Bioinspired artificial photonic nanoarchitecture using the elytron of the beetle Trigonophorus rothschildi varians as a 'blueprint'.

An unusual, intercalated photonic nanoarchitecture was discovered in the elytra of Taiwanese Trigonophorus rothschildi varians beetles. It consists of a multilayer structure intercalated with a random distribution of cylindrical holes normal to the plane of the multilayer. The nanoarchitectures were characterized structurally by scanning electron microscopy and optically by normal incidence, integrated and goniometric reflectance measurements. They exhibit an unsaturated specular and saturated non-specular component of the reflected light. Bioinspired, artificial nanoarchitectures of similar structure and with similar properties were realized by drilling holes of submicron size in a multilayer structure, showing that such photonic nanoarchitectures of biological origin may constitute valuable blueprints for artificial photonic materials.

Taiwan's population and family planning efforts: an historical perspective.

The unprecedented decline of Taiwan's natural population increase rate from 3% in 1963 to 1.9% in 1973, attributed primarily to an increasing use of contraception, brought universal attention to one of the first and most successful national family planning programs, at a time when successes were few. Taiwan met its goal of decreasing its natural increase rate despite its young population, increasing numbers of women of childbearing ages, a strong preference for sons and a per capita income at the outset in 1963 of less than U.S.$200. Recognition of this achievement brought thousands of professionals, particularly from developing countries, to study the program firsthand: more than 3,000 during 1970--73 alone. This was matched by an avalanche of publications about the program that appeared around the world, written by practitioners, academics and others. This article tells the story of this success.

Serum insulin-like growth factor-II as a serologic marker of small hepatocellular carcinoma.

OBJECTIVE: Alpha-fetoprotein (AFP) is not a useful tumor marker for diagnosis of small hepatocellular carcinoma (HCC). There is over-expression of insulin-like growth factor (IGF)-II in HCC tissue. This study investigates the diagnostic application of IGF-II in small HCC. MATERIAL AND METHODS: Serum levels of IGF-II and AFP were determined in 41 patients with small cirrhotic HCC (< or = 3 cm), 41 sex- and age-matched patients with cirrhosis alone (LC), and 41 healthy adults. The optimal cut-off values for diagnosing HCC were determined with receiver operating characteristics (ROC) curve. RESULTS: Both IGF-II and AFP levels in HCC were higher than those in LC patients or controls (each p = 0.0001). The IGF-II levels in LC patients were lower than those in controls (p = 0.001). In HCC patients, multivariate analysis indicated that that both IGF-II (odds ratio, 4.54; 95% confidence interval, 2.15-9.55; p = 0.0001) and AFP (odds ratio, 1.05; 95% confidence interval, 1.01-1.08; p = 0.003) were found to be associated with an increased risk of presence of HCC. The optimal cut-off values of IGF-II (4.1 mg/g prealbumin) and AFP (50 ng/ml) were determined with ROC curves. The sensitivity, specificity, and diagnostic accuracy values for IGF-II were 63%, 90%, and 70%, respectively. Those for AFP were 44%, 95%, and 70%, respectively. Determination of both markers in parallel significantly increase the diagnostic accuracy (88%) and sensitivity (80%), with a high specificity (90%). CONCLUSIONS: Serum IGF-II level can be used as an independent serologic marker or a complementary tumor marker to AFP for diagnosis of small HCC.

Clinical evaluation of the COBAS Amplicor HBV monitor test for measuring serum HBV DNA and comparison with the Quantiplex branched DNA signal amplification assay in Taiwan.

AIMS: To evaluate the performance characteristics and clinical usefulness of the COBAS Amplicor HBV monitor (COBAS-AM) test in Taiwan and to examine its correlation with the Quantiplex branched DNA signal amplification (bDNA) assay for measuring serum hepatitis B virus (HBV) DNA concentrations. METHODS: HBV DNA was measured by the COBAS-AM test in 149 sera from chronic HBV infected patients that had previously been analysed by the bDNA assay. RESULTS: The COBAS-AM test showed good reproducibility, with acceptable intra-assay and interassay coefficients of variation (1.6% and 0.9%, respectively) and good linearity (r2=0.98). The overall sensitivity of the COBAS-AM test was significantly higher than that of the bDNA assay (95.3% v 83.2%): 69.6% of samples with HBV DNA below the detection limit of the bDNA assay could be measured by the COBAS-AM test. There was a significant correlation between the results of the two assays (r=0.901; p<0.0001). On average, the results derived from the COBAS-AM test were 0.55 log lower than those of the bDNA assay. HBV DNA concentrations were significantly higher among HBV e antigen (HBeAg) positive patients than negative ones, and higher among patients with abnormal alanine aminotransferase (ALT) concentrations than those with normal ALT concentrations (p=0.0003). CONCLUSIONS: The COBAS-AM assay, more sensitive in HBeAg negative samples than the bDNA assay, can effectively measure HBV DNA concentrations in Taiwanese patients. HBV DNA values measured by the COBAS-AM test and bDNA assay correlate significantly.

Influence of age on intrarenal resistive index measurement in normal subjects.

BACKGROUND: We investigated the influence of age on intrarenal arterial resistive index (RI) measurement in 135 normal subjects (71 male, 64 female; age range = 17-68 years, median age = 37 years). METHODS: Each subject underwent color Doppler measurement of the intrarenal RI from three distinct interlobar arteries in the superior, middle, and inferior parts of both kidneys. The mean of six RI values obtained from both kidneys was used for analysis. The correlation of RI with different variables was investigated by linear regression and stepwise multiple linear regression. Variables analyzed were age, systolic blood pressure, diastolic blood pressure, mean blood pressure, pulse pressure, and pulse rate. RESULTS: The results of linear regression showed that age had a significantly positive correlation ( r = 0.276, p = 0.0012) and diastolic blood pressure had a significantly negative correlation ( r = -0.186, p = 0.0311) with the RI. The results of stepwise multiple linear regression showed that the combination of age and diastolic blood pressure could explain approximately 15% of the RI changes ( r(2) = 0.1535). CONCLUSION: Although there is a statistically significant positive correlation between intrarenal RI and age, the correlation is weak. This suggests that the influence of age on RI measurement is small and may be of no clinical importance.

Serum insulin-like growth factor-II and alpha-fetoprotein as tumor markers of hepatocellular carcinoma.

To evaluate the diagnostic application of serum insulin-like growth factor-II (IGF-II) and alpha-fetoprotein (AFP) levels in hepatocellular carcinoma (HCC), IGF-II and AFP were determined in 100 cirrhotic patients with HCC, 100 sex- and age-matched patients with cirrhosis alone and 50 healthy controls. The results indicated that IGF-II and AFP levels in patients with HCC were higher than in those with cirrhosis alone (p = 0.0001). There is an inverse correlation between IGF-II and (log)AFP (r = -0.410, p = 0.0001) in patients with HCC. Multivariate analysis indicated that IGF-II and AFP were closely associated, in a dose-related fashion, with the presence of HCC. Receiver operating characteristic curves were used to determine the optimal cutoff values of IGF-II (4.5 mg/g prealbumin) and AFP (100 ng/ml), respectively. Both IGF-II and AFP show a high specificity and positive likelihood ratio. The sensitivity was 42.0% for IGF-II and 73.0% for AFP. Determination of both markers in parallel significantly increased the diagnostic accuracy (96.5%) and sensitivity (97.9%), with a high specificity (95.1%) and positive likelihood ratio (19.9). In conclusion, IGF-II and AFP may be used as complementary tumor markers to discriminate HCC from cirrhosis.

Influence of posture change on intrarenal arterial resistive index measurement.

BACKGROUND: We investigated the influence of posture change on intrarenal arterial resistive index measurement in 80 subjects (38 male, 42 female). METHODS: Three interlobar arteries in the superior, middle, and inferior parts of the right kidney in each subject were examined by color Doppler ultrasound in two different positions (left lateral decubitus and supine). Based on the movement of the kidney caused by posture change, 23 subjects were classified as having a highly mobile kidney (group I) and the other 57 subjects were classified as not having a highly mobile kidney (group II). RESULTS: Fifty-eight kidneys (72.5%), 19 in group I (82.6%) and 39 in group II (68.4%), showed higher resistive index values in the lateral decubitus position than in the supine position. The influence of posture change on resistive index measurement was significant ( p < 0.001 for all subjects, p < 0.01 for group I, p < 0.05 for group II). The ranges of resistive index differences caused by posture change were 0-0.13 for group I and 0-0.11 for group II. The difference in resistive index caused by posture change was not significant between groups. CONCLUSION: Posture change is a potential confounding factor for intrarenal resistive index measurement.

The prevalence of TT virus and GB virus C/hepatitis G virus infection in individuals with raised liver enzymes but without HBV or HCV infection in Taiwan.

The prevalence of TT virus (TTV) and GB virus-C/hepatitis G virus (GBV-C/HGV) infection and the association with raised liver function tests in 546 Taiwanese with negative HBsAg, anti-HCV and HCV RNA was elucidated. They were tested for serum alanine aminotransferase (ALT), GBV-C/HGV RNA, anti-envelope protein 2 antibody (anti-E2) and TTV DNA. Direct sequencing and phylogenetic analyses were performed on 58 isolates for TTV genotype determination. The prevalence of TTV DNA, GBV-C/HGV RNA, anti-E2 and over all GBV-C/HGV exposure was 24.9, 3.4, 8.2 and 11.1%, respectively. Using uni- and multi-variate analyses, male gender and TTV viremia were associated significantly with raised ALT values. Sixty-nine percent of TTV isolates were deduced to be TTV genotype 1 and they had significantly lower mean age than genotype non-1 isolates. In the population, raised ALT may be related to male gender and be attributable to TTV infection but not to GBV-C/HGV among individuals with no evidence of current HBV and HCV infection. TTV genotype 1 is the most prevalent genotype and associated with younger age.

GB virus C/hepatitis G virus infection in chronic hepatitis C patients with and without interferon-alpha therapy.

GB virus C/hepatitis G virus (GBV-C/HGV) RNA, detected by polymerase chain reaction, and antibodies to the GBV-C/HGV envelope protein (anti-E2), detected by an enzyme-linked immunosorbent assay, were used to evaluate both the impact of GBV-C/HGV on the coexistent hepatitis C virus (HCV) infection and the course of GBV-C/HGV infection in chronic hepatitis C patients with and without interferon-alpha (IFN-alpha) treatment. Of the 162 chronic hepatitis C patients treated with INF-alpha, 17.9% were GBV-C/HGV RNA-positive and 18.5% anti-E2-positive (total exposure, 35.2%). Neither present nor past GBV-C/HGV infection had impact on the clinical features, HCV virological characteristics and response to IFN-alpha treatment in chronic hepatitis C patients. Among patients with ongoing HCV/GBV-C/HGV coinfection, 20.7% (6/29) in IFN-alpha-treated patients lost GBV-C/HGV RNA concomitant with anti-E2 seropositivity, which was significantly higher than 4.8% (2/42) in patients without INF-alpha treatment (P<0.05). Based on multivariate analyses, the significant factors associated with clearance of GBV-C/HGV viremia combined with anti-E2 seropositivity were baseline anti-E2 seropositivity and IFN-alpha treatment. In summary, GBV-C/HGV did not alter the course of coexistent HCV. IFN-alpha treatment was effective in some patients against GBV-C/HGV and might facilitate anti-E2 seroconversion in chronic hepatitis C patients with GBV-C/HGV viremia.

Changing prevalence of hepatitis C virus genotypes: molecular epidemiology and clinical implications in the hepatitis C virus hyperendemic areas and a tertiary referral center in Taiwan.

To determine the hepatitis C virus (HCV) genotype distribution in Taiwan and to clarify the relationship between genotype and the pathogenesis of HCV infection, 1,164 subjects positive for serum HCV antibodies and HCV RNA from three HCV hyperendemic areas (Masago, Tzukuan, and Taoyuan) and a tertiary referral center in Taiwan were studied during 1995-1997. HCV genotypes and viral loads were determined using Okamoto's method and branched DNA assay, respectively. Genotype 1b was the most prevalent in Tzukuan (61.9%), Taoyuan (76.9%), and the referral center (47.0%). By contrast, genotype 2a was the major HCV type in Masago (63.5%). Prevalence of genotype 1b positively and that of genotype 2a negatively correlated to age, regardless of study populations (P < 0.01). Based on multivariate analysis, the significant factors associated with the presence of cirrhosis, with or without hepatocellular carcinoma, in chronic hepatitis C patients were genotype 1b and age. In conclusion, these results underline that independent HCV outbreaks continue in HCV hyperendemic areas in Taiwan, concomitant with a changing relative prevalence of HCV genotypes in relation to age. Both the correlation of genotype 1b with age (cohort effect) and intrinsic properties of HCV genotypes are probably responsible for the association between genotype and the pathogenesis of HCV infection.

The molecular epidemiology and clinical significance of TT virus (TTV) infection in healthy blood donors from southern Taiwan.

To evaluate the molecular epidemiology and clinical significance of th

Influence of hepatitis C virus on the profiles of patients with chronic hepatitis B virus infection.

BACKGROUND: Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the most common causes of chronic liver disease, cirrhosis and hepatocellular carcinoma. The influence of HCV infection on the clinicopathological and virological profiles of chronic HBV infection was investigated. METHODS: A total of 100 chronic HBV carriers with histopathological diagnoses by liver biopsy were studied. Hepatitis B e antigen (HBeAg) and anti-HCV antibody were tested. Serum HCV-RNA was detected by using a nested reverse transcription-PCR assay. A branched DNA (bDNA) assay was used to detect HBV-DNA and quantitate the serum levels. RESULTS: Eighteen (18%) of 100 patients were positive for anti-HCV and HCV-RNA. Patients with concurrent HCV and HBV infection were significantly older than those without HCV infection (P < 0.05). The positive rates of HBeAg and HBV-DNA as well as the serum levels of HBV-DNA in patients with concurrent HCV and HBV infection were significantly lower than those without concurrent HCV and HBV infection (P < 0.01, P < 0.05, and P < 0.001, respectively). By using multivariate analysis, the factors of seroconversion of HBeAg and decreasing level of HBV-DNA were significantly correlated to concurrent HCV and HBV infection in chronic HBV carriers. The factors of increasing age and concurrent HCV and HBV infection were significantly correlated to seroconversion of HBeAg. CONCLUSIONS: The concurrent HCV and HBV infection in chronic HBV carriers might result in a suppression of HBV replication that presented with a lower level of serum HBV-DNA and HBeAg seroconversion. Nevertheless, neither more obvious increase in biochemical parameters nor histopathological progression to more advanced liver diseases was observed.

Betel quid chewing as a risk factor for hepatocellular carcinoma: a case-control study.

The role of betel quid chewing in the aetiology of hepatocellular carcinoma (HCC) was evaluated in a case-control study including 263 pairs of age- and sex-matched HCC patients and healthy controls. Serum hepatitis B surface antigen (HBsAg), and antibodies to hepatitis C virus (anti-HCV) were determined, and standardized personal interview conducted using a structured questionnaire. Multivariate analysis indicated that betel quid chewing (odds ratio (OR), 3.49; 95% confidence interval (CI), 1.74-6.96), HBsAg (OR, 16.69; 95% CI, 9.92-28.07), anti-HCV (OR, 38.57; 95% CI, 18.15-81.96), and educational duration of less than 10 years (OR, 1.71; 95% CI, 1.05-2.78) are independent risk factors of HCC. In addition, there was an additive interaction between betel quid chewing and chronic infection with either hepatitis B virus (synergy index, 5.37) or hepatitis C virus (synergy index, 1.66). Moreover, risk on HCC increased as duration of betel quid chewing increased, or amount of betel quid consumed (each P for trend < 0.0001).

The serological and molecular epidemiology of GB virus C/hepatitis G virus infection in a hepatitis C and B endemic area.

OBJECTIVES: To investigate the serological and molecular characteristics of GB virus C/hepatitis G virus (GBV-C/HGV) infection in the hepatitis C virus (HCV)/hepatitis B virus (HBV)-endemic areas in Taiwan. METHODS: Sera from 200 residents from Masago, an HCV/HBV-endemic community in Taiwan, and 400 blood donors were tested for GBV-C/HGV RNA by using nested reverse transcription-polymerase chain reaction and for antibodies to GBV-C/HGV E2-protein (anti-E2) by an enzyme-linked immunosorbent assay. Phylogenetic analysis of GBV-C/HGV was performed. RESULTS: The prevalence of GBV-C/HGV viraemia, anti-E2 and GBV-C/HGV exposure among residents of Masago was significantly higher than that among donors (17.0%, 25.5% and 39.5% vs. 3.3%, 7.5% and 10.3%, respectively; all P < 0.0001). In Masago, the prevalence of GBV-C/HGV exposure was significantly higher in residents exposed to HCV than in those without HCV exposure (45.8% vs. 24.1%;P< 0.005). Based on multivariate analyses, HCV viraemia was the only significant factor associated with elevated levels of alanine aminotransferase in Masago. Phylogenetic analysis showed all 34 GBV-C/HGV isolates from Masago clustered within genotype 3. CONCLUSIONS: GBV-C/HGV was highly prevalent in Masago, an HCV/HBV-endemic community in Taiwan. HCV viraemia played the most important clinical hepatopathic role in the area. Infections with other hepatitis viruses did not influence the anti-E2 seroconversion from GBV-C/HGV infections.

Percutaneous ethanol injection of the supplying artery to hepatocellular carcinoma that is not amenable to conventional treatment.

The purpose of this study was to evaluate the clinical usefulness of ultrasound-guided percutaneous ethanol injection of the supplying artery (PEISA) to the tumour in the palliative management of hepatocellular carcinoma (HCC) that is not amenable to conventional treatments. A total of 23 cases of HCC, measuring from 3.1 cm to larger than 15 cm (median 5.4 cm) in 17 cirrhotic patients, were treated by PEISA. PEISA was used to control rapid growth of the tumour in seven patients and to reduce abdominal discomfort caused by rapid expansion of the tumour in 10 patients. Tumours with arterial Doppler signals persisting after PEISA underwent repeated treatment. The follow-up period ranged from 2-48 months. PEISA was achieved in 69 out of 76 attempts (90.8%). The amount of ethanol injected on each occasion ranged from 2.5-33 ml. Follow-up colour Doppler scanning showed complete elimination of tumour Doppler signals in 22 out of 23 lesions (95.7%). Following treatment, one tumour disappeared, 13 tumours shrank and nine tumours were unchanged in size. All patients with abdominal discomfort had relief after treatment. The common complications of PEISA were local pain and fever. In conclusion, PEISA is effective at treating painful HCC unsuitable for conventional treatment.

Sex differences in relation to serum hepatitis B e antigen and alanine aminotransferase levels among asymptomatic hepatitis B surface antigen carriers.

This study aimed to investigate sex differences in relation to hepatitis B e antigen (HBeAg) and serum alanine aminotransferase (ALT) levels in chronic asymptomatic hepatitis B virus (HBV) infection. HBeAg and ALT level were determined in 636 asymptomatic hepatitis B surface antigen carriers. There was no significant sex differences in the age-adjusted prevalence of HBeAg. Abnormal ALT level (>45 IU/l) was more frequent in carriers with HBeAg (17.5% vs 7.6%; P = 0.001). Multivariate analysis indicated that male sex (odds ratio, 2.0; 95% confidence interval, 1.1-3.6) and HBeAg (odds ratio, 2.6; 95% confidence interval, 1.6-4.3) were independent risk factors for abnormal ALT levels. Male sex and HBeAg-positivity are independent risk factors for abnormal ALT activity in chronic HBV infection. This observation may be related to sex differences in chronic HBV infection.

Epidermal growth factor receptor-binding growth factors in the urine of patients with cancers of the digestive tract.

We aimed to assess the diagnostic application of urinary epidermal growth factor receptor (EGFR)-binding growth factors in cancers of the digestive tract. By radioreceptor assay and radioimmunoassay, we determined these growth factors in 115 patients with various cancers of the digestive tract, 30 patients with benign disease, and 40 healthy controls. The receiver operating characteristic (ROC) curve and likelihood ratio were employed to determine the best diagnostic efficiency. Urinary EGFR-binding growth factors in each cancer group were significantly higher than those in the non-cancer groups. Multivariate analysis indicated that the growth factors, determined by both the radioreceptor assay (odds ratio, 1.184; 95% confidence interval,1.077-1.302; P = 0.001) and radioimmunoassay (odds ratio,1.055; 95% confidence interval, 1.002-1.111; P = 0.039), were associated, in a dose-related fashion, with the presence of cancers. By ROC curve analysis, the optimal cutoff values for EGFR-binding growth factors were 25.5 microg/g creatinine (radioreceptor assay) and 33.6 microg/g creatinine (radioimmunoassay). The resulting sensitivity, specificity, diagnostic accuracy, and positive and negative likelihood ratios were 84.4%. 87.5%, 85.2%, 6.75 and 0.18 (for radioreceptor assay) and 86.1%, 67.5%, 81.3%, 2.64 and 0.21 (for radioimmunoassay), respectively. Except for pancreatic cancer the growth factors showed moderate diagnostic efficiency for the other digestive tract cancers. In conclusion, urinary EGFR-binding growth factors were increased in cancers of the digestive tract. They may be used as diagnostic tumor markers.

Serotyping and genotyping of hepatitis C virus in Taiwanese patients with type C chronic liver disease and uraemic patients on maintenance haemodialysis.

BACKGROUND: To evaluate a recombinant immunoblot hepatitis C virus (HCV) serotyping assay, which determines HCV serotypes 1, 2, and 3 by detecting type-specific antibodies to core-and NS-4-derived peptides. METHODS: Immunoreactivity of type-specific antibodies among 173 chronic hepatitis C patients and 43 haemodialysis patients in Taiwan was examined and the serotyping results were compared with genotyping by Okamoto's method. Serial specimens from 29 patients undergoing interferon-alpha therapy were also evaluated. RESULTS: Of the 205 specimens for which genotyping data were available, 51.2% were of serotype 1, 31.7% of serotype 2, 1.0% of serotype 3, 2.4% of either serotype 1 or 3, and the remaining 13.7% were untypable. The serotypable rate was significantly lower in haemodialysis patients than in chronic hepatitis C patients (70.0% vs 94.9%; P < 0.001). Serotyping of genotype 2b specimens was significantly more dependent on core peptide bands than other genotypes. Using genotyping as the reference, the overall sensitivity, specificity and concordance of the recombinant immunoblot HCV serotyping assay were 86.3%, 97.2% and 83.9%, respectively. However, the serotyping assay had significantly lower sensitivity (69.2%), specificity (77.8%) and concordance (53.8%) for genotype 2b specimens. Of nine HCV complete responders, one lost type-specific antibodies 6 months after the cessation of interferon-alpha treatment. CONCLUSIONS: These results suggest that, except for less than optimal performance with immunocompromised or genotype 2b patients, the HCV serotyping assay is a practical and useful method for HCV typing in the clinical setting in Taiwan.

Role of serum C-reactive protein as a marker of hepatocellular carcinoma in patients with cirrhosis.

BACKGROUND: The usefulness of C-reactive protein (CRP) as a tumour marker in patients with hepatocellular carcinoma (HCC) is controversial. The purpose of this study was to determine whether CRP estimation could be used to identify patients with HCC among those with cirrhosis. METHODS: Serum levels of CRP and alpha-fetoprotein (AFP) were investigated in 122 previously untreated patients with cirrhosis and HCC. Another 76 patients with cirrhosis alone were also investigated as controls. RESULTS: Of the subjects tested, 47.5% of patients with HCC and 39.5% of controls had elevated CRP values (> 6 microg/mL). Although using elevated CRP and/or AFP (> 20 ng/mL) as a criterion showed a significant difference between controls and patients with multiple nodular, massive, or diffuse type HCC (all P < 0.005), the clinical application of this criterion was limited because of low specificity (58%) and accuracy (all < 73%). By using receiver-operating characteristic curves no valuable threshold value of CRP was found to discriminate various types of HCC, except for distinguishing the diffuse type from controls. The CRP value of 12 microg/mL could be used as the cut-off value to differentiate diffuse-type HCC from controls (sensitivity 82.4%, specificity 82%, accuracy 82.1%, P<0.005). CONCLUSIONS: Serum CRP is not a good marker for HCC. However, very high values of CRP in patients with cirrhosis may suggest the presence of a diffuse-type HCC.

Incidence and associated factors of neutralizing anti-interferon antibodies among chronic hepatitis C patients treated with interferon in Taiwan.

BACKGROUND: The administration of interferon (IFN) could be complicated by the development of neutralizing anti-interferon antibodies (NA). This study evaluates the frequency and associated factors of NA among chronic hepatitis C patients treated with different IFNs. METHODS: Ninety-five chronic hepatitis C patients were randomized to be treated with recombinant IFN-alpha2a (n = 28), IFN-alpha2b (n = 39) or lymphoblastoid IFN-alpha1 (n = 28) given intramuscularly, 3-6 million units, thrice weekly for 24 weeks. Serum samples collected before, during and after the cessation of treatment were checked for NA. RESULTS: Three patients were withdrawn from treatment. All patients were negative for NA before treatment and 13 (14%) patients developed neutralizing antibodies. Of the 26 patients treated with IFN-alpha2a, 6 (23.1%) developed NA. whereas NA were detected in only 6 (15.4%) of 39 and 1 (3.7%) of 27 patients treated with IFN-alpha2b and IFN-alphanl, respectively. Age, gender, HCV genotype, ALT level, IFN total dose and liver histology were not associated with the development of NA. By using multivariate logistic regression it was shown that pretreatment HCV RNA level and IFN preparation were the two major factors related to the production of NA. The response of treatment was related to pretreatment viremia but not to the presence of NA. CONCLUSIONS: The frequency of development of NA among Taiwanese patients with chronic hepatitis C might be related to different IFN preparations and pretreatment HCV RNA level. The response of treatment was related to pretreatment HCV RNA level but not to the presence of NA.