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Reiichiro Kuwahara,
Ryukichi Kumashiro,
Tatsuya Ide,
Yuriko Koga,
Teruko Hino,
Akiko Hisamochi, Kazuo Tanaka,
Kei Ogata,
Hiroyuki Koga,
Yukari Takao,
Michio Sata
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ABSTRACT: The aims of this study were to select the patients with a potential for progression to hepatic failure due to lamivudine-resistant HBV and to standardize the treatment for patients with lamivudine-resistant HBV. Patients (n = 47) with reactivated hepatitis due to lamivudine-resistant HBV were classified into two groups, with and without potential for progression to hepatic failure, according to the criteria using the data of serum bilirubin level and prothrombin activity after the reactivated hepatitis. Multivariate analysis showed that prothrombin activity at the initiation of lamivudine therapy was related to the deterioration of the liver function after the emergence of lamivudine-resistant HBV (P = 0.0025, 95%CI 0.8269-0.9601). We assume that earlier additional or substitutive treatment with other antiviral agent, such as adefovir dipivoxil, should be recommended when the lamivudine-resistant HBV is detected in patients with the history of decompensated liver disease before the administration of lamivudine, even when hepatitis has not been reactivated yet.
Digestive Diseases and Sciences 08/2008; 53(11):2999-3006. · 2.12 Impact Factor
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Hiroyuki Koga,
Tatsuya Ide,
Kazuhiko Oho,
Reiichiro Kuwahara,
Teruko Hino,
Kei Ogata,
Akiko Hisamochi, Kazuo Tanaka,
Ryukichi Kumashiro,
Atsushi Toyonaga,
Michio Sata
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ABSTRACT: Aim: Many studies have reported the therapeutic effects of lamivudine on cirrhotic patients with hepatitis B; however, no study has investigated the morphological changes of esophageal varices after lamivudine treatment. Method: The morphological changes of esophageal varices in patients with cirrhosis were retrospectively compared between 12 patients treated with lamivudine and six historical untreated patients. Results: In the treated group, the HBV DNA and hyaluronic acid (HA) levels in the serum were significantly lower than those in the untreated group (P = 0.013 and P = 0.009, respectively) at the end of follow-up, with a significant improvement in the Child-Pugh-Turcotte score (P = 0.022). In the treated group, the disappearance or reduction of esophageal varices was observed in six (50%) of the 12 patients. In three (25%) of the 12 patients, esophageal varices worsened. In the remaining three patients (25%), there were no changes in esophageal varices. In the untreated group, all patients showed the worsening of esophageal varices during the follow-up period, with a significant difference between this group and the treated group (P = 0.009). The serum HA level decreased in the nine treated patients without worsening of esophageal varices. However, in the three patients with worsening, the HA level significantly increased. Conclusion: Lamivudine treatment for patients with cirrhosis improves not only liver function but also esophageal varices.
Hepatology Research 08/2007; 37(7):503-9. · 2.20 Impact Factor
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Reiichiro Kuwahara,
Hiroki Saitsu,
Mitsuhiko Abe,
Akio Takata, Kazuo Tanaka,
Teruko Hino,
Tatsuya Ide,
Ryoko Kuromatsu,
Ken Tanikawa,
Masayoshi Kage,
Ryukichi Kumashiro,
Michio Sata
Digestive Diseases and Sciences 05/2007; 52(4):908-13. · 2.12 Impact Factor
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Ryukichi Kumashiro,
Yuriko Koga,
Reiichirou Kuwahara,
Tatsuya Ide,
Teruko Hino, Kazuo Tanaka,
Akiko Hisamochi,
Kei Ogata,
Yukari Takao,
Hiroyuki Koga,
Hidemi Nishida,
Seiya Okuda,
Teruo Sakamoto,
Michio Sata
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ABSTRACT: To evaluate the efficacy of granulocytapheresis therapy in alcoholic hepatitis.
We attempted to trap leukocytes in the peripheral circulation using the granulocytapheresis (GCAP) technique in patients with severe alcoholic hepatitis who showed a marked elevation of peripheral leukocytes. Corticosteroids were co-administered.
The Maddrey's indices for these patients varied between 42 and 117 and MELD scores for alcoholic hepatitis (Mayo) ranged from 20 to 44. Survival rate was 50% (3/6), which is better than the results reported recently for similar patients in a national survey (29%). The effect of GCAP was reflected in decreases in interleukin-6 and interleukin-8 levels as well as in serum concentrations of soluble intercellular adhesion molecule. White blood cell counts were not affected. In the surviving patients, the Maddrey's indices and MELD scores for alcoholic hepatitis varied between 49 and 67, and 20 and 22, respectively, showing that GCAP is effective in patients with disease of moderate severity. Hemolytic anemia occurred in one patient after GCAP therapy. Other events such as pancreatitis, pneumonia, and cerebral hemorrhage were considered to be related to the alcoholic hepatitis itself.
GCAP therapy deserves further evaluation as a new therapeutic modality for a moderately severe alcoholic hepatitis.
Hepatology Research 12/2006; 36(3):229-36. · 2.20 Impact Factor
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ABSTRACT: Several studies have reported that antibody to hepatitis B core antigen (anti-HBc) positivity may influence the development of hepatocellular carcinoma (HCC) in chronic hepatitis C patients, but the evidence is still not conclusive. In this study, we examined whether the presence of anti-HBc positive was associated with the development of HCC in hepatitis C virus (HCV)-infected subjects among the residents in an HCV hyperepidemic area who were followed up for 12 years. In an HCV hyperendemic area (positive rate of anti-HCV: 23.4%), 509 residents were examined by health screening in 1990. After 12 years of follow-up, we evaluated the risk factors for HCC. The incidence of HCC was compared between anti-HBc positive and anti-HBc negative subjects after 12 years of prospective observation. Univariate and multivariate analyses were conducted to determine risk factors for the development of HCC. The incidence of HCC was significantly higher in the anti-HBc positive group (13 subjects) than in the anti-HBc negative group (0 subjects) (P=0.012). Multivariate analysis identified positivity for anti-HBc and HCV RNA, history of icterus, and female gender as independent determinants of the development of HCC. Our findings provide clear evidence in a prospective study that presence of anti-HBc, that is, past hepatitis B virus (HBV) infection, is a risk factor for the development of HCC in HCV-infected people.
International Journal of Molecular Medicine 06/2006; 17(5):827-32. · 1.98 Impact Factor
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ABSTRACT: Hepatitis C virus (HCV) causes extrahepatic manifestations as well as liver diseases, and contributes to insulin resistance and type 2 diabetes mellitus. The purpose of the present study was to evaluate the relationship of extrahepatic manifestations and insulin resistance in an HCV hyperendemic area. We investigated the incidence of extrahepatic manifestations among 139 inhabitants living in an HCV hyperendemic area in 2002 and compared it to 1999 data for the same inhabitants. Insulin resistance was tested for some non-HCV or HCV-infected inhabitants we had identified during mass screenings in 1999 and 2002. For some of the inhabitants in 2002, we examined records on the prevalence of insulin resistance seven years earlier. The prevalence of extrahepatic manifestations among individuals with positivity for anti-HCV antibodies was higher than among those without HCV in both 1999 and 2002. The prevalence of each extrahepatic manifestation which we identified in 2002 was higher than in 1999. Moreover, in some non-HCV or HCV-infected inhabitants, insulin resistance in 2002 was significantly higher than in 1999. Among inhabitants who had HCV infection with extrahepatic manifestations, fasting insulin levels or HOMA-IR findings seven years prior was significantly higher than for inhabitants who had neither HCV infection nor extrahepatic manifestations (p = 0.03, p = 0.01, respectively). Insulin resistance induces HCV infection, which causes an increase in the incidence of extrahepatic manifestations in HCV-infected individuals.
International Journal of Molecular Medicine 09/2005; 16(2):291-6. · 1.98 Impact Factor
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ABSTRACT: Hepatitis C virus (HCV) infection may contribute to the development of type 2 diabetes mellitus. However, this association at the population level remains unclear. The aim of this pilot study is to examine the relationship between HCV infection and the development of type 2 diabetes mellitus in an HCV hyperendemic area where we conducted health screenings in 1995. After 7 years of follow-up, we evaluated the relative risk of the development of type 2 diabetes mellitus in anti-HCV-inhabitants. Among 71 subjects free of diabetes mellitus in 1995, 7 developed type 2 diabetes mellitus during the 7-year follow-up evaluation. Overall, anti-HCV-positive subjects were nearly 3-fold as likely as anti-HCV-negative subjects to develop diabetes mellitus, but this difference was not statistically significant (p=0.08). After stratification of the anti-HCV-positive group according to serum HCV core titer, a significant increase in the incidence of diabetes was seen in subjects with high titer of HCV core compared to anti-HCV-negative subjects (p=0.02; relative hazard, 5.60; 95% confidence interval, 1.41 to 37.42). In conclusion, HCV infection potentially has a significant role in the development of type 2 diabetes mellitus at the population level. Further large-scale studies are needed to confirm these preliminary findings.
International Journal of Molecular Medicine 08/2005; 16(1):109-14. · 1.98 Impact Factor
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ABSTRACT: We evaluated the clinical course of patients with chronic hepatitis B who showed viral breakthrough during long-term lamivudine therapy.
We initially studied 141 patients treated with lamivudine for 1 year or more, and 49 patients who showed viral breakthrough were the subjects of this study. Their mean lamivudine administration period was 2.3 +/- 0.9 years.
After viral breakthrough, breakthrough hepatitis occurred in 47 patients (95.9%), but did not occur in the other 2 (4.1%). Four of the 47 patients with breakthrough hepatitis were observed without further treatment, and the alanine transferase (ALT) level was normalized in 2 of them but fluctuated in the other 2. Breakthrough hepatitis was treated by injection of glycyrrhizin or ursodeoxycholic acid administration in 36 of the remaining 43 patients, and by antiviral drug administration in the other 7 (entecavir in 2 patients, adefovir in 2, and interferon in 3). The ALT level was normalized in 5 of the 36 patients treated with glycyrrhizin or ursodeoxycholic acid, but persistently fluctuated in the other 31. In those with normalized ALT after the occurrence of breakthrough hepatitis, the peak ALT level at that point was significantly lower (86 +/- 47 IU/l) than that in the patients without normalization (206 +/- 167 IU/l).
These results showed that there were a few patients who did not develop breakthrough hepatitis after showing viral breakthrough, and some who showed normalization of the ALT level after the occurrence of breakthrough hepatitis, but in many patients, ALT continuously fluctuated.
Journal of Gastroenterology 07/2005; 40(6):625-30. · 4.16 Impact Factor
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Nippon rinsho. Japanese journal of clinical medicine 08/2004; 62 Suppl 7(Pt 1):258-63.
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ABSTRACT: In 1990, we conducted an epidemiological study of 509 residents in a hepatitis C virus (HCV) hyperendemic area in Japan. The purpose of the present study was to examine the approach to therapy for liver diseases accompanied by HCV and hepatitis B virus (HBV) infections among the surviving residents in the town after 12 years. Fifty-three with HCV or HBV infections among 385 people who resided in the town were clearly analyzed in 2002. The number of persons diagnosed with the liver diseases was as follows: HCV-related asymptomatic healthy carrier (1), past history of HCV infection (15), chronic hepatitis C (22), HCV-related liver cirrhosis (6), HCV-related hepatocellular carcinoma (HCC) (5), and HBV-related asymptomatic healthy carrier (4). HCC was detected in residents who did not have periodic regular hospital checkups. Only 19% of the 53 inhabitants consulted liver medical specialists, and 75% (3/4) who received interferon therapy received treatment from a liver medical specialist. It is necessary to provide continuous medical treatment to HCV carriers, minimizing difference in treatment quality in different medical institution. An efficient HCV medical checkup and a program of subsequence health management are important problems to be solved for improved health care.
Hepatology Research 02/2004; 28(1):30-35. · 2.20 Impact Factor
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Reiichiro Kuwahara,
Ryukichi Kumashiro,
Shiro Murashima,
Kei Ogata, Kazuo Tanaka,
Akiko Hisamochi,
Teruko Hino,
Tatsuya Ide,
Eisuke Tanaka,
Yuriko Koga,
Michio Sata
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ABSTRACT: It has been reported that spontaneous or interferon (IFN)-induced hepatitis B e (HBe) seroconversion has usually been associated with the development of a stop codon in the precore region. However, the difference between lamivudine-induced seroconversion and spontaneous or IFN-induced seroconversion is not known. The aim of this study was to investigate the correlation between the evolution of the precore and core promoter mutations and lamivudine-induced seroconversion. Forty-five patients with chronic hepatitis B virus (HBV) infection who were treated with lamivudine for more than 1 year were enrolled. The nucleotide sequence of the precore and core promoter region was determined before and after treatment with lamivudine for 1 year. Among 29 patients who were hepatitis B e antigen (HBeAg)-positive before treatment, 12 (41.3%) lost HBeAg during the course of treatment for 1 year. Of these, eight patients (66.7%) still had precore wild type HBV after 1 year. After 1 year, reversion to precore wild type HBV was detected in 11 (64.7%) of 17 patients who had precore mutant HBV before treatment. Twelve (70.6%) of 17 patients who were persistently HBeAg-positive had precore wild type HBV before and after treatment for 1 year. Despite the loss of HBeAg, two thirds of the patients still had precore wild type HBV after the 1-year treatment. It is suggested that lamivudine-induced seroconversion differs from spontaneous or IFN-induced seroconversion in the change of nucleotides in the precore region. The reversion in the precore region may be caused by the difference of drug-susceptibility to lamivudine. The antiviral effect of lamivudine may be more effective in the precore mutant HBV than in the precore wild type HBV.
Journal of Medical Virology 02/2004; 72(1):26-34. · 2.82 Impact Factor
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Tatsuya Ide,
Ryukichi Kumashiro,
Yuriko Koga,
Eisuke Tanaka,
Teruko Hino,
Akiko Hisamochi,
Shiro Murashima,
Kei Ogata, Kazuo Tanaka,
Reiichiro Kuwahara,
Michio Sata
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ABSTRACT: During treatment of chronic hepatitis B with lamivudine, changes in the level of hepatitis B virus (HBV) DNA were investigated using a real-time polymerase chain reaction (PCR) method with a detection limit of 1.7 log copies/ml (50 copies/ml) to clarify its clinical significance, particularly the association between HBV DNA levels and the emergence of tyrosine-methionine-aspartate-aspartate (YMDD) mutants.
Twenty-four patients who had received lamivudine therapy for >1 yr were studied. HBV DNA levels were determined using transcription-mediated amplification for sera with >3.7 log genome equivalents/ml, the Roche Monitor kit for sera with >/=2.6 log copies/ml, and real-time PCR for sera with < 2.6 log copies/ml (the detection limit was 1.7 log copies/ml). Patients were classified into three groups according to the minimal HBV DNA level attained during lamivudine therapy: the <1.7 log copies/ml group (eight patients), the 1.7-2.5 log copies/ml group (five patients), and the >/=2.6 log copies/ml group (11 patients).
Pretreatment HBV DNA levels were significantly lower in the <1.7 copies/ml group than in the other two groups (p < 0.05). Neither the emergence of YMDD mutants nor a virological breakthrough of serum HBV DNA was observed in any of the eight patients in the <1.7 copies/ml group. In contrast, in the 1.7-2.5 copies/ml and >/=2.6 copies/ml groups, virological breakthroughs resulting from the emergence of YMDD mutants were observed in two of five patients and in all 11 patients, respectively (p < 0.001). Virological breakthroughs were observed at a mean of 49.6 +/- 18.4 wk in 11 the patients in the >/=2.6 copies/ml group and at wk 107 and 115 in two patients in the 1.7-2.5 copies/ml group.
The real-time PCR method is useful for predicting the emergence of YMDD mutants and the estimated time of their emergence.
The American Journal of Gastroenterology 09/2003; 98(9):2048-51. · 7.28 Impact Factor
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Gastroenterology 09/2003; 125(2):628-9. · 11.68 Impact Factor
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Teruko Hino,
Ryukichi Kumashiro,
Tatsuya Ide,
Yuriko Koga,
Kunihide Ishii,
Eisuke Tanaka,
Yasuyo Morita,
Akiko Hisamochi,
Shiro Murashima, Kazuo Tanaka,
Kei Ogata,
Reiichiro Kuwahara,
Michio Sata
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ABSTRACT: The prognosis of patients with autoimmune hepatitis (AIH) has not been clearly defined. The aim of this study was to define the prognostic factors of AIH in a population with long-term follow-up in Japan. Seventy-three patients who were diagnosed as having type 1 AIH between January, 1972 - August, 1999 were enrolled in this study. Initial treatment included prednisolone (PSL) (n=62), other drug regimens (n=7), and none (n=4). We examined the relation between several factors obtained at diagnosis in relation to disease activity found at the final observation point (January, 2000 - April, 2000). Multivariate logistic regression and Cox regression were used for statistical analysis. During the observation period, 8 patients died of the following: hepatic failure (n=4), hepatocellular carcinoma (n=1), severe infection (n=1), and unknown causes (n=2). At the end point, the number of patients in complete remission was 13, those with a normal alanine aminotransferase (ALT) level requiring some treatment was 35, and those with an abnormal ALT level despite medication was 17. Factors related to remission were total bilirubin (TB) (Odds ratio, 0.87), and immunoglobulin G (IgG) (Odds ratio, 1.00). Factors related to death were the aspartate aminotransaminase (AST)/ALT ratio (Odds ratio, 11.67) and response to initial PSL regimen (Odds ratio, 0.03). The results of this study show an importance of achieving a good PSL response at onset, and that initial TB, the AST/ALT ratio, and IgG levels are useful for therapeutic strategy.
International Journal of Molecular Medicine 07/2003; 11(6):749-55. · 1.98 Impact Factor
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Tatsuya Ide,
Takashi Okamura,
Ryukichi Kumashiro,
Yuriko Koga,
Teruko Hino,
Akiko Hisamochi,
Kei Ogata, Kazuo Tanaka,
Reiichiro Kuwahara,
Ritsuko Seki,
Michio Sata
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ABSTRACT: One of the major side effects of ribavirin/interferon alpha combination therapy for chronic hepatitis C is hemolytic anemia. One of the causes of hemolytic anemia is considered to be decreasing deformability of erythrocytes resulting from the accumulation of phosphorylated ribavirin in erythrocytes. The administration of eicosapentaenoic acid (EPA), which has a wide variety of pharmacological actions, increases the deformability of erythrocytes. We conducted an uncontrolled pilot study of EPA therapy for patients with ribavirin-related anemia. Six patients with chronic hepatitis C, who had developed anemia while receiving combination therapy, were treated with an oral ethyl ester of EPA (1800 mg/day) for two months. The hemoglobin level of all six patients increased following EPA therapy. The mean hemoglobin level significantly increased from 10.8 g/dl to 11.4 g/dl one month after therapy was initiated (P<0.05), and this level was obtained again one month later (11.5 g/dl). None of the patients developed an adverse reaction. These findings suggest that EPA has a beneficial effect in patients with ribavirin-related anemia. Further study is required to confirm our results.
International Journal of Molecular Medicine 06/2003; 11(6):729-32. · 1.98 Impact Factor
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ABSTRACT: Breakthroughs during lamivudine therapy were assessed according to hepatitis flares and mutational polymorphism of hepatitis B virus (HBV) infecting patients. Of 42 patients with chronic hepatitis B and positive for hepatitis B e antigen in serum, 13 (30%) harbored HBV mutants with lamivudine resistance after a mean duration of 29 months on lamivudine. The virological breakthrough occurred 14.5 months after the start of lamivudine treatment, and all the patients with it developed breakthrough hepatitis 3 months later. The clinical course of breakthrough hepatitis was self-limited except in one patient who had already developed cirrhosis at the baseline. One year after breakthrough hepatitis, serum ALT, albumin, prothrombin time and platelet counts were maintained well on conventional treatments without resorting to interferon. Major HBV mutants during breakthrough hepatitis were those with M552I in the YMDD motif of viral DNA polymerase/reverse transcriptase in 7 patients (54%), M552I/L528M in 4 patients (31%) and M552V/L528M in 2 patients (15%). There were no patients in whom mutations at nucleotide 529 occurred including the 2 who later developed hepatocellular carcinoma. There was no clear relationship between distinct mutational patterns and clinical courses. Further studies are needed for making out the effects of lamivudine-resistant mutants on clinical outcomes, taking into considerations genotypes of HBV.
Intervirology 02/2003; 46(6):350-4. · 2.34 Impact Factor
