Identification of a strong genetic risk factor for major depressive disorder in the human virome.

The heritability of major depressive disorder (MDD) is reportedly 30-50%. However, the genetic basis of its heritability remains unknown. Within SITH-1, a risk factor for MDD in human herpesvirus 6B (HHV-6B), we discovered a gene polymorphism with a large odds ratio for an association with MDD. It was a sequence whose number of repeats was inversely correlated with SITH-1 expression. This number was significantly lower in MDD patients. Rates for 17 or fewer repeats of the sequence were 67.9% for MDD and 28.6% for normal controls, with an odds ratio of 5.28. For patients with 17 or less repeats, the rate for presence of another MDD patient in their families was 47.4%, whereas there were no MDD patients in the families of patients with more than 17 repeats. Since HHV-6B is transmitted primarily mother to child and within families and persists for life, this gene polymorphism could potentially influence heritability of MDD.

Relationship between human herpesvirus 6 infection and inflammatory bowel disease using novel biomarker.

Objective: Inflammatory bowel disease (IBD) is closely related to stress and fatigue. Human herpesvirus 6B (HHV-6B) is reactivated by stress and fatigue and is associated with IBD. This study aimed to clarify the relationship between IBD and HHV-6B. Methods: Antibody titers to SITH-1, a protein specific to HHV-6B latent infection, were measured in 163 patients with IBD (107 with ulcerative colitis [UC] and 56 with Crohn's disease [CD]); clinical and endoscopic scores and depression scores of UC and CD were analyzed to examine the relationship between SITH-1 and IBD. The SITH-1 cut-off value was set as 1.96, according to known reports. Results: In patients with UC, C-reactive protein (CRP) level was significantly higher (1.5 vs 0.6 mg/L, P = 0.006) and disease exacerbation within 6 months after entry was significantly more common in the SITH-1 (+) group (20% vs 0%, P < 0.001). In the subanalysis comparing with and without UC exacerbation, the optimal cut-off value for SITH-1 to detect UC exacerbation was 3.44 (area under the curve: 0.81; 95% confidence interval: 0.72-0.90). CRP levels, SITH-1 levels, and disease activity scores by the clinical or endoscopic index were significantly higher in the exacerbation group than in the non-exacerbation group (2.6 vs 0.9 mg/L, P = 0.03; 4.90 vs 1.71, P < 0.001; 4 vs 3, P = 0.03; 5 vs 3, P = 0.02; respectively). Conclusion: Patients with UC with high titers of SITH-1 have high disease activity and frequent disease exacerbation. SITH-1 can be associated with UC disease activity.

SARS-CoV-2 S1 protein causes brain inflammation by reducing intracerebral acetylcholine production.

Neurological complications that occur in SARS-CoV-2 infection, such as olfactory dysfunction, brain inflammation, malaise, and depressive symptoms, are thought to contribute to long COVID. However, in autopsies of patients who have died from COVID-19, there is normally no direct evidence that central nervous system damage is due to proliferation of SARS-CoV-2. For this reason, many aspects of the pathogenesis mechanisms of such symptoms remain unknown. Expressing SARS-CoV-2 S1 protein in the nasal cavity of mice was associated with increased apoptosis of the olfactory system and decreased intracerebral acetylcholine production. The decrease in acetylcholine production was associated with brain inflammation, malaise, depressive clinical signs, and decreased expression of the cytokine degrading factor ZFP36. Administering the cholinesterase inhibitor donepezil to the mice improved brain inflammation, malaise and depressive clinical signs. These findings could contribute to the elucidation of the pathogenesis mechanisms of neurological complications associated with COVID-19 and long COVID.

VP26, a herpes simplex virus type 1 capsid protein, increases DNA methylation in COASY promoter region.

It has been reported that some specific changes in DNA methylation can be due to aging or infection by tumor-related viruses but the effect of herpes simplex virus type 1 (HSV-1) in this regard is unknown. HSV-1 is a well-known virus that causes cold sores. After the primary infection, the virus switches to latent infection and remains in the body for the whole life. As the location of DNA methylation, we focused on the promoter region of the COASY gene, which codes for coenzyme A synthase, because methylation in this region is reportedly associated with Alzheimer's disease (AD). During HSV-1 lytic infection, compared to non-infected cells, COASY DNA methylation decreased but when HSV-1 replication was inhibited by acyclovir, an anti-herpes agent, COASY DNA methylation increased. In addition, for expression of immediate early protein only, there was no significant change in COASY DNA methylation, while for expression of the capsid protein VP26, a late protein known to bind with DNA methyltransferase DNMT3A, in the nucleus only, COASY DNA methylation significantly increased compared to the control, without changes in DNMT3A mRNA. Our results suggested that DNA methylation occurred not due to transcriptional changes in DNMT3A but through translational regulation. In this research, we showed that host COASY DNA methylation is altered by HSV-1 infection, in particular by HSV-1 VP26. It is a potential cause of various diseases, and this is particularly relevant for AD.

HMM-Based Action Recognition System for Elderly Healthcare by Colorizing Depth Map.

Addressing the problems facing the elderly, whether living independently or in managed care facilities, is considered one of the most important applications for action recognition research. However, existing systems are not ready for automation, or for effective use in continuous operation. Therefore, we have developed theoretical and practical foundations for a new real-time action recognition system. This system is based on Hidden Markov Model (HMM) along with colorizing depth maps. The use of depth cameras provides privacy protection. Colorizing depth images in the hue color space enables compressing and visualizing depth data, and detecting persons. The specific detector used for person detection is You Look Only Once (YOLOv5). Appearance and motion features are extracted from depth map sequences and are represented with a Histogram of Oriented Gradients (HOG). These HOG feature vectors are transformed as the observation sequences and then fed into the HMM. Finally, the Viterbi Algorithm is applied to recognize the sequential actions. This system has been tested on real-world data featuring three participants in a care center. We tried out three combinations of HMM with classification algorithms and found that a fusion with Support Vector Machine (SVM) had the best average results, achieving an accuracy rate (84.04%).

Suppressors of Cytokine Signaling Are Decreased in Major Depressive Disorder Patients.

There is strong evidence for an association between major depressive disorder (MDD) and inflammation. However, some studies have not observed an increase in inflammatory cytokines in MDD, and the mechanism behind this is unknown. In the present study, we evaluated MDD severity using the Montgomery-Åsberg Depression Rating Scale (MADRS) and quantified mRNA levels of the blood inflammatory cytokines interleukin (IL) 1ß, IL-6 and tumor necrosis factor alpha (TNF-α), as well as negative regulators of cytokine signaling-comprising IL-10, IL-1RA, SOCS1, SOCS2 and SOCS3-in MDD patients (n = 36), with a focus on mild MDD, and normal controls (NC, n = 30). We also measured the serum levels of IL-1ß and IL-6. Neither the blood mRNA nor the protein levels of inflammatory cytokines were significantly elevated in the MDD group compared with the NC group. However, we observed significant decreases in SOCS1, SOCS2 and SOCS3 mRNA in the MDD group compared to the NC group. A significant finding was a decrease in SOCS3 mRNA after remission from MDD, suggesting that SOCS3 is a trait marker in depressive symptoms. We consider that our findings would be useful in elucidating the pathophysiological mechanism of depression.

A case of V180I genetic mutation Creutzfeldt Jakob disease (CJD) with delusional misidentification as an initial symptom.

An 84-year-old woman who had been diagnosed as having dementia with Lewy body (DLB) upon initial examination exhibited cognitive impairments and person delusional misidentification (DMS): she transiently claimed that her spouse was a stranger. She was re-examined at the age of 89 years; her frequency of speech and activities of daily living had both decreased, leading to verbal communication difficulties complicated by sensory aphasia, and brain diffusion-weighted (DW) magnetic resonance imaging (MRI) showed cortical hyperintensities in some areas of both hemispheres. About 4 months later, the DW high-intensity areas were observed to have expanded into diffuse cortical areas. While the clinical features of Creutzfeldt Jakob disease (CJD) (myoclonus; ataxia; parkinsonism; rapidly progressive cognitive impairments; periodic sharp discharges on electroencephalograms) were not observed, a genetic analysis of the prion protein (PRNP) gene, which was performed because of a family history of dementia, revealed a V180I mutation (heterozygosis: valine/isoleucine) suggesting genetic CJD (g-CJD). Her activity progressively decreased, reaching akinetic mutism about 11 months after the re-examination. Finally, she suffered from severe bedsores and died from aspiration pneumonia at the age of 90 years. The present report describes the first case of person DMS as an initial neuropsychiatric symptom for V180I g-CJD; the typical long-term clinical symptoms of CJD were not observed in this patient. The inclusion of person DMS as an initial clinical symptom and the presence of expansive cortical hyperintensity areas may be useful for clinicians attempting to diagnosis V180I g-CJD in patients with elusive symptoms.

Real-Time Action Recognition System for Elderly People Using Stereo Depth Camera.

Smart technologies are necessary for ambient assisted living (AAL) to help family members, caregivers, and health-care professionals in providing care for elderly people independently. Among these technologies, the current work is proposed as a computer vision-based solution that can monitor the elderly by recognizing actions using a stereo depth camera. In this work, we introduce a system that fuses together feature extraction methods from previous works in a novel combination of action recognition. Using depth frame sequences provided by the depth camera, the system localizes people by extracting different regions of interest (ROI) from UV-disparity maps. As for feature vectors, the spatial-temporal features of two action representation maps (depth motion appearance (DMA) and depth motion history (DMH) with a histogram of oriented gradients (HOG) descriptor) are used in combination with the distance-based features, and fused together with the automatic rounding method for action recognition of continuous long frame sequences. The experimental results are tested using random frame sequences from a dataset that was collected at an elder care center, demonstrating that the proposed system can detect various actions in real-time with reasonable recognition rates, regardless of the length of the image sequences.

Blood DNA Methylation Levels in the WNT5A Gene Promoter Region: A Potential Biomarker for Agitation in Subjects with Dementia.

BACKGROUND: Behavioral and psychological symptoms of dementia (BPSD) cause a heavy burden for both patient and caregivers. These symptoms are diverse, and their mechanism is still unclear. Agitation is the most common and difficult to treat among BPSD. In recent years, while changes in DNA methylation levels have been receiving attention as a biomarker of aging and dementia, associations with BPSD have not been examined. OBJECTIVE: Focusing on agitation, the objective of the present study was to identify a region where changes in DNA methylation levels are associated with agitation. METHODS: Using genome-wide DNA methylation analysis data for 7 dementia subjects with agitation, 5 dementia subjects without agitation, and 4 normal elderly controls, we determined a signaling pathway in the WNT5A gene promoter region to be associated with agitation. Based on this result, we measured DNA methylation levels in this region for 26 dementia subjects with agitation and 82 dementia subjects without agitation by means of methylation-sensitive high-resolution melting (MS-HRM) analysis. RESULTS: The WNT5A DNA methylation level in dementia subjects with agitation was significantly lower than in those without agitation (p = 0.001). Changes in WNT5A DNA methylation levels were not influenced by age, sex, body mass index, APOE ɛ4, medication, or inflammatory cytokines. CONCLUSION: Our results suggested an association of agitation with Wnt signaling, in particular with changes in WNT5A DNA methylation levels, which could be a potentially useful biomarker for predicting the appearance of agitation. It may contribute to the elucidation of the mechanism of BPSD.

Intensive diagnostic management of coronavirus disease 2019 (COVID-19) in academic settings in Japan: challenge and future.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first emerged in Wuhan, China, and has spread globally to most countries. In Japan, the first COVID-19 patient was identified on January 15, 2020. By June 30, the total number of patients diagnosed with COVID-19 reached 18,000. The impact of molecular detection of pathogens is significant in acute-care settings where rapid and accurate diagnostic measures are critical for decisions in patient treatment and outcomes of infectious diseases. Polymerase chain reaction (PCR)-based methods, such as quantitative PCR (qPCR), are the most established gene amplification tools and have a comprehensive range of clinical applications, including detecting a variety of pathogens, even novel agents causing emerging infections. Because SARS-CoV-2 contains a single-stranded RNA genome, reverse-transcription qPCR (RT-qPCR) has been broadly employed for rapid and sensitive quantitative measurements of viral RNA copy numbers. The RT-qPCR method, however, still requires time-consuming reactions with two different enzymes in addition to isolation of RNA from patient samples, limiting the numbers of testing institutions for diagnosing SARS-CoV-2 infection. Japan is known to have performed a relatively small number of PCR tests as well as confirmed cases among developed nations; as of June 30, 2020, approximately 390,000 people in Japan had undergone PCR tests. Given the devastating impact on medical services and the scale of demand for diagnostic testing of COVID-19, it has been proposed that academic settings such as basic research departments in university/college can be engaged in diagnosing, especially in university hospitals or academic medical centers. In collaboration with established diagnostic laboratories, academic facilities can divert their function to detecting virus from patients with suspected COVID-19, adopting existing specialized expertise in virus handling, molecular work, and data analysis. This in-house testing strategy facilitates the rapid diagnosing of thousands of samples per day and reduces sample turnaround time from 1 week to less than 24 h. This review provides an overview of the general principles, diagnostic value, and limitations of COVID-19 diagnosis platforms in Japan, in particular in-house testing at academic settings.

Cooperative activation of the human herpesvirus 6B U79/80 early gene promoter by immediate-early proteins IE1B and IE2B.

The human herpesvirus 6B (HHV-6B) U79/80 gene belongs to the early gene class and appears as early as 3 hr postinfection. It is one of the most abundantly expressed transcripts and a useful diagnostic marker for viral reactivation. However, the expression mechanisms of the U79/80 gene remain unclear. To identify the viral factor(s) that activates the U79/80 promoter along with other HHV-6B core early gene promoters, p41, DNA polymerase, and U41, we examined the activities of U79/80 and other early gene promoters. In HHV-6B-infected MT-4 cells, U79/80 promoter activity was the highest among early gene promoters. In addition, we identified that HHV-6B immediate-early (IE)2B protein is one of the viral proteins involved in the activation of the U79/80 and other early gene promoters. Although the IE2B could independently activate these early gene promoters, the presence of IE1B significantly augmented the activities of early gene promoters. We also found that IE2B bound three human cytomegalovirus IE2-binding consensus, cis repression signal (CRS), within the U79/80 promoter. Moreover, the U79/80 promoter was activated by cellular factors, which are highly expressed in MT-4 cells, instead of HeLa cells because it was upregulated by mock infection and in the absence of IE2B. These results suggested that the activation mechanism of the U79/80 gene differs from other HHV-6B core early genes, apparently supporting its rapid and abundant expression. Therefore, the U79/80 early gene is an actually suitable biomarker of HHV-6B reactivation.

Neutrophil-to-Lymphocyte Ratio and Intratumoral CD45RO-Positive T Cells as Predictive Factors for Longer Survival of Patients with Colorectal Liver Metastasis after Hepatectomy.

Colorectal cancer is the fourth most common malignancy across the world, and over 50% of patients had colorectal liver metastases (CLM). Activated neutrophils and tumor-infiltrating lymphocytes (TILs) are considered to interrupt progression of primary colorectal cancer; however, immunological host reactions to CLM have not been fully elucidated. We thus aimed to explore the prognostic implication of neutrophil-to-lymphocyte ratio (NLR) in peripheral blood and TILs in resected metastatic cancer tissues of 29 patients with CLM who underwent hepatectomy. To evaluate local immunological responses in CLM, we examined the infiltration of CD66b+ neutrophils and TILs, such as CD8+ T cells, CD45RO+ T cells, and forkhead box P3+ (FOXP3+) T cells. The presence of fewer than 4 tumors (p = 0.0005), the absence of distant metastasis (p = 0.018), adjuvant anti-cancer chemotherapy (p = 0.0013), and elevated NLR over 4.1 (p = 0.026) were found to be significant parameters related to longer survival after hepatectomy. Further, high numbers of infiltrated CD45RO+ T cells in CLM were significantly associated with longer patient survival (p = 0.020). The numbers of CD45RO+ T cells were correlated with those of CD8+ T cells (p = 0.008). The numbers of peripheral blood neutrophils were negatively correlated with those of CD45RO+ T cells (p = 0.038) and of CD66b+ neutrophils (p = 0.008) in CLM. The present data indicate that elevated peripheral blood NLR and high numbers of intratumoral CD45RO+ T cells are predictive of longer CLM patient survival after hepatectomy among current biomarkers.

Increased blood COASY DNA methylation levels a potential biomarker for early pathology of Alzheimer's disease.

Early diagnosis of dementia including Alzheimer's disease (AD) is an urgent medical and welfare issue. However, to date, no simple biometrics have been available. We reported that blood DNA methylation levels of the COASY gene, which encodes coenzyme A synthase, were increased in individuals with AD and amnestic mild cognitive impairment (aMCI). The present study sought to replicate these findings with larger numbers of samples. Another objective was to clarify whether COASY methylation is associated with neurodegeneration through a comparison of AD, AD with cardiovascular disease (CVD), and vascular dementia (VaD). We measured blood COASY methylation levels in normal controls (NCs) (n = 200), and individuals with aMCI (n = 22), AD (n = 151), and VaD (n = 21). Compared with NCs, they were significantly higher in individuals with aMCI and AD. Further, they were significantly higher in AD patients without cardiovascular diseases compared to AD patients with them. These findings suggest that COASY methylation levels may be related to neurodegeneration in AD.

Human Herpesvirus 6B Greatly Increases Risk of Depression by Activating Hypothalamic-Pituitary -Adrenal Axis during Latent Phase of Infection.

Little is known about the effect of latent-phase herpesviruses on their host. Human herpesvirus 6B (HHV-6B) is one of the most ubiquitous herpesviruses, and olfactory astrocytes are one of the most important sites of its latency. Here, we identified SITH-1, an HHV-6B latent protein specifically expressed in astrocytes. Mice induced to produce SITH-1 in their olfactory astrocytes exhibited olfactory bulb apoptosis, a hyper-activated hypothalamic-pituitary-adrenal (HPA) axis and depressive symptoms. The binding of SITH-1 to the host protein calcium-modulating ligand (CAML) to form an activated complex promoted the influx of extracellular calcium. The serum antibody titers for depressive patients with respect to this activated complex were significantly higher than for normal controls (p = 1.78 × 10-15), when the antibody positive rates were 79.8% and 24.4%, respectively, and the odds ratio was 12.2. These results suggest that, in the latent phase, HHV-6B may be involved in the onset of depression.

Impact of Anatomical Resection for Hepatocellular Carcinoma With Microportal Invasion (vp1): A Multi-institutional Study by the Kyushu Study Group of Liver Surgery.

OBJECTIVE: The aim of the present study was to evaluate the value of anatomical resection for hepatocellular carcinoma (HCC) with microportal vascular invasion (vp1) between 2000 and 2010. BACKGROUND: Vascular invasion has been reported as a prognostic factor of liver resection for HCC. Anatomical resection for HCC has resulted in optimum outcomes of eradicating intrahepatic micrometastases through the portal vein, but opposite results have also been reported. METHODS: A clinical chart review was performed for 546 patients with HCC with vp1. We retrospectively evaluated the recurrence-free survival (RFS) between anatomical (AR) and nonanatomical resection (NAR). The site of recurrence was also compared between these groups. The influence of AR on the overall survival (OS) and RFS rates was analyzed in patients selected by propensity score matching, and the prognostic factors were identified. RESULTS: A total of 546 patients were enrolled, including 422 in the AR group and 124 in the NAR group. There was no difference in the 5-year OS and RFS rates between the 2 groups. Local recurrence was significantly more frequent in the NAR group than in the AR group. In a multivariate analysis, hepatitis C virus, serum protein induced by vitamin K absence II of 380 mAU/mL or more, tumor diameter of 5 cm or more, and age of 70 years or older were significant predictors of a poor RFS after liver resection. There were no significant differences in the OS or RFS between the AR and NAR groups by a propensity score-matched analysis. CONCLUSIONS: Although local recurrence around the resection site was suppressed by AR, AR for HCC with vp1 did not influence the RFS or OS rates after hepatectomy in the modern era.

Intratumoral reciprocal expression of monocarboxylate transporter 4 and glypican-3 in hepatocellular carcinomas.

OBJECTIVE: We previously reported the identification of monocarboxylate transporter 4 (MCT4) and glypican-3 (GPC3) as prognostic factors for hepatocellular carcinoma (HCC), which are now considered significant poor prognostic factors for the disease. This study aimed to clarify the detailed interaction of these two factors in HCC to improve our understanding of aggressive HCC phenotypes. A total of 225 Japanese patients with HCC from our previous study were subjected to immunohistochemical analyses. RESULTS: The number of MCT4-positive (MCT4+) HCC cases was 47 (21%), and most MCT4+ HCC showed high GPC3 expression (94%, 44/47 cases). In 44 MCT4+/GPC3+ HCC cases, intratumoral heterogeneity of GPC3 or MCT4 expression was further evaluated. We observed reciprocal (inverse), synergistic, mixed reciprocal and synergistic, or irrelevant interaction of MCT4 and GPC3 expression in 29 (66%), 5 (11%), 1 (2%), and 9 cases (21%), respectively. The cases exhibiting reciprocal expression of both markers tended to have cirrhosis without a history of neoadjuvant therapy. In summary, although MCT4+ HCC cases are mostly GPC3+, intratumoral expression patterns of MCT4 and GPC3 are frequently reciprocal each other, suggesting that dual targeting of MCT4 and GPC3 may achieve a better antitumor effect for MCT4+ HCC cases.

Attenuation of human herpesvirus 6B reactivation by aging.

OBJECTIVE: There has been little research on human herpesvirus 6B (HHV-6B) in healthy adults and prevalences in different age groups have been unclear. Therefore, the major objective of this study was to evaluate seroprevalence to HHV-6 antibodies in ordinary working people and examine the effect of aging on seroprevalence. Also, as HHV-6B is reactivated in saliva, another objective was to investigate an association between age and HHV-6B reactivation based on measured salivary HHV-6 DNA levels. METHODS: Our subjects were 77 ordinary office workers who underwent a health checkup. In this population, we measured anti-HHV-6 antibody titers using enzyme-linked immunosorbent assay and salivary HHV-6 DNA levels. In addition to examining an association with age, we examined associations with body mass index, smoking habit, and alcohol consumption as confounding factors. RESULTS: There was a significant decrease in the seropositivity of HHV-6 antibodies in subjects of 50 years and older, and age was significantly negatively correlated with anti-HHV-6 antibody titers. Age and salivary HHV-6 DNA levels were also significantly negatively correlated but there were no significant correlations with other factors. CONCLUSIONS: Our results suggest that HHV-6B reactivation is attenuated by aging. Thus, HHV-6 antibodies steadily decrease in the body with aging.

Clinical significance of cancer-related fatigue in multiple myeloma patients.

Cancer-related fatigue (CRF) is one of the adverse events in multiple myeloma (MM) patients treated with cytotoxic agents, proteasome inhibitors (PIs), and immunomodulatory drugs (IMiDs) such as bortezomib, lenalidomide, and thalidomide. The aims of our study were to prospectively analyze the clinical significance of CRF, and to evaluate the cumulative incidence of CRF and the survival rates of 16 MM patients who were treated with PIs and IMiDs. Reactivation of salivary human herpes virus (HHV)-6 and HHV-7 was analyzed using real-time quantitative polymerase chain reaction (qPCR). CRF was evaluated using a visual analog scale (VAS). Eleven newly diagnosed multiple myeloma (NDMM) and five relapsed or refractory MM patients were enrolled in this study. The cumulative incidence of CRF was 54.9%. The treatment types were not associated with the CRF incidence. The cumulative incidence of reactivation of HHV-6 and HHV-7 was 73.1% and 45.6%, respectively. However, the reactivation of HHV-6 and HHV-7 was not related to CRF. The overall survival (OS) and progression-free survival (PFS) in NDMM patients with CRF was significantly shorter than in those without CRF. In conclusion, CRF was one of the major symptoms in MM patients, and predicted shorter OS and PFS in NDMM patients.

Prediction of Posthepatectomy Liver Failure Proposed by the International Study Group of Liver Surgery: Residual Liver Function Estimation With 99mTc-Galactosyl Human Serum Albumin Scintigraphy.

PURPOSE: The International Study Group of Liver Surgery (ISGLS) proposed a definition and grading system for posthepatectomy liver failure (PHLF). We evaluated the usefulness of residual liver function estimation using Tc-galactosyl human serum albumin (Tc-GSA) for the prediction of PHLF. METHODS: Patients with liver tumors (n = 136) and scheduled for hepatectomy underwent Tc-GSA scintigraphy. Based on their imaging data, the maximal GSA removal rate (GSA-Rmax)was calculated using multicompartment analysis. We also calculated GSA-Rmax in the predicted residual liver (GSA-RL) whose volume was determined on computed tomography (CT) scans. We compared the age, sex, 15-minute indocyanine green retention rate; albumin, bilirubin, hyaluronic acid, and type 4 collagen levels; the Child-Pugh classification; residual liver volume; residual liver percentage; GSA-Rmax; and GSA-RL in patients with and without PHLF. Univariate and multivariate logistic analyses were used for statistical assessments. RESULTS: Of 136 patients, 17 (12.5%) met the ISGLS criteria for PHLF (ISGLS-PHLF). There was a statistically significant difference in the age, albumin level, Child-Pugh classification, residual liver volume, residual liver percentage, GSA-Rmax, and GSA-RL between patients with and without PHLF. Based on multivariate analysis, GSA-RL and the residual liver volume were significant independent predictors of ISGLS-PHLF (P = 0.004 and P = 0.038, respectively). The odds ratio was 149423 for GSA-RL and 1.003 for the residual liver volume. CONCLUSIONS: GSA-RL calculated using Tc-GSA scintigraphy was the most useful independent predictor for ISGLS-PHLF.