Autoimmune cholangitis with features of autoimmune hepatitis: successful treatment with immunosuppressive agents and ursodeoxycholic acid.

We report a 42-year-old Chinese female with elevated serum levels of liver aminotransferases, alkaline phosphatase, gamma-glutamyl transpeptidase, cholesterol and immunoglobulin M. Serum antimitochondrial antibody was negative, but antinuclear antibody was strongly positive. Liver histology showed features of both autoimmune cholangitis and autoimmune hepatitis. Combination therapy with immunosuppressive (prednisone and azathioprine) and choleuretic agents (ursodeoxycholic acid) was given. Serum aminotransferases and biliary enzymes showed much improvement after treatment. A follow-up liver biopsy showed improvement of both hepatic necroinflammation and bile duct damage. Biliary enzymes rose after withdrawal of the immunosuppressive agents and declined again with reinstitution of prednisone. This case demonstrates that a combination of immunosuppressive agents and ursodeoxycholic acid may effectively treat patients with features of both autoimmune cholangitis and autoimmune hepatitis.

The changes in quantitative HCV RNA titers during interferon alpha 2B therapy in patients with chronic hepatitis C infection.

OBJECTIVE: Our aim was to analyze the outcomes and the patterns of response to interferon treatment in patients with chronic hepatitis C using serum HCV RNA as the primary endpoint of therapy. METHODS: Seventy anti-HCV-positive patients were treated with 3 million U of interferon-alpha-2b thrice weekly for 24 wk and followed for an additional 24 wk after cessation of therapy (wk 48). Serum HCV RNA was measured by a reverse transcriptase-polymerase chain reaction method that has a sensitivity of < 100 viral copies per ml. RESULTS: The mean pretreatment HCV RNA was 2.8 +/- 2.2 x 10(6) viral copies per ml. Genotype 1 patients had significantly higher mean baseline viral titers than those with genotype 2 (p = 0.03). At wk 48, 12 (17%) patients were HCV RNA negative and considered virological complete responders (CR) to treatment. The remaining patients were HCV RNA positive at wk 48 and were considered nonresponders to therapy. There were two types of virological nonresponder patients, responder relapse (RR) and no response (NR). The mean baseline HCV RNA level was significantly lower in the virological CR patients (p = 0.0004). At wk 12 and 24 of interferon treatment, both the virological CR and RR patients had lower serum HCV RNA concentrations than the patients in the NR category (p = 0.0001), while at wk 48, only. the virological CR patients had undetectable HCV RNA when compared to the RR and NR patients (p = 0.04). Transient decreases in the HCV RNA titers of > or = 1 log in magnitude were observed in 49% of the NR patients, which rose to pretreatment levels either during or after interferon therapy. CONCLUSIONS: Our findings indicate that measurement of serum HCV RNA precisely defined the responses to interferon therapy. Because the goal is to eliminate virus in patients with chronic hepatitis C infection, then HCV RNA should be used as the primary endpoint of treatment.

Prediction of response during interferon alfa 2b therapy in chronic hepatitis C patients using viral and biochemical characteristics: a comparison.

Patients with chronic hepatitis C (n = 103) were treated for 24 weeks with interferon alfa 2b and followed up for 24 weeks after cessation of therapy (week 48). When hepatitis C virus (HCV) RNA at week 48 was used to assess interferon response, 15 (14.6%) were virological complete responders, and all have remained HCV RNA negative for a mean of 3 years. At week 48, 3 of 15 virological complete responders had elevated alanine transaminase (ALT) values. When serum ALT level was used at week 48 to determine response to interferon, 20 (19.4%) were biochemical complete responders. However, 8 of the 20 patients with normal ALT levels were HCV RNA positive at week 48, and 7 of these individuals have had a recurrence of elevated ALT levels within 3 years after cessation of treatment. These findings indicate that measurement of HCV RNA was more accurate than ALT in determining true responses to interferon therapy. Identification of nonresponders early during the course of interferon treatment showed that an elevated ALT level at week 12 was 92% predictive (odds ratio 3.7) but misidentified 33% (5 of 15) of the patients who were virological complete responders at week 48. In contrast, a positive HCV RNA at week 12 of treatment was 98% predictive (odds ratio 35.5) and misidentified only 6.7% (1 of 15) of the virological complete responders. Thus, positive HCV RNA at week 12 of therapy was more accurate in identifying eventual virological nonresponders than measurement of ALT at this time. Termination of interferon therapy in patients who were HCV RNA positive at week 12 would result in a 27% reduction in the direct medical costs and keep patients from undergoing unnecessary treatment. Therefore, testing for HCV RNA at week 12 to identify nonresponders and then discontinuing their treatment is practical, cost-efficient and beneficial both to patients and to third-party payers.

Comparison of three different hybridization assays in the quantitative measurement of serum hepatitis B virus DNA.

The measurement of hepatitis B virus (HBV) DNA, is important for monitoring and evaluating the efficacy of anti-viral agents in the treatment of patients with chronic hepatitis B. Three different hybridization assays for quantitative measurement of HBV DNA: direct membrane (dot-blot) hybridization, liquid hybridization (Abbott HBV DNA assay) and branched DNA signal amplification assay (Quantiplex, Chiron), were applied to 114 serial serum samples obtained from 13 patients with chronic active hepatitis B who had received ribavirin 600 mg daily for four weeks. Among the three assays, the correlation was found to be highest between Quantiplex and Abbott HBV DNA assay (r = 0.71, p < 0.01), moderate between Quantiplex and dot-blot hybridization (r = 0.58, p < 0.01) and lowest between dot-blot hybridization and Abbott HBV DNA assay (r = 0.27, p < 0.01). Quantiplex detected 107 (94%) of 114 specimens and was the most sensitive assay. All specimens positive by dot-blot hybridization and Abbott HBV DNA assays were detected positive by Quantiplex. The Dot-blot hybridization assay detected all 89 (100%) specimens with a high HBV DNA level (> or = 10 million genome equivalent (Meq)/ml by Quantiplex), but detected only 7 (50%) of 14 specimens with a low HBV DNA level (< 10 Meq/ml). The Abbott HBV DNA assay detected 85 (95%) of 89 specimens with a high HBV DNA level, but detected only 3 (17%) of 18 specimens with a low HBV DNA level. Among 7 negative specimens in the Quantiplex assay, 2 were detected positive by polymerase chain reaction. In conclusion, Quantiplex assay was more sensitive than Abbott HBV DNA assay and dot-blot hybridization assay for quantitative measurement of serum HBV DNA and can be used in the evaluation of the therapeutic drug effect on chronic hepatitis B patients.

Evaluation of hepatitis B and C viral markers: clinical significance in Asian and Caucasian patients with hepatocellular carcinoma in the United States of America.

In order to evaluate the roles of hepatitis B virus (HBV) and hepatitis C virus (HCV) and their clinical significance in Asian-American and Caucasian patients with hepatocellular carcinoma (HCC) in the USA, 110 HCC patients, seen in a community-based teaching hospital in the Los Angeles area over a 10 year period, were enrolled. Seventy-nine (72%) patients were Asian-American and 31 (28%) were Caucasians. Of the 110 HCC patients, 69 (63%) were positive for serum hepatitis B surface antigen (HBsAg), 26 (24%) were positive for serum antibody to hepatitis C virus (anti-HCV), five (all Asian-Americans) were positive for both markers; 11 (10%) patients had a history of alcoholism. HBsAg was detected in 63 (80%) Asian-American patients, significantly higher than in the six (19%) Caucasian HCC patients (P < 0.01). Anti-HCV was detected in 10 (32%) Caucasian and in 16 (20%) Asian-American HCC patients (P > 0.05). Among Asian-American HCC patients, anti-HCV was more prevalent in those who were HBsAg-negative than in the HBsAg-positive patients (69 vs 8%; P < 0.01). A history of alcoholism was obtained in nine (29%) Caucasian HCC patients, significantly higher than in the two (3%) Asian-American HCC patients (P < 0.05). Comparing HCC patients with positive HBsAg and with anti-HCV, HBsAg-positive HCC patients were younger, Asian-Americans and predominantly male; 38% had a family history of liver disease. In contrast, anti-HCV-positive HCC patients were older by nearly a decade and 46% had a history of blood transfusion. Using a stepwise logistic regression analysis, Asian race and patient age < 50 years were found to be independent predictors for HBsAg-positivity, while a history of blood transfusion was the only predictor for anti-HCV-positivity in HCC patients. There was no significant difference in the rate of cirrhosis, serum levels of alpha-fetoprotein and survival between HBsAg-positive and anti-HCV-positive HCC patients. In conclusion, chronic HBV infection was the major aetiological factor in Asian-American HCC patients, while chronic HCV infection and alcoholism were major aetiological factors in Caucasian HCC patients in the USA.

Clinical outcomes after transfusion-associated hepatitis C.

BACKGROUND: The extent of serious complications in people who have acquired chronic hepatitis C infection after a blood transfusion is unclear. METHODS: We studied 131 patients with chronic post-transfusion hepatitis C who were referred to our center between February 1980 and June 1994. Eighty-two other patients were excluded because they had multiple transfusions, hemophilia, intravenous drug use, human immunodeficiency virus infection, hepatitis B infection, hemochromatosis, or alcoholic liver disease. Liver biopsies were performed in 101 patients; biopsies were not performed in the other 30 patients, all with signs of cirrhosis, because the results of coagulation tests were abnormal. RESULTS: The mean age of the patients was 57 years (range, 21 to 81) at the time of our initial evaluation. The mean age at the time of the blood transfusion was 35 years (range, 1 to 76). The mean duration of follow-up after presentation to us was 3.9 years (range, 1 to 15). Eighty-eight of the patients (67.2 percent) initially had fatigue, and 89 (67.9 percent) had hepatomegaly. Twenty-seven patients (20.6 percent) initially had chronic hepatitis, 30 (22.9 percent) had chronic active hepatitis, 67 (51.1 percent) had cirrhosis, and 7 (5.3 percent) had hepatocellular carcinoma. Hepatocellular carcinoma developed in an additional seven patients an average of 36 months (range, 7 to 121) after the initial visit. During follow-up, 20 patients (15.3 percent) died: 8 from complications of cirrhosis (1 after a liver transplantation); 11 from hepatocellular carcinoma; and 1, with chronic active hepatitis, from pneumonia. CONCLUSIONS: In a group of patients seen at a referral center, chronic post-transfusion hepatitis C was a progressive disease and, in some patients, led to death from either liver failure or hepatocellular carcinoma.

A pilot, open-labelled, phase II study using oral ribavirin in the treatment of patients with chronic active hepatitis B.

BACKGROUND: Ribavirin is a synthetic purine nucleoside with demonstrated antiviral activity against several DNA and RNA viruses. OBJECTIVES: An open-labelled pilot study to evaluate the safety and effect of ribavirin in the treatment of patients with chronic active hepatitis B (CAH-B). STUDY DESIGN: 24 CAH-B patients were treated with oral ribavirin 1200 mg daily in 3 divided doses for 4 weeks. Biochemical and virological parameters were monitored at regular interval during and after treatment. RESULTS: The serum hepatitis B e antigen (HBeAg) and HBV DNA measured by dot-blot hybridization were positive in all patients before treatment. At the end of 4 weeks of therapy, the HBV DNA levels decreased in 15 (63%) patients and became undetectable in 1 (4%) of these individuals. The mean HBV DNA decreased from 288+/-78 pg/ml at baseline to 219+/-79 pg/ml at the end of the 4 weeks of treatment (p = 0.046). Eight weeks after cessation of treatment, HBV DNA was undetectable in 10 (42%) patients, and the mean HBV DNA was 46+/-23 pg/ml (p < 0.01 when compared to mean baseline value). Seven (29%) patients seroconverted from HBeAg positive to anti-HBe positive but no patients lost hepatitis B surface antigen (HBsAg) during the 8 weeks of follow-up. At the end of 4 weeks of ribavirin treatment, serum levels of alanine aminotransferase (ALT) decreased in all but 1 patient; only 1 patient normalized serum ALT at this time. The mean serum ALT decreased significantly from 416+/-72 IU/l at baseline to 179+/-35 IU/l at the end of 4 weeks of treatment (p = 0.001). Eight weeks after cessation of therapy, the mean serum ALT value was 151+/-32 IU/l (p < 0.001 when compared to mean baseline value) and 5 (21%) patients normalized serum ALT at this time. During ribavirin treatment, the main side effect was a decrease in the hemoglobin level which returned to the pretreatment level in each instance within 2 months after discontinuance of therapy. CONCLUSIONS: Results of this pilot study indicated that oral ribavirin was well tolerated in CAH-B patients and resulted in lowering of serum ALT and HBV DNA values. A randomized controlled trial is needed to fully evaluate the beneficial effects of ribavirin in CAH-B patients.

Evaluation of sexual transmission in patients with chronic hepatitis C infection.

BACKGROUND: The transmission of hepatitis C virus (HCV) by parenteral exposure is well documented. However, a proportion of patients with acute or chronic HCV infection have an unknown source of infection. OBJECTIVES: The purpose of this study is to evaluate the role of sexual transmission in HCV infection. STUDY DESIGN: 68 patients (median age, 50 years) with chronic hepatitis C and their spouses were tested for the presence of antibody to HCV (anti-HCV) by multi-antigen and chimeric C25 antigen enzyme immunoassays and for HCV RNA by the polymerase chain reaction. Information on sexual activity and risk factors for HCV infection were obtained from all couples via a questionnaire. RESULTS: All index patients were positive for both anti-HCV and HCV RNA. Antibody to HCV was detected in four (5.9%) of their spouses. One anti-HCV-positive spouse had a history of blood transfusion while the other three (4.4%, 95% CI = 1.5-12.2%) had no known risk factors for HCV infection and thus may have been exposed to HCV via sexual transmission. Two of these 3 spouses had positive serum HCV RNA and had identical HCV genotype to the index patients. The length of sexual exposure was significantly longer in the couples who both were anti-HCV-positive than in patients whose spouses were anti-HCV negative (median: 25 vs. 10 years, P = 0.02, Mann-Whitney test). In our 68 index patients, 96% had antibodies to the recombinant proteins from the C22 (core) and C33C (NS3) regions, and 82% and 76% had antibodies to the proteins from the NS5 and C100-3 (NS4) regions. Identical anti-HCV profiles were noted in two of the four anti-HCV-positive couples. CONCLUSIONS: Our results indicate that sexual transmission, although uncommon, should be considered as a risk factor for HCV infection, especially in spouses who have had long-term intimate relationships with a chronic hepatitis C patient.

Correlation of serum HCV RNA and alanine aminotransferase levels in chronic hepatitis C patients during treatment with ribavirin.

To evaluate the effect of ribavirin on serum hepatitis C virus (HCV) RNA and alanine aminotransferase (ALT) levels, 22 patients with chronic HCV infection were treated with oral ribavirin 1200 mg daily in three divided doses for 4 weeks. At the end of 4 weeks treatment, the serum ALT decreased in all but one patient and became normal in three individuals. The mean pretreatment serum ALT was reduced significantly from 193 +/- 45 i.u./L to 95 +/- 16 i.u./L after 4 weeks therapy (P = 0.009). However, 8 weeks after cessation of treatment, the serum ALT rose to a mean value of 154 +/- 21 i.u./L. The mean pretreatment serum HCV RNA was not significantly decreased at the end of 4 weeks treatment (7.0 x 10(5) vs. 4.1 x 10(5) copies/mL, P > 0.05). However, serum HCV RNA levels were decreased in 12 and increased in 10 patients at the end of 4 weeks therapy. Eight weeks after cessation of therapy, the serum HCV RNA of 22 patients rose to a mean value of 4.9 +/- 10(5) copies/mL. Six patients who continued to have elevated serum ALT and positive HCV RNA after the initial 4 weeks treatment received oral ribavirin at the same dosage for an additional 24 weeks. The serum ALT again decreased in all six patients during therapy, but rose to pretreatment values by 8 weeks after cessation of the treatment. In addition, no significant changes were noted in the mean serum HCV RNA levels during and after 24 weeks of ribavirin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence for hepatitis C viral infection in patients with primary hepatocellular carcinoma.

In testing for antibodies to the hepatitis C virus (anti-HCV) in 112 patients with primary hepatocellular carcinoma, 10 of 33 white patients (30%) and 15 of 79 Asian patients (19%) had a positive response to the antibody. The antibody profile to individual hepatitis C viral antigens and the presence of circulating hepatitis C viral RNA were determined in the 25 patients. The anti-HCV antibodies most frequently detected were toward the antigens from the core (C22) and NS3 regions. Serum hepatitis C viral RNA was present in 17 of the 25 patients (68%), and these patients tended to have serum levels of alanine and aspartate aminotransferases higher than those patients without viremia (136 +/- 22 U per liter versus 64 +/- 11 U per liter and 161 +/- 26 U per liter versus 79 +/- 14 U per liter, respectively, both P < .05). Of the 15 Asian patients with hepatocellular carcinoma and anti-HCV, 4 (27%) had coexisting hepatitis B surface antigen (HBsAg) and 13 (87%) had antibodies to either hepatitis B core or surface antigen. Of the 10 white patients with anti-HCV, however, only 1 (10%) had hepatitis B virus antibodies (P < .01). Among 4 Asian patients with coexisting anti-HCV and HBsAg, 1 was found to have serum hepatitis B viral DNA and the other 3 had hepatitis C viral RNA. A history of blood transfusion was obtained from 12 of the 25 patients with anti-HCV (48%); 20 (80%) had coexisting cirrhosis. Our findings support the hypothesis that hepatitis C virus is an important etiologic agent in the development of primary hepatocellular carcinoma in both white and Asian patients in the United States.

Risk factors for hepatitis C virus infection among health care personnel in a community hospital.

OBJECTIVE: To determine the prevalence of and risk factors for antibody to the hepatitis C virus in hospital employees. METHODS: Retrospective testing of serum samples obtained from 1677 hospital employees during a prehepatitis B vaccination program in a private teaching community hospital. RESULTS: Twenty-three employees (1.4%) were found to have antibody to hepatitis C virus. The prevalence of antibody to hepatitis C virus was higher in blacks (3.4%) than in whites (1.1%, p = 0.03) and Hispanics (2.6%, p = 0.88). In a logistic regression model, factors significantly associated with antibody to hepatitis C virus seropositivity included antibody to hepatitis B core antigen (p = 0.002), a history of blood transfusion (p = 0.03), and needlestick injuries (p = 0.04). CONCLUSION: Although the prevalence of antibody to hepatitis C virus in health care workers was not high, needlestick injuries were associated with an increased risk for acquiring hepatitis C virus infection.

Hepatitis A vaccination.

The safety and immunogenicity of an inactivated hepatitis A virus vaccine were assessed in 101 healthy adults. Seronegative persons with normal serum aminotransferase levels were grouped according to age: Group 1 (n = 24) and group 3 (n = 22) were between 18 and 40 years of age, and group 2 (n = 25) and group 4 (n = 30) were older than 40 years. Groups 1 and 2 received vaccine on a 0-, 1-, and 2-month schedule (schedule A), and groups 3 and 4 received the vaccine on a 0-, 1-, and 12-month schedule (schedule B). Of the 101 vaccinated subjects, 98 (97%) seroconverted with antibody titers to hepatitis A virus of > or = 20 IU per liter after the first dose, and all subjects seroconverted after the second dose. The geometric mean titers a month after the third vaccine dose were significantly greater (P < .03) on both schedules for younger subjects (schedule A, 1,743 IU per liter, and schedule B, 7,882 IU per liter) than for older subjects (schedule A, 826 IU per liter, and schedule B, 4,279 IU per liter). Also, the differences in geometric mean titers a month after the third dose were significantly greater (P < .001) for subjects in both age groups on schedule B (group 3, 7,882 IU per liter, and group 4, 4,279 IU per liter) than for those on schedule A (group 1, 1,743 IU per liter, and group 2, 826 IU per liter). The hepatitis A virus was well tolerated, with mild discomfort at the injection site being the main side effect. This vaccine is both safe and highly immunogenic.

A cost comparison analysis for screening and vaccination of hospital personnel with high- and low-prevalence hepatitis B virus antibodies in California.

We compared the cost of antibody screening and the projected cost for hepatitis B vaccination of antibody-negative individuals at hospitals with "high prevalence" and "low prevalence" rates for hepatitis B virus antibodies among their employees. The use of hepatitis B core antibody for screening and subsequent hepatitis B vaccination of antibody-negative personnel was most cost-effective for hospitals considered to have high prevalence for hepatitis B virus antibodies among its staff, although use of hepatitis B surface antibody in this setting only increased costs by 1.4%. In a hospital with low prevalence for hepatitis B virus antibodies among its staff, use of hepatitis B surface antibody and subsequent vaccination of antibody-negative individuals was the most cost-effective approach, while use of hepatitis B core antibody for the above purposes would have increased costs by 3.4%. The use of both hepatitis B surface antibody and core antibody in either setting followed by immunization was least economical, as costs were increased by 13% and 13.5% respectively. We concluded that hepatitis B core antibody should be used for screening in hospitals with high prevalence for hepatitis B virus antibodies among employees while hepatitis B surface antibody be used for screening in hospitals with low prevalence for hepatitis B virus antibodies among employees. A prediction of high and low prevalence for hepatitis B virus antibodies in hospital personnel may be made by knowledge of the distribution in ethnicity of staff.

Spontaneous reactivation of hepatitis B in Chinese patients with HBsAg-positive chronic active hepatitis.

Eleven patients of Chinese origin experienced spontaneous reactivation of chronic active hepatitis B. Eight HBsAg-positive patients were followed for an average of 15 months prior to, while three others presented during reactivation. Fatigue, hepatomegaly and jaundice were frequent findings. Elevation of both serum ALT (average = 1,212 units per liter) and hepatitis B virus DNA levels were noted in all patients, and reactivation lasted an average of 4.4 months. During resolution, clinical symptoms abated, serum ALT levels reverted toward normal, and in nine patients, the hepatitis B virus DNA values became undetectable. All patients lacked evidence for acute hepatitis A, Epstein-Barr Virus, cytomegalovirus or hepatitis delta virus infection. Histologic findings of liver tissue from eight patients showed piecemeal necrosis and fibrosis. Within the parenchyma, varying degrees of hepatocytolysis with cuffing, perivenular necrosis and acidophilic bodies were noted. Ground-glass cells and regenerative changes also were observed. Cirrhosis was not present in any of the liver biopsies. These findings suggest that spontaneous reactivation of hepatitis B occurs in heterosexual patients with chronic active hepatitis B and contributes to chronic inflammation and to the progression of their liver disease.

Persistence of serum hepatitis B virus deoxyribonucleic acid in hepatitis B surface antigen-positive patients with chronic persistent hepatitis treated with prednisone.

The effect of a short course of prednisone therapy was evaluated in 8 patients with liver biopsy-verified chronic persistent hepatitis B. In 6 of the 8 (75%) patients, an abrupt fall in serum alanine aminotransferase levels after the initiation of prednisone was noted, and in 4 patients, there was an increase in serum alanine aminotransferase values after prednisone was discontinued. However, the serum levels of hepatitis B virus deoxyribonucleic acid were consistently greater than or equal to 200 pg before, during, and after the course of treatment in 7 of the 8 (87.5%) patients. All patients were initially hepatitis B e antigen-positive and remained so during the study period. These findings indicate that, unlike some patients with chronic active hepatitis B, immunosuppression with prednisone had no effect in altering hepatitis B viral replication in patients with chronic persistent hepatitis.

A hepatitis B vaccination program in a community teaching hospital.

Prior to offering the hepatitis B (HB) vaccine, a prescreen for hepatitis B virus (HBV) antibodies was conducted in a 565 bed hospital in Pasadena, California. Antibodies to the hepatitis B virus were detected in 14.5% of 1,745 employees tested. There was a significantly higher prevalence in those with a previous history of hepatitis, blood transfusions, exposure to needlesticks, number of years in the same occupation, and in the same hospital work area. Employees of Asian extraction (33.3%) and blacks (23.1%) had a higher prevalence of antibodies to the hepatitis B virus than Hispanics (13.7%) and whites (10.2%). Anti-HBs was detected in 92.6% of 865 employees who received three doses of the hepatitis B vaccine. Only 28.6% of nonresponders receiving a fourth dose of hepatitis B vaccine produced anti-HBs. The nonresponders to the HB vaccine were older (average age 64.9 years) when compared to the responders (average age 37.5 years), and more males failed to produce anti-HBs after vaccination than females. Hepatitis B vaccination of the majority of individuals with either "low level" anti-HBs alone or anti-HBc alone did not elicit an anamnestic response after one dose of vaccine, implying that these "low level" antibodies are nonspecific and do not represent antiviral antibodies. Adverse reactions to the hepatitis B vaccine were minor and included a flu-like syndrome, sore arm, and rash and swelling at the injection site. The reasons for nonparticipation were obtained from 179 individuals, and the main issue was concern about safety of the hepatitis B vaccine.