Norihiro Furusyo

The longitudinal quantitative assessment by transient elastography of chronic hepatitis C patients treated with pegylated interferon alpha-2b and ribavirin

The aim of this study was to assess the association between liver stiffness measured by transient elastography (FibroScan) and the efficacy of pegylated interferon alpha-2b plus ribavirin combination treatment for patients with chronic hepatitis C virus (HCV) infection. We prospectively studied 145 Japanese patients with chronic HCV infection. FibroScan was done at baseline, at the end of treatment, and at 48 and 96 weeks after the end of treatment. The FibroScan values were significantly decreased for sustained virological response (SVR) patients (the mean rate of change; -16.2%, -32.2% and -43.5%) in comparison with non-SVR patients (-7.2%, -2.1% and +17.3%) at the end of treatment (P=0.0127), and 48 weeks (P<0.0001) and 96 weeks (P<0.0001) after the end of treatment. Among the non-SVR patients, the FibroScan values were significantly decreased for patients with biochemical response (BR) (-17.9%, -30.0% and -27.1%) in comparison with non-BR (-4.1%, +6.4% and +30.6%) at the end of treatment (P=0.0270), and 48 weeks (P<0.0001) and 96 weeks (P<0.0001) after the end of treatment. The FibroScan values may predict a progressively better clinical outcome for patients with successful virological and biochemical responses.

Efficacy of pegylated interferon alpha-2b and ribavirin treatment on the risk of hepatocellular carcinoma in patients with chronic hepatitis C: A prospective, multicenter study ☆

BACKGROUND & AIMS The effects of pegylated interferon (PegIFN) α and ribavirin (RBV) treatment of chronic hepatitis C on the incidence of hepatocellular carcinoma (HCC) have not been well established. This study investigated the impact of treatment outcome on the development of HCC by chronic hepatitis C patients treated with PegIFNα2b and RBV. METHODS This large-scale, prospective, multicenter study consisted of 1013 Japanese chronic hepatitis C patients with no history of HCC (non-cirrhosis, n=863 and cirrhosis, n=150). All patients were treated with PegIFNα2b and RBV and the follow-up period started at the end of the antiviral treatment (median observation period of 3.6 years). The cumulative incidence rate of HCC was estimated using the Kaplan-Meier method, according to treatment outcome. RESULTS Forty-seven patients (4.6%) developed HCC during the observation period. In the non-cirrhosis group, the 5-year cumulative incidence rates of HCC for the sustained virological response (SVR) (1.7%) and transient virological response (3.2%) (TVR: defined as relapse or breakthrough) groups were significantly lower than those of the non-virological response (NVR) group (7.6%) (p=0.003 and p=0.03, respectively). A significantly low rate of incidence of HCC by TVR patients in comparison with NVR patients was found for patients aged 60 years and over, but not for those under 60 years of age. In the cirrhosis group, the 5-year cumulative incidence rates of HCC for the SVR (18.9%) and TVR groups (20.8%) were also significantly lower than those of the NVR group (39.4%) (p=0.03 and p=0.04, respectively). CONCLUSIONS SVR and complete viral suppression during treatment with relapse (TVR) were associated with a lower risk of HCC development when compared with NVR.

Transient elastography for patients with chronic hepatitis B and C virus infection: Non-invasive, quantitative assessment of liver fibrosis.

Aim/Methods:  The aim of the present study was to compare the diagnostic performance of transient elastography (FibroScan) with that of serum fibrosis markers and stages of hepatic fibrosis by biopsy in 68 patients with chronic hepatitis B virus (HBV) and in 161 patients with hepatitis C virus (HCV) infection.

A Relationship between the Evolution of Hepatitis C Virus Variants, Liver Damage, and Hepatocellular Carcinoma in Patients with Hepatitis C Viremia

To clarify the mechanism of liver damage induced by hepatitis C virus (HCV) and to determine whether the damage is related to hepatocellular carcinoma (HCC), HCV RNA levels were measured serially, and HCV genome mutations were analyzed from serum of 274 Japanese patients with chronic HCV viremia during 1993-1998. All patients had alanine aminotransferase (ALT) levels measured during 1986-1998. Patients with consistently normal ALT levels had identical and highly conserved HCV core regions; however, those with consistently abnormal ALT levels had quasi species, and the population of the quasi species changed over time. HCV RNA levels did not change in the 274 patients. HCC developed in 31% of 80 patients with consistently abnormal ALT levels and in 4% of 92 patients with intermittently abnormal ALT levels but never in 102 patients with ALT levels consistently normal during 1993-1998. In patients with chronic HCV viremia, persistent liver damage plays an important role in the development of HCC.

Maintenance hemodialysis decreases serum Hepatitis C virus (HCV) RNA levels in hemodialysis patients with chronic HCV infection

OBJECTIVE:Hepatitis C virus (HCV) infection is a major complication among hemodialysis patients the world over. To determine the natural course of HCV viremic levels in patients on maintenance hemodialysis, we prospectively quantified the HCV RNA levels in serial blood samples from hemodialysis patients and compared them with those in nonuremic subjects.METHODS:The population studied included 98 hemodialysis patients and 228 nonuremic subjects with chronic HCV infection. HCV RNA was detected by polymerase chain reaction (PCR) and the levels were determined by branched DNA probe assay. HCV RNA genotypes were determined by PCR using type-specific primers.RESULTS:HCV RNA levels were significantly lower in hemodialysis patients (median, 0.4 × 106 genome equivalent [Meq;[sol;ml) than in nonuremic subjects (median, 3.0 Meq/ml) (p < 0.05). HCV of genotype 1b was prevalent in the hemodialysis patients (81.6%) and nonuremic subjects (88.6%). HCV RNA levels in 20 hemodialysis patients with genotype 1b were significantly reduced after each hemodialysis procedure (p < 0.05). The 3-yr prospective observation from 1995 to 1998 showed a significant decrease of HCV RNA levels in 47 hemodialysis patients with genotype 1b (median, 1.9–0.9 Meq/ml, p < 0.05), whereas levels in 155 nonuremic subjects with genotype 1b did not decrease (median, 2.6–3.0 Meq/ml). There were no patients or nonuremic subjects with undetectable HCV RNA by a PCR assay during the observation period.CONCLUSIONS:These observations suggest that maintenance hemodialysis decreases the HCV RNA levels in hemodialysis patients with chronic HCV infection, but does not produce clearance of the viremia.

Telaprevir can be successfully and safely used to treat older patients with genotype 1b chronic hepatitis C

BACKGROUND & AIMS This study was performed to evaluate the efficacy of a triple therapy in older Japanese patients; telaprevir (TVR) was added to pegylated interferon α2b and ribavirin. METHODS This prospective study enrolled 120 genotype 1b patients with chronic hepatitis C who received 12 weeks of triple therapy followed by a 12-week dual therapy that included pegylated interferon α2b and ribavirin. Patients were categorized according to age: group A, 64 patients aged >60 and group B, 56 patients aged ⩽60. Serum HCV RNA levels were monitored by COBAS TaqMan HCV test. RESULTS The rates of undetectable HCV RNA at week 4 (rapid virological response, RVR) were 73.4% in group A and 73.2% in group B. No significant difference in sustained virological response (SVR) was found between groups A (76.6%) and B (83.9%) (p=0.314). The SVR rates for patients with interleukin 28B (IL28B) (rs8099917) TT allele (89.4% and 91.9% for groups A and B) were significantly higher than for those with the IL28B TG/GG allele (41.2% and 68.4%, respectively) (both p<0.05). Multivariate analysis extracted IL28B TT and RVR as independent factors associated with SVR. Adverse effects resulted in treatment discontinuation by 12.5% in each group. Hemoglobin decrease significantly differed between groups A and B: the decrease to ≤100 g/L, to 85 - <100g/L, and to <85 g/L, was 9.4%, 40.6%, and 50% in group A patients, respectively, and 41.1%, 25%, and 33.9% in group B patients, respectively (p=0.0006). CONCLUSIONS TVR-based triple therapy can be successfully used to treat older patients with genotype 1b chronic hepatitis C.

Acute hepatitis C among Japanese hemodialysis patients: a prospective 9-year study.

Abstract OBJECTIVES: The aims of this prospective survey were to determine the incidence and clinical characteristics of newly acquired hepatitis C virus (HCV) infection in hemodialysis patients after the start of antibody to HCV (anti-HCV) screening for blood products in Japan in 1989. METHODS: In serial serum samples from 269 hemodialysis patients who were followed over a mean period of 6.6 yr (± 2.1 yr) from 1990 to 1998, HCV RNA and anti-HCV were detected by reverse transcription-polymerase chain reaction and second generation ELISA, respectively. RESULTS: During the observation period, newly acquired HCV infection was found in 26 (15.4%) of the 169 hemodialysis patients without anti-HCV or HCV RNA at entry, an annual incidence rate of 2.59%. Of these 26, only four had a history of blood transfusion, one of whom had received the blood transfusion after 1992, the year in which screening of blood products for anti-HCV by second-generation ELISA was introduced in Japan. Persistent HCV viremia was found in 17 (65.4%) of the 26 patients; the other nine (34.6%) had transient HCV infection. The mean period of continuous ALT abnormality was significantly longer in the former (12.4 ± 13.6 months) than in the latter (1.9 ± 3.5 months) ( p = 0.0067). However, only three (17.6%) of 17 patients with chronic HCV viremia had continuous ALT abnormality for more than 24 months; in all of them, ALT eventually normalized. CONCLUSIONS: These findings indicate that newly acquired HCV infection has continued to occur in hemodialysis patients after the initiation of anti-HCV screening of blood products and that the abnormal ALT found in these patients is related to HCV chronicity.

Glycated albumin and diabetes mellitus.

BACKGROUND Diabetes is a growing worldwide problem that is strongly associated with atherosclerosis. Screening and intervention for diabetes in the earliest stages are advocated for the prevention of diabetic complications and cardiovascular disease. SCOPE OF REVIEW This review gives a background of and discusses the potential clinical utility of glycated albumin (GA) in diabetes. MAJOR CONCLUSIONS GA is a ketoamine formed via a non-enzymatic glycation reaction of serum albumin and it reflects mean glycemia over two to three weeks. GA can be used for patients with anemia or hemoglobinopathies for whom the clinically measured hemoglobin A1c level may be inaccurate. Because both serum and plasma samples can be used, GA can be analyzed from the same samples as common biological markers. GA is a useful marker for the screening of diabetes in a medical evaluation. It can be also used to determine the effectiveness of treatment before initiating or changing medications for diabetic patients. GA is potentially an atherogenic protein in the development of diabetic atherosclerosis. GENERAL SIGNIFICANCE GA measurement is useful as part of a routine examination to screen for both diabetes and atherosclerosis. This article is part of a Special Issue entitled Serum Albumin.

Liver damage in hemodialysis patients with hepatitis C virus viremia : A prospective 10-year study

Hepatitis C virus (HCV) infection is a major problem associated with hemodialysis. The extent of liver damage in hemodialysis patients with chronic HCV infection has not been thoroughly documented. The aim of this study was to evaluate liver damage of hemodialysis patients infected with HCV. A total of 233 hemodialysis patients were categorized into two groups at entry: group X, 80 positive for serum HCV RNA, and group Y, 153 negative for serum HCV RNA. All were tested for serum alanine aminotransferase (ALT) serially from 1989 to 1998, and serum hyaluronic acid (HA), serum type-IV collagen (IV-C), platelet counts, and ultrasonographic examination of the liver was done in 1998. In group X, 61.3% had continuously abnormal ALT levels for over six months followed by normal ALT levels. Of the group X patients, 11.3% had abnormal ALT levels in 1998, and in three, hepatocellular carcinoma occurred. Mean HA and IV-C levels in group X (648.8 and 188.7 ng/ml, respectively) were significantly higher than in group Y (213.1 and 165.5 ng/ml, respectively) (P < 0.05). Ultrasonographic findings significantly correlated with serum HA level and platelet counts and showed significantly more abnormalities in group X than in group Y (P < 0.05). From these findings, a combined examination with ultrasonography and serum fibrogenesis markers is useful for detection of liver damage in hemodialysis patients with HCV viremia.

Association between the treatment length and cumulative dose of pegylated interferon alpha-2b plus ribavirin and their effectiveness as a combination treatment for Japanese chronic hepatitis C patients : Project of the Kyushu University Liver Disease Study Group

Aim:  The aim of the present study was to investigate the association between the length of the treatment period and the cumulative dose of pegylated interferon alpha‐2b (peg‐IFN alpha‐2b) plus ribavirin (RBV) and their effectiveness in the treatment of chronic hepatitis C.