Hepatitis C virus in chronic hemodialysis patients with non-A, non-B hepatitis.

Sixteen of 110 hemodialysis (HD) patients fulfilling criteria of non-A, non B hepatitis (NANBH), i.e. alanine aminotransferase (ALT) greater than 50 U/ml in the absence of both serologic markers for acute HBV and HAV infections and clinical evidence of another cause of hepatitis, were tested for the presence of antibodies against hepatitis C virus (anti-HCV) by enzyme immunoassay (Ortho, Diagnostics). All (100%) were anti-HCV-positive. There were 5 patients with a monophasic (M) rise pattern (1 or 2 ALT rises), and 11 cases demonstrated a polyphasic (P) rise elevation pattern (more than 2). The mean ALT value of the M group was 202.3 +/- 209 U/ml and that of the P group was 116.6 +/- 39.1 U/ml. The patients received a mean of 19.1 +/- 16.2 units of packed red cells during the follow-up period (69.9 months). Only 1 patient received no blood transfusion. Six patients had a past HBV infection and 3 became HIV-infected in the course of this study. The high rate of infection of hemodialysis patients with hepatitis C virus in our setting points to the need for improved control measures.     

Outbreak of hemodialysis-associated non-A, non-B hepatitis and correlation with antibody to hepatitis C virus.

Between January 1987 and October 1988, 35 (45%) of 77 patients undergoing chronic hemodialysis at one unit developed serum alanine aminotransferase (ALT) elevations suggestive of non-A, non-B hepatitis (NANBH). Patients were grouped by level of ALT elevation and presence of other etiologies for liver injury. All dialysis patients and staff were tested for antibody to hepatitis C virus (anti-HCV) by enzyme immunoassay on three occasions, 9 months apart; anti-HCV repeatedly reactive specimens were tested by the HCV neutralization assay. Household and sexual contacts of patients were tested once for anti-HCV. Case-patients were classified on the basis of clinical case definitions as probable, possible, questionable, and noncases, and by anti-HCV testing. Case-patients who had no history of transfusions or parenteral drug use were compared with noncases for common exposures. A total of 35% (27/77) of patients and none (0/24) of staff were anti-HCV-positive. Anti-HCV was found in 82% of probable cases, compared with 44% of possible cases, 44% of questionable cases, and 12% of noncases (P less than 0.01). Neither a common source nor direct person-to-person transmission could be documented; however, inadequate infection control measures demonstrated by lack of glove use and poor handwashing occurred during the exposure period. The incidence of HCV infection in patients over an 18-month period was 5%. Transmission of HCV to household or sexual contacts of patients did not appear to occur.(ABSTRACT TRUNCATED AT 250 WORDS)     

Transfusion transmitted non-A, non-B hepatitis

Non-A, non-B of hepatitis (NANBH) may occur following blood transfusions or administration of blood products. The causative agent(s) is still not identified and the symptoms are usually mild. The only indication of infection may be increased serum alanine transferase levels. The incidence of posttransfusion NANBH has been reported as high as 4–12% in the US (average 7%) while in Sweden it is according to recent studies on the average 2%. An estimated 2–3% of Swedish blood donors are probably carriers of the NANBH agent(s). Of patients acquiring posttransfusion NANBH, 40–60% will develop chronic hepatitis which in 15–20% will progrediate to cirrhosis.     

Histological features of non-A, non-B hepatitis in hemodialysis patients.

In 12 hemodialysis (HD) patients with persistently raised serum alanine amino-transferase concentrations, 6 of which with anti-HCV antibodies, a liver biopsy was performed. The histological examination showed chronic persistent hepatitis or less significant changes in 11 patients and mild chronic active hepatitis in only 1. Non-A, non-B hepatitis seems to demonstrate in HD patients a low tendency to induce an active and progressive liver disease.     

Chronic active hepatitis of hepatitis B and non-A, non-B etiology

Sixty-six consecutive liver biopsies demonstrating chronic hepatitis (CAH) were stained for the presence of HBsAg using the three-step peroxidaseantiperoxidase technique. Only cases of CAH thought to be attributable to either hepatitis B or non-A, non-B hepatitis were included in this series. Twenty-three of 30 biopsies taken from 24 patients with HBsAg-positive serum stained positively. None of the HBsAg sero-negative cases stained postively. Hepatocytes staining positively for HBsAg were generally few in number and randomly distributed within the liver lobules. Three cases of membranous staining were noted. After grading both the degree of inflammatory activity and the amount of HBsAg staining, we found that a statistically significant inverse relationship exists. The biopsies of six of the GBsAg sero-positive patients who had received steroid therapy for their liver disease did not stain differently from the biopsies of the remaining 18 HGsAg sero-positive patients. Stains for HBsAg may help in distinguishing acute hepatitis B (HB) superimposed on preexisting liver disease from hepatitis B-CAH (CAHB). This distinction may be possible because tissue staining almost always is negative in acute HB, whereas it often is focally positive in CAHB. This application of immunoperoxidase may be especially useful in patients who are drug addicts.     

Hepatitis C virus-related acute and chronic hepatitis in hemodialysis patients.

The incidence of HCV antibodies has been evaluated in 123 chronic hemodialysis (HD) patients (Group A; 55 M and 68 F) and in 37 consecutive HD patients (group B) admitted to our hospitals for acute hepatitis. In group A, HCV antibodies were present in 27% of the patients. 20 of 36 (55%) had previously received blood transfusions. 21 patients (58%) were also positive for HBV Ab. In 8 patients, ALT were significantly increased. In group B, the diagnosis of HCV-related acute hepatitis was made in 11 patients. 8 of them had previously received blood transfusions. Seroconversion occurred 2-3 months after onset of the disease.     

Prevalence of non-A non-B hepatitis and anti-HCV antibodies in a Portuguese dialysis population.

Non-A Non-B hepatitis (NANBH) is nowadays one of the most common causes of hepatic dysfunction in dialysis patients. We reviewed the records of 231 HBsAg-negative patients in our unit and found 119 patients with biochemical criteria of NANBH (51.5%), 88 of them (68.9%) with circulating antibodies against HCV (chi 2 P less than 0.0001). Such high prevalence of NANBH was due to an outbreak of NANBH in the late 70s and early 80s. Time on haemodialysis (HD) was the major risk factor of NANBH in this population, and no other risk factors were identified. Prevalence of anti-HCV was similar to reports from non-uraemic populations. Anti-HCV seems to be a reliable test to confirm NANBH, but not better than using common biochemical criteria of NANBH to manage these patients in dialysis units.     

Transfusion-related non-A, non-B hepatitis in elective spine deformity surgery patients in Gothenburg, Sweden

This study presented a retrospective analysis of the incidence and clinical course of non-A, non-B hepatitis in patients after receiving homologous blood transfusion for elective spine deformity surgery, at Sahlgren Hospital. The medical records of all patients who underwent surgical procedures for scoliosis and spondylolisthesis between January 1, 1971 and December 31, 1986 were reviewed. From this group, 918 patients with negative medical histories for prior homologous blood transfusion, hepatitis, or the exposure to hepatotoxic medications were selected. All of the patients received two or more units of homologous blood and were followed for at least 1 year postoperatively. Eight hundred fifty-nine (94%) of the patients were either personally interviewed or contacted by mail. The group included 697 scoliosis patients (average age 16.2) and 162 spondylolisthesis patients (average age, 16.8). The scoliosis and spondylolisthesis patients received an average of 5.6 and 3.4 units of homologous blood, respectively. Three patients (0.35%) developed posttransfusion hepatitis, all non-A non-B. The incubation period was 9 to 12 weeks. Presenting symptoms varied widely, ranging from no symptoms to marked icterus. Two of the three patients went on to develop chronic persistent hepatitis, which was confirmed by liver biopsy. The incidence identified in this retrospective study was low when compared with an overall incidence of 4 to 15%, as presented in several larger prospective studies. Non-A, non-B hepatitis is a major risk associated with the homologous transfusion of blood and must be considered one of the more serious complications in surgery for spinal deformity.     

Non-A, non-B hepatitis and chronic dialysis--another dilemma

To define the incidence of non-A, non-B (NANB) hepatitis and evaluate possible risk factors, we reviewed records of 163 patients on chronic dialysis during a 3-year period. 23 cases of NANB hepatitis occurred, 13 (27%) in 49 center dialysis, 8 (10%) in 77 home hemodialysis (p less than 0.02) and 2 (5%) in 37 peritoneal dialysis patients (p less than 0.01). Hepatitis patients received significantly more transfusions than controls. Numbers of transfusions and of patients transfused were not significantly different in center patients compared to home and peritoneal. 8 NANB patients received no transfusions. NANB was the most common cause of hepatitis in our unit (68%). Although transfusions were a likely etiologic factor, to explain the increased risk in center dialysis patients, disease in patients not transfused and development of NANB hepatitis without a known parenteral exposure in a physician assigned to the Nephrology Service, we feel another etiologic factor was important, the dialysis center.     

Hepatitis C virus infection in chronic haemodialysis patients, a clinicopathologic study.

Fifty-two patients on regular haemodialysis at our institution were evaluated for the presence of HCV infection. Evaluation included detailed history, clinical examination, and monthly screening for anti-HCV antibody, liver enzymes (ALT, AST), serum iron and ferritin. Also, three-monthly screening for other viral markers, HBV (HBsAg, HBsAb, HBcAb), CMV (IgG and IgM), EBV, and HIV. Anti-HCV antibody was found in 21 patients (40.4%). There was a significant (P less than 0.05) relationship between presence of anti-HCV antibody and proportion of patients who received blood transfusion. During a 12-month follow-up, four (11.4%) patients seroconverted to be Anti-HCV positive while one case (4.8%) seroconverted to be anti-HCV negative. The frequency of elevation of liver enzymes was significantly higher in Anti-HCV positive cases (14/18) than in negative cases (11/28, P = 0.01). Evaluation of liver biopsies of 13 patients showed chronic persistent hepatitis in six and chronic active hepatitis in seven cases. We concluded that hepatitis C is a common problem among chronic haemodialysis patients at our institution; HCV infection is documented in 70% of all clinically diagnosed NANB hepatitis. Presence of anti-HCV antibodies cannot differentiate between active and past infection and cases with early HCV infection can be missed when relying on the mere detection of anti-HCV antibodies.     

Gamma globulin prophylaxis to reduce post-transfusion non-A, non-B hepatitis after cardiac surgery with cardiopulmonary bypass

A prospective, randomized study of immune serum globulin (ISG) for prevention of post-transfusion hepatitis was performed on 196 patients (100 controls without gammaglobulin or placebo and 96 who received ISG) undergoing valve replacement or coronary artery bypass with extracorporeal circulation. The dose of ISG was 2 ml i.m. at premedication and 2 ml i.m. on postoperative day 3. Probable non-A, non-B hepatitis developed postoperatively in ten of the 100 controls and two of the 96 in the ISG group. Two ISG patients and three controls with non-A, non-B hepatitis still have increased serum aminotransferase values after 3-5 years, but liver biopsy revealed hepatitis, which histologically was very mild, in only two control and two ISG patients. Low-dose gamma globulin thus reduced the incidence of acute, probable non-A, non-B hepatitis in cardiac surgery with cardiopulmonary bypass.     

Retrospective study on the prevalence of B and non-A, non-B hepatitis in a dialysis unit: 17-year follow-up.

To evaluate the prevalence of HBV, non-A, non-B hepatitis (NANBH) and HCV, their evolution and the route of transmission, we performed a retrospective study (17 years) on 65 hemodialyzed patients (mean dialytical age 5 years, range 1-16) who developed acute viral hepatitis. Twenty-six percent of them were affected by HBV; 5 of them (29%) became chronic. Fourty-eight of 65 patients were affected by NANBH; in 1990, 42 of them were tested for antibody to HCV with the C-100 Elisa assay: 27 patients (64%) were positive. Seven of 27 patients demonstrated normal values of ALT. The evaluation of intrafamiliar transmission of HBV showed 8 sexual partners infected. In the family, no one was anti-HCV positive. In agreement with the current literature, we have observed: (1) a decrement in HBV infection; (2) that HCV is the major cause of NANBH; its rate of chronicity is over 50%; (3) that the prevalent mode of HCV transmission is the parenteral route while the sexual route seems to be negligible.     

Detection of antibody to hepatitis C virus in renal transplant recipients.

Non-A, non-B hepatitis is a significant cause of liver disease among renal allograft recipients. In order to assess the impact and prevalence of hepatitis C in a series of renal allograft recipients, we retrospectively screened 621 consecutive patients transplanted between 1979 and 1989 and 484 cadaver organ donors retrieved in the same interval for serologic evidence of hepatitis C viral (HCV) infection using the enzyme-linked assay for anti-HCV antibody. Of 596 HBsAg negative patients, 180 (30%) were anti-HCV positive at the time of transplant. One-year posttransplant, 117 (22%) had detectable levels of anti-HCV antibody. Chemically significant hepatitis developed in 52/234 (22%) anti-HCV positive patients, and 26 of these followed a clinical course consistent with chronic hepatitis. Significantly more males and patients with antibody to HCV detectable at 1 year posttransplant were in the group experiencing an increase in liver enzymes. Ten-year patient and graft survival was 78% and 50%, respectively, for the anti-HCV positive patients who had an elevation of alanine aminotransferase, and 76% and 57% for the cohort maintaining normal liver function (P = NS). There were also no differences in patient and graft survival among the anti-HCV positive group and the consistently sero-negative patients. Of 484 cadaver organ donors with serum available for analysis (out of 1200 retrieved), 67 (14%) were anti-HCV positive at the time of organ donation. Among 23 anti-HCV negative kidney recipients who received a kidney from an HCV antibody positive donor, only one had seroconverted at 1 year posttransplant. Antibody to HCV appears to be widespread among renal transplant recipients and cadaver organ donors. We were unable to demonstrate any evidence of long-term adverse effects on patient and graft survival among anti-HCV positive patients employing the first generation anti-HCV assay.     

Hepatitis C virus infection and acute or chronic glomerulonephritis: an epidemiological and clinical appraisal

Background. The relationship between hepatitis C virus (HCV) infection and acute or chronic glomerulonephritis (GN) is not well understood. Methods. Two hundred and eighty-four patients with biopsy-proven GN and other renal diseases were studied in a multicentre survey performed during the period 1992-1995. Several clinical parameters were collected for each patient at the time of renal biopsy. We made a multivariate analysis by logistic regression model to evaluate the independent association of clinical and histological patient characteristics with HCV infection, as detected by anti-HCV antibody testing. In addition, three patients with HCV-related liver disease; membranous nephropathy, and proteinuria in the nephrotic range received therapy with interferon-alpha in standard doses. Results. The prevalence of anti-HCV positivity was 13% (38/284). The frequency of anti-HCV positivity ranged between 0 and 100% in the different types of renal diseases, the difference was statistically significant (P = 0.0001). The anti-HCV rate was significantly higher in patients with cryoglobulinaemic membrano-proliferative and mesangioproliferative GN than among the other individuals (14/14 (100%) vs 24/270 (9%), P = 0.0002). Our multivariate analysis by logistic regression model showed that age (P = 0.0017) and type of renal diseases (P = 0.0007) were independently and significantly associated with anti-HCV antibody. At the completion of treatment with interferon-alpha, 67% (2/3) of patients with membranous nephropathy had lowering of hepatic enzyme levels into the normal range whereas 100% (3/3) of these did not show significant reduction of proteinuria. Conclusions. We observed strong association between HCV infection and cryoglobulinaemic GN. Age and type of renal disease were important independent predictors of anti-HCV positivity in our cohort of patients. Three anti-HCV-positive patients with membranous nephropathy did not show significant remission of nephrotic proteinuria after treatment with interferon-alpha. Our data do not appear to support an association between HCV and non-cryoglobulinaemic GN. Further epidemiological surveys, experimental studies and clinical trials are warranted to fully elucidate the role of HCV in non-cryoglobulinaemic GN.     

日本慢性肝炎治疗指南中有关丙型肝炎的建议

为了补充、修订2004年版的慢性肝炎治疗标准化指南,进行了针对乙型及丙型肝炎病毒感染者治疗标准化临床研究的实况调查,该调查由日本国家公务员共济组合联合会虎门医院熊田博光副院长主持,有山口大学等13家单位参加.其综述研究报告书发表于2006年3月,现将调查报告中有关慢性丙型肝炎部分摘译以飨国内相关专业人士.