japan, both PQ and CLDM are licensed drugs but neither of them is approved for treatment of PCP. Considering the potentially fatal nature of PCP, approval of PQ-CLDM for treating this illness should be urged.

Different interaction of onset age and duration of type 1 diabetes on the dynamics of autoantibodies to insulinoma-associated antigen-2 and zinc transporter 8.

AIMS/INTRODUCTION: This study aimed to investigate the dynamics associated with autoantibodies to insulinoma-associated antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A) relating to the onset age and disease duration in patients with type 1 diabetes. METHODS: Using bridging-type enzyme-linked immunosorbent assay, IA-2A, ZnT8A and glutamic acid decarboxylase autoantibodies were evaluated in 269 patients with type 1 diabetes (median onset age 18.2 years, range 0.8-86 years; median diabetes duration 7 years, range 0-58 years). We then compared the prevalence of these autoantibodies among the different age groups, along with the duration of diabetes using the Cochran-Armitage trend test and multivariate logistic regression analysis. RESULTS: The prevalence of IA-2A, ZnT8A and glutamic acid decarboxylase autoantibodies in patients with duration of ≤3 years was 41.1, 36.7 and 72.2%, respectively, with 80.0% expressing one or more of these autoantibodies. This prevalence declined according to the disease duration (P < 0.005). Both IA-2A and ZnT8A were more frequently observed in younger patients, whereas glutamic acid decarboxylase autoantibodies was more common in older patients. Multivariate logistic regression analysis showed that there was a significant interaction between the onset age and duration of diabetes in patients diagnosed when aged ≤10 years regarding all anti-islet autoantibodies (P < 0.05). However, for patients diagnosed in the middle tertile (aged 11-30 years), the interaction was significant only for ZnT8A, and for those with late-onset diabetes (aged ≥31 years) only for IA-2A. CONCLUSIONS: The current study showed that the rate of disappearance of anti-islet autoantibodies is faster in patients aged ≤10 years, and that even though both proteins are localized in the insulin granule membrane, humoral autoimmunity to IA-2 and ZnT8 differs according to the age of onset.

Factors associated with clearance of hepatitis B virus surface antigen in patients infected with human immunodeficiency virus.

Owing to similar routes of transmission, hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfection commonly occurs. Compared with patients infected with only HBV, coinfected patients develop persistent HBV infection followed by advanced liver diseases. However, the characteristics of HIV-infected patients who can achieve the clearance of HBV surface antigen (HBsAg) have not been clarified. In this study, we retrospectively examined patients coinfected with HBV and HIV and determined the host factors associated with HBsAg clearance.Among HIV-infected patients who visited our hospital between 1994 and 2017, we examined medical records of those who were seropositive for HBsAg at least once. Among them, patients who cleared HBsAg afterward were regarded as "cured," while those who remained HBsAg-seropositive until 2017 were "chronic."HBsAg seropositivity was found in 57 patients, and among them, 27 male patients were cured whereas 18 were chronic. The cured patients were significantly younger and had higher CD4 cell and platelet counts than the chronic patients. In addition, the cured patients had higher levels of transaminases after the detection of HBsAg. Multivariate analysis revealed age as an independent factor. Analyses of the patients infected with genotype A also showed that the cured patients had significantly higher CD4 cell counts.Considering that the CD4 cell and platelet counts were higher in the cured patients, immunological and liver functions were closely associated with HBsAg clearance. Higher levels of transaminases in the cured patients may also reflect the immunological function leading to HBsAg clearance.

Zinc transporter 8 autoantibodies complement glutamic acid decarboxylase and insulinoma-associated antigen-2 autoantibodies in the identification and characterization of Japanese type 1 diabetes.

AIMS/INTRODUCTION: This study aimed to investigate the significance of zinc transporter 8 autoantibody (ZnT8A) in identifying and characterizing autoimmune-mediated type 1 diabetes in Japanese individuals. METHODS: ZnT8A were determined in 324 patients with type 1 diabetes, 191 phenotypic type 2 diabetes and 288 healthy control individuals using bridging-type enzyme-linked immunosorbent assay in addition to autoantibodies to glutamic acid decarboxylase and insulinoma-associated antigen-2. RESULTS: We set a cut-off value of 10.0 U/mL, and 25% of the type 1 diabetic patients had ZnT8A levels exceeding this level. The prevalence of ZnT8A was significantly higher in patients with acute-onset type 1 diabetes than in those with slowly progressive and fulminant type 1 diabetes (P < 0.05). ZnT8A were more frequent in patients aged ≤10 years, but less frequent in patients with duration ≥5 years (P < 0.05). ZnT8A were detected in 5.2% of phenotypic type 2 diabetic patients, with 90% of these being ZnT8A-single-positive. Furthermore, the ZnT8A levels in the phenotypic type 2 diabetes cohort (143.8 ± 194.9 U/mL) were significantly higher than those in the type 1 diabetes cohort (22.9 ± 8.3 U/mL, P < 0.05). In the acute-onset and slowly progressive type 1 diabetic patients with duration ≤5 years, additional measurement of glutamic acid decarboxylase autoantibodies significantly increased the disease sensitivity in patients aged ≤10 years, but not in patients aged ≥11 years (11.7 vs 3.6%, P < 0.05). Multivariate analysis showed that ZnT8A positivity was independently associated with age at sampling and insulinoma-associated antigen-2 autoantibody positivity. CONCLUSIONS: These results suggest that the bridging-type ZnT8A enzyme-linked immunosorbent assay might provide a valuable additional marker for Japanese patients with type 1 diabetes, which could, in turn, allow for an increase in the number of identifiable cases and differentiate clinical phenotypes.

Efficacy of protocol-based non-invasive positive pressure ventilation for acute respiratory distress syndrome: a retrospective observational study.

AIM: The efficacy of non-invasive positive pressure ventilation (NPPV) in acute respiratory distress syndrome (ARDS) remains unclear. Variation in both the etiology of ARDS and patient factors has resulted in inconsistent application of NPPV. We have developed a protocol-based NPPV strategy as a first-line intervention for ARDS. The aim of this observational study was to determine if protocol-based NPPV improves the outcome in patients with ARDS. METHODS: We identified patients with ARDS treated by protocol-based NPPV at our institution between March 2006 and March 2010 and categorized them according to NPPV success or failure. Success was defined as avoidance of intubation and remaining alive during NPPV. RESULTS: Eighty-eight of 169 patients diagnosed with ARDS during the study period were treated using the protocol. Fifty-two (76%) of 68 patients who were eligible for the study were successfully treated and did not require endotracheal intubation. The overall mortality rate at 28 days after initiation of NPPV was 12%. The mortality rate was significantly lower in the success group than in the failure group (P < 0.01). The PaO2/FiO2 ratio after 12-24 h of NPPV was significantly higher in the success group than in the failure group (202 ± 63 versus 145 ± 46; P < 0.01). CONCLUSIONS: The success rate was higher and the mortality was lower in patients than in historical controls. Protocol-based NPPV could be effective in patients with ARDS.

Comparison of the Clinical Features of Hepatitis A in People Living with HIV between Pandemics in 1999-2000 and 2017-2018 in the Metropolitan Area of Japan.

Since 2017, hepatitis A virus (HAV) infection has been an epidemic among men who have sex with men (MSM) in Japan. We have come across 11 MSM patients with hepatitis A who were also infected with HIV. In 1999-2000, we came across 5 HIV-infected patients with hepatitis A. Since the conditions of current HIV-infected patients have changed owing to the recent progress in anti-HIV therapies, we compared clinical features of hepatitis A between patients in 2017-2018 and those in 1999-2000. By comparing the background characteristics of the patients, we found that the CD4/CD8 ratio was significantly higher in the 2017-2018 group. After the onset of hepatitis, peak levels of hepatic transaminases were found to be higher in the 2017-2018 group, suggesting severe hepatocellular damage. In contrast, neither the peak level of total bilirubin nor the nadir of prothrombin time was significantly different among the 2 groups. We also analyzed the HAV genome derived from some of the recently infected patients, and found that the HAV strains were almost the same among these patients; slight differences were observed from the previously identified strain. Thus, we concluded that the recovery of immunity by recent anti-HIV therapies may result in more severe hepatocellular damages and differences in clinical features.

Prevalence of Hepatitis A Immunity and Decision-tree Analysis Among Men Who Have Sex With Men and Are Living With Human Immunodeficiency Virus in Tokyo.

BACKGROUND: Hepatitis A virus (HAV) can be sexually transmitted. However, the level of HAV immunity among patients living with human immunodeficiency virus (HIV) in Japan is unknown. Determining the epidemiology of HAV infections among men who have sex with men (MSM) and who are living with HIV is essential for an HAV vaccination program. This study examined HAV immunity in patients living with HIV and applied the decision-tree analysis to explore the factors of immunoglobulin G (IgG)-hepatitis A (HA) antibodies in MSM living with HIV. METHODS: We examined the presence of IgG-HA antibodies among patients living with HIV from January to December 2017 in The Hospital of The Institute of Medical Science, The University of Tokyo. We recorded each patient's age, sex, mode of HIV transmission, year of HIV diagnosis, HAV vaccine status, history of HAV infection, and history of other infectious diseases. A decision-tree algorithm was used to reveal the factors and profiles most relevant to the anti-HAV prevalence. RESULTS: Overall, 378 MSM patients living with HIV were examined for IgG-HA antibodies. After excluding 24 patients who had received a HAV vaccine, the data of 354 MSM were analyzed (median age 45 years, interquartile range 39-51 years). Of the 354 patients, 60 (16.9%) were positive for IgG-HA antibodies. The HA positivity rate increased with patients' age, and age (> 63.5 years) was extracted as the most important variable by classification of the decision-tree algorithm. CONCLUSIONS: Our study, conducted just before the HAV outbreak among MSM in Tokyo, showed that age was the most relevant factor in anti-HAV prevalences. An extensive HAV vaccination program for MSM patients living with HIV is urgently needed, particularly for younger people.

Total knee arthroplasty in Japanese patients aged 80 years or older.

OBJECTIVE: The population of Japan is aging rapidly, and, since the aging of patients who undergo total knee arthroplasty (TKA) is also expected, it is necessary to determine the efficacy and safety of TKA among old adult patients. METHODS: This study retrospectively analyzed the cases of patients who underwent a primary TKA for osteoarthritis at Bange Kosei General Hospital between January 2009 and June 2014 and were postoperatively followed-up for ≥1 year. Among the 2,945 knees of the 1,968 patients, 1,003 knees of 679 patients aged ≥80 years at the time of surgery were designated as the older group, and we compared their cases with those of the younger group of 1,044 knees of 673 patients aged <75 years. RESULTS: The rates of improvement of the Japanese Orthopaedic Association (JOA) score were not significantly different between the older and younger groups. Postoperative ranges of motion were significantly improved in both groups. The number of postoperative days of hospital stay in the older group was 2 days longer than that of the younger group. Concerning postoperative complications, confusion, delayed wound healing, and acute heart failure were significantly more frequent in the older group. The frequencies of pneumonia, cerebral infarction, peroneal nerve palsy, and bedsore did not differ significantly. Loosening of implants was observed: older group, n=0 joints; younger group, n=5 joints. The number of prosthetic joint infections: older group, n=5; younger group, n=2 (non-significant). CONCLUSION: The rate of improvement in the JOA score did not differ significantly between the groups. TKA is an effective and safe treatment for osteoarthritis, even in old adult patients, when the surgical indication is based on careful preoperative screening and attention to specific postoperative complications.