Yasunori Sawayama

Effects of probucol and pravastatin on common carotid atherosclerosis in patients with asymptomatic hypercholesterolemia: Fukuoka atherosclerosis trial (FAST)

OBJECTIVES This study investigated the effect of reducing serum lipids on carotid artery intima-media thickness (IMT) in asymptomatic patients with hypercholesterolemia from Fukuoka, Japan. BACKGROUND Carotid atherosclerosis is a strong, independent predictor of morbidity and mortality in patients with coronary heart disease (CHD). METHODS A total of 246 asymptomatic hypercholesterolemic patients (mean age 66 years) were randomized to receive either probucol (500 mg/day, n = 82) or pravastatin (10 mg/day, n = 83) or to enter a control group (diet alone, n = 81); they were followed for two years. The change in IMT in the common carotid artery was the primary end point measure, and the incidence of major cardiovascular events was the secondary measure. RESULTS Over the two-year period, serum low-density lipoprotein (LDL) cholesterol was significantly reduced in the pravastatin group (36%), the probucol group (29%) and the control group (12%) (p < 0.0001, p < 0.0001 and p < 0.05, respectively). After two years, the probucol and pravastatin groups showed a significant reduction in IMT (-13.9% and -13.9% and p < 0.01 and p < 0.01, respectively), but there was significant IMT thickening (23.2%; p < 0.05) in the control group. Probucol reduced the rate of IMT increase, independently of its reduction of LDL or high-density lipoprotein cholesterol. Moreover, there was a significantly lower incidence of cardiac events in the probucol group (2.4%) than in the control group (13.6%) (p = 0.0136). CONCLUSIONS Probucol reduced cholesterol levels and stabilized plaque, leading to a lower incidence of cardiac events in these hypercholesterolemic patients.

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.

Hepatitis C virus infection in institutionalized psychiatric patients: Possible role of transmission by razor sharing

The objective of this study was to determine if HCV can be transmitted from patient to patient in psychiatric institutions and to determine possible routes of infection. We did a cross-sectional survey of 196 Japanese psychiatric patients tested for HCV and HBV markers and 400 age- and sex-matched controls. Anti-HCV was detected in 10.2% and antibody to hepatitis B core antigen was detected in 44.4% of the patients, a significantly higher prevalence than found among matched controls. A multiple regression logistic analysis was used to identify risk factors that could indicate the route of infection by HCV. Duration of hospitalization, age, razor sharing, and history of surgery proved to be statistically significant independent risk factors associated with positive anti-HCV results [odds ratio (OR), 4.00; 95% confidence interval (CI), CI, 1.74–9.19; OR, 2.19; 95% CI, 1.27–1.3.77; OR, 4.90; 95% CI, 1.29–18.86; OR, 3.35; 95% CI, 0.997–11.3, respectively]. These observations suggest that razor sharing played an important role in the spread of the HCV infection in the institutionalized psychiatric patients we studied.

Differences between interferon-α and -β treatment for patients with chronic hepatitis C virus infection

To compare virological, biochemical, and immuneresponses to human lymphoblastoid interferon(IFN-α) and human fibroblast interferon(IFN-β) in patients with chronic hepatitis C virus(HCV) infection, 120 patients were randomly assigned to threegroups (group A, 60 patients receiving IFN-α, 6million units (MU) once a day, daily for one month andthrice weekly for five months; group B, 40 patients receiving 6 MU IFN-β once a day daily fortwo months; and group C, 20 patients receiving 3 MUIFN-β twice a day (6 MU/day) daily for two months).Serum soluble interleukin-2 receptor (sIL-2R) and interleukin-6 (IL-6) levels were measured byenzyme-linked immunosorbent assay. Patients withsustained clearance of serum HCV RNA detected bypolymerase chain reaction (PCR) at six months after IFNtreatment were defined as having complete response to IFNtreatment. A low level of HCV RNA (≤10-4copies/50 mul, measured by competitive PCR) and HCV RNAof genotype 2a were favorable factors for a completeresponse to both IFNs. Complete response in group Atreatment was strongly associated with early HCV RNAclearance, in contrast with group B. A significantlyhigher HCV RNA negativity at the second week from start of treatment was noted in group C (80.0%),compared with groups A (41.6%) and B (27.5%). sIL-2Rlevels rose in each group during IFN administration. Ingroup C, alanine aminotransferase (ALT) and IL-6 levels were remarkably elevated. These findingsindicate that timing of serum HCV RNA negativity insustained response differs between IFN-α andIFN-β administrations and that early HCV RNAclearance was induced by twice-a-day IFN-βtreatment.

Intrafamilial transmission of Helicobacter pylori among the population of endemic areas in Japan.

Background:  Helicobacter pylori (H. pylori) infection is a worldwide phenomenon related to several gastrointestinal diseases. However, because many aspects concerning the route of transmission remain unclear, we performed this epidemiologic study to clarify the route of intrafamilial transmission of H. pylori.

Human lymphoblastoid interferon treatment for patients with hepatitis C virus-related cirrhosis

To evaluate the efficacy and safety of human lymphoblastoid interferon treatment (interferon alfa) for patients with compensated cirrhosis caused by hepatitis C virus (HCV) infection, we randomly assigned 82 cirrhotic patients with chronic HCV infection (44 men, 38 women; mean age, 58.6 years) to two groups: 41 patients were treated with interferon alfa (480 million U over 6 months), and the other patients received no drug treatment. HCV RNA genotypes were determined by polymerase chain reaction (PCR) testing using type-specific primers. HCV RNA levels were measured by competitive PCR testing. No untreated patients eliminated HCV RNA from the serum or had a decrease in the level of alanine aminotransferase to normal during the observation period. Of the 34 patients who completed interferon alfa treatment, 6 (17.6%) who were considered complete responders eliminated HCV RNA from the serum by the end of treatment and sustained this elimination throughout a 6-month follow-up period. Complete responders constituted 6 (46.2%) of 13 patients with HCV RNA levels < or = 10(5) copies/50 microL, but none of the 21 patients with levels > 10(5) copies/50 microL were complete responders. Two (7.1%) of 28 patients with genotype 1b infection and 4 (66.7%) of 6 with genotype 2a were complete responders. Five patients withdrew because of interferon alfa-induced side effects (1 for thrombocytopenia, 3 for severe general malaise, and 1 for impotence), and 2 withdrew after being diagnosed with hepatocellular carcinoma. Hepatic failure did not occur in any treated patient in the present study. These findings indicate that interferon alfa treatment is useful for compensated cirrhosis caused by HCV infection if the HCV RNA levels are low and the infection is of genotype 2a.

Carotid artery lesions and atherosclerotic risk factors in Japanese hemodialysis patients

To determine the prevalence and severity of carotid artery lesions and which risk factors might be responsible for atherosclerosis in end-stage renal disease (ESRD) patients, we tested for carotid atherosclerosis (CA) by ultrasonography and compared the CA prevalence with well-known or suspected atherosclerotic risk factors in 226 hemodialysis (HD) patients and 2410 healthy residents of Japan. The CA prevalence was higher in the HD patients than in the healthy residents. Univariate analysis showed that HD patients with CA had a higher frequency of diabetes mellitus and left ventricular hypertrophy, and were significantly older, had significantly higher systolic blood pressure and pulse pressure, and lower albumin levels than those without. Multivariate analysis showed that age, pulse pressure, phosphorus, duration of HD, and diabetes mellitus were independent, significant predictors for CA in the HD patients. Neither Chlamydia pneumoniae seropositivity nor elevated homocysteine level was independently, significantly associated with CA. Our results suggest that HD patients had more advanced CA than the healthy residents. CA in the HD patients may be associated not only with several conventional risk factors but also with non-conventional risk factors such as phosphorus and the HD procedure itself.

Increased frequency of interferon-γ-producing peripheral blood CD4+ T cells in chronic hepatitis C virus infection

Increased frequency of interferon-γ-producing peripheral blood CD4 + T cells in chronic hepatitis C virus infection