Biomedical subjects

Shiro Iino

Publications and source records attributed to Shiro Iino.

At least 19 recordsLinked to original sources

PubMed2006

Molecular epidemiology of hepatitis A virus in metropolitan areas in Japan.

BACKGROUND: Transmission routes of hepatitis A virus (HAV) in Japan have changed. The present study investigated changes of transmission routes in relation to genetic drift. METHODS: All 60 patients who were admitted between 1993 and 2003 with a diagnosis of hepatitis A were retrospectively analyzed. Nucleotide sequences of the VP1/2A region of the HAV recovered from their sera were determined. RESULTS: The suspected transmission routes were household contact, 19 (31%); food or waterborne, 16 (27%); homosexual activity, 11 (18%); international travel, 4 (7%); and unknown 10. (17%). The 11 patients presumably infected through homosexual activity were found exclusively in 1998 and 1999. The proportion of patients exposed through homosexual behavior and household contact was higher in those 2 years than in other years. Nucleotide sequences could be determined for 58 patients. Fifty-seven of the 58 sequences belonged to genotype IA HAV, with less than 10% nucleotide diversity. Of the 27 sequences isolated during 1998 and 1999, 25 had an identical nucleotide sequence regardless of the suspected transmission route. In contrast, sequences obtained in the other years differed from one another. A phylogenetic tree constructed from sequences recovered from patients without a history of travel abroad showed several clusters. CONCLUSIONS: Our results suggest that (1) HAV acquired through homosexual activity may be transmitted to nonhomosexual individuals; (2) hepatitis A in metropolitan areas in Japan is caused mainly by sporadic infection with genotype IA HAV; and (3) several subtypes of genotype IA HAV are endemic in Japan.

Adult↗

PubMed2006

Spatial and chronological differences in hepatitis B virus genotypes from patients with acute hepatitis B in Japan.

Genotypes of hepatitis B virus (HBV) were determined in 485 patients with acute hepatitis B from all over Japan. They were A in 92 (19%), Ba in 26 (5%), Bj in 32 (7%), C in 330 (68%) and D in 5 (1%). Sexual contacts were the main route of transmission in them. Overall, HBV persisted in only 5 of the 464 (1%) followed patients. Genotypes C accounted for more than 68% in northern as well as southern areas, contrasting with genotype A accounting for 34% in and around the Metropolitan areas. During 24 years from 1982 to 2005, genotype A increased from 5% to 33%, while genotype B gradually decreased from 26% to 8%. Fulminant hepatitis was significantly more frequent in infection with genotype Bj (41%) than those with the other genotypes (p<0.01). The core-promoter double mutation (T1762/A1764) and precore stop-codon mutation (A1896) were more frequent in patients with fulminant than acute self-limited hepatitis (57% versus 15% and 58% versus 10%, respectively, p<0.01 for both). In conclusion, genotype A distributes unevenly over Japan, prevails in younger patients through sexual transmission and has increased with years. Furthermore, fulminant outcome was more frequent in patients with genotype Bj than those with the other genotypes.

Journal Article↗

PubMed2006

Risk factors for retinopathy associated with interferon alpha-2b and ribavirin combination therapy in patients with chronic hepatitis C.

AIM: To elucidate the frequency and risk factors for retinopathy in patients with chronic hepatitis C who are treated by interferon-ribavirin combination therapy. METHODS: We prospectively analyzed 73 patients with histologically confirmed chronic hepatitis C, who underwent combination therapy for 24 wk. Optic fundi were examined before, and 2, 4, 12 and 24 wk after the start of combination therapy. RESULTS: Fourteen patients (19%) developed retinopathy, which was initially diagnosed by the appearance of a cotton wool spot in 12 patients. Retinal hemorrhage was observed in 5 patients. No patient complained of visual disturbance. Retinopathy disappeared in 9 patients (64%) despite the continuation of combination therapy. However, retinopathy persisted in 5 patients with retinal hemorrhage. A comparison of the clinical background between the groups with and without retinopathy showed no significant differences in age, gender, viral genotype, RNA level, white blood cell count, platelet count, prothrombin time, complications by diabetes mellitus or hypertension, or pretreatment arteriosclerotic changes in the optic fundi. However, multiple logistic regression analysis revealed that complication by hypertension was observed with a high frequency in the group with retinopathy (P = 0.004, OR = 245.918, 95% CI = 5.6-10786.2). CONCLUSION: Retinopathy associated with combination therapy of interferon alpha-2b and ribavirin tends to develop in patients with hypertension.

Adult↗

PubMed2006

Measurement of hepatitis B virus core-related antigen is valuable for identifying patients who are at low risk of lamivudine resistance.

OBJECTIVE: The clinical usefulness of hepatitis B virus core-related antigen (HBVcrAg) assay was compared with that of HBV DNA assay in predicting the occurrence of lamivudine resistance in patients with chronic hepatitis B. PATIENTS: Of a total of 81 patients who were treated with lamivudine, 25 (31%) developed lamivudine resistance during a median follow-up period of 19.3 months. RESULTS: The pretreatment positive rate of HBe antigen, or pretreatment levels of HBVcrAg or HBV DNA did not differ between patients with and without lamivudine resistance. Levels of both HBVcrAg and HBV DNA decreased after the initiation of lamivudine administration; however, the level of HBVcrAg decreased significantly more slowly than that of HBV DNA. The occurrence of lamivudine resistance was significantly less frequent in the 56 patients whose HBV DNA level was less than 2.6 log copy/ml at 6 months of treatment than in the remaining 25 patients. The cumulative rate of lamivudine resistance was as high as 70% within 2 years in the latter group, while it was only 28% in the former group. Lamivudine resistance did not occur during the follow-up period in the 19 patients whose HBVcrAg level was less than 4.6 log U/ml at 6 months of treatment, while it did occur in 50% of the remaining patients within 2 years. CONCLUSION: These results suggest that measurement of HBV DNA is valuable for identifying patients who are at high risk of developing lamivudine resistance, and that, conversely, measurement of HBVcrAg is valuable for identifying those who are at low risk of lamivudine resistance.

Adult↗

PubMed2005

Timing of interferon therapy and sources of infection in patients with acute hepatitis C.

BACKGROUND/AIMS: Controversy over the selection of patients and optimum therapeutic method for acute hepatitis C has continued. The aims of this study were to investigate the source of infection, and to evaluate the timing of interferon (IFN) therapy in patients with acute hepatitis C in Japan. METHODS: The records of 102 patients from 12 facilities in Japan who developed acute hepatitis C after 1990 were investigated. In the patients treated with IFN, we performed multivariate analysis to investigate factors related to sustained virological response (SVR). RESULTS: Medical procedure was the most common source of infection, accounting for 32.4% in the 102 patients (33/102). Of 81 patients treated with IFN, 71 patients were followed after IFN therapy, and 57/71 (80.3%) had SVR. The SVR rate was significantly higher in patients treated with IFN within 24 weeks from onset of symptoms than the SVR rate in those treated after 25 weeks (P=0.0016). Multivariate analysis revealed that only the duration between onset of symptoms and initiation of IFN therapy (within 24 weeks) was related to SVR. CONCLUSIONS: Our multicenter cooperative survey revealed that medical procedure was the most frequent source of infection in acute hepatitis C. As concerns the therapy, interferon treatment should be initiated within 24 weeks after onset of symptoms.

Journal Article↗

PubMed2005

Efficacy of lamivudine for preventing hepatocellular carcinoma in chronic hepatitis B: A multicenter retrospective study of 2795 patients.

A retrospective survey of Japanese patients histologically diagnosed with chronic hepatitis B was conducted to determine the effectiveness of lamivudine in preventing hepatocellular carcinoma (HCC). Of the 2795 patients who satisfied criteria for analysis after treatment from any of 30 medical institutions, 657 had received lamivudine and the remaining 2138 had not. A Cox regression model with liver biopsy as the starting point revealed seven factors related to HCC: lamivudine therapy, gender, family clustering of hepatitis B, age at liver biopsy, hepatic fibrosis stage, serum albumin level, and platelet count. In a matched case-controlled study, 377 patients in a lamivudine-treated group and 377 matched patients in a non-treated group were selected based on their propensity scores. The mean follow-up period was 2.7 years in the lamivudine group and 5.3 years in the control group. In the lamivudine group, HCC occurred in four patients (1.1%) with an annual incidence rate of 0.4%/(patient/year), whereas in the control group HCC occurred in 50 patients (13.3%) for a rate of 2.5%/(patient/year). A comparison of the cumulative HCC incidence between the two groups by the Kaplan-Meier method showed a significantly lower incidence of HCC in the lamivudine group (p<0.001). These findings suggest that lamivudine effectively reduces the incidence of HCC in patients with chronic hepatitis B.

Journal Article↗

PubMed2005

Pancreatic involvement in chronic viral hepatitis.

AIM: To elucidate the frequency and characteristics of pancreatic disorders in the course of chronic viral hepatitis. METHODS: We prospectively assessed the serum pancreatic enzyme levels and imaging findings in patients with chronic viral hepatitis and healthy control subjects. RESULTS: Serum amylase (t-Amy), salivary amylase (s-Amy), pancreatic amylase (p-Amy) and serum lipase levels were higher in hepatitis patients in comparison to control subjects. However, in asymptomatic viral carriers, only the serum t-Amy levels were higher than those of the controls. The levels of each enzyme rose with the progression of liver disease in patients with hepatitis B or C; whereas the levels of each enzyme within the same clinical stage of the disease did not differ between patients diagnosed with either hepatitis B or hepatitis C virus. Imaging findings demonstrated chronic pancreatitis in only 1 out of 202 patients (0.5%). CONCLUSION: Our data suggest that serum levels of pancreatic enzymes increase with the progression of liver disease in patients diagnosed with viral hepatitis. Pancreatic disease, asymptomatic in most cases, may represent an extrahepatic manifestation of chronic viral hepatitis.

Adult↗

PubMed2005

Distinct geographic distributions of hepatitis B virus genotypes in patients with acute infection in Japan.

Genotypes of hepatitis B virus (HBV) were determined in 145 patients with acute hepatitis B from various districts in Japan to establish their geographic distribution and evaluating the influence on the clinical illness and outcome. Genotypes were A in 27 (19%) patients, B in 8 (5%), C in 109 (75%) and mixed with B and C in the remaining one (1%). Genotype A was more frequent in metropolitan than the other areas (21/69 (30%) vs. 6/76 (8%), P < 0.001). On phylogenetic analysis, seven of the nine (78%) HBV/A isolates selected at random clustered with those from Europe and the United States, while the remaining two with those of subgroup A' prevalent in Asia and Africa. Maximum ALT levels were lower (2069 +/- 1075 vs. 2889 +/- 1867 IU/L, P = 0.03) and baseline HBV DNA titers were higher (5.90 +/- 1.45 vs. 5.13 +/- 1.36 log genome equivalents (LGE)/ml, P = 0.002) in patients infected with genotype A than C. Hepatitis B surface antigen persisted longer in patients infected with genotype A than C (1.95 +/- 1.09 vs. 1.28 +/- 1.42 months, P = 0.02). HBV infection became chronic in one (4%) patient with genotype A and one (1%) with genotype C infection. Fulminant hepatic failure developed in none of the patients with genotype A, one (13%) with genotype B and five (5%) with genotype C. The point mutation in the precore region (A1896) or the double mutations in the basic core promoter (BCP) region (T1762/A1764) were detected in none of the patients with genotype A, two (25%) with genotype B and 27 (26%) with genotype C. In conclusion, genotype A is frequent in patients with acute hepatitis B in metropolitan areas of Japan, probably reflecting particular transmission routes, and associated with longer and milder clinical course than genotype C.

Adult↗

PubMed2005

Impact of daily high-dose IFNalpha-2b plus ribavirin combination therapy on reduction of ALT levels in patients with chronic hepatitis C with genotype 1 and high HCV RNA levels.

The possibility of delaying progression to hepatocellular carcinoma in chronic hepatitis C patients with genotype 1 and high viral titers with baseline ALT levels of >/=50IU/L was examined by administration of IFN plus ribavirin combination therapy using ALT normalization as index and IFN monotherapy as control. The rate of sustained ALT normalization (ALT normal at 24 weeks after the end of treatment) was 28.1% with combination therapy and 10.5% with IFN monotherapy (P=0.001). Furthermore, the number of patients with sustained viral response (SVR) and with sustained ALT normalization in non-SVR patients was also significantly higher in the combination therapy versus monotherapy group. Mean ALT values during treatment and for 6 months after the end of treatment were significantly lower with combination therapy versus monotherapy even in virological nonresponders, as well as significantly lower during the post-treatment observation period in patients who relapsed after the end of treatment. Since increase in the rate of sustained ALT normalization and SVR were successfully achieved, inhibition of progression to hepatocellular carcinoma should be studied with long-term IFN and ribavirin combination therapy.

Journal Article↗

PubMed2004

A significant reduction in serum alanine aminotransferase levels after 3-month iron reduction therapy for chronic hepatitis C: a multicenter, prospective, randomized, controlled trial in Japan.

BACKGROUND: Increasing evidence indicates that iron cytotoxicity plays an important role in the pathogenesis of chronic hepatitis C (CHC). However, the biochemical effects of iron reduction therapy on CHC remain to be confirmed in a controlled study. This study aimed to test whether iron removal by repeated phlebotomy improves serum alanine aminotransferase (ALT) levels in patients with CHC. METHODS: Patients were randomly assigned to an iron reduction therapy or control group. The patients in the treatment group received 3-month iron reduction therapy by biweekly phlebotomy, while the patients in the control group were followed up for 3 months with regular blood tests alone. RESULTS: Thirty-three patients completed the 3-month treatment, while 29 patients received the complete follow-up. The serum ALT levels were reduced from 118 +/- 79 to 73 +/- 39 IU/L in the treatment group, but did not change in the control group (106 +/- 45 versus 107 +/- 48 IU/L). Posttreatment enzyme activity was decreased significantly from the baseline. Furthermore, it was significantly lower than the 3-month control level. Although 5 patients withdrew from the study, none was affected by any side effects of repeated phlebotomy that required them to discontinue the treatment. CONCLUSIONS: This short-term controlled trial demonstrated the biochemical efficacy and safety of iron reduction therapy for patients with CHC.

Adult↗

PubMed2004

Prediction of treatment outcome with daily high-dose IFN alpha-2b plus ribavirin in patients with chronic hepatitis C with genotype 1b and high HCV RNA levels: relationship of baseline viral levels and viral dynamics during and after therapy.

Data on 334 patients with HCV genotype 1b and high viral levels were extracted from two multicenter double-blind studies conducted in Japan comparing IFN alpha-2b plus ribavirin (n = 209) with IFN alpha-2b alone (n = 125) for 24 weeks. HCV RNA assay was conducted before and 4, 12, and 24 weeks after the start and 4, 12, and 24 weeks after the end of treatment. Both sustained viral response (SVR) rate and relapse rate after the end of treatment were analyzed in relation to baseline viral levels and the time of first disappearance of virus. In the combination treatment group, the percentage of patients who were HCV RNA-negative within 4 weeks decreased with increase in baseline viral levels (i.e. 42%, 15%, and 11% were HCV RNA-negative in the groups exhibiting <500, 500 to <850, and >/=850kcopies/mL, respectively). In the IFN monotherapy group, the response rates were lower at 13%, 15%, and 1%, respectively. Disappearance of virus within 12 weeks after the start of combination treatment was indicative of higher probability of SVR. The risk of relapse was more highly correlated with the timing of initial viral disappearance than with baseline HCV levels; it was 4.8 and 10.3 times higher in patients who became HCV-negative at 4-12 and 13-24 weeks compared with in those who were HCV-negative within 4 weeks.

Journal Article↗

PubMed2004