Takeshi Sodeyama

Hepatitis C in Hospital Employees with Needlestick Injuries

Hepatitis virus infection has been a problem among hospital employees. Hepatitis B virus (HBV) infection is now controlled by hospital safety practices limiting exposure to blood and other body flu...

Anti‐gp210 and anti‐centromere antibodies are different risk factors for the progression of primary biliary cirrhosis

The predictive role of antinuclear antibodies (ANAs) remains elusive in the long‐term outcome of primary biliary cirrhosis (PBC). The progression of PBC was evaluated in association with ANAs using stepwise Cox proportional hazard regression and an unconditional stepwise logistic regression model based on the data of 276 biopsy‐proven, definite PBC patients who have been registered to the National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ). When death of hepatic failure/liver transplantation (LT) was defined as an end‐point, positive anti‐gp210 antibodies (Hazard ratio (HR) = 6.742, 95% confidence interval (CI): 2.408, 18.877), the late stage (Scheuers stage 3, 4) (HR = 4.285, 95% CI:1.682,10.913) and male sex (HR = 3.266, 95% CI: 1.321,8.075) were significant risk factors at the time of initial liver biopsy. When clinical progression to death of hepatic failure/LT (i.e., hepatic failure type progression) or to the development of esophageal varices or hepatocellular carcinoma without developing jaundice (Total bilirubin < 1.5 mg/dL) (i.e., portal hypertension type progression) was defined as an end‐point in the early stage (Scheuers stage 1, 2) PBC patients, positive anti‐gp210 antibodies was a significant risk factor for hepatic failure type progression [odds ratio (OR) = 33.777, 95% CI: 5.930, 636.745], whereas positive anti‐centromere antibodies was a significant risk factor for portal hypertension type progression (OR = 4.202, 95% CI: 1.307, 14.763). Histologically, positive anti‐gp210 antibodies was most significantly associated with more severe interface hepatitis and lobular inflammation, whereas positive anticentromere antibodies was most significantly associated with more severe ductular reaction. Conclusion: These results indicate 2 different progression types in PBC, hepatic failure type and portal hypertension type progression, which may be represented by positive‐anti‐gp210 and positive‐anticentromere antibodies, respectively. (HEPATOLOGY 2007;45:118–127.)

Transmission of hepatitis C in an isolated area in Japan : community-acquired infection

Abstract Background/Aims: The spread of hepatitis C virus (HCV) infection not due to drug needle sharing or transfusion is largely unknown in communities. A search for risk factors for HCV infection in an endemic area might elucidate inapparent modes of transmission. Methods: We conducted screening for hepatitis virus markers and parenteral exposures to blood among 435 inhabitants in an isolated area known for its endemicity for non-A, non-B hepatitis and in a nonendemic area with 1542 inhabitants. Results: The prevalence of hepatitis B surface antigen was the same in both areas. The prevalence of antibody to HCV verified by the recombinant immunoblot assay was 32.4% in the highly endemic area and 2.3% in the nonendemic area ( P Conclusions: Folk remedies such as acupuncture and cutting of the skin using nonsterilized knives should be considered as possible routes of HCV transmission not associated with blood transfusion or sharing of drug paraphernalia.

HIGH PREVALENCE OF ANTIBODY TO HEPATITIS C VIRUS IN HEAVY DRINKERS WITH CHRONIC LIVER DISEASES IN JAPAN

To investigate the prevalence of antibody to hepatitis C virus (anti‐HCV) in heavy drinkers with liver disease in Japan, we tested serum samples from 113 heavy drinkers with liver disease and 121 without liver disease. All were negative for HBsAg with no history of blood transfusion. These subjects had consumed more than 80 g of ethanol daily for 5 years or more. Findings for anti‐HCV determined by recombinant immunoblot assay testing were positive in 14 (35.9%) of the 39 patients with liver cirrhosis, 14 (58.3%) of the 24 patients with hepatocellular carcinoma and in 8 (53.3%) of the 15 patients with chronic hepatitis. The anti‐HCV positive rate in the drinkers with these liver diseases was significantly higher than in those with such disorders as fatty liver (0/10), hepatic fibrosis (0/22), and alcoholic hepatitis (0/3), as well as in the alcoholics without liver disease (5/121, 4.2%). Considering histologic findings in the anti‐HCV positive cirrhotics, the occurrence of lymph follicle formation (71.4%), piecemeal necrosis (78.6%) and loose fibrosis (64.3%) were observed to a significantly higher extent than in cirrhotics who were negative for anti‐HCV. These findings suggest that advanced chronic liver disease among heavy drinkers in Japan, especially of hepatocellular carcinoma, is closely associated with HCV infection. In the livers of heavy drinkers who were positive for anti‐HCV, histologic findings indicated the possibility of viral infection.

Natural History of Hepatitis C

With advances in tools for the diagnosis of hepatitis C virus (HCV) infection, it has become easier to evaluate the natural course of hepatitis C. Although HCV infection initially occurs in adult individuals, in most patients with acute hepatitis C (68%) it develops into chronic hepatitis. Once chronic hepatitis is established, the rate of spontaneous cure of the liver disease is very rare (below 2%). The duration from the onset of acute hepatitis until the time of diagnosis of cirrhosis of the liver and of hepatocellular carcinoma is about 20 and 30 years, respectively. The long-term clinical course of hepatitis C is divided into the three phases of acute, silent, and reactivated. The acute phase lasts from the onset of disease until 2-3 years thereafter, and the silent phase which follows lasts for 10-15 years. In the silent phase, the serum transferase level remains relatively low, below 100 IU/l, and is sometimes within the normal range. In the reactivated phase, the level of serum aminotransferase increases and remains at a high or moderate level until hepatocellular carcinoma develops. The mechanism of the chronicity of hepatitis C is unknown. However, recent advances in molecular analysis may soon elucidate this. Successive antigenic change of the HCV E2/NS1 hypervariable domain as a result of mutations may represent a mechanism by which this virus escapes the host immunosurveillance system, as well as a mechanism of its chronicity.

Acute hepatitis C transmitted by needlestick accident despite short duration interferon treatment

Hepatitis C virus (HCV) transmission by needlestick accidents involving hospital employees has become an important problem. The present report is of a case of acute hepatitis C that developed after a needlestick injury, despite short duration interferon treatment performed just after the accident in a trial effort to prevent HCV transmission. Nosocomial infection of HCV in medical employees is reviewed, and the current prospects for protecting them from HCV transmission after needlestick accident are discussed.

Detection of anti-double and anti-single stranded DNA antibodies in chronic liver disease : significance of anti-double stranded DNA antibody in autoimmune hepatitis

Anti-DNA antibodies were determined by an enzyme-linked immunosorbent assay in 116 patients with chronic liver disease consisting of 21 cases of autoimmune hepatitis (AIH), 17 of primary biliary cirrhosis (PBC), and 78 of non-autoimmune-type of chronic liver disease. The assay was also performed on 83 patients with collagen disease, as a control group. Anti-double stranded DNA antibody (anti-dsDNA) was detected in 10/21 (48%) of the AIH patients and in 3/17 (17%) of the PBC patients, but not in those with other liver diseases. In contrast, anti-single stranded DNA antibody (anti-ssDNA) was positive not only in AIH and PBC, but also in those with non-autoimmune-types of chronic liver disease. Follow-up liver histology disclosed that the 2 patients with AIH who were positive for anti-dsDNA developed liver cirrhosis, whereas the 4 patients who were negative for anti-dsDNA, and those who showed a disappearance of anti-dsDNA following corticosteroid therapy, improved from chronic active to chronic persistent hepatitis.

Development of hepatocellular carcinoma in a man with auto‐immune chronic active hepatitis

A 57 year old man with auto‐immune chronic active hepatitis, regularly treated with immunosuppressive therapy, had hepatocellular carcinoma (HCC) 10 years after diagnosis of the hepatitis. Assays of the hepatitis C virus antibodies against capsid and non‐structural proteins revealed seronegativity in serial serum samples of this patient stored in the previous 10 years during follow up. The seronegative hepatitis C antibodies excluded hepatitis C virus as the cause of the HCC. The occurrence of HCC in this case suggests the necessity of surveillance for early detection of liver cancer in patients with auto‐immune chronic active hepatitis undergoing long‐term immunosuppressive therapy.

Clinical application of hepatitis C virus core protein in early diagnosis of acute hepatitis C

Abstract: A fluorescence enzyme immunoassay (FEIA) for the quantitative measurement of hepatitis C virus (HCV) core protein has recently been developed. In this study, we studied the clinical usefulness of this measurement in patients with acute hepatitis C. Eighteen patients with post-transfusion acute hepatitis C were enrolled in the study; 5 patients showed resolution of hepatitis with disappearance of HCV viremia, while the remaining 13 patients did not. A second generation HCV antibody, HCV RNA, and HCV core protein were measured in serial serum samples taken within 1 month of the onset of acute hepatitis and 3, 6, 12, 24, and 36 months after onset. Within the first month after disese onset, the positivity rates of HCV RNA (100%; P = 0.0014) and HCV core protein (89%; P = 0.0300) were both significantly higher than that of HCV antibody (56%). Six months after disease onset, the positivity rate of HCV antibody had increased, to 100%, and the pasitivity rates of HCV RNA and HCV core protein began to decrease. HCV core protein levels did not differ between patients with resolved and unresolved disease in the first month after disease onset. These findings indicate that FEIA, a simple assay, for the measurement of HCV core protein was useful for the early diagnosis of acute hepatitis C.

Antibody to hepatitis C virus in patients with chronic schistosomiasis.

To clarify the effect of hepatitis C virus (HCV) infection in patients with chronic schistosomiasis, 96 patients with schistosomiasis and 137 patients with chronic liver disease without schistosomal infection were analysed by domination of antibody to HCV (anti-HCV). In 45 of 96 schistosomiasis patients, the serum alanine aminotransferase (ALT) level was continuously elevated, and the positive rate of anti-HCV was 52.9%, which is almost the same prevalence rate as in patients with chronic liver disease (48.9%). In contrast, in the remaining 51 schistosomiasis patients, serum ALT level was continuously within the normal range and the positive rate of anti-HCV was 0%. Histological investigation showed that the positive rate of anti-HCV in HBsAg-negative schistosomiasis patients was 14% for hepatic fibrosis, 71% for chronic hepatitis, 80% for liver cirrhosis and 56% for hepatocellular carcinoma. In all anti-HCV-positive patients, serum ALT level was continuously elevated. The serum transaminase levels in anti-HCV-positive patients were higher than those in anti-HCV-negative patients. These data suggest that in patients with chronic schistosomiasis, HCV infection accelerates the derangement of liver function, and may be a major aetiological factor in the development of chronic hepatitis and liver cirrhosis, supporting a causative association between HCV infection and hepatocellular carcinoma.