Effects of Exercise Therapy and Nutrition Therapy on Patients with Possible Malnutrition and Sarcopenia in a Recovery Rehabilitation Ward.

We compared the effects of an exercise intervention with that of exercise combined with nutrition therapy in patients with possible malnutrition and sarcopenia admitted to a recovery rehabilitation ward, and we examined the differences in the patients' physical function and activities of daily living (ADLs). There were 16 patients in the Exercise group with exercise therapy and ADL exercises, and 14 patients in the Combined intervention group with exercise therapy, ADL exercises, and nutrition therapy. The survey items were body weight, body mass index, grip strength, lower-leg circumference, gait speed, and ADLs, each of which was measured at the baseline and at 2 weeks, 4 weeks, and at discharge. Significant improvements in grip strength were observed in the Combined intervention group as follows: at 4 weeks>at 2 weeks (p<0.05), and at discharge>baseline and 2 weeks (p<0.05). There were no significant changes in the Exercise group, and an interaction was recognized in both groups. Comprehensive rehabilitation including nutrition therapy is necessary for patients with possible malnutrition and/or sarcopenia, as our results indicate that nutrition therapy in addition to exercise therapy has the effect of promoting improvements of physical function in such patients.

AFP and eGFR are related to early and late recurrence of HCC following antiviral therapy.

BACKGROUND: An unexpected recurrence of hepatocellular carcinoma (HCC) sometimes occurs in patients with hepatitis C virus (HCV) after treatment with direct-acting antivirals (DAAs). However, the characteristics of patients with HCC recurrence may differ depending on time after DAA treatment. We aimed to identify risk factors related to HCC recurrence according to time after DAA treatment. METHODS: Of 1663 patients with HCV treated with a DAA, 199 patients had a previous history of HCC. We defined HCC recurrence within 1 year after DAA treatment as 'early recurrence', and recurrence more than 1 year after as 'late recurrence'. The different risk factors between the early and late phases of HCC recurrence after the end of DAA therapy were investigated. RESULTS: Ninety-seven patients experienced HCC recurrence during the study period. Incidences of recurrence were 29.8, 41.0, and 53.4% at 1, 2, and 3 years, respectively, after the end of DAA therapy. Multivariate analysis identified post-treatment α-fetoprotein (AFP) as an independent factor contributing to HCC recurrence in the early phase (hazard ratio, 1.056; 95% confidence interval, 1.026-1.087, p < 0.001) and post-treatment estimated glomerular filtration rate (eGFR) (hazard ratio, 0.98; 95% confidence interval, 0.96-0.99, p = 0.032) as a predictor of HCC recurrence in the late phase. CONCLUSION: Patients with higher post-treatment AFP in the early phase and those with lower post-treatment eGFR in the late phase had a high risk of HCC recurrence. The risk factors associated with HCC recurrence after DAA treatment were different between the early and late phases.

Sex difference in the development of hepatocellular carcinoma after direct-acting antiviral therapy in patients with HCV infection.

Sex differences in the predictors for hepatocellular carcinoma (HCC) development after direct-acting antiviral (DAA) therapy was investigated. DAA therapy was given to 1438 (663 male, 775 female) patients. Sex differences in the HCC development rate and the factors contributing to HCC development after DAA therapy were investigated. Male patients had a significantly higher cumulative HCC incidence (log-rank test, P = .007). On multivariate analysis, the fibrosis-4 index (HR = 1.11; 95%CI, 1.042-1.202, P = .002) and posttreatment α-fetoprotein (AFP) (HR = 1.11; 95%CI, 1.046-1.197, P = .001) were found to be independent factors that contributed to HCC development following DAA therapy in female patients, whereas only posttreatment AFP (HR = 1.090; 95%CI, 1.024-1.160, P = .007) was an independent factor in male patients. The optimal posttreatment AFP cut-off values were set based on receiver operating characteristic curve analyses. The optimal posttreatment AFP cut-off value was much higher in females (6.0 ng/mL) than in male (3.5 ng/mL) patients. In conclusion both in male and female patients, posttreatment AFP was an independent predictor of HCC development after DAA therapy. However, the cut-off values differed between the sexes. In male patients, HCC could be seen in patients with relatively low posttreatment AFP levels; more careful observation might be needed in such patients.

Predictors of hepatocellular carcinoma occurrence after direct-acting antiviral therapy in patients with hepatitis C virus infection.

AIM: The predictors for the development of hepatocellular carcinoma (HCC) after direct-acting antiviral (DAA) treatment were investigated. METHODS: A total of 1174 patients with chronic hepatitis C virus infection were treated with DAA therapy (sofosbuvir and ledipasvir [n = 615], sofosbuvir and ribavirin [n = 380], and daclatasvir and asunaprevir [n = 179]) and achieved sustained virologic response (SVR). The HCC development rate and the factors that might contribute to the development of HCC after the end of DAA treatment were analyzed. RESULTS: During the median observation period of 537 days, HCC developed in 33 cases. The incidence of HCC was 1.9%, 3.2%, and 4.1% at 1, 1.5, and 2 years after the end of DAA therapy, respectively. Multivariate analysis with pre- and post-treatment factors identified the Fibrosis-4 (FIB-4) index (hazard ratio [HR] = 1.09; 95% confidence interval [CI], 1.021-1.178; P = 0.011) and post-treatment α-fetoprotein (AFP) (HR = 1.11; 95% CI, 1.054-1.172; P < 0.001) as independent factors that contributed to the development of HCC after DAA therapy. Using these identified parameters, a new scoring system (0 to 2 points) was established. Patients in the high-score group (2 points) could be identified as having a significantly higher risk of HCC development, and the respective 1- and 2-year cumulative incidence rates of HCC were 6.1% and 14.4%. CONCLUSIONS: A high FIB-4 index and a high post-treatment AFP at the end of DAA treatment were the independent predictors for developing HCC after DAA treatment. For patients with these risk factors, extra attention to the possibility of HCC development is needed.

Predictors of treatment efficacy and ALT non-normalization with sofosbuvir/ribavirin therapy for patients with hepatitis C virus genotype 2.

The tolerability and efficacy of sofosbuvir and ribavirin in patients infected with hepatitis C virus (HCV) genotype 2 were investigated under actual clinical conditions. A total of 208 patients with chronic HCV genotype 2 infection were treated with sofosbuvir 400 mg and ribavirin (weight-based dosing) for 12 weeks. Treatment discontinuation and sustained virological response 12 (SVR12) were evaluated. Moreover, factors associated with SVR12, hemoglobin decreasing to less than 10 g/dL during treatment, and alanine aminotransferase (ALT) non-normalization after treatment were evaluated. In all patients, SVR12 responses were 96.1% (200/208). About 6 of 8 patients (3.8%) who did not achieve SVR12 were re-treatment patients, and eight patients who did not achieve SVR all had liver cirrhosis. Multivariate analysis also identified body mass index (OR = 0.79; P < 0.001), platelet count (OR = 0.88; P = 0.003), and estimated glomerular filtration rate (eGFR) (OR = 0.96; P = 0.007) as independent contributing factors associated with hemoglobin decreasing to less than 10 g/dL during treatment, and only Mac-2 Binding Protein Glycosylation isomer (M2BpGi) (OR = 2.46; P = 0.017) as an independent contributing factor associated with ALT non-normalization after treatment. Cirrhotic patients may have a relatively high rate of treatment failure. In patients whose M2BpGi levels are elevated, their ALT tended to not normalize after treatment completion. These patients who did not achieve normalization of ALT after sofosbuvir plus RBV treatment need more careful observation for emergence of hepatocellular carcinoma even after achievement of SVR.

Simple new clinical score to predict hepatocellular carcinoma after sustained viral response with direct-acting antivirals.

The time point of the most precise predictor of hepatocellular carcinoma (HCC) development after viral eradication with direct-acting antiviral (DAA) therapy is unclear. In this study we developed a scoring system that can accurately predict the occurrence of HCC using data from the optimal time point. A total of 1683 chronic hepatitis C patients without HCC who achieved sustained virological response (SVR) with DAA therapy were split into a training set (999 patients) and a validation set (684 patients). The most accurate predictive scoring system to estimate HCC incidence was developed using each of the factors at baseline, end of treatment, and SVR at 12 weeks (SVR12). Multivariate analysis identified diabetes, the fibrosis-4 (FIB-4) index, and the α-fetoprotein level as independent factors at SVR12 that contributed to HCC development. A prediction model was constructed with these factors that ranged from 0 to 6 points. No HCC was observed in the low-risk group. Five-year cumulative incidence rates of HCC were 1.9% in the intermediate-risk group and 15.3% in the high-risk group. The prediction model at SVR12 most accurately predicted HCC development compared with other time points. This simple scoring system combining factors at SVR12 can accurately evaluate HCC risk after DAA treatment.

Characteristics of small bowel tumors detected by double balloon endoscopy.

BACKGROUND: A few reports suggest that the emergence of double balloon endoscopy (DBE) has likely changed the clinical picture of small bowel tumors (SBTs). AIM: To further clarify the characteristics of SBTs detected by DBE. METHODS: A retrospective chart review was conducted in 227 patients who had undergone DBE. RESULTS: The SBT group contained more symptomatic patients than the non-SBT group (90% vs. 49%, P<0.0005) with a significantly higher rate of gastrointestinal symptoms at presentation (72% vs. 33%, P<0.005). Twenty patients (8.8%) were eventually diagnosed with SBT, and their indications for DBE were obscure gastrointestinal bleeding (n=5), abdominal pain (n=5), abdominal fullness (n=5), vomiting (n=2), and diarrhea (n=1). Tumors were located in the jejunum in 14 patients (70%) and in the ileum in 6 (30%). A final histological diagnosis was assigned to all 20 patients: primary adenocarcinoma (n=8, 40%), malignant lymphoma (n=5, 25%), metastatic cancer (n=4, 20%), gastrointestinal stromal tumor (n=1, 5%), carcinoid tumor (n=1, 5%) and inflammatory fibroid polyp (n=1, 5%). Stenosis or ulceration were the most frequently observed endoscopic findings (n=13, 65%). All primary adenocarcinomas and three of four (75%) metastatic cancers showed stenosis or ulceration. Three of five (60%) malignant lymphomas showed multiple lymphomatous polyps. All patients but one underwent surgical resection or chemotherapy or both. CONCLUSION: DBE is a safe and useful procedure that enables a precise diagnosis of SBTs.

Radiofrequency ablation therapy for hepatocellular carcinoma in elderly patients.

BACKGROUND AND AIM: With the aging of society, the number of elderly patients with hepatocellular carcinoma (HCC) has been increasing in Japan. The Government of Japan defines elderly as being over 65 and has divided the elderly into two stages: the first elderly stage (< 75 years old) and the second elderly stage (> or = 75). We investigated the efficacy and safety of radiofrequency ablation therapy (RFA) in patients in the second elderly stage in comparison with other HCC patients, retrospectively. METHODS: Two hundred six patients with HCC, who were within the Milan criteria, with low-grade performance status (0 or 1) and a Child-Pugh classification of A or B were enrolled. All were treated with RFA from January 2000 to December 2008 as an initial therapy and were divided into elderly HCC group (e-HCC group; > or = 75, n = 63) and non e-HCC group (< 75, n = 143), and their clinical data and survival rates were compared. RESULTS: Age and the level of protein induced by vitamin K absence or antagonist (PIVKA-II) were higher in the e-HCC group as compared with the non e-HCC group (78.3 +/- 3.2 vs 64.2 +/- 7.5 years, 676.3 +/- 2643.7 vs 142.4 +/- 442.2 mAU/mL: P < 0.01, respectively). There were no significant differences for Child-Pugh class, tumor node metastasis stage, and Japan Integrated Stage score and in survival rates after 3, and 5 years between the groups (e-HCC group: 82.5% and 49.7%, respectively; non e-HCC group: 78.3% and 57.5%, respectively). There were no severe complications in the e-HCC group. CONCLUSIONS: Elderly HCC patients, who have good performance status, should be treated in the same manner and with the same strategy as young HCC patients.

Prospective study of chronic hepatitis C treated with reduced initial ribavirin dose.

BACKGROUND/AIMS: We prospectively examined the effects of a reduced initial dose of ribavirin (RBV) combined with pegylated interferon (Peg-IFN) to prevent RBV discontinuation due to adverse events in patients with chronic hepatitis C (CH-C) infection aged > 60y or with low hemoglobin values. METHODOLOGY: We enrolled 42 patients with hepatitis C virus (HCV) serotype 1. Twenty-one of them with hemoglobin values < 14g/dl or who were aged > 60y comprised group A. The other 21 patients (sex-and age-matched with group A) comprised group B, and received Peg-IFN (1.5 microg/ kg/week) and RBV (10-13 mg/kg/day) for 48 weeks. Group A initially received 200 mg less RBV than group B. RESULTS: Higher hemoglobin values persisted at 16, 20, 24 and 44 weeks, and the sustained viral response (SVR) ratio was lower in group A than in group B (17% vs. 57%). RBV therapy was discontinued due to severe anemia in group B, but not in group A. CONCLUSIONS: The reduced initial dose of ribavirin prevented discontinuation due to anemia. However, this protocol cannot be recommended even for patients with CH-C accompanied by low hemoglobin or advanced age, since a sufficient SVR ratio is not achievable.

Diabetes pattern on the 75 g oral glucose tolerance test is a risk factor for hepatocellular carcinoma in patients with hepatitis C virus.

BACKGROUND: Patients with hepatitis C virus (HCV) frequently show glucose intolerance. Diabetes mellitus (DM) has been proposed to be a risk factor for hepatocellular carcinoma (HCC). AIMS: The aim of this study is to clarify the influence of glucose intolerance as evaluated by the 75 g oral glucose tolerance test (OGTT) on hepatocarcinogenesis in patients with HCV. METHODS: This study was carried out in a cohort of 197 patients with HCV who had not been previously diagnosed as having DM. All patients underwent the 75 g OGTT at entry. They were also screened for HCC and, thereafter, the rate of hepatocarcinogenesis was compared between the patients with and without glucose intolerance. RESULTS: Based on the results of the 75 g OGTT, 125 (63%) had normal glucose tolerance (NGT), 49 (25%) had impaired glucose tolerance (IGT) and 23 (12%) had the DM pattern. HCC occurred more frequently in patients with the DM pattern than in patients with either NGT or IGT. Even in patients without advanced liver fibrosis, HCC was more frequently observed in patients with DM than in patients with NGT. A multiple logistic regression analysis showed advanced liver fibrosis, the DM pattern on the 75 g OGTT, an older age and gamma-glutamyltransferase to all be independent risk factors related to hepatocarcinogenesis. CONCLUSIONS: A DM pattern on the 75 g OGTT was thus found to be associated with hepatocarcinogenesis and the 75 g OGTT is considered to be useful for identifying this risk factor for HCC in patients with HCV.

Drug-induced liver injury in Japan: An analysis of 1676 cases between 1997 and 2006.

At the 44th Annual Meeting of the Japan Society of Hepatology, 1674 cases of drug-induced liver injury (DILI), occurring between January 1997 and December 2006, were reviewed. Data were obtained by questionnaires completed by the 29 presenters of the special DILI session during the meeting. This article presents the review's findings, including the role of dietary supplements and Chinese herbal medicines in DILI.

Risk factors for death in 224 cases of hepatocellular carcinoma after transcatheter arterial chemoembolization.

BACKGROUND/AIMS: Transcatheter arterial chemoembolization (TACE) has been reported as effective therapy for unresectable hepatocellular carcinoma (HCC), however, few have described methods for predicting prognosis, especially in patients treated by repeated TACE. To determine risk factors for death and try to predict the prognosis, we evaluated clinical data. METHODOLOGY: We retrospectively analyzed the clinical parameters of 224 patients with unresectable HCC treated with repeated TACE from January 1997 to December 2007. TACE was repeated when recurrence was diagnosed by tumor marker elevation and/or dynamic computed tomography findings. Factors affecting survival were evaluated using multivariate analysis after univariate analysis. Next, we combined the score for each significant factor into a single prognostic score and added up the positive factors in each case, then analyzed the significance of prognosis, after which the results were compared with other prognostic scoring systems. RESULTS: Multivariate analysis revealed that bilobular HCC, alpha-fetoprotein (> or = 400 ng/ml), tumor invasion of the portal vein, tumor size (> or = 10 cm), and albumin (< 2.8 g/dl) were related to poor prognosis, and developed a prognostic scoring system from those. According to that score, patients were classified into 5 groups. CONCLUSION: Our scoring system was easily performed and the results showed that repeated TACE should not be administered to patients with scores of 3 or more.

Familial Pancreatic Cancer at Elderly Siblings in Japan.

Two female siblings aged 87 and 90 years were clinically diagnosed as pancreatic cancer by abdominal ultrasonography and abdominal contrast-enhanced CT. Pancreatic cancer of these patients was confirmed during the autopsy. Both patients shared risk factors of pancreatic cancer; old age, diabetes, and passive smoking. Strong family history of pancreatic cancer was found in these two patients as their father and younger brother were also suffering from this cancer. The present study seems to report two eldest cases of familial pancreatic cancer in siblings. How to cite this article: Kashimoto Y, Onji M, et al. Familial Pancreatic Cancer at Elderly Siblings in Japan. Euroasian J Hepatogastroenterol 2019;9(1):52-54.

Liver/spleen volume ratio as a predictor of prognosis in primary biliary cirrhosis.

BACKGROUND: The course of primary biliary cirrhosis (PBC) is determined by clinical symptoms and histological findings. The present study examined the prognostic importance of imaging parameters in PBC. METHODS: The volumes of the liver and spleen of patients with PBC were assessed by computed tomography (CT). The volume ratio of liver to spleen (LV/SV ratio) was evaluated and used for further analyses. RESULTS: The prognosis was significantly poorer in PBC patients with a low, rather than high, LV/SV ratio. The Cox proportional hazard regression model showed that the serum bilirubin level and the LV/SV ratio could predict the prognosis of PBC patients. In addition, the LV/SV ratio was significantly lower in patients who developed symptoms (s-PBC) than in those who remained asymptomatic (a-PBC) during the observation period. CONCLUSIONS: The LV/SV ratio is of prognostic importance in patients with PBC.

Neuropsychiatric dysfunction in patients with chronic hepatitis and liver cirrhosis.

AIM: The aim of this study is to clarify the cerebral functions in patients with chronic hepatitis (CH) as well as those with liver cirrhosis (LC). METHODS: We studied 58 patients with CH (20 in fibrosis stage F1, 20 in F2, 18 in F3), 77 with LC (46 rated as Child-Pugh class A, 24 as B, 7 as C), and 20 healthy volunteers (HV). Computer-aided quantitative neuropsychiatric function test systems, including eight neuropsychiatric tests were performed. RESULTS: Subjects with results over the cut-off value for healthy subjects ranged from 11.1-28.6% in CH and 19.5-36.4% in LC. The percentages with abnormality in at least one test in CH and LC were 72.4% and 80.6%, respectively, which were significantly higher than that in the HV group (35.0%) (P = 0.003, P = 0.0003, respectively). Among CH subjects, those with three or more abnormal results in the F1, F2 and F3 subgroups were 15.0%, 20.0% and 38.9%, respectively. Among LC subjects, those with three or more abnormal results in the Child-Pugh class A, B and C subgroups comprised 30.4%, 50.0% and 57.1%, respectively. The rate in the CH F3 subgroup (P = 0.011) and in all three LC subgroups (P = 0.023, P = 0.001, P = 0.002, respectively) were significantly higher than that in the HV group. CONCLUSION: The percentage of patients with neuropsychiatric function impairment was high in both LC and CH, especially in stage F3. Neuropsychiatric dysfunction may initiate in CH in a considerable number of patients.

Treatment of hepatocellular carcinoma using arterial chemoembolization with degradable starch microspheres and continuous arterial infusion of 5-fluorouracil.

OBJECTIVE: Transcatheter arterial embolization (TAE) with gelatin sponge particles and iodized oil often yields poor results when used to treat unresectable multifocal hepatocellular carcinoma (HCC). The present study retrospectively investigated the utility of a novel combination chemotherapy regimen for treating multifocal HCC resistant to TAE. METHODS: Thirteen consecutive patients with unresectable multifocal HCC and resistance to TAE were treated with combination chemotherapy consisting of arterial chemoembolization with degradable starch microspheres (DSM) (150-4500 mg on Day 1), mitomycin-C (4-8 mg on Day 1), continuous arterial infusion of 5-fluorouracil (1250 mg/120 h), cisplatin (25-50 mg/120 h) and l-leucovorin (125 mg/120 h) for 10-19 weeks. RESULTS: The response rate was 84.6%, with complete response in one patient and partial response (PR) in 10 patients. In four of 10 patients with PR, the tumor was not observable, although the tumor marker did not completely decline to the normal range. The 1-, 2- and 3-year survival rates were 100, 28.9 and 9.6% in all, and 100, 33.3 and 0% in six patients with portal vein tumor thrombosis (PVTT). The median survival was 22.1 months in all and 17.1 months in six patients with PVTT. Thrombocytopenia of Grade III or higher was observed in eight patients. Laparoscopic splenectomy was performed before therapy in four patients with platelet counts of <70,000/mm(3), and during therapy in five patients with severe thrombocytopenia. CONCLUSIONS: This novel chemotherapy regimen achieved favorable results and may be useful in treating patients with unresectable multifocal HCC resistant to TAE.

Efficacy of radiofrequency ablation therapy compared to surgical resection in 164 patients in Japan with single hepatocellular carcinoma smaller than 3 cm, along with report of complications.

BACKGROUND/AIMS: Radiofrequency ablation therapy (RFA) has become widely used against hepatocellular carcinoma (HCC), mainly because of its ease of use, lower level of invasiveness, and high level of effectiveness. To compare the efficacy and safety of RFA with surgery, we retrospectively investigated relevant patient clinical data. METHODOLOGY: The patients with a single HCC (3 cm > or =, Child-Pugh A or B) who were treated with RFA (RFA-group: n=105) or surgery (Surgery-group: n=59) from January 2000 to June 2007 were enrolled. RESULTS: The ratio of patients classified as Child-Pugh B was greater in RFA-group (24.8% vs. 8.5%, P=0.011), though the sizes of the tumors were not significantly different. There were no significant differences for survival rates or disease free survival rates after 3- and 5-years (RFA-group vs. Surgery-group; survival: 87.8 and 59.3% vs. 91.4 and 59.4%, disease free survival: 58.7 and 24.6% vs. 64.3 and 22.4%, respectively). As for complications, in RFA-group there was no severe complication while there was 1 case of postoperative hepatic failure death and 2 with a postoperative abscess in Surgery-group. CONCLUSIONS: In the present study, patients with a single HCC smaller than 3cm who underwent RFA had a lower frequency of severe complications, thus the efficacy of RFA was thought to be equal to a surgical procedure.

Clinicopathologic features of the severe form of acute type 1 autoimmune hepatitis.

BACKGROUND & AIMS: Acute onset autoimmune hepatitis (acute AIH) is difficult to diagnose by using serologic data. In addition, some patients with the severe form of acute AIH do not respond to immunosuppressive therapy and have a poor outcome. In this study, we analyzed the clinicopathologic features of patients who were diagnosed as having acute AIH. METHODS: Retrospective review of patients with presumed acute AIH at Ehime University Graduate School of Medicine was performed. RESULTS: In liver tissue, infiltrates in the portal area and plasma cell infiltration are more common in acute AIH compared with acute hepatitis caused by other causes. Patients with acute AIH who did not have severe jaundice at the time of diagnosis exhibited a very good response to corticosteroid therapy, despite lower titers of antinuclear antibody (ANA). Most patients with acute AIH with higher levels of bilirubin and titers of ANA in sera respond poorly to corticosteroid therapy. CONCLUSIONS: Histologic findings might be useful for the early diagnosis of acute AIH. Acute AIH patients with high levels of bilirubin and high titers of ANA in sera often do not respond to corticosteroid therapy.

Prevalence of hepatitis E virus among wild boar in the Ehime area of western Japan.

AIMS: Transmission of hepatitis E virus (HEV) from wild boar to humans has been reported, particularly from Japan. We attempted to clarify this issue. METHODS: We assessed the IgG class antibodies against HEV (anti-HEV) in serum samples taken from 406 boar living in the Ehime area of western Japan from 2001 to 2004, of which 392 were captured in the wild (wild-caught boar) and 14 had been kept in a breeding farm (bred boar). RESULTS: Anti-HEV positive rate in the bred boar (10/14, 71.4%) was significantly higher than in the wild-caught boar (100/392, 25.5%) (P < 0.001). Of the 392 wild-caught boar, 12 (3.1%) were positive for HEV-RNA, 10 of which were then subjected to phylogenetic analyses by sequencing an 821-nt fragment within ORF1. All the 10 isolates segregated to genotype 3, and eight of them were mutually related to form a cluster. All the eight HEV isolates in this cluster were from the wild-caught boar living in one and the same habitat within the studied area, while the other two independent isolates were from different regions. CONCLUSION: HEV infection is endemic in wild boar in the Ehime area, and we should regard the wild boar as an important reservoir of HEV.

Characteristics of geographic distributions and route of infection for hepatitis B virus genotype D in Ehime area in western Japan.

AIMS: Hepatitis B virus genotype D (HBV/D) is rare in Japan, and has been shown to circulate in Ehime prefecture in western Japan. HBV/D is suspected to have been transferred into Ehime from Russia as a result of the Japanese-Russian War. This study examined the current geographic spread and infectious route for HBV/D in Ehime. METHODS: HBV genotype was determined for 508 patients with chronic HBV infection and 46 patients with acute HBV infection hepatitis (acute hepatitis, AH), all of whom were living in Ehime. Ehime was divided into three areas and genotypic distributions were studied. RESULTS: The ratio of genotypes A,B,C and D in chronically infected patients were 1.8%, 4.5%, 87.8% and 5.9%, respectively. Most patients chronically infected with HBV/D lived in the central area. Only two patients lived in the east and south-west areas, and both had lived in the central area in childhood. Patients with AH due to HBV/D were found only in the central area. CONCLUSION: HBV/D has not yet spread widely to areas other than central Ehime, although small numbers of infected people have moved to other areas. The major infectious route for patients with AH is sexual transmission, regardless of HBV genotype.