Survey of Medical Referral by Japanese Dentists for Patients With Hepatitis B, Hepatitis C, and Lichen Planus.

OBJECTIVES: This study aimed to investigate the referral rates of oral lichen planus (OLP) and untreated hepatitis virus-infected patients by dentists to hepatologists. MATERIALS AND METHODS: The study was conducted at three dental clinics in the Oita prefecture between November 2021 and June 2023. Two distinct groups of patients who visited the dentist for dental treatment were included: those with liver disease and concurrent hepatitis C virus (HCV) or hepatitis B virus (HBV) infection and those diagnosed with OLP. The rate of medical referrals to a hepatologist was investigated. Data on the number of patients, gender, age, diagnosis of liver disease, and referral practices were collected from the records submitted by each dental clinic. Information about the HCV and HBV infection status was collected through interviews with the dentists. RESULTS: A total of 1,665 patients were included, of which 10 were HCV-infected, five were HBV-infected, and six were diagnosed with OLP. None of the 15 patients with liver disease were referred to a hepatologist by their dentists. Nine out of the 10 HCV-infected patients had achieved sustained virological response (SVR) after antiviral treatment. Of the six patients with OLP, one had a history of HBV infection, one had severe fatty liver, and the remaining four had normal livers; five of the OLP patients were referred to a hepatologist (83.3%). CONCLUSION: A high referral rate from dentists to hepatologists was observed among the OLP patients. However, the study highlighted the difficulties in identifying hepatitis patients and establishing appropriate medical coordination in dental institutions.

Hepatitis B and C infections among Japanese dental health workers: Insights from vaccination rates and screening results in the Oita prefecture.

OBJECTIVE: This study examined the hepatitis B virus (HBV) and hepatitis C virus (HCV) infection rates and vaccination rates for hepatitis B (HB) among dental healthcare workers (DHCWs) in the Oita prefecture, Japan. METHODS: Hepatitis virus testing was conducted on 1920 participants (486 dentists and 1434 dental staff). Anonymous data on age, gender, occupation, hepatitis B surface antigen (HBsAg), antibodies to hepatitis B surface antigen (anti-HBs), antibodies to HCV (anti-HCV), history of HB vaccination, and antiviral treatment for individuals with positive anti-HCV were collected. RESULTS: The positivity rates for HBsAg, anti-HBs, and anti-HCV were 0.5%, 39.7%, and 0.6%, respectively. Dentists had significantly higher rates of anti-HBs positivity (53.9% vs. 34.9%; p < .0001) and anti-HCV positivity (1.4% vs. 0.3%; p = .0080) compared to dental staff. The vaccination and non-vaccination rates among 1395 with a known HB vaccination history were 59.1% and 40.9%, respectively. Dentists had a significantly higher HB vaccine vaccination rate than the dental staff (73.6% vs. 54.0%; p < .0001). Those in the vaccination group were younger (p < .0001), had a higher proportion of males (p = .0022) and dentists (p < .0001), a lower HBsAg positivity rate (p < .0097), and a higher anti-HBs positivity rate (p < .0001) compared to those in the non-vaccination group. The positivity rate of HBsAg and anti-HBs in the unvaccinated group increased with age, with HBsAg positivity reaching 3.8% in the 70s and anti-HBs positivity reaching 40.4% in the 70s and 66.7% in the 80s. CONCLUSIONS: This study highlights the need to raise awareness about hepatitis prevention vaccination, particularly among dental staff, due to differences in HB vaccination rates across occupations. In particular, they indicated that elderly DHCWs may be more vulnerable to HBV infection. Regular monitoring of the vaccination rate and infection risk is crucial.

Onset of Oral Lichen Planus Led to Direct-Acting Antiviral Therapy in a Patient with Long-Term Hepatitis C: The Role of a Dentist as Gatekeeper.

Oral lichen planus (OLP), a chronic inflammatory mucocutaneous disease, is an extrahepatic manifestation of a hepatitis C virus infection. In recent years, direct-acting antivirals (DAAs) have made great strides in the treatment of hepatitis C. However, there might be a lack of information about the treatment strategies available among those with this condition. Herein, we report a case of an 85-year-old female patient who was diagnosed with hepatitis C at the age of 55 but had not received antiviral treatment over the past 30 years. She underwent DAA treatment following a recommendation from her oral surgeon after the onset of OLP. The patient had declined interferon therapy in the past, owing to concerns about its side effects. She was unaware of the benefits of DAA treatment, probably due to communication difficulties caused by senile hearing loss. Consultation with an oral surgeon for an erosive form of OLP led her to receive antiviral therapy for hepatitis C. She achieved a sustained virologic response (SVR) following the DAA treatment, along with improvements in the signs and symptoms of OLP. Oral surgeons play an important role as gatekeepers in guiding untreated hepatitis patients toward appropriate treatment.

Education and Awareness Activities Regarding Hepatitis B and C Among Japanese Dental Health Workers in the Oita Prefecture.

OBJECTIVES: Hepatitis B virus (HBV) and Hepatitis C virus (HCV) infections are known to pose a major threat for dental health workers (DHWs). Previously, we reported that the HBV and HCV infection rates among DHWs in the Oita Prefecture in Japan were higher than those among the general population. The aim of this study was to disseminate knowledge about hepatitis and its prevention among the DHWs. MATERIALS AND METHODS: Educational booklets were mailed to 2,197 DHWs working in 487 dental clinics. After anonymously responding to online questions about their experience with HBV and HCV testing, Hepatitis B vaccination, and percutaneous injury, the subjects were required to respond to additional questions about their understanding of hepatitis. RESULTS: A total of 521 DHWs (205 males and 316 females) responded to the questionnaires. Among them, 61.6% had experienced percutaneous injuries, but only 19.4% were fully aware of how to deal with them before reading the booklet, and also 10.6% had sufficient knowledge about hepatitis. The past Hepatitis B vaccination, past HBV testing rate, and past HCV testing rate were 62.4%, 71.8%, and 43.2%, respectively. The DHWs who are not dentists (n = 293) had significantly lower rates of past testing for their own hepatitis virus, knowledge about treatment of percutaneous injuries, and awareness of hepatitis as compared to dentists (n = 228). After reading the booklet, 99.5% of subjects found the booklet useful and 87.3% said it would influence their future hepatitis testing. CONCLUSION: The educational booklet was effective way to increase DHWs' knowledge about Hepatitis B and C and how to manage percutaneous injuries.

Effects of Hepatitis C Virus Elimination by Direct-Acting Antiviral Agents on the Occurrence of Oral Lichen Planus and Periodontal Pathogen Load: A Preliminary Report.

OBJECTIVE: The association between hepatitis C virus (HCV) and oral lichen planus (OLP) is well known, but the association with periodontal disease has been reported less often. The purpose of this study was to investigate the effects of periodontal bacteria and OLP lesions before and after HCV elimination. Subjects and Methods. The subjects were four OLP patients (mean age 72.5 years) with HCV infection. Six types of periodontal bacteria (Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, and Fusobacterium nucleatum) were quantified in saliva, and changes in OLP were examined before and after elimination of HCV by antiviral therapy. Biochemical blood tests also were performed. RESULTS: The total number of periodontal bacteria, the numbers of P. gingivalis, T. forsythia, T. denticola, and F. nucleatum, and the risk of presenting with the red-complex bacteria (P. gingivalis, T. forsythia, and T.denticola), leading to periodontal disease progression, decreased after HCV elimination. OLP disappeared in three of the four patients and decreased in the other after sustained virological responses (SVRs). CONCLUSION: HCV elimination not only improved OLP lesions but also reduced the number of periodontal pathogens and the amount of red-complex periodontal pathogens.

Effect of Oral Care in a Patient with Depression and Burning Mouth Syndrome during the COVID-19 Pandemic.

Burning mouth syndrome (BMS) is a burning sensation that occurs in the mouth without any underlying cause. There is no satisfactory treatment for BMS, so far. Herein, we report the case of a 74-year-old female with untreated depression who presented with BMS. Despite taking antidepressants, she developed suicidal thoughts, particularly due to the increasing number of coronavirus disease 2019 (COVID-19) cases and suicides in Japan. The symptoms of BMS and the oral discomfort were eliminated using a multifaceted approach, which included the following: continuous application of the oral care gel "REFRECARE-H®" to the mucous membranes, regular dental visits, collaboration with medical and dental professionals, and administration of zinc preparations. Her suicidal thoughts had disappeared, and her quality of life, assessed using the visual analogue scale, was improved following the treatment. Dentists should strive to provide oral care, while providing treatment in collaboration with specialists, for the early detection of depression and zinc deficiency in patients with BMS.

The role of dentists in controlling hepatocellular carcinoma in Japan (Review).

In Japan, the method of treatment for hepatitis is well established due to the high rates of hepatitis C. However, the identification of patients with hepatitis who do not receive appropriate treatment poses a major problem. Some patients with this disease may need to consult with a dentist due to the development of extrahepatic manifestations, such as lichen planus, in the oral cavity. Alternatively, the dentist might discover patients with untreated hepatitis C and hepatitis B during routine dental examination. In such cases, the patient should be referred to a hepatologist for further examinations and treatment. Thus, dentists are required to act as 'gatekeepers of hepatitis'. Furthermore, Japanese dentists need to increase hepatitis B vaccine coverage for infection control. By acting as a 'care coordinator of hepatitis', the dentist will be able to contribute to the eradication of liver cancer in Japan, thereby eliminating the discrimination and prejudice against patients with hepatitis. Dentists need to have a deep understanding of liver disease from the viewpoints of both nosocomial infection control and treatment of oral diseases.

Analysis of hepatitis B and C virus infections amongst members of the Dental National Health Insurance Society in the Oita Prefecture.

In Japan, ~3 million individuals are estimated to be infected with hepatitis B virus (HBV) or hepatitis C virus (HCV). The rates of hepatitis virus infection amongst dentists is higher than that amongst other healthcare workers due to increased exposure to both saliva and blood. However, an efficient method for the testing of hepatitis virus infections amongst dentists remains to be established. The aim of the present study was to examine the rate of hepatitis virus infection amongst dental healthcare workers (DHWs) by introducing a health checkup that included screening for HBV and HCV infections. A total of 1,834 members of the Dental National Health Insurance Society in the Oita Prefecture, consisting of dentists and other employees, were tested for hepatitis B surface antigen (HBsAg), antibodies to HBsAg (anti-HBs) and antibodies to HCV (anti-HCV) during routine medical checkups. Anonymized data, including the age, sex, occupation (dentist or employee), and presence of a hepatitis virus marker, was collected and analyzed. The positive rates of HBsAg, anti-HBs and anti-HCV in the study sample were 0.6, 44.1 and 0.5%, respectively; the positive rates were higher amongst dentists than the employees. Furthermore, the positive rates of HBsAg and anti-HCV increased with age and were higher in subjects aged 50-79 (1.7-2.2%). The positive rate of presence of anti-HBs was significantly higher in the dentists compared with employees (56.4 vs. 39.6%; respectively; P<0.0001). The three factors associated with anti-HB positivity were HBsAg negativity, occupation (dentist) and age (20-29 years) with adjusted odds ratios of 8.29, 2.27 and 1.59, respectively (P<0.05). These results suggest that introducing a hepatitis virus examination during routine health checkups of DHWs may prove useful in identifying infected individuals.

Red complex periodontal pathogens are risk factors for liver cirrhosis.

Periodontal disease has been associated with liver disease; however, the identities of the periodontal disease-causing bacteria in patients with viral liver disease remain unknown. The aim of the present study was to determine the counts of the 3 periodontal pathogens that form the red complex in chronic periodontitis (Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola) and 3 other bacteria (Aggregatibacter actinomycetemcomitans, Prevotella intermedia and Fusobacterium necrophorum) in patients with liver disease. A total of 47 patients with liver disease were divided into two groups based on the counts of the red complex bacteria: group A (high counts of red complex bacteria) and group B (low counts of red complex bacteria). The counts of the 6 types of bacteria in saliva and the prevalence of P. gingivalis-specific fimA genotype were determined. In addition, salivary occult blood tests and serological assays were performed. Univariate and multivariate logistic regression analyses were used to analyze the risk factors between the two groups of patients. Hepatitis C virus-related liver disease was the most frequent (41/47; 87.2%) occurrence followed by liver cirrhosis (LC; 12/47; 25.5%) and oral lichen planus (32/47; 68.1%). The significant risk factors between the two groups were LC, albumin (Alb) level, ratios of each bacteria and prevalence of the fimA II genotype. The 3 factors identified in the multivariate analysis to be associated with the red complex bacteria count were low Alb level (<3.7 g/dl), LC and fimA II genotype, with adjusted odds ratios of 6.93, 4.72 and 4.08, respectively (P<0.05). These data indicated that patients with LC were at increased risk of presenting with the red complex bacteria leading to periodontal disease progression. Therefore, these patients may need to take additional care of their oral health compared with patients without LC, which may prove beneficial for the maintenance of their general health.

Effect of Oral Care Gel for Burning Mouth Syndrome in a Patient with Hepatitis C: A Case Report.

Burning mouth syndrome (BMS) is a burning sensation in the mouth with no underlying dental or medical cause. To date, there is no satisfactory treatment for BMS. Herein, we present the case of a 42-year-old female presenting with hepatitis C virus infection along with BMS. Despite two interferon therapies and a sustained virologic response, the discomfort in her oral mucosa persisted. At the age of 51, the patient complained of burning sensation and tingling pain in the tongue; a thin layer of REFRECARE-H®, an oral care gel (therapeutic dentifrice), was applied on the oral membrane after each meal for 60 days. Application of REFRECARE-H® decreased the various symptoms including tingling pain, oral discomfort, breath odor, sleep disorder, depressive mood, and jitteriness. The improvement in quality of life continued for 30 days after application of the gel. These findings indicate that REFRECARE-H® may be effective in reducing the symptoms associated with BMS. Long-term follow-up studies with larger number of patients are required to elucidate the therapeutic effects of this gel.

Genome-Wide Association Study Identifies Risk Variants for Lichen Planus in Patients With Hepatitis C Virus Infection.

BACKGROUND & AIMS: There is a close relationship between hepatitis C virus (HCV) infection and lichen planus, a chronic inflammatory mucocutaneous disease. We performed a genome-wide association study (GWAS) to identify genetic variants associated with HCV-related lichen planus. METHODS: We conducted a GWAS of 261 patients with HCV infection treated at a tertiary medical center in Japan from October 2007 through January 2013; a total of 71 had lichen planus and 190 had normal oral mucosa. We validated our findings in a GWAS of 38 patients with HCV-associated lichen planus and 7 HCV-infected patients with normal oral mucosa treated at a medical center in Italy. RESULTS: Single-nucleotide polymorphisms in NRP2 (rs884000) and IGFBP4 (rs538399) were associated with risk of HCV-associated lichen planus (P < 1 × 10-4). We also found an association between a single-nucleotide polymorphism in the HLA-DR/DQ genes (rs9461799) and susceptibility to HCV-associated lichen planus. The odds ratios for the minor alleles of rs884000, rs538399, and rs9461799 were 3.25 (95% confidence interval, 1.95-5.41), 0.40 (95% confidence interval, 0.25-0.63), and 2.15 (95% confidence interval, 1.41-3.28), respectively. CONCLUSIONS: In a GWAS of Japanese patients with HCV infection, we replicated associations between previously reported polymorphisms in HLA class II genes and risk for lichen planus. We also identified single-nucleotide polymorphisms in NRP2 and IGFBP4 loci that increase and reduce risk of lichen planus, respectively. These genetic variants might be used to identify patients with HCV infection who are at risk for lichen planus.

Successful Treatment of Oral Lichen Planus with Direct-Acting Antiviral Agents after Liver Transplantation for Hepatitis C Virus-Associated Hepatocellular Carcinoma.

Hepatitis C virus (HCV) infection is frequently associated with various extrahepatic manifestations, such as autoimmune features and immune complex deposit diseases. Oral lichen planus (OLP) is one such extrahepatic manifestation of HCV infection. Recently, direct-acting antivirals (DAA) have proved to be highly effective and safe for the eradication of HCV. Herein, we report a case of OLP accompanied by HCV-related hepatocellular carcinoma (HCC) that disappeared after liver transplantation and achievement of sustained virological response following interferon (IFN)-free treatment with ledipasvir (LDV) and sofosbuvir (SOF). The 50-year-old patient developed erosive OLP during IFN therapy, with hyperthyroidism at 53 years of age and HCC at 55 years. He received immunosuppressive drugs and IFN-free DAA treatment after liver transplantation at 60 years of age, which led to disappearance of the symptoms of OLP. The patient was treated safely and effectively with LDV/SOF, although it is not known whether the disappearance of OLP resulted from the eradication of HCV or the immunosuppressive therapy.

Use of Direct-Acting Antivirals for the Treatment of Hepatitis C Virus-Associated Oral Lichen Planus: A Case Report.

Hepatitis C virus (HCV) is frequently associated with various extrahepatic manifestations such as autoimmune features and immune complex deposit diseases. Oral lichen planus (OLP) is one of the representative extrahepatic manifestations of HCV infection. Direct-acting antivirals (DAA) are highly effective and safe for the eradication of HCV. However, there is a lack of information regarding the association between HCV-associated OLP and interferon (IFN)-free DAA therapy. Herein, we present the case of a 60-year-old female who was diagnosed with OLP during routine periodontal treatment by a dentist. The patient was referred for hepatitis C treatment using IFN-free DAA, which resulted in the improvement of the symptoms of OLP. This case represents the safety and efficacy of IFN-free DAAs in patients with HCV-associated OLP. However, long-term follow-up studies are required to elucidate the therapeutic effects of this therapy in these patients.

Successful Treatment of Hepatitis C Virus-associated Oral Lichen Planus by Interferon-free Therapy with Direct-acting Antivirals.

OBJECTIVES: Oral lichen planus (OLP) is one of the extrahepatic manifestations of hepatitis C virus (HCV) infection. Presently developed interferon (IFN)-free direct-acting antivirals (DAAs) used to treat HCV infection have low side effect profiles and high efficacy. However, there are no studies examining the relationship between OLP and IFN-free DAAs. The aim of this study was to evaluate the disease course in patients with HCV-associated OLP, who received treatment with IFN-free DAAs. METHODS: Seven patients with HCV-related OLP (including one with cutaneous LP), who received IFN-free treatment with daclatasvir (DCV)/asunaprevir (ASV) at our hospital in Japan from October, 2014 to February, 2015 were enrolled in the study. The subjects included four males and three females (average age, 73.9 years). We compared the symptoms of OLP in the patients before and at 24 weeks after the end of DAA therapy. RESULTS: No worsening of symptoms was observed during treatment with the DAAs. The symptoms of OLP had subsided in all seven patients. Lesions of OLP and cutaneous LP disappeared in four, and improved in three of the seven patients after sustained virological response 24. No systemic clinical adverse events were observed in all patients. CONCLUSIONS: Herein, we have reported the outcomes of HCV-associated OLP in patients who received successful treatment with IFN-free DAAs, using the DCV/ASV combination therapy.

Effects of branched-chain amino acids and zinc-enriched nutrients on prognosticators in HCV-infected patients: a multicenter randomized controlled trial.

Branched­chain amino acids (BCAAs) and trace element deficiencies are associated with poor prognosis in hepatitis C virus (HCV)­infected patients. The aim of this study was to investigate the effects of BCAA and zinc­enriched supplementation on prognostic factors in HCV­infected patients. Fifty­three HCV­infected patients were enrolled in this multicenter randomized controlled trial. The patients were assigned to either the placebo (n=27) or supplement group (n=26; 6,400 mg/day BCAAs and 10 mg/day zinc) and were followed up for 60 days. Primary outcomes were prognostic factors for chronic liver disease, including the serum BCAA­to­tyrosine ratio (BTR), zinc levels and α­fetoprotein (AFP) levels. There were no significant differences in any of the prognostic factors between the placebo and supplement groups at baseline. In the supplement group, the BTR and zinc levels were significantly increased compared with the placebo group (BTR: 5.14 ± 1.59 vs. 4.23 ± 1.14, P=0.0290; zinc: 76 ± 11 vs. 68 ± 11 µg/dl, P=0.0497). No significant differences were observed in AFP levels between the groups in the whole analysis. However, a stratification analysis showed a significant reduction in ΔAFP levels in the supplement group, with elevated AFP levels compared with the other groups (­2.72 ± 3.45 ng/ml, P=0.0079). It was demonstrated that BCAA and zinc­enriched supplementation increased the BTR and zinc levels in the HCV­infected patients. Furthermore, the supplementation reduced the serum AFP levels in patients who had elevated serum AFP levels at baseline. Thus, BCAA and zinc­enriched supplementation may prolong the survival of HCV­infected patients by improving amino acid imbalance and zinc deficiency, and by partly downregulating AFP.

Disappearance of Oral Lichen Planus After Liver Transplantation for Primary Biliary Cirrhosis and Immunosuppressive Therapy in a 63-year-Old Japanese Woman.

INTRODUCTION: There are few reports concerning association between primary biliary cirrhosis (PBC) and lichen planus. In addition, there is only one report about lichen planus after liver transplantation. CASE PRESENTATION: We describe a case of oral lichen planus (OLP) accompanied with PBC that resolved following liver transplantation 14 years later. This patient received immunosuppressive drugs after liver transplantation. DISCUSSION: The disappearance of OLP might be due to immunosuppressive therapy following liver transplantation. Further observations and studies are necessary to clarify the relationship between OLP and PBC.

Association of Periodontal Diseases and Liver Fibrosis in Patients With HCV and/or HBV infection.

BACKGROUND: Periodontal disease and systemic health are closely associated. However, there is no data supporting the association between periodontal disease and patients with liver diseases associated with hepatitis C virus (HCV) and/or hepatitis B virus (HBV) infection. OBJECTIVES: The aim of this study was to evaluate the association between periodontitis and progression of liver diseases in patients with HCV and/or HBV infection. PATIENTS AND METHODS: In this retrospective study, 351 patients with HCV- and/or HBV-related liver diseases underwent screening for periodontal disease using the Salivaster® salivary occult blood test from February 2010 to June 2014. Furthermore, we examined the prevalence of fimbrillin (fimA) genotype of Porphyromonas gingivalis (P. gingivalis) in 28 HCV-infected patients visited at our hospital between January 2013 and June 2014. P. gingivalis with fimA genotype with types I to V was further detected using a PCR method. RESULTS: Of 351 patients, 76 patients (group 1) had a strong positive result for salivary occult blood test and 275 patients (group 2) had weak positive or negative test results. Significant factors between the groups were obesity, level of AST, ALT, LDH, ALP, Alb, D.Bil, T.cho, AFP, platelets (Plt), IRI, HOMA-IR, current interferon (IFN) treatment and the daily frequency of tooth brushing. Between-groups analysis indicated that total protein (T.pro) level and liver fibrosis were significant factors. According to multivariate analysis, five factors were associated with periodontal disease as Plt count below 80000, brushing teeth only once a day, current IFN treatment, aged 65 years or older and obesity. The adjusted odds ratios for these five factors were 5.80, 3.46, 2.87, 2.50 and 2.33, respectively, and each was statistically significant. Twenty-eight saliva specimens had positive results for P. gingivalis with fimA genotype types I to V. The prevalence of fimA genotype II was higher in 14 patients with liver cirrhosis or a history of hepatocellular carcinoma treatment (group B, 50.00%) than 14 patients with only hepatitis C (group A, 21.43%). CONCLUSIONS: Periodontitis might be associated with progression of viral liver disease; hence, controlling oral disease is essential for the prevention and management of liver fibrosis.

Independent factors associated with altered plasma active ghrelin levels in HCV-infected patients.

BACKGROUND & AIMS: Metabolic disorders are frequently seen in hepatitis C virus (HCV)-infected patients. Ghrelin, a gut hormone, regulates hepatic metabolisms, and must be activated to exert its biological effects. The aims of this study were to investigate changes in plasma active ghrelin levels and identify independent factors associated with plasma active ghrelin levels in HCV-infected patients. METHODS: We enrolled patients with HCV infection (n = 96), hepatitis B virus (HBV) infection (n = 49), non-alcoholic fatty liver disease (NAFLD; n = 20) and healthy subjects (CON; n = 16). Plasma active ghrelin levels were measured using ELISA. Factors associated with plasma active ghrelin levels were assessed by multivariate and Spearman's correlation analyses. RESULTS: Plasma active ghrelin levels were significantly lower in relation to the severity of liver disease in both the HBV and HCV groups. Furthermore, HCV infection was identified as an independent factor associated with decreased plasma active ghrelin levels in the multivariate analysis (OR -3.05; 95% CI -0.93 to -19.51; P = 0.0192). Plasma active ghrelin levels were significantly correlated with serum albumin levels in the HCV group (ρ = 0.497, P < 0.0001). CONCLUSIONS: We demonstrated that liver cirrhosis and HCV infection were independent factors associated plasma active ghrelin levels. Moreover, plasma active ghrelin levels were positively correlated with serum albumin levels among HCV-infected patients. Therefore, active ghrelin levels may be regulated by both progression of liver disease and HCV infection and could be involved in the regulation of serum albumin levels in HCV-infected patients.

Chronic HCV infection was associated with severe insulin resistance and mild atherosclerosis: a population-based study in an HCV hyperendemic area.

BACKGROUND: Hepatitis C virus (HCV) affects glucose and lipid metabolism in vitro; however, it is unclear whether HCV infection is associated with insulin resistance and atherosclerosis at the population level. We aimed to investigate this association in a Japanese cohort of the Seven Countries Study, and our investigation was conducted in Tanushimaru, an HCV hyperendemic area. METHODS: A total of 1908 inhabitants of Tanushimaru were classified into 3 groups according to HCV infection status: those who were uninfected (n = 1780), those with transient infection (n = 88), and those with chronic infection (n = 40). Insulin resistance and atherosclerosis were evaluated by homeostasis model assessment for insulin resistance (HOMA-IR) and carotid intima-media thickness (IMT), respectively. Intergroup differences in variables were evaluated by age- and sex-matched multivariate regression analysis. RESULTS: Significant intergroup differences were seen in fasting glucose and insulin levels. The HOMA-IR value was significantly higher in the group with chronic infection than the values in the uninfected and transiently infected groups (3.0 ± 0.39 vs. 1.3 ± 0.03 vs. 1.5 ± 0.14; P < 0.001). In contrast, low-density lipoprotein (LDL)-cholesterol and triglyceride levels were significantly lower in the group with chronic infection than the levels in the other groups. IMT was reduced in the group with chronic infection, with a significant intergroup difference (0.67 ± 0.02 vs. 0.71 ± 0.003 vs. 0.72 ± 0.01 mm; P = 0.003). CONCLUSIONS: This population-based study in an HCV hyperendemic area revealed that chronic HCV infection was associated with severe insulin resistance and with mild atherosclerosis, suggesting a unique characteristic of HCV-related metabolic abnormality.

Development and application of an indirect enzyme-linked immunosorbent assay for serological survey of Japanese encephalitis virus infection in dogs.

Japanese encephalitis virus (JEV) causes serious acute encephalitis in humans and horses. Although dogs are good sentinels for assessing the risk of JEV infection to humans, a virus neutralization test has been the only method available for measuring the levels of JEV antibody in dogs. In this study, an indirect enzyme-linked immunosorbent assay (ELISA) using purified viral particles as an antigen, was developed for serological survey of JEV infection in dogs. In dogs inoculated experimentally with JEV, the ELISA detected anti-JEV IgM 3 days after infection, with IgM levels peaking 7 days after infection. Anti-JEV IgG was detected 14 days after infection and peaked on 21-28 days after infection. Virus neutralization titers correlated with anti-JEV immunoglobulins measured by the ELISA. To test the utility of the new assay, the seroprevalence of JEV infection among 102 dogs in Kyushu, Japan, was examined by IgG ELISA and by virus neutralization. The correlation coefficient between the IgG ELISA and virus neutralization was 0.813 (p<0.001); comparison of the IgG ELISA and virus neutralization showed a sensitivity and specificity of 82% and 98%, respectively. The IgG ELISA was used to survey dogs in Bangkok, Thailand and 51% of these dogs were found seropositive for JEV. These data suggest that in the capital city of Thailand, the risk of infection with JEV remains high.