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Biomedical subjects

Shiro Iino

Publications and source records attributed to Shiro Iino.

32 records · Page 2Linked to original sources
PubMed2003

Autoantibodies to CD69 in patients with chronic hepatitis type C: a candidate marker for predicting the response to interferon therapy.

OBJECTIVE: To understand the autoimmunity associated with chronic hepatitis C (CHC), we investigated autoantibodies (autoAbs) to CD69. METHODS: With this aim, we tested the reactivity of serum samples from patients with CHC and asymptomatic carriers of hepatitis C virus (HCV), as well as from patients with chronic hepatitis B (CHB) and autoimmune hepatitis (AIH), to recombinant CD69 molecules. RESULTS: Frequencies of anti-CD69 autoAbs were 38.7% in CHC, 15.8% in AIH and 12.3% in CHB. None of the tested asymptomatic HCV carriers had autoAbs to CD69. It is important clinically that the presence of anti-CD69 autoAbs was found to be associated with a poor response to interferon-alpha (IFN-alpha) therapy. In the epitope analysis, multiple epitopes were mapped on CD69, indicating antigen-driven production of the autoAbs. CONCLUSION: We evidenced existence of anti-CD69 autoAbs in patients with CHC, and found that the anti-CD69 autoAb may have potential for predicting responses to IFN-alpha therapy.

Adult↗
PubMed2003

Short-term lamivudine for the treatment of chronic hepatitis B.

Short-term lamivudine and its withdrawal were evaluated as regards an immunomodulatory therapy of chronic hepatitis B. Lamivudine was given for 3 or 6 months to 23 patients with chronic hepatitis B who were infected with hepatitis B virus (HBV) genotype C, including 15 with hepatitis B e antigen (HBeAg) and 8 without it. It decreased serum levels of alanine aminotransferase (ALT) and HBV DNA in HBeAg-positive patients. Flare-ups of ALT and HBV DNA after treatment were observed in most patients, and 4 of the 12 (33%) patients with 6-month lamivudine treatment remained in remission 6 months after withdrawal of the therapy. In HBeAg-negative patients, however, flare-ups of ALT and HBV DNA were mild. Normalization of ALT and a decrease in serum HBV DNA were accomplished in 6 of the 9 (75%) patients. Breakthroughs or serious side effects were not observed in any patients. Short-term lamivudine is safe and may offer a therapeutic option to patients with chronic hepatitis B.

Adult↗
PubMed2002

Precore and core promoter mutations, hepatitis B virus DNA levels and progressive liver injury in chronic hepatitis B.

BACKGROUND/AIMS: To elucidate the viral factors responsible for progressive liver injury in chronic hepatitis B. METHODS: We analyzed 179 persistently infected patients (21 asymptomatic carriers, 126 with chronic hepatitis and 32 with cirrhosis) with genotype C hepatitis B virus (HBV). HBeAg/anti-HBe, levels of HBV DNA, mutations in the basic core promoter (BCP) region at nucleotides 1762/1764 and mutation in the precore (preC) region at nucleotide 1896 were determined. Serial samples from 18 patients also were analyzed. RESULTS: HBeAg/anti-HBe and HBV DNA levels per se were not related to liver fibrosis. The frequency of BCP mutations increased with progression of liver fibrosis. Although the preC mutation was detected more often among the LC group, the role of this mutation in progression of fibrosis seems less than that of the BCP mutations. Sequential analysis showed that (1) rapidly progressing cases were positive continuously for double mutations in the BCP with a wild-type precore sequence, and (2) asymptomatic cases with anti-HBe acquired the preC mutation during their clinical course. CONCLUSIONS: Double mutations in the BCP region at nucleotide 1762/1764 are closely related to progression of chronic liver disease. Acquisition of mutation in the preC region at nucleotide 1896 may contribute to inactivation of chronic liver disease.

Adult↗
PubMed2002

A case of complete necrosis of well-differentiated early hepatocellular carcinoma by percutaneous transhepatic portal embolization.

The patient was a 49-year-old male under observation for chronic hepatitis B. In July 1997, abdominal ultrasonography showed multiple hyperechoic nodules in the right lobe, the largest with a diameter of 3.5 cm. Abdominal computed tomography did not reveal enhanced nodules, and the patient was hospitalized for suspected multiple liver tumors. All biochemical tests were normal, except for a slight decrease in platelets. The patient was positive for HBs antigen, negative for HBe antigen and positive for anti-HBe antibody. Hepatocellular carcinoma (HCC) with patent portal blood flow was strongly suspected based on the results of various imaging techniques. A tumor biopsy was conducted, and findings of multiple early hepatocellular carcinoma of a well-differentiated type were observed. Based on the HCC stage and liver function, an extensive right hepatectomy was indicated. Before the surgical resection, a percutaneous transhepatic portal embolization (PTPE) was performed using gerfoam sponzel in the right portal vein. Complete necrosis of the tumor lesions was observed in the resected liver. Early HCC thought to have developed multifocally concurrently with chronic inactive hepatitis was observed. It is highly possible that complete necrosis of these tumors occurred due to PTPE, suggesting that they are supplied by the portal blood flow.

Journal Article↗
PubMed2002

Different hepatitis B virus genotype distributions among asymptomatic carriers and patients with liver diseases in Nanning, southern China.

To determine the hepatitis B virus (HBV) genotype distribution among asymptomatic carriers and patients with liver diseases in Nanning, China, where the prevalence of HBV infection is high, the serum samples from 39 asymptomatic HBV carriers and 103 liver diseases patients were examined for the presence of HBV DNA by polymerase chain reaction and for genotypes by restriction fragment length polymorphism analysis. All patients were positive for HBV DNA and 135 (95.1%) patients were classified by RFLP, the remaining seven were classified by sequencing. Finally, six (4.2%), 20 (14.1%), 113 (78.9%) and two (1.4%) patients were identified with genotype A, B, C and D, respectively. One (0.7%) case was confirmed to be co-infected with both genotypes B and C. Genotype C was more frequently observed in cases with advanced liver diseases and relatively less frequently in case with mild liver diseases. In contrast, genotype B showed an opposite distribution pattern, although there was no statistically significant difference (P=0.05). The rate of positivity for anti-HBe was higher, but that for HBeAg was lower in chronic infection patients with genotype B than in those with genotype C, (P<0.05, P<0.05, respectively). Severe liver damage was observed in patients with genotype C compared with those with genotypes A or B (P<0.01, P<0.01, respectively). These results suggest that (1) genotype C is the predominant genotype in Nanning, China, (2) genotype C maybe more associated with development of severe liver diseases than genotype B.

Journal Article↗
PubMed2002

Serum HCV RNA levels during early phase of recombinant interferon alfa-2a (Roferon A) therapy for chronic hepatitis C and efficacy of short-term therapy with earlier loss of viremia.

We conducted a prospective, controlled, multicenter trial to assess if earlier changes of serum HCV RNA levels were predictable for long-term effect, and if a short-term therapy was effective in such patients. All 377 chronic hepatitis C (CH-C) patients were treated with interferon (IFN) daily 9 MU for 4 weeks. Patients positive for HCV RNA at week 1 were treated with IFN three times weekly for additional 22 weeks (group A), while those negative for HCV RNA were randomized into either regimens; three times weekly for another 22 (group B) or 12 weeks (group C). When complete responders (CR) were defined as the subjects showing sustained loss of viremia with therapy, CR rates were 17.7% (25/141) for group A, 80.0% (36/45) for group B and 61.0% (36/59) for group C, respectively. Group B showed a significantly higher CR rate than group C, indicating that a 16-week treatment period was inadequate. Patients with CR showed a rapid decrease in virus levels by day 2 after starting therapy. The CR ratio in patients with HCV RNA levels of <1.0 Kcopy/ml by day 2 was 64.6% (82/127), while the ratio without <1.0 Kcopy/ml was 12.7% (15/118). CR ratio in patients who became negative by week 2 was 65.7%, whereas only 2.9% after week 2. The results indicate that the determination of HCV RNA levels at day 2 and the qualitative assay at week 2 with IFN are useful in predicting the therapeutic effect.

Journal Article↗
PubMed2002

A randomized clinical trial with natural interferon-alpha monotherapy for 24 or 48 weeks on patients with chronic hepatitis C having genotype 1b infection in high viral titers.

Patients with chronic hepatitis C who are infected with hepatitis C virus of genotype 1b and have a high viral load in serum (>1 Mega equivalents/ml) poorly respond to interferon with the standard regimen. Natural interferon-alpha (nIFN-alpha: OPC-18) was given to 106 such patients randomized into two different therapeutic schedules. One group consisting of 53 patients received daily intramuscular injection with 10 mega units (Meq) for 2-4 weeks and then 5 Meq three times per week until 24 weeks and the other group of 53 patients were placed on the same regimen until 48 weeks. At 24 weeks after the completion of therapy, HCV RNA turned negative in 11 (25%) patients with the 48-week therapy, significantly more frequently than in two (5%) patients with the 24-week therapy (P=0.014). There were no differences in the incidence and severity of adverse effects between the patients who received 24- and 48-week nIFN-alpha. Based on these results, nIFN-alpha with a high-dose induction and extended to 48 weeks would be a reasonable therapeutic option for the patients infected with HCV/1b in high viral loads who do not respond to the standard regimen with a 24-week schedule.

Journal Article↗
PubMed2002

Outcomes of small nodular lesions in heavy drinkers.

BACKGROUND: Increased detection of nodular lesions in patients not yet definitively diagnosed with hepatocellular carcinoma (HCC) has occurred with the use of advanced imaging techniques. In heavy drinkers, decrease in the size of nodular lesions during on-going observation, and negation of diagnoses of HCC after surgical resection have been reported, suggesting the need for caution in diagnosis in such cases. METHODS: The subjects were eight heavy drinkers with small nodular lesions, 20 mm or less in diameter. All patients were male, with a mean age of 53 years. Five had single and three had multiple nodular lesions. Five of the eight patients were followed up for more than 4 years after an initial biopsy, while three patients were recent cases. Of the three recent cases, two were positive for antibody to hepatitis C virus (HCV) and two had hypervascular nodular lesion. Biopsies were performed percutaneously, under ultrasonography, for histological diagnosis of all cases, and the recent cases were also assessed using a variety of imaging techniques. RESULTS: On initial biopsy, no atypism (NO) was found in two patients, and borderline lesions (Border) were present in six patients. Of the five cases followed up long-term, only one of the two with NO progressed to HCC, and the three with Border showed disappearance, decrease, and no change, respectively, during the follow-up period. Of the three recent cases, no changes in size or morphology as revealed by imaging were observed following biopsy. CONCLUSIONS: In heavy drinkers, no fixed relationship was observed between initial biopsy finding and clinical course, suggesting that indication for biopsy requires reassessment, refinement, and discussion. Furthermore, tumor staining may occur in hyperplastic nodules, which are histologically similar to early HCC by needle biopsy, and care needs to be exercised for diagnosis in heavy drinkers.

Biopsy↗
PubMed2002

Natural history of hepatitis B and C virus infections.

Thirty-five years have already elapsed since the discovery of hepatitis B virus (HBV), and 10 years since that of hepatitis C virus (HCV). Nonetheless, the natural history of HBV and HCV infections has not been fully defined, partly because they do not have subjective symptoms in most cases. Even when liver disease is induced by these hepatitis viruses, the clinical course is slow and mostly insidious. HBV and HCV are much alike in that they both cause a spectrum of clinical conditions ranging from the symptom-free carrier state through chronic hepatitis and liver cirrhosis to eventual hepatocellular carcinoma. Despite a close similarity, infections with HBV and HCV are very different in many aspects, from the early to end stage. Large-scale unbiased studies to sort out the natural history of HBV and HCV infections are lacking, however. Understandably, in view of the fact that only a few decades have passed since these hepatitis viruses were discovered. My personal account on the natural history of HBV and HCV infections is given here, which is based on my experience of over 40 years as a clinical and research hepatologist in Japan, although I am aware that it invites more questions than it answers.

Age Factors↗
PubMed2002

[Clinical study of the combination of small amount of nedaplatin (CDGP)/5-FU with radiation for the treatment of esophageal cancer].

Recently chemoradiotherapy for esophageal cancer has been drawing public attention to the issue of quality of life maintenance for patients. Although the standard method of chemoradiotherapy is CDDP/5FU, it has been claimed that CDGP (a derivative of CDDP) alone is more effective than CDDP for the treatment of esophageal cancer due to its low nephro- and digestive toxicity. We used a small amount of CDGP/5-FU in combination with radiation instead of CDDP, for the treatment of esophageal cancer and performed clinical examination of patients. The partial response rate was 80% and the complete response rate was 50%. Major side-effects were leukopenia, neutropenia, thrombocytopenia and anemia. Further study of dosage and schedule is necessary, however, CDGP/5-FU combined with radiation therapy could be used as choices of chemoradiotherapy for esophageal cancer in the future.

Aged↗