Hepatitis: Matsuda Y

Morita S, Matsuda Y, Oshima T, Kubota T, Kawauchi Y, Kobayashi M, Nomoto M, Aoyagi Y. · The Third Department of Internal Medicine, Niigata University School of Medicine, Japan. · Nippon Shokakibyo Gakkai Zasshi. · Pubmed #19262054 No free full text.

Abstract: A 73-year-old man with chronic hepatitis C was Successfully treated for hepatocellular carcinoma (HCC) by localized treatment. During the follow-up period, abdominal computed tomography (CT) revealed no HCC recurrence in the liver. However, 9 months after the treatment, abdominal lymph nodes appeared enlarged on CT. Laparoscopic biopsy of the lymph nodes showed that the lesion was HCC, and TS-1/cisplatin chemotherapy was performed. However, extra-hepatic lymph nodes rapidly grew, leading to obstructive jaundice and finally death 10 months after of HCC metastasis. Although abdominal lymph node metastasis of HCC has been widely considered to be rare, the confirmation of effective therapy is awaited because histological studies have suggested that this pathologic lesion may occur more often than expected.

Kogure T, Ueno Y, Fukushima K, Nagasaki F, Kondo Y, Inoue J, Matsuda Y, Kakazu E, Yamamoto T, Onodera H, Miyazaki Y, Okamoto H, Akahane T, Kobayashi T, Mano Y, Iwasaki T, Ishii M, Shimosegawa T. · Division of Gastroenterology, Tohoku University Hospital, 1-1, Seiryo, Aobaku, Sendai 980-8574, Japan. · World J Gastroenterol. · Pubmed #19084938 links to  free full text

Abstract: AIM: To evaluate the efficacy of pegylated interferon alpha-2b (peg-IFN alpha-2b) plus ribavirin (RBV) therapy in Japanese patients with chronic hepatitis C (CHC) genotype Ib and a high viral load. METHODS: One hundred and twenty CHC patients (58.3% male) who received peg-IFN alpha-2b plus RBV therapy for 48 wk were enrolled. Sustained virological response (SVR) and clinical parameters were evaluated. RESULTS: One hundred (83.3%) of 120 patients completed 48 wk of treatment. 53 patients (44.3%) achieved SVR. Early virological response (EVR) and end of treatment response (ETR) rates were 50% and 73.3%, respectively. The clinical parameters (SVR vs non-SVR) associated with SVR, ALT (108.4 IU/L vs 74.5 IU/L, P = 0.063), EVR (76.4% vs 16.4%, P < 0.0001), adherence to peg-IFN (>or= 80% of planned dose) at week 12 (48.1% vs 13.6%, P = 0.00036), adherence to peg-IFN at week 48 (54.7% vs 16.2%, P < 0.0001) and adherence to RBV at week 48 (56.1% vs 32.1%, P = 0.0102) were determined using univariate analysis, and EVR and adherence to peg-IFN at week 48 were determined using multivariate analysis. In the older patient group (> 56 years), SVR in females was significantly lower than that in males (17% vs 50%, P = 0.0262). EVR and adherence to Peg-IFN were demonstrated to be the main factors associated with SVR. CONCLUSION: Peg-IFN alpha-2b plus RBV combination therapy demonstrated good tolerability in Japanese patients with CHC and resulted in a SVR rate of 44.3%. Treatment of elderly female patients is still challenging and maintenance of adherence to peg-IFN alpha-2b is important in improving the SVR rate.

Matsuda Y, Inada M, Maeda H, Matsuyama T. · Division of Internal Medicine, Toyonaka Municipal Hospital. · Intern Med. · Pubmed #12412994 links to  free full text

Abstract: OBJECTIVE: Inflammatory liver damage and viral persistence after hepatitis C virus (HCV) infection are known to be related in host immunity. Suplatast tosilate is an immunomodulator that selectively inhibits type 2 cytokine production by helper T cells. We investigated the efficacy and safety of the administration of suplatast tosilate for patients with HCV infection by examining the level of serum alanine aminotransferase (ALT) and viremia. PATIENTS AND METHODS: Thirty-eight patients who had shown resistance to ursodeoxycholic acid (UDCA) therapy (600 mg/day tid) over 6 months for HCV-related chronic liver disease were randomized into two groups and received UDCA alone (600 mg/day tid) or UDCA (600 mg/day tid) plus suplatast tosilate (300 mg/day tid) by means of sealed envelopes. RESULTS: After 24 weeks, serum ALT was decreased in the patients receiving UDCA plus suplatast tosilate, with the mean reduction being 40.2% (from 132 to 79 IU/l; p=0.001). In the patients receiving UDCA alone, ALT decreased by 8.3% (from 133 to 122 IU/l; ns). Multiple comparison of individual ALT changes showed that the UDCA plus suplatast tosilate achieved significantly greater improvement (p = 0.001). However, serum HCV RNA was unchanged in both groups. Two patients developed adverse reactions to suplatast tosilate, which resolved promptly after the discontinuation of the therapy. CONCLUSION: These findings suggest that suplatast tosilate promotes biochemical improvement in the patients with chronic hepatitis C.

Tani H, Akimitsu N, Fujita O, Matsuda Y, Miyata R, Tsuneda S, Igarashi M, Sekiguchi Y, Noda N. · Department of Life Science and Medical Bio-Science, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan. · Biochem Biophys Res Commun. · Pubmed #19150342 No free full text.

Abstract: We have developed a novel high-throughput screening assay of hepatitis C virus (HCV) nonstructural protein 3 (NS3) helicase inhibitors using the fluorescence-quenching phenomenon via photoinduced electron transfer between fluorescent dyes and guanine bases. We prepared double-stranded DNA (dsDNA) with a 5'-fluorescent-dye (BODIPY FL)-labeled strand hybridized with a complementary strand, the 3'-end of which has guanine bases. When dsDNA is unwound by helicase, the dye emits fluorescence owing to its release from the guanine bases. Our results demonstrate that this assay is suitable for quantitative assay of HCV NS3 helicase activity and useful for high-throughput screening for inhibitors. Furthermore, we applied this assay to the screening for NS3 helicase inhibitors from cell extracts of microorganisms, and found several cell extracts containing potential inhibitors.

Fukushima K, Ueno Y, Inoue J, Wakui Y, Obara N, Kimura O, Kido O, Nakagome Y, Kakazu E, Matsuda Y, Kogure T, Kondo Y, Nagasaki F, Yamagiwa Y, Ashino Y, Shimosegawa T. · Department of Internal Medicine, Tohoku University Hospital, Sendai, Japan. · Hepatol Res. · Pubmed #18498361 No free full text.

Abstract: We report a case of a HIV and hepatitis B virus (HBV)-co-infected patient to whom entecavir (ETV) was administered initially before the notification regarding the potential mutagenesis effect on HIV against the nucleoside analog. Since initial evaluations indicated the advanced stage of chronic hepatitis B and preserved numbers of peripheral CD4+ lymphocytes without the manifestation of immunodeficiency, priority was given to the management of HBV. We started HBV therapy with ETV at a dose of 0.5 mg daily without using any HIV drugs. The viral loads of both HBV and HIV-1 decreased gradually during the 5 months following the initial administration of ETV. HBV was well controlled by the gradual replacement of ETV with highly-active antiretroviral therapy against HIV with a regimen including atazanavir, emtricitabine, and tenofovir. HBV was genotyped as A2 with the quasispecies pool consisting of the -1G precore/core deletion mutant strain.

Yamagiwa S, Matsuda Y, Ichida T, Honda Y, Takamura M, Sugahara S, Ishikawa T, Ohkoshi S, Sato Y, Aoyagi Y. · Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan. · Hepatol Res. · Pubmed #18328072 No free full text.

Abstract: Aim: Previous studies have revealed that functional impairment of innate immune cells, including natural killer (NK) and natural killer T (NKT) cells, might be associated with the persistence of hepatitis C virus (HCV) infection. However, the involvement of innate immune cells, which predominate in the liver, in therapeutic HCV clearance is still unclear. Methods: To clarify the role of intrahepatic innate immune cells in the clinical outcome of patients with chronic hepatitis C (CHC) treated with interferon-alpha plus ribavirin (IFN/RBV), we prospectively investigated the status of NK and NKT cells in paired liver biopsy and peripheral blood (PB) samples obtained from 21 CHC patients before and immediately after IFN/RBV treatment by flow cytometry. Normal liver and PB samples were obtained from 10 healthy donors for living donor liver transplantation. Results: Before treatment, intrahepatic NK and NKT cells constituted a significantly lower proportion in CHC patients than in healthy individuals (P < 0.05). After IFN/RBV treatment, the proportions and absolute numbers of CD3(-)CD161(+) NK and CD3(+)CD56(+) NKT cells in the liver, but not in PB, were significantly increased in sustained responders (SR) as compared with poor responders (P < 0.05). The proportion of CD3(+)CD161(+) NKT cells was also increased in the liver of SR after the treatment. Moreover, there was a striking increase of activated CD152(+) cells among CD3(+)CD56(+) NKT cells in the liver of SR (P = 0.041). Conclusion: These findings demonstrate that sustained response to IFN/RBV treatment for patients with CHC is closely associated with increased dynamism of NK and NKT cells in the liver.

Inoue J, Ueno Y, Kogure T, Nagasaki F, Kimura O, Obara N, Kido O, Nakagome Y, Kakazu E, Matsuda Y, Fukushima K, Segawa H, Nakajima I, Itoyama Y, Takahashi M, Okamoto H, Shimosegawa T. · Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan. · J Clin Virol. · Pubmed #18291715 No free full text.

Abstract: Although many extrahepatic manifestations have been described in patients with acute or chronic hepatitis B, there are few reports about neurological disorders. We describe a 55-year-old man who contracted acute hepatitis B virus (HBV) infection and transverse myelitis. His neurological findings were gradually reduced along with the recovery from hepatitis. The cerebrospinal fluid (CSF) was revealed to be positive for HBsAg and HBV DNA. Full-length sequences of HBV in his serum and CSF were determined, and it was revealed that these two isolates had mutations at nucleotide (nt) 1762/1764 in the core promoter region and nt 1896 in the precore region. They were identical to each other except for two ambiguous codes at nt 2020 and 2631 in the CSF isolate. After cloning of the amplicons, substitutions at nt 2020 and 2631 were found in 6 (38%) of the 16 CSF clones. One clone of the 6 CSF clones had an additional substitution at nt 2119. These substitutions were not found in 16 serum clones. The presence of HBV clones unique to CSF suggests that HBV was a possible causative agent of the myelitis.

Yamazaki K, Suzuki K, Ohkoshi S, Yano M, Kurita S, Aoki YH, Toba K, Takamura MA, Yamagiwa S, Matsuda Y, Aoyagi Y. · Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences of Niigata University, 1-754, Asahimachi-Dori, Niigata-city 951-8122, Japan. · J Hepatol. · Pubmed #18083266 No free full text.

Abstract: BACKGROUND/AIMS: The preventive effect of interferon (IFN) against hepatocellular carcinoma (HCC) has been confirmed clinically. We sought to determine whether the temporal administration of IFN-beta prevents hepatocarcinogenesis in a mouse model where HCC develops without necroinflammation. METHODS: Hepatocarcinogenic mice that are transgenic for the hepatitis B virus X gene (HBx-Tg) were treated with IFN-beta or saline (control) for three months, from 3 to 6 months of age, and the incidence of HCC was determined at 18 months of age. The effects of IFN-beta on DNA synthesis and apoptosis were tested. RESULTS: The incidence of HCC was significantly lower in the IFN-beta-treated mice than the controls (0 vs. 50%, P<0.01). Inhibition of DNA synthesis in hepatocytes by IFN-beta was observed in the livers of HBx-Tg, without any significant induction of apoptosis. Although the treatment of IFN-beta was temporal, the number of hepatocytes with DNA synthesis remained lower 3 and 12 months later in life. CONCLUSIONS: Temporal administration of IFN-beta has a significant preventive effect on the occurrence of HCC in a mouse model where HCC develops without inflammation. The mechanisms are the inhibition of DNA synthesis and cell cycle progression of hepatocytes.

Fukushima K, Ueno Y, Kanegane H, Yamagiwa Y, Inoue J, Kido O, Nagasaki F, Kogure T, Kakazu E, Nakagome Y, Matsuda Y, Obara N, Kimura O, Shimosegawa T. · Department of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan. · Hepatol Res. · Pubmed #18021227 No free full text.

Abstract: Severe hepatitis with an indistinct etiology manifested in a 16-year-old boy who had no particular history. The histological features of the liver and clinical course of the patient were similar to those of patients with autoimmune hepatitis characterized by interface hepatitis and severe lobular inflammation of the liver and recurrent exacerbations of hepatitis. We administered intravenous glycyrrhizin preparation daily or three times a week combined with the oral administration of ursodeoxycholic acid daily throughout the term after the initial onset of disease for the control of disease activity. The normalization of the concentration of alanine aminotransferase in serum was achieved in response to the therapy during the course. The serum concentration of immunoglobulins of the patient gradually decreased from the onset of the disease to an unacceptable level without globulin preparation during the following period of 17 months. Immunological tests revealed impairment of immunoglobulin production bythe B cell population of the patient, which led to the diagnosis of the patient as common variable immunodeficiency (CVID). The patient, with improved liver histology after 27 months from the onset of disease, benefited from the current combination therapy without severe infection through the avoidance of overimmunosuppression. CVID is defined as a heterogeneous syndrome characterized by various degrees of hypogammaglobulinemia without any specific predisposing causes, frequently associated with autoimmunity. Diagnostic criteria and therapeutic options of persistent hepatitis with CVID are to be established, as discussed in the current report.

Kogure T, Ueno Y, Fukushima K, Nagasaki F, Inoue J, Kakazu E, Matsuda Y, Kido O, Nakagome Y, Kimura O, Obara N, Wakui Y, Iwasaki T, Shimosegawa T. · Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aoba, Sendai City 980-8574, Japan. · World J Gastroenterol. · Pubmed #17708618 links to  free full text

Abstract: A 27-year-old Caucasian female with hepatitis C virus (HCV) infection treated with interferon (IFN) who developed severe autoimmune hepatitis (AIH) is described. The infecting viral strain was of genotype Ib and the pre-treatment HCV viral load was at a high level. The patient was treated with pegylated IFN-alpha 2b and ribavirin, and her HCV-RNA became negative at wk 12, but after that she developed fulminant hepatic failure. The patient recovered after steroid pulse therapy consisting of methylprednisolone 1000 mg/d for three days which was administered twice. A needle liver biopsy revealed the typical pathological findings of AIH.

Yamazaki K, Ohkoshi S, Maruyama M, Aoki YH, Yano M, Kurita S, Suzuki K, Matsuda Y, Sugimura K, Aoyagi Y. · Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences of Niigata University, Niigata-city, Japan. · Hepatol Res. · Pubmed #17539819 No free full text.

Abstract: A patient with chronic hepatitis B and C undergoing treatment with interferon and ribavirin showed an upsurge in hepatitis B virus surface antibody (anti-HBs) titer, accompanied by a decrease in hepatitis B virus surface antigen (HBsAg) during the early treatment phase. Simultaneously, elevation of alanine aminotransferase (ALT) was observed. Subsequently, the hepatitis B virus (HBV) DNA titer decreased and HBV e antigen (HBeAg) to anti-HBe seroconversion occurred. The anti-HBs titer gradually returned to the pretreatment level after cessation of ribavirin treatment and HBV-DNA became undetectable. We found no nucleotide mutations in HBV-DNA that could explain the sudden elevation in anti-HBs titer. The appearance of anti-HBs was considered to be a break in immune tolerance against some epitopes in HBsAg, possibly the r epitope, stimulated by interferon/ribavirin treatment. The immunomodulatory effect of ribavirin might have caused this unexpected early immune response to HBsAg that preceded seroconversion to anti-HBe.

Honda Y, Yamagiwa S, Matsuda Y, Takamura M, Ichida T, Aoyagi Y. · Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, 757, Asahimachi-Dori 1, Niigata 951-8510, Japan. · J Hepatol. · Pubmed #17448566 No free full text.

Abstract: BACKGROUNDS/AIMS: Toll-like receptors (TLRs) have emerged as a key component of the innate immune system that triggers antimicrobial responses. Altered monocyte responses to ligands for TLRs have been reported in patients with primary biliary cirrhosis (PBC), yet the precise mechanism remains unknown. METHODS: We investigated in vitro responses to a TLR4 ligand, lipopolysaccharide (LPS), using peripheral blood mononuclear cells and monocytes from 25 patients with PBC, 10 patients with chronic viral hepatitis (CVH), and 20 healthy individuals. RESULTS: After stimulation with LPS, we found significantly higher amounts of IL-1beta, IL-6, and IL-8 production in PBC patients. Through the TLR4 signaling pathway, activation of NF-kappaB and expression of MyD88 mRNA were significantly increased in PBC patients, and the level of TLR4 expression was significantly increased on PBC monocytes as compared with CVH patients and controls. Of significance, the surface expression of RP105, which has recently been shown to be involved in negative regulation of TLR4 signaling, on PBC monocytes was significantly decreased in comparison with CVH patients (P=0.016) and controls (P<0.001). CONCLUSIONS: These results suggest that expression of RP105 and TLR4 is altered on PBC monocytes, which appear to be hypersensitive to LPS, resulting in increased secretion of pro-inflammatory cytokines.

Nagasaki F, Ueno Y, Yamamoto T, Nakagomi Y, Kido O, Kakazu E, Matsuda Y, Kogure T, Yamagiwa Y, Kikuchi K, Fukushima K, Kanno N, Niitsuma H, Shimosegawa T. · Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan. · Tohoku J Exp Med. · Pubmed #16960342 links to  free full text

Abstract: Hepatitis B virus (HBV) infection, which causes liver cirrhosis and hepatocellular carcinoma, remains a major health problem in Asian countries. Recent development of vaccine for prevention is reported to be successful in reducing the size of chronically infected carriers, although the standard medical therapies have not been established up to now. In this report, we encountered a patient with decompensated HBV-related cirrhosis who exhibited the dramatic improvements after antiviral therapy. The patient was a 50-year-old woman. Previous conventional medical treatments were not effective for this patient, thus this patient had been referred to our hospital. However, the administration of lamivudine, a reverse transcriptase inhibitor, for 23 months dramatically improved her liver severity. During this period, no drug resistant mutant HBV emerged, and the serum HBV-DNA level was continuously suppressed. These virological responses were also maintained even after the antiviral therapy was discontinued. Moreover, both hepatitis B surface antigen and e antigen were observed to have disappeared in this patient. The administration of lamivudine to patients with HBV-related cirrhosis, like our present case, should be considered as an initial medical therapeutic option, especially in countries where liver transplantation is not reliably available.

Kogure T, Ueno Y, Kanno N, Fukushima K, Yamagiwa Y, Nagasaki F, Kakazu E, Matsuda Y, Kido O, Nakagome Y, Ninomiya M, Shimosegawa T. · Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aoba, Sendai 980-8574, Japan. · World J Gastroenterol. · Pubmed #16937453 links to  free full text

Abstract: A 29-year-old nurse with a hepatitis C virus (HCV) infection caused by needle-stick injury was treated with interferon-beta starting about one year after the onset of acute hepatitis. The patient developed acute hepatitis C with symptoms of general fatigues, jaundice, and ascites 4 wk after the needle-stick injury. When these symptoms were presented, the patient was pregnant by artificial insemination. She hoped to continue her pregnancy. After delivery, biochemical liver enzyme returned to normal levels. Nevertheless, HCV RNA was positive and the pathological finding indicated a progression to chronicity. The genotype was 1b with low viral load. Daily intravenous injection of interferon-beta at the dosage of six million units was started and continued for eight weeks. HCV was eradicated without severe adverse effects. In acute hepatitis C, delaying therapy is considered to reduce the efficacy but interferon-beta therapy is one of the useful treatments for hepatitis C infection in chronic phase.

Takamura M, Ichida T, Yokoyama J, Matsuda Y, Nomoto M, Aoyagi Y. · Division of Gastroenterology and Hepatology, Department of Cellular Function, Course for Molecular and Cellular Medicine, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan. · J Gastroenterol. · Pubmed #15293140 No free full text.

Abstract: We report a 54-year-old Japanese woman who developed liver tumors 102 months after hepatic resection for hepatocellular carcinoma (HCC) and percutaneous transluminal angioplasty (PTA) for membranous obstruction of the inferior vena cava (MOVC), which is one form of Budd-Chiari syndrome. In the present admission workup showed no evidence of co-infection with hepatitis B and C viruses. Dynamic computed tomography (CT) and magnetic resonance imaging showed an enhanced lesion, 1.5 cm in diameter, in segment 3 of the liver, and no obstruction of the inferior vena cava after PTA. CT during both arterial portography and hepatic arteriography revealed another lesion, showing different hemodynamics, in segment 2. The patient therefore underwent hepatic resection, and the tumors were diagnosed histologically as HCC. The two tumors differed in their morphological features, one containing abundant fibrous stroma, whereas the other did not. The nontumorous liver tissue showed central zonal fibrosis, i.e., reversed lobulation, and partial expansion of nodule-like formations, indicating lack of progression since the situation seen at the initial hepatectomy. The presence of nontumorous liver tissue showing the above features suggests that, even after successful treatment for relief of congestion, patients who have had MOVC should be followed closely for as long as possible because of the risk of HCC recurrence. This is the first reported case of HCC recurrence after successful treatment of MOVC.

Ito T, Matsuda Y, Oguchi Y, Ito T, Matsuda H. · Department of Surgery, Otemae Hospital, 1-5-34 Otemae, Chuo-ku, Osaka 540-0008, Japan. · Hepatogastroenterology. · Pubmed #11995482 No free full text.

Abstract: BACKGROUND/AIMS: To evaluate portal vascular resistance using Doppler ultrasound intraoperatively. METHODOLOGY: We measured maximum flow velocities and pressures of umbilical portion of the left portal branch before and after clamping of the right main branch of the Glisson's sheath. We proposed a new index, simplified portal resistive index, that was the ratio of the difference of the portal venous pressure to the difference of maximum portal flow velocity. RESULTS: There were good correlations between portal vascular resistance and simplified portal resistive index. Simplified portal resistive index was found to become higher as fibrotic changes progressed, and there were significant differences between normal liver, chronic hepatitis, and liver cirrhosis. CONCLUSIONS: Simplified portal resistive index evaluated using intraoperative Doppler ultrasound is an easy and reliable index for assessing portal vascular resistance during liver surgery.

Yabuuchi I, Imai Y, Kawata S, Tamura S, Noda S, Inada M, Maeda Y, Shirai Y, Fukuzaki T, Kaji I, Ishikawa H, Matsuda Y, Nishikawa M, Seki K, Matsuzawa Y. · Department of Internal Medicine and Molecular Science, Osaka University Medical School, Japan. · Liver. · Pubmed #10959807 No free full text.

Abstract: AIMS/BACKGROUND: The aim of this study was to determine the characteristics of patients with chronic hepatitis C showing long-term normalization of alanine aminotransferase (ALT) without eradication of HCV RNA, as well as to investigate the incidence of hepatocellular carcinoma (HCC) in such patients. METHODS: Four hundred and nineteen patients with histologically-proven chronic hepatitis C who had received interferon (IFN) therapy were studied. Complete response (CR) was defined as persistent normalization of ALT levels with eradication of serum HCV RNA (n= 126). Long-term biochemical response with positive HCV RNA (HCV-positive BR) was defined as a normal ALT level at 6 months after IFN therapy with further persistent normalization of ALT levels for 2 or more years without eradication of serum HCV RNA (n=49). All other patterns were classified as non-response (NR, n=244). RESULTS: Mean follow-up periods of CR, HCV-positive BR and NR groups were 4.9, 5.2 and 4.9 years, respectively. The HCV-positive BR group had significantly higher serum HCV RNA levels and a higher rate of HCV serological group 1 classification than the CR group. The other characteristics of the HCV-positive BR group were lower histologic activity, lower ALT levels, and a higher rate of females when compared with both the CR and NR groups. Histologic staging in the HCV-positive BR group was significantly lower than that in the NR group. Cumulative incidences of HCC estimated by the Kaplan-Meier method in both the CR and HCV-positive BR groups were significantly lower than those in the NR group (log-rank test, CR vs NR p<0.001, HCV-positive BR vs NR p=0.026). CONCLUSION: The patients with HCV-positive BR were virologically different from those with CR, and had lower ALT levels and histologic activity when compared to those with CR and NR.