Insulin resistance is a major determinant of sustained virological response in genotype 1 chronic hepatitis C patients receiving peginterferon alpha-2b plus ribavirin.

BACKGROUND: Cross-sectional studies suggest insulin resistance is strongly associated with hepatic steatosis and fibrosis in patients with chronic hepatitis C (CHC), which might affect the efficacy of antiviral therapy. Aim To investigate retrospectively the impact of insulin resistance on treatment response in Chinese genotype 1 CHC patients receiving a 24-week course therapy with peginterferon alpha-2b/ribavirin. METHODS: A total of 133 biopsy-proven CHC patients were enrolled for analyses. Insulin resistance was evaluated by homeostasis model assessment of insulin resistance (HOMA-IR). Hepatic fibrosis was graded by the METAVIR scoring system. RESULTS: Mean HOMA-IR progressively elevated along with the severity of hepatic fibrosis (F1-F2 fibrosis: 2.55 +/- 0.16 vs. F3-F4 fibrosis: 3.61 +/- 0.20, P < 0.001). Compared with patients with sustained virological response (SVR), patients without SVR had significantly higher percentages of F3-F4 fibrosis (62.2% vs. 21.6%, P < 0.001) and baseline high viral load (>or=600,000 IU/mL; 64.4% vs. 35.6%, P = 0.038). In addition, patients without SVR had significantly higher plasma levels of insulin (15.03 +/- 0.89 vs. 10.19 +/- 0.55 microU/mL, P < 0.001) and HOMA-IR values (3.76 +/- 0.23 vs. 2.50 +/- 0.15, P < 0.001). Multivariate analyses showed that F1-F2 fibrosis (odds ratio: 4.49, P = 0.001), HOMA-IR < 2 (odds ratio: 7.15, P = 0.005) and pre-treatment hepatitis C virus RNA < 600,000 IU/mL (odds ratio: 3.26, P = 0.012) were the independent factors associated with SVR. CONCLUSIONS: Insulin resistance is a major determinant of SVR in genotype 1 CHC patients receiving peginterferon alpha-2b/ribavirin. Strategies to modify insulin resistance may be effective in enhancing SVR before or during anti-viral therapy.

Need for vaccination of susceptible food handlers against hepatitis A in Taiwan.

BACKGROUND: With the improvement in the socioeconomic situation and general hygiene standards in Taiwan, the prevalence of antibodies to the hepatitis A virus (anti-HAV) in the general population has declined markedly in recent years. To avoid food-borne outbreaks of HAV infection caused by susceptible food handlers in Taiwan, we investigated the seroprevalence of anti-HAV among the target population and also evaluated the immunogenicity and reactogenicity of the inactivated hepatitis A vaccine in this study group. METHODS: Two hundred and forty-four food handlers employed in four restaurants at Taipei Veterans General Hospital participated in the anti-HAV serologic screening program in July 1997. Of them, 48 susceptible food handlers received three doses of 720 enzyme-linked immunosorbent units of inactivated hepatitis A vaccine at 0, 1 and 6 months. RESULTS: Of the 244 food handlers who underwent anti-HAV serologic screening, 169 (69.3%) were anti-HAV positive. The seroprevalence of anti-HAV was related to age: 91.5% of food handlers over 30 years of age were positive for anti-HAV but only 22.8% of food handlers younger than 30 were anti-HAV positive. Anti-HAV response was observed in all vaccinees after a booster vaccination at month 6. The response persisted to 1 year. The side-effects of the vaccinations were minimal. CONCLUSIONS: Susceptible food handlers should receive hepatitis A vaccination. Hepatitis A vaccine is safe and immunogenic in this target population.

Hepatitis B vaccination in patients with chronic hepatitis C.

The aim of the study was to evaluate the safety, immunogenicity, and possible therapeutic effect of hepatitis B vaccine in patients with chronic hepatitis C. The subjects studied included three groups: group I, 26 patients with chronic hepatitis C who were susceptible to hepatitis B virus infection; group II, 35 healthy subjects who were susceptible to both hepatitis B and hepatitis C virus infection; and group III, 30 patients with chronic hepatitis C receiving no hepatitis B vaccination as controls. Three 20 microg/dose of recombinant hepatitis B vaccines were given to subjects of groups I and II in months 0, 1, and 6. Blood samples from the subjects were collected before and 1 month after each dose of vaccination for serological testing. The subjects of groups I and II had similar antibody to hepatitis B surface antigen (anti-HBs) response rates after the first (30.8% vs. 17.1%), second (61.5% vs. 60.0%), and third (88.5% vs. 91.4%) doses of vaccination. Also, their geometric mean titers of anti-HBs did not differ much when vaccination completed in 7 months (360 vs. 581 mIU/ml). During vaccination period, patients with chronic hepatitis C demonstrated no significant change of serum cytokines and HCV RNA levels, but significantly lowered ALT levels after three doses of vaccination. Hepatitis B vaccination is safe and immunogenic in patients with chronic hepatitis C. It did not significantly affect their levels of HCV RNA, but tended to lower ALT levels.

A two dose combined hepatitis A and B vaccine in Chinese youngsters.

This open, randomized study was conducted in healthy Chinese youngsters, aged between 10 and 19 years to compare the reactogenicity and immunogenicity of two vaccines: the combined vaccine against hepatitis A and B was administered in a two-dose schedule with the profile of the corresponding monovalent vaccines, while the concomitant vaccine was administered also on a two-dose schedule but simultaneously in opposite arms. All vaccinees had antibodies against hepatitis A (anti-HAV) after the 2-dose administration, whereas all but four in the first and two in the second group had protective titres against hepatitis B (anti-HBs). At month 7, the geometric mean titres for both antibodies were more than double for the group of subjects receiving the combined vaccine: 3,701 vs. 1,705 mIU/ml for the anti-HAV, and 1,524 vs. 720 mIU/ ml for the anti-HBs response. Injection site pain was the most commonly reported local symptom and headache was the most reported general symptom. It is concluded that this combined vaccine against hepatitis A and B, administered according to a two-dose schedule, is well-tolerated and highly immunogenic.

Long-term follow-up of hepatitis A vaccination in children.

We conducted this follow-up study to evaluate the long-term immunogenicity of an inactivated hepatitis A vaccine in children. Ninety-six children who had seroconversion to antibody to HAV (anti-HAV) after receiving a three-dose schedule of inactivated hepatitis A vaccine were enrolled into this study. Sixty months after the initial vaccination, all vaccinees who received annual follow-up still had protective levels of anti-HAV. The geometric mean titer (GMT) of anti-HAV, peaking at month 7 (4133 mIU/mL), kept declining throughout the follow-up period. The GMTs in months 12, 24, 36, 48 and 60 were 1722, 896, 896, 645 and 403 mIU/mL, respectively. Nine of the vaccinees were hepatitis B virus carriers. Their anti-HAV titers tended to be lower than those of the remaining vaccinees at all time-points, but the difference was not significant (p > 0.05). Natural booster was noted in one vaccinee during the follow-up period. In conclusion, inactivated hepatitis A vaccine is safe and immunogenic in children, the duration of protection against HAV infection is longer than five years.

Safety and immunogenicity of inactivated hepatitis A vaccine in patients with chronic liver disease.

The safety and immunogenicity of inactivated hepatitis A vaccine was evaluated in patients with chronic liver disease. Sixty hepatitis A virus antibody (anti-HAV) seronegative patients with chronic liver disease (56 chronic hepatitis B and four chronic hepatitis C) and from 17 to 47 years of age received a dose of 1440 ELISA units of the inactivated hepatitis A vaccine at month 0, and a booster at month 6. Anti-HAV seroconversion (> or = 33 mIU/mL) was 57.6% (34/59) on day 15, and reached 93.2% (55/59) 1 month after primary vaccination. At month 6, the seropositivity of anti-HAV decreased before the booster to 69.0% (40/58). All vaccinees had measurable titers of anti-HAV 1 month after booster vaccination, and were still seropositive at month 12. After initial vaccination, the geometric mean titers of anti-HAV among vaccine responders were 158, 264, 74, 1309, and 409 mIU/ml at day 15 and months 1, 6, 7, and 12. Overall, 59.7% (71/119) of the vaccine doses administered were followed by mostly minor reactions. The majority of symptoms reported were local, all of which resolved within 3 days after vaccination. No significant changes in serum liver enzyme levels were detected after vaccination. Thus, an inactivated hepatitis A vaccine was safe in patients with chronic liver disease while the immune response was inferior to that observed in healthy subjects reported in a previous study.

Single dose-inactivated hepatitis A vaccination schedule for susceptible youngsters.

OBJECTIVE: To investigate the feasibility of a single-dose primary hepatitis A vaccination for young travelers. METHODS: One hundred and nineteen susceptible youngsters, 9-18 yr old, received a dose of 720 ELISA units of the inactivated hepatitis A vaccine at month 0, and then a booster at month 6. RESULTS: Antibodies to hepatitis A virus (anti-HAV) seroconversion ( > or = 20 mIU/ml) in these vaccinees was 91% (106/117) on day 15, and reached 99% (118/119) 1 month after the single-dose vaccination. At month 6 before the booster, 97% (110/113) of the vaccinees still had detectable anti-HAV. All vaccinees (113/113) had measurable titers of anti-HAV 1 month after booster vaccination, and were still seropositive (68/68) at month 12. The anti-HAV response was found to be slower in vaccinees positive for hepatitis B surface antigen (11/16, 68.8%), compared with noncarrier vaccinees (95/101, 94.1%; p < 0.01) 15 days after the priming dose. After initial vaccination, the geometric mean titers of anti-HAV among vaccine responders were 220, 255, 117, 3308, and 1094 mIU/ml at day 15 and months 1, 6, 7, and 12, respectively. CONCLUSION: These results suggest that a single dose of hepatitis A vaccine could be a good alternative to immune serum globulin administration for immunoprophylaxis in young healthy travelers.

Long-term follow-up of hepatitis B virus carrier infants.

One hundred twenty-two hepatitis B surface antigen (HBsAg) carrier infants were followed-up for 8-10 years. One hundred eleven had antibody to hepatitis B core antigen (anti-HBc; 83 had been vaccinated) and the remaining 11 were without anti-HBc (7 had been vaccinated). During the follow-up period, 29 (26.1%) carrier infants with anti-HBc had one or more episodes of alanine aminotransferase (ALT) elevation and up to 32.8% (21/64) of the carriers in this group lost their hepatitis B e antigen (HBeAg) before the age of 10. In addition, 2 (1.8%) carriers lost their HBsAg at the age of 3 and 8, respectively. No significant symptom or sign was noted during HBeAg seroconversion. In contrast, all the carrier infants without anti-HBc were still positive for both HBeAg and hepatitis B virus (HBV) DNA and none displayed abnormal ALT levels or any symptom related to liver disease. One became anti-HBc positive at the age of 9, and 5 other carriers had inconsistent borderline or weakly positive titers of anti-HBc. The episodes of ALT elevation and the prevalence of HBeAg seroconversion were not significantly different between immunized carrier infants. In conclusion, HBeAg seroconversion may occur in about one third of the anti-HBc-positive carrier infants during the first decade. On the other hand, the anti-HBc-negative HBsAg carrier infants' immune incompetence to the HBV antigens could persist for more than 10 years. Hepatitis B immunization did not have significant effect on the clinical course in carriers.