HCV genotypes in patients with chronic hepatitis C in Croatia.

The determination of hepatitis C virus (HCV) genotype is an important epidemiological parameter in patients with chronic hepatitis C, while its clinical significance is still a matter of debate. The HCV genotypes in a group of 203 Croatian patients with chronic hepatitis C were examined. Genotypes were correlated to different risk factors, age, duration of the disease, liver histology activity and level of viremia. HCV-RNA was detected in each serum by means of reverse transcription PCR. Genotypes were determined from the amplificate by reverse hybridization in a line probe assay. The level of viremia was assessed by branched DNA (bDNA) signal amplification. The most common genotype was 1b (61.1% of patients), followed by 3a (26.1%), and 1a (10.8%). Other genotypes such as 2a and 4 were only rarely found in our patients (2%). Genotype 1b was most commonly acquired via blood transfusion, while genotype 3a was strongly related to intravenous drug use. Genotype 1b was associated with older age (mean 42.6 vs 29.3 years), longer duration of the disease (mean 6.0 vs 3.5 years), higher histologic activity score (mean 13.2 vs 10.6) and higher viremia (mean 9.06 vs 5.93 Meq/ml) at statistically significant levels (p < 0.001) when compared to genotype 3a. The prevalence of HCV genotypes follows the patterns of southeastern European countries, except for a lower prevalence of genotype 2. The observation that genotype 1b is associated with higher viremia and more severe liver injury is confirmed.

-Immunization of hospital personnel at the Sestre Milosrdnice Hospital against viral hepatitis B. / Zastita djelatnika klinicke bolnice "Sestre milosrdnice" od infekcije virusom hepatitisa B.

The results of vaccination against hepatitis B among health-care workers in "Sestre Milosrdnice" University Hospital are presented. Out of 1884 health-care workers 920 (48.8%) were tested for serum HbsAg, as well as anti-HBs and anti-HBc antibodies. There were 111 (12.1%) persons with one or more positive HBV markers. Seven of them (0.8%) were HBV (HbsA-positive) carriers, and 104 (11.3%) had positive anti-HBc and/or anti-HBs. A significant difference of frequency of positive HBV markers between women and men was not found using the chi 2 test for statistical analysis. The vaccination was started in 583 (72.1%) out of 809 examinees with negative HBV markers, out of which 339 (41.9%) received complete three doses and 244 (30.2%) only one or two doses of vaccine. Even 226 (27.9%) persons susceptible to HBV infection refused the vaccination, and other 244 (30.2%) examinees did not receive the complete vaccination course. Therefore, the pre-testing showed that in 12.1% of examinees there was no need for vaccination, which means the saving of 333 bottles of vaccine. Totally 470 health-care workers out of 809 liable to HBV infection were not protected by this action, in full 58.1%! Out of 1884 health-care workers in "Sestre Milosrdnice" University Hospital even 964 (51.2%) refused the testing.

Vaccination against hepatitis B: results of the analysis of 2000 population members in Croatia.

The results of the analysis of vaccination against hepatitis B performed in 2,000 persons of high-risk groups in Croatia are described. All susceptible non-immunocompromised persons (HBsAg, anti-HBs, and anti-HBc negative) received either plasma-derived vaccine (HB-Vax MSD, 20 micrograms per dose) or recombinant HB vaccine (ENGERIX-B, SKB, 20 micrograms per dose) according to a 0.1 and 6-month schedule. Hemodialysis patients received four doses of HB vaccine (40 micrograms per dose). Seroconversion occurred in 98% of health care workers, 98.5% of family members of HBsAg chronic carriers, 98% of infants born to HBsAg carrier-mothers and 92% of hemodialysis patients. The percentage of poor-responders (titer of anti-BHs = 1-10 mIU/ml) for the groups was 2, 2, 8 and 20%, respectively, while low-responders (titer of anti-BHs = 10.1-100 mIU/ml) were 5, 4.5, 12 and 26%, respectively. A significant prevalence of non-responders, poor-responders and low-responders among male health care workers was noticed (p = 0.01, 0.026 and 0.002, respectively). Females significantly prevailed among excellent-responders (p = 0.0039). In hemodialysis patients, there were 8% non-responders, 19.5% poor-responders, and 26% low-responders. A significant difference between the percentage of good-responders (titer of anti-HBs = 101-1,000 mIU/ml) and excellent-responders (titer of anti-HBs over 1,000 mIU/ml) among health care workers and hemodialysis patients was documented (91% versus 46.5%, p < 0.0001). The combined passive-active immunization (hyperimmune hepatitis B globulin + hepatitis B vaccine) was effective in 98% of infants born to HBsAg carrier-mothers, and only one boy developed subclinical HBV infection (HBsAg and anti-HBc positive findings with normal ALT-values).(ABSTRACT TRUNCATED AT 250 WORDS)

[Prevention of hepatitis B virus infection in individuals at high risk in the Cakovec Medical Center]. / Sprecavanje hepatitis B-virusne infekcije u osoba visokog rizika u Medicinskom centru Cakovec.

The results of hepatitis B vaccination (H-B-VAX, 1 ml = 20 micrograms HBsAg, scheme 0, 1, 6) in nine susceptible health care workers of hemodialysis unit are described. Seroconversion was achieved in 100% of recipients. The mean titer of anti-HBs was 11,691 mIU/ml at three years, 5,879 mIU/ml at four years and 2,770 mIU/ml at five years after the beginning of vaccination. H-B-VAX vaccine (first dose 40 micrograms HBsAg, second and third = 20 micrograms) was administered in three patients on hemodialysis (scheme 0, 1, 2). In all of these patients, seroconversion occurred (titers of anti-HBs from 23 to 104 mIU/ml). Of the 55 workers of dental units, nine (16.4%) showed signs of previous HBV infection. Twenty were vaccinated with H-B-VAX vaccine (scheme 0, 1, 2) and of these patients one (5%) was nonresponder, two (10%) poor responders, 13 (65%) good responders and four (20%) excellent responders, with the mean anti-HBs titer of 1,540 mIU/ml. Seven dental workers received recombinant vaccine also using a scheme 0, 1, 2. Four (57%) of these workers were poor responders, and three (43%) good responders, with the mean anti-Hbs titer of 168 mIU/ml. All of our vaccinated subjects had no serious side effects except local soreness at the injection site. Thus, vaccination against hepatitis B in health care personnel and other high-risk patients may control efficiently the spread of HBV infection.

Prevention of hepatitis B virus (HBV) infection in health-care workers after accidental exposure: a comparison of two prophylactic schedules.

The efficacy of hepatitis B (HB) vaccine alone or combined with hepatitis B immunoglobulin (HBIg) in preventing hepatitis B virus (HBV) infection was studied in a controlled trial. Recombinant HB vaccine (Engerix-B, 20 micrograms) was given to 40 susceptible health-care workers within three days of exposure (Group B). In another group of 37 medical professionals a single dose of HBIg (0.06 mg/kg) was administered intramuscularly within three days of exposure, followed immediately by the first dose of vaccine (20 micrograms dose) (Group A). In both groups the next doses of recombinant vaccine were administered one, two and six months later. One month after the fourth dose of vaccine the percentage of incidence of antibody to hepatitis B virus surface antigen (anti-HBs) was 94.6% in group A and 95% in group B with geometric mean titer of antibodies of 340 and 380 mIU/ml, respectively. A control group consisted of 34 persons who did not receive any specific immunoprophylaxis (Group C). All subjects were followed for at least ten months. The protective value of immunization, both active alone and combined passive and active, was clearly effective since none of the recipients developed acute symptomatic HBV infection compared with two (6%) of 34 not immunized persons (Fisher's exact test p = 0.01). Thus, in the absence of evidence of lesser efficacy for the use of HB vaccine alone after exposure to HBsAg-positive blood, this schedule would seem to be the treatment of choice in adult persons.

[Results of vaccination with the hepatitis B vaccine in patients and personnel at the Hemodialysis Center in Karlovac]. / Rezultati cijepljenja hepatitis B vakcinom bolesnika i osoblja Centra za dijalizu u Karlovcu.

Hepatitis B remains a significant risk to patients and staff members of hemodialysis unit. Prior to immunization, 38 hemodialysis patients and 24 staff members were screened for HBs antigen, HBc antibodies and HBs antibodies using ELISA method (Abbott). Of 18 (47%) patients, five were chronic carriers of HBsAg and 13 had anti-HBs and anti-HBc while anti-HBs and anti-HBc were found in four (17%) members of medical staff. A total of 20 (53%) susceptible patients (mean 51.2 years) and 19 (79%) susceptible staff members (mean 28.1 years) received hepatitis B vaccine (H-B-VAX, Merck, Sharp and Dohme). Between patients were four (20%) non-responders and seven (35%) low-responders while among medical staff were two (10.5%) non-responders and one (5.2%) low responder only. The geometric mean titer of anti-HBs was 724 IU/L in patients and 3407 IU/L in staff members. Non-responders (5 of 6) who were given a fourth vaccine dose also failed to mount an antibody response. In none of vaccinated patients antibody to human immunodeficiency virus (HIV-1) occurred in their sera three and six months after complete vaccination. Consideration should be given to a prevaccinal screening of presumptive vaccinees between patients and staff members of hemodialysis units because of high level of preexisting HBV infection among them. The data suggest a high non-responder and low-responder rate in vaccinated hemodialysis patients and serial surveillance for anti-HBs is warranted especially in persons aged over 40 years. Additional booster dose or some doses of HB vaccine should be given to low-responders and they should be retested thereafter. Non-responders still remain the unresolved problem.

[Hepatitis A--results of the analysis of 3,111 hospitalized patients]. / Hepatitis A--rezultati obrade 3.111 hospitaliziranih bolesnika.

The results of the analysis of 3.111 patients admitted to the hospital with hepatitis A (HA) were reported. The serodiagnosis of acute type A hepatitis was confirmed by presence of IgM antibody to hepatitis A virus (IgM anti-HAV) detected by solid-phase radioimmunoassay (RIA HAVAB-M, Abbott). The majority of patients were between 11-15 (24%) and 21-30 (25%) years of age and even 15% of a total number were older than 30 years. The number of males and females with HA was not significantly different and the minority of patients were admitted during the summer. A few of the admitted patients had a history of anicteric form of the disease (14%), while most (80%) were icteric. Only 6% of the affected patients had severe form of HA and no fulminant form of hepatitis among them occurred. The relapsing HA (RHA) was observed even in 308 (10%) of the patients, which did not alter the benign prognosis of HA. Forty three chronic HBV carriers were found to be infected with HAV and this did not cause more severe disease or influence adversely the course of chronic HBV infection. Nine pregnant women with HA in the third trimester of pregnancy had no severe form of the disease, but HA significantly increased the average incidence of prematurity (27%:10%). Although HA is neither severe illness nor one with important sequelae, it remains a frequent cause of morbidity. Therefore, a wide program of effective vaccination should be applied.

Prevention of hepatitis B infection in health care workers after accidental exposure.

The efficacy of hepatitis B immune globulin (HBIg) alone or combined with hepatitis B (HB) vaccine in preventing hepatitis B virus (HBV) infection after accidental exposure to blood of HBV carriers was studied in a controlled trial. HBIg (0.06 ml/kg) was administered intramuscularly within 3 days after exposure to 56 recipients. A second dose was given 1 month later. In another group of 28 persons, a single dose of HBIg was given within 3 days followed by the first dose of HB vaccine (HEVAC-B Pasteur 10 micrograms) within 7 days after exposure. A control group consisted of 53 health care workers who reported more than 3 days after exposure and who did not receive any specific immuno-prophylaxis. The recipients were followed for at least 10 months. Immunisation, both passive and combined passive and active, was clearly effective since none of the recipients developed acute symptomatic HBV infection compared with four (8%) of 47 not immunised (Fisher's exact test P = 0.02). The number in each group immunised was too small to allow valid comparison of the relative efficacy of the two schedules. Nevertheless, in the absence of evidence of lesser efficacy for the combination of HBIg and HB vaccine after exposure, the combined passive/active schedule would seem the treatment of choice since it offers the additional benefit of long-term protection.