Revolutionizing our understanding of Parkinson's disease: Dr. Heinz Reichmann's pioneering research and future research direction.

Millions of individuals around the world are afflicted with Parkinson's disease (PD), a prevalent and incapacitating neurodegenerative disorder. Dr. Reichmann, a distinguished professor and neurologist, has made substantial advancements in the domain of PD research, encompassing both fundamental scientific investigations and practical applications. His research has illuminated the etiology and treatment of PD, as well as the function of energy metabolism and premotor symptoms. As a precursor to a number of neurotransmitters and neuromodulators that are implicated in the pathophysiology of PD, he has also investigated the application of tryptophan (Trp) derivatives in the disease. His principal findings and insights are summarized and synthesized in this narrative review article, which also emphasizes the challenges and implications for future PD research. This narrative review aims to identify and analyze the key contributions of Reichmann to the field of PD research, with the ultimate goal of informing future research directions in the domain. By examining Reichmann's work, the study seeks to provide a comprehensive understanding of his major contributions and how they can be applied to advance the diagnosis and treatment of PD. This paper also explores the potential intersection of Reichmann's findings with emerging avenues, such as the investigation of Trp and its metabolites, particularly kynurenines, which could lead to new insights and potential therapeutic strategies for managing neurodegenerative disorders like PD.

Dermatoscopic patterns of cutaneous metastases: A multicentre cross-sectional study of the International Dermoscopy Society.

BACKGROUND: The detection of cutaneous metastases (CMs) from various primary tumours represents a diagnostic challenge. OBJECTIVES: Our aim was to evaluate the general characteristics and dermatoscopic features of CMs from different primary tumours. METHODS: Retrospective, multicentre, descriptive, cross-sectional study of biopsy-proven CMs. RESULTS: We included 583 patients (247 females, median age: 64 years, 25%-75% percentiles: 54-74 years) with 632 CMs, of which 52.2% (n = 330) were local, and 26.7% (n = 169) were distant. The most common primary tumours were melanomas (n = 474) and breast cancer (n = 59). Most non-melanoma CMs were non-pigmented (n = 151, 95.6%). Of 169 distant metastases, 54 (32.0%) appeared on the head and neck region. On dermatoscopy, pigmented melanoma metastases were frequently structureless blue (63.6%, n = 201), while amelanotic metastases were typified by linear serpentine vessels and a white structureless pattern. No significant difference was found between amelanotic melanoma metastases and CMs of other primary tumours. CONCLUSIONS: The head and neck area is a common site for distant CMs. Our study confirms that most pigmented melanoma metastasis are structureless blue on dermatoscopy and may mimic blue nevi. Amelanotic metastases are typified by linear serpentine vessels and a white structureless pattern, regardless of the primary tumour.

Neural Correlates and Molecular Mechanisms of Memory and Learning.

Memory and learning are essential cognitive processes that enable us to obtain, retain, and recall information [...].

The Impact of C-3 Side Chain Modifications on Kynurenic Acid: A Behavioral Analysis of Its Analogs in the Motor Domain.

The central nervous system (CNS) is the final frontier in drug delivery because of the blood-brain barrier (BBB), which poses significant barriers to the access of most drugs to their targets. Kynurenic acid (KYNA), a tryptophan (Trp) metabolite, plays an important role in behavioral functions, and abnormal KYNA levels have been observed in neuropsychiatric conditions. The current challenge lies in delivering KYNA to the CNS owing to its polar side chain. Recently, C-3 side chain-modified KYNA analogs have been shown to cross the BBB; however, it is unclear whether they retain the biological functions of the parent molecule. This study examined the impact of KYNA analogs, specifically, SZR-72, SZR-104, and the newly developed SZRG-21, on behavior. The analogs were administered intracerebroventricularly (i.c.v.), and their effects on the motor domain were compared with those of KYNA. Specifically, open-field (OF) and rotarod (RR) tests were employed to assess motor activity and skills. SZR-104 increased horizontal exploratory activity in the OF test at a dose of 0.04 µmol/4 µL, while SZR-72 decreased vertical activity at doses of 0.04 and 0.1 µmol/4 µL. In the RR test, however, neither KYNA nor its analogs showed any significant differences in motor skills at either dose. Side chain modification affects affective motor performance and exploratory behavior, as the results show for the first time. In this study, we showed that KYNA analogs alter emotional components such as motor-associated curiosity and emotions. Consequently, drug design necessitates the development of precise strategies to traverse the BBB while paying close attention to modifications in their effects on behavior.

Peripheral Venous Pressure Measurements to Evaluate Congestion in Heart Failure.

BACKGROUND: Accurate bedside assessment of congestion in the management of patients with heart failure remains challenging. As a continuous conduit of circulating fluid, systemic congestion represented by high right atrial pressure (RAP) may be reflected by peripheral venous pressure (PVP). We evaluated the reliability of PVP measurements for assessing congestion beyond conventional clinical assessments. METHODS AND RESULTS: We performed conventional congestion assessments and PVP measurements in 95 patients undergoing pulmonary artery catheterization. PVP was measured via the 22-gauge peripheral venous access placed in the upper extremity. The median RAP and PVP was 7 (interquartile range [IQR]: 5-11) mmHg and 9 (IQR: 7-12) mmHg, respectively, with a mean bias of 1.8 ± 2.6 mmHg. PVP exhibited a strong linear correlation with RAP (Spearman R = 0.81; P < 0.001). PVP demonstrated greater discriminatory power for both RAP ≤ 8 mmHg (area under the curve [AUC]: 0.91 [95% confidence interval: 0.85-0.97]; sensitivity: 75%; specificity: 87%) and RAP > 12 mmHg (AUC: 0.98 [0.95-1.00]; sensitivity: 88%; specificity: 95%) than edema, jugular venous pressure, pulmonary congestion on chest radiograph, B-type natriuretic peptide levels, and inferior vena cava diameter. CONCLUSIONS: PVP measured via peripheral venous access strongly correlates with invasively obtained RAP. PVP measurements may improve current bedside assessments of congestion.

Optically Transparent and Color-Stable Elastomer with Structural Coloration under Elongation.

Optically transparent and colored elastomers with high toughness are expected to play an important role in the construction of advanced medical materials, wearable displays, and soft robots. In this study, we found that composite elastomers consisting of amorphous SiO2 particles homogeneously dispersed in high concentrations within a biocompatible acrylic polymer network exhibit optical transparency and bright structural colors. In the composite elastomers, the system in which the SiO2 particles form a colloidal amorphous array hardly changes its structural color hue despite deformation due to elongation. Furthermore, the composite elastomer of the SiO2 particles with the acrylic polymer network also results in high mechanical toughness. In summary, we have shown that the elastomer that exhibits fade-resistant structural coloration formed from safe materials can combine stable coloration and mechanical strength independent of their shape. This is expected to have new potential in future technologies to support our daily life.

Posterior lumbar fusion surgery doesn't change sexual activities in patients with lumbar degenerative disease: an observational study.

BACKGROUND: There are few studies about sexual function in the patient with posterior lumbar spinal fusion for degenerative lumbar disease. The aim of this study is to investigate sexual activities in patients with lumbar degenerative disease before and after lumbar fusion surgery. METHODS: We recruited 35 patients who underwent lumbar spinal fusion at the age of 55 years or younger. They were 17 men and 18 women with a mean age of 47.4 years. After informed consent, the patients were asked to complete anonymous questionnaire concerning sexual desire, activity, and satisfaction before and after surgery. RESULTS: In the presick period, 69% of the patients had sexual desire, and 79% achieved satisfaction during sexual activity. Lumbar degenerative disease decreased sexual desire and frequency of sexual activity in 40%, and 74% respectively. Before surgery, satisfaction in sexual activities decreased in 53%, and 55% of the patients felt discomfort during sexual activity. Adjustment in sexual position was required in 44% of man and 54% of woman. After surgery, Sexual desire, frequency of sexual activity and satisfaction did not regain after surgery in 94%, 93% and 92%, respectively. Those who did not feel discomfort after surgery was significantly lower VAS in both low back pain and leg pain than the patients felt discomfort (low back pain; p = 0.024, leg pain; p = 0.046). CONCLUSION: This study demonstrated that lumbar degenerative diseases decreased sexual desire, frequency of sexual activity and satisfaction, and little of the patients regained their sexual activities after posterior lumbar fusion surgery in the middle-aged patients.

Characteristics of older patients with postmenopausal osteoporosis who developed loss of muscle mass during the COVID-19 pandemic - a case-control study.

BACKGROUND: Under the restriction of social activities during the coronavirus disease 2019 (COVID-19) pandemic, there was concern about the loss of muscle mass due to a decrease in physical activity for the elderly. The purpose of this study was to investigate the characteristics of older patients with postmenopausal osteoporosis who developed loss of muscle mass during the COVID-19 pandemic in Japan. METHODS: A total of 54 patients with postmenopausal osteoporosis were evaluated in this study. Whole-body dual-energy X-ray absorptiometry was performed pre- and post-COVID-19 pandemic to measure trunk and lower limb muscle mass. At the time of the post-COVID-19 pandemic, we conducted a survey to compare lifestyle before pandemic (the frequency of going out, the frequency of meeting acquaintances or families living apart, regular exercise habits, walking time, family structure), and comorbidities between the muscle mass loss (ML) group and the muscle mass maintenance (MM) group. The ML group consisted of patients with at least a 5% decrease in lower limb muscle mass or trunk muscle mass. RESULTS: A significant difference was found only for the family structure (P = 0.0279); in the ML group, those living alone were the largest group, while in the MM group they were the smallest group. CONCLUSIONS: The ML group was significantly more likely to live alone than the MM group. The current study showed that loss of muscle mass was more common in patients living alone.

Potential of whole-body dual-energy X-ray absorptiometry to predict muscle size of psoas major, gluteus maximus and back muscles.

BACKGROUND: Measurement of trunk muscle cross-sectional area (CSA) using axial magnetic resonance imaging (MRI) is considered clinically meaningful for understanding several spinal pathologies, such as low back pain and spinal sagittal imbalance. However, it remains unclear whether trunk muscle mass (TMM) measured using dual-energy X-ray absorptiometry (DXA) can predict the trunk muscle CSA. The aim of this study is to determine if DXA-derived TMM is associated and predicts with CSA of paraspinal muscles and gluteus maximus measured using MRI in healthy volunteers. METHODS: A total of 48 healthy volunteers underwent whole-body DXA and MRI of the spinopelvic region. The CSA of the psoas major, back muscles, and gluteus maximus were measured on axial MRI. Correlations and linear regressions between the TMM measured using DXA and the CSA of each musculature were investigated. RESULTS: There was a weak correlation between TMM and CSA of the psoas major in men (r = 0.39, P = 0.0678), and the linear regression was y = 301.74x - 401.24 (R2 = 0.2976, P = 0.0070). A moderate correlation was found in women (r = 0.58, P = 0.0021), and the linear regression was y = 230.21x - 695.29 (R2 = 0.4445, P = 0.0003). Moderate correlations were observed between TMM and CSA of the back muscles in both men (r = 0.63, P = 0.0012) and women (r = 0.63, P = 0.0007), the linear regression was y = 468.52x + 3688.5 (R2 = 0.5505, P < 0.0001) in men and y = 477.39x + 2364.1 (R2 = 0.564, P < 0.0001) in women. There was a strong correlation between TMM and CSA of the gluteus maximus in men (r = 0.72, P < 0.0001), and the linear regression was y = 252.69x - 880.5 (R2 = 0.6906, P < 0.0001). A moderate correlation was found in women (r = 0.69, P < 0.0001), and the linear regression was y = 230.74x - 231.32 (R2 = 0.6542, P < 0.0001). CONCLUSIONS: The DXA-derived TMM was able to predict the CSA of the psoas major, back muscles, and gluteus maximus, and significantly correlated with the CSA of the back muscles and gluteus maximus. It might be a safer and cheaper alternative for evaluating the size of the back muscles and gluteus maximus.

Chromatographic printed array strip (C-PAS) method for cultivar-specific identification of sweetpotato cultivars 'Beniharuka' and 'Fukumurasaki'.

Sweetpotato (Ipomoea batatas) cultivars grown in Japan are highly valued for their excellent sweetness, high quality, and good texture. The export volume of sweetpotato from Japan has been rising rapidly, with a 10-fold increase on a weight basis over the last 10 years. However, since sweetpotato is propagated vegetatively from storage roots, it is easy to cultivate and propagate this crop, prompting concerns that Japanese sweetpotato cultivars/lines are being exported overseas, cultivated without permission, or reimported. Therefore, a rapid and accurate cultivar identification methodology is needed. In this study, we comprehensively analyzed the insertion sites of Cl8 retrotransposon to develop a cultivar identification technique for the Japanese cultivars 'Beniharuka' and 'Fukumurasaki'. These two cultivars were successfully distinguished from other cultivars using a minimum of two marker sets. Using the chromatographic printed array strip (C-PAS) method for DNA signal detection, 'Beniharuka' and 'Fukumurasaki' can be precisely identified using a single strip of chromatographic paper based on multiplex DNA signals derived from the amplicons of the Cl8 insertion sites. Since this method can detect DNA signals in only ~15 minutes, we expect that our method will facilitate rapid, reliable, and convenient cultivar discrimination for on-site inspection of sweetpotato.

Exploring Novel Therapeutic Targets in the Common Pathogenic Factors in Migraine and Neuropathic Pain.

Migraine and neuropathic pain (NP) are both painful, disabling, chronic conditions which exhibit some symptom similarities and are thus considered to share a common etiology. The calcitonin gene-related peptide (CGRP) has gained credit as a target for migraine management; nevertheless, the efficacy and the applicability of CGRP modifiers warrant the search for more effective therapeutic targets for pain management. This scoping review focuses on human studies of common pathogenic factors in migraine and NP, with reference to available preclinical evidence to explore potential novel therapeutic targets. CGRP inhibitors and monoclonal antibodies alleviate inflammation in the meninges; targeting transient receptor potential (TRP) ion channels may help prevent the release of nociceptive substances, and modifying the endocannabinoid system may open a path toward discovery of novel analgesics. There may exist a potential target in the tryptophan-kynurenine (KYN) metabolic system, which is closely linked to glutamate-induced hyperexcitability; alleviating neuroinflammation may complement a pain-relieving armamentarium, and modifying microglial excitation, which is observed in both conditions, may be a possible approach. Those are several potential analgesic targets which deserve to be explored in search of novel analgesics; however, much evidence remains missing. This review highlights the need for more studies on CGRP modifiers for subtypes, the discovery of TRP and endocannabinoid modulators, knowledge of the status of KYN metabolites, the consensus on cytokines and sampling, and biomarkers for microglial function, in search of innovative pain management methods for migraine and NP.

Emerging Translational Research in Neurological and Psychiatric Diseases: From In Vitro to In Vivo Models.

Revealing the underlying pathomechanisms of neurological and psychiatric disorders, searching for new biomarkers, and developing novel therapeutics all require translational research [...].

Simple Detection and Culture of Circulating Tumor Cells from Colorectal Cancer Patients Using Poly(2-Methoxyethyl Acrylate)-Coated Plates.

Here we aimed to establish a simple detection method for detecting circulating tumor cells (CTCs) in the blood sample of colorectal cancer (CRC) patients using poly(2-methoxyethyl acrylate) (PMEA)-coated plates. Adhesion test and spike test using CRC cell lines assured efficacy of PMEA coating. A total of 41 patients with pathological stage II-IV CRC were enrolled between January 2018 and September 2022. Blood samples were concentrated by centrifugation by the OncoQuick tube, and then incubated overnight on PMEA-coated chamber slides. The next day, cell culture and immunocytochemistry with anti-EpCAM antibody were performed. Adhesion tests revealed good attachment of CRCs to PMEA-coated plates. Spike tests indicated that ~75% of CRCs from a 10-mL blood sample were recovered on the slides. By cytological examination, CTCs were identified in 18/41 CRC cases (43.9%). In cell cultures, spheroid-like structures or tumor-cell clusters were found in 18/33 tested cases (54.5%). Overall, CTCs and/or growing circulating tumor cells were found in 23/41 CRC cases (56.0%). History of chemotherapy or radiation was significantly negatively correlated with CTC detection (p = 0.02). In summary, we successfully captured CTCs from CRC patients using the unique biomaterial PMEA. Cultured tumor cells will provide important and timely information regarding the molecular basis of CTCs.

Subjective symptoms contributing to the quality of life of rheumatoid arthritis patients with clinical remission from the IORRA database.

OBJECTIVES: To explore patient-reported outcomes (PROs) related to quality of life (QOL) in patients with rheumatoid arthritis (RA) who achieved clinical remission. METHODS: In the Institute of Rheumatology, Rheumatoid Arthritis dataset, RA patients >18 years old who met the simplified disease activity index (SDAI) remission criteria in April 2017 were enrolled in this analysis. Pain-visual analogue scale (pain-VAS) (0-100 mm), patient's global assessment of disease activity (Pt-GA; 0-100 mm), Japanese version of the Health Assessment Questionnaire, duration of morning joint stiffness, and fatigue [Checklist Individual Strength 8R (CIS)] were the tools used to evaluate PROs. To assess the contribution of each PRO to the European QOL-5 Dimensions-5 Level (EQ-5D-5L) score, an analysis of variance was conducted. RESULTS: Among the 2443 patients with remission, the mean EQ-5D-5L was 0.9. The mean pain-VAS and Pt-GA were 7.2 and 7.4, respectively. Factors that significantly contributed to the EQ-5D-5L were pain-VAS (48.8%), CIS score (18.1%), and Pt-GA (15.6%). Around 82.5% of the variance in EQ-5D-5L was explained by the three PROs. CONCLUSIONS: This study demonstrated that pain-VAS, CIS, and Pt-GA were significant contributors to the EQ-5D-5L score in patients with RA who achieved the simplified disease activity index remission criteria.

Association between patient-reported outcomes and impairments in work and activity in patients with rheumatoid arthritis in clinical remission: A retrospective analysis using the IORRA database.

OBJECTIVES: To explore the patient-reported outcomes (PROs) associated with work productivity and activity impairment (WPAI) in patients with rheumatoid arthritis (RA) in clinical remission. METHODS: We enrolled patients with RA ≥18 years and with a simplified disease activity index ≤3.3 from the Institute of Rheumatology, Rheumatoid Arthritis data set collected in October 2017. The pain-visual analogue scale, patients' global assessment visual analogue scale (VAS), Japanese version of the Healthcare Assessment Questionnaire (J-HAQ) Disability Index, and duration of morning joint stiffness were selected as the PROs. To evaluate work productivity and activity, the WPAI for RA instrument (WPAI-RA) was used. To assess the contribution of each PRO to the WPAI-RA score, an analysis of variance model was constructed. RESULTS: The mean age of the 2614 patients was 62.4 years; 85.1% were female. Median values of the WPAI-RA score were 1.1% for absenteeism, 6.5% for presenteeism, 7.4% for work impairment, and 10.2% for activity impairment. Morning joint stiffness contributed the most to absenteeism (18.0%), while pain-VAS contributed the most to presenteeism (57.4%), work productivity loss (51.1%), and daily activity impairment (53.7%). J-HAQ was the second most contributing factor to presenteeism (17.4%), work productivity loss (16.3%), and daily activity impairment (26.0%). CONCLUSIONS: The pain-VAS and J-HAQ highly contributed to WPAI in patients with RA in clinical remission.

[Outcomes of COVID-19 due to omicron variant infection complicated with hematological disorders].

When the omicron variant became the most dominant severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) variant causing coronavirus disease 2019 (COVID-19) in Japan, 11 patients with hematological diseases infected with this new variant were treated at our institution. Among them, four of the five patients who had been treated with chemotherapy progressed to moderate-II COVID-19, and two of them died. In contrast, five of the six patients who did not receive the treatment remained at mild to moderate-I stage of COVID-19, except for a single case progressing to moderate-II COVID-19. While all four patients infused with anti-coronavirus monoclonal antibodies within 8 days after the onset survived, the other two patients, being withheld from treatment or treated later, died. In these two cases, anti-SARS-Cov-2 immunoglobulin G antibodies remained at low titers. Although the omicron variant is considered a less harmful SARS-Cov-2 variant, patients with hematological disorders, particularly those who are immunosuppressed caused by chemotherapy, should be continuously cared for as they remain at a higher risk of severe COVID-19 due to insufficient or delayed anti-viral humoral immunity development. Thus, the rapid introduction of antiviral monoclonal antibodies together with anti-viral reagents may rescue these patients.

Clinical efficacy and tolerability of 1.5 g/day oral amoxicillin therapy without probenecid for the treatment of syphilis.

OBJECTIVES: Intramuscular benzathine penicillin G is not available in certain countries. In a previous report, 3 g/day amoxicillin with probenecid was shown to be effective in treating syphilis in patients with HIV; however, 7.3% of patients changed their therapy owing to adverse events. The objective of this study was to assess the clinical efficacy and tolerability of 1.5 g/day amoxicillin without probenecid for the treatment of syphilis. METHODS: The routine clinical records of patients diagnosed with syphilis and treated with 1.5 g/day amoxicillin at a tertiary care hospital between 2006 and 2018 were retrospectively analysed. Syphilis was diagnosed if serum rapid plasma reagin (RPR) titres were ≥8 RU and the Treponema pallidum latex-agglutination test was positive. Serological cure was defined as a ≥fourfold decrease in the RPR titre within 12 months in symptomatic early syphilis and within 24 months in latent syphilis. RESULTS: Overall, 138 patients (112 with HIV) were analysed. The percentages of primary, secondary, early latent, late latent and latent syphilis of unknown duration were 8.0%, 50.0%, 25.4%, 5.8% and 10.9%, respectively. The median treatment duration was 4.5 weeks (IQR 4-8 weeks), which was not related to the stage of syphilis. Two patients (1.5%) changed treatment due to skin rash. The rate of serological cure was 94.9% (131/138; 95% CI 89.8% to 97.9%) overall; 93.8% (105/112; 95% CI 87.5% to 97.5%) in patients with HIV and 100% (26/26; 95% CI 86.8% to 100%) in patients without HIV. Treatment duration was not related to the treatment efficacy. CONCLUSION: The regimen of 1.5 g/day amoxicillin without probenecid is highly effective with a low switch rate in patients with and without HIV.

Hydration Mechanism in Blood-Compatible Polymers Undergoing Phase Separation.

Interactions involving intermediate water are crucial for the design of novel blood-compatible materials. Herein, we use a combination of atomic force microscopy, quartz crystal microbalance measurements, and soft X-ray emission spectroscopy to investigate the local hydrogen-bonded configuration of water on blood-compatible poly(2-methoxyethyl acrylate) and non-blood-compatible poly(n-butyl acrylate) grafted on a gold substrate. We find that the initially incorporated water induces polymer-dependent phase separation, facilitating further water uptake. For the blood-compatible polymer, tetrahedrally coordinated water coexists with water adsorbed on C═O groups in low-density regions of the grafted polymer surface, providing a scaffold for the formation of intermediate water. The amount of intermediate water is determined by the type of functional groups, local polymer configuration, and polymer morphology. Thus, blood compatibility is governed by the complex water/polymer interactions.

Modelling the neurodevelopmental pathogenesis in neuropsychiatric disorders. Bioactive kynurenines and their analogues as neuroprotective agents-in celebration of 80th birthday of Professor Peter Riederer.

Following introduction of the monoamine oxidase type B inhibitor selegiline for the treatment of Parkinson's disease (PD), discovery of the action mechanism of Alzheimer's disease-modifying agent memantine, the role of iron in PD, and the loss of electron transport chain complex I in PD, and development of the concept of clinical neuroprotection, Peter Riederer launched one of the most challenging research project neurodevelopmental aspects of neuropsychiatric disorders. The neurodevelopmental theory holds that a disruption of normal brain development in utero or during early life underlies the subsequent emergence of neuropsychiatric symptoms during later life. Indeed, the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition and the International Classification of Diseases, 11th Revision categorize autism spectrum disorder and attention deficit hyperactivity disorder in neurodevelopmental disorders (NDDs). More and more evidence, especially from preclinical studies, is revealing that neurodevelopmental pathology is not limited to the diagnostic class above, but also contributes to the development of other psychiatric disorders such as schizophrenia, bipolar disorder, and obsessive-compulsive disorder as well as neurodegenerative diseases such as PD and Huntington's disease. Preclinical animal research is taking a lead in understanding the pathomechanisms of NDDs, searching for novel targets, and developing new neuroprotective agents against NDDs. This narrative review discusses emerging evidence of the neurodevelopmental etiology of neuropsychiatric disorders, recent advances in modelling neurodevelopmental pathogenesis, potential strategies of clinical neuroprotection using novel kynurenine metabolites and analogues, and future research direction for NDDs.

Bile acid dysmetabolism in the gut-microbiota-liver axis under hepatitis C virus infection.

BACKGROUND & AIMS: We recently analysed and reported the features of the micro biome under hepatitis C virus (HCV) infection, but the effect of HCV infection on bile acid (BA) metabolism in the gut-liver axis remains poorly understood. The aim of this study was to clarify the characteristics of the gut-liver axis in HCV-infected patients. METHODS: The faecal BAs composition and gut microbiota from 100 chronic hepatitis C (CHC) patients were compared with those from 23 healthy individuals. For transcriptional analysis of the liver, 22 mild CHC (fibrosis stages [F] 0-2) and 42 advanced CHC (F3-4) cases were compared with 12 healthy individuals. The findings were confirmed using chimeric mice with human hepatocytes infected with HCV HCR6. RESULTS: Chronic hepatitis C patients, even at earlier disease stages, showed BA profiles distinct from healthy individuals, in which faecal deoxycholic acid (DCA) was significantly reduced and lithocholic acid or ursodeoxycholic acid became dominant. The decrease in faecal DCA was correlated with reduction in commensal Clostridiales and increase in oral Lactobacillales. Impaired biosynthesis of cholic acid (CA) was observed as a reduction in the transcription level of cytochrome P450 8B1 (CYP8B1), a key enzyme in CA biosynthesis. The reductions in faecal DCA and liver CYP8B1 were also observed in HCV-infected chimeric mice. CONCLUSIONS: Chronic hepatitis C alters the intestinal BA profile, in association with the imbalance of BA biosynthesis, which differs from the pattern in NAFLD. These imbalances appear to drive disease progression through the gut-microbiome-liver axis.