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.

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.

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).

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.

Simultaneous multiple viral infections in childhood acute lower respiratory tract infections in southern Taiwan.

Thirty paediatric patients with acute lower respiratory tract infections (ALRI) caused by simultaneous multiple viral infections (SMV) in a 3-year interval were reviewed. Twenty patients were infected with two viruses simultaneously; nine patients with three viruses; and one patient with four viruses. The frequency of individual viruses were: adenovirus, 18 (60 per cent); respiratory syncytial virus, 7 (23 per cent); influenza virus type A, 6 (20 per cent); influenza virus type B, 15 (50 per cent); parainfluenza virus type 1, 11 (37 per cent); parainfluenza virus type 3, 13 (43 per cent). There was no difference between the clinical presentations of ALRI with SMV and those of ALRI with a single virus. In conclusion, SMV was not uncommon in children with ALRI; the clinical presentations of multiple viral infection were similar to those of single viral infection.

Immunoglobulin- and hepatitis B surface antigen-specific circulating immune complexes in chronic hepatitis B virus infection.

For assessing the role of circulating immune complexes (CIC) in chronic hepatitis B virus (HBV) infection, CICs containing IgM, IgG, and HBsAg were determined by C1q and conglutinin (K) assays in 216 patients with chronic HBV infection and 54 healthy controls. The concentration of each type of CIC in patients is higher than in controls (P = 0.0001). CIC is a common feature of chronic HBV infection with 95.8% of cases having at least one abnormal test result. At least one type of HBsAg-CIC is positive in 54.2% of patients. HBsAg-CIC positivity is associated with HBeAg positivity (P = 0.0001), higher aminotransferase levels (P < 0.002), and younger age (P = 0.001). IgG-CIC or IgM-HBsAg-CIC correlates with higher aminotransferase activity (P = 0.001). In conclusion, HBsAg-CIC correlates with HBV replication. IgG-CIC and/or IgM-HBsAg-CIC correlate with disease activity. Immune-mediated injury may play a role in the pathogenesis of chronic HBV infection.

Clinical relevance of transforming growth factor-beta 1 in the urine of patients with hepatocellular carcinoma.

To assess the clinical relevance of transforming growth factor-beta 1 (TGF-beta 1) in the urine of patients with hepatocellular carcinoma (HCC), TGF-beta 1 was measured, by radioimmunoassay, in 140 patients with HCC, 50 cirrhotic patients, 30 patients with chronic active hepatitis, and 50 healthy controls. The results indicate that there were significantly increased urinary TGF-beta 1 levels in patients with HCC. Raised TGF-beta 1 levels were associated, in a dose-related fashion, with increased risk for development of HCC (odds ratio, 1.05, 95% confidence interval, 1.03-1.07). HCC patients with raised TGF-beta 1 levels had shorter survival than those with normal TGF-beta 1 levels (p = 0.038). TGF-beta 1 levels decreased after successful anticancer therapy (p < 0.0001). There was an inverse correlation between TGF-beta 1 and serum alpha-fetoprotein (AFP) (r = -0.199, p < 0.04). Receiver operating characteristics (ROC) curve analysis indicated that parallel determination of TGF-beta 1 and AFP significantly increased the sensitivity and diagnostic accuracy, with a high specificity. In conclusion, raised urinary TGF-beta 1 was associated with HCC development. It is a predictor of poor prognosis, and a tumor marker for diagnosis and therapeutic follow-up of HCC.

Urinary transforming growth factor beta1 levels in hepatitis C virus-related chronic liver disease: correlation between high levels and severity of disease.

To assess the clinical relevance of transforming growth factor beta1 (TGF-beta1) in chronic liver disease, urinary TGF-beta1 and circulating aminoterminal propeptides of type III procollagen (PIIINP) levels were determined by radioimmunoassay in 100 cirrhotic patients, 44 patients with chronic hepatitis, and 50 healthy controls. TGF-beta1 and PIIINP levels in cirrhotic patients were higher than those in patients with chronic hepatitis (each P < .0001) or healthy controls (each P < .0001), respectively. There was a correlation between TGF-beta1 and PIIINP levels in patients (r = .858, P < .0001). The higher the urinary TGF-beta1 level, the worse the severity of chronic liver disease (P < .001). TGF-beta1 levels in cirrhotic patients with antibodies to hepatitis C virus (anti-HCV) were higher than in those without (P < .0001). Compared with cirrhotic patients with hepatitis B surface antigen (HBsAg) alone, those with HBsAg and anti-HCV had higher TGF-beta1 levels (P < .001), a higher frequency of raised TGF-beta1 (P < .005), and a higher frequency of patients with Child-Pugh C (P < .005). Multivariate analysis indicated that the TGF-beta1 level was significantly correlated with the presence of cirrhosis. In conclusion, urinary TGF-beta1 levels may be used as a marker for hepatic fibrogenesis. Higher urinary TGF-beta1 levels correlate with more severe liver disease.

Urinary transforming growth factor-beta 1 in relation to serum alpha-fetoprotein in hepatocellular carcinoma.

BACKGROUND: Our aim was to assess the relationship between transforming growth factor beta 1 (TGF-beta 1) and alpha-fetoprotein (AFP) levels in hepatocellular carcinoma (HCC). METHODS: Urinary TGF-beta 1 and serum AFP were determined in 123 HCC patients, 50 patients with chronic liver disease (CLD), and 50 healthy controls. RESULTS: Both TGF-beta 1 and AFP levels were higher in HCC patients than in CLD patients or controls (each, P = 0.0001). There was a negative correlation between TGF-beta 1 and logAFP (r = -0.196, P = 0.029). Multivariate analysis indicated that TGF-beta 1 and AFP were associated with an increased risk of HCC development. By receiver-operating characteristic curve analysis, determination of AFP and TGF-beta 1 in parallel significantly increased the sensitivity and diagnostic accuracy in detecting HCC. CONCLUSION: Increased urinary TGF-beta 1 level can be used as a complementary marker to AFP for detection of HCC with low AFP production.

Serum alanine aminotransferase level in relation to hepatitis B and C virus infections among blood donors.

To assess the serum alanine aminotransferase (ALT) activity in relation to hepatitis B virus (HBV) and hepatitis C virus (HCV) infections among blood donors, antibodies to HCV (anti-HCV) and hepatitis B surface antigen (HBsAg) were detected in 400 blood donors with normal ALT level (< or = 750 mumol/s per liter), and 76 blood donors with raised ALT level. The prevalence of anti-HCV (10.5%) and HBsAg (28.9%) in the latter was higher than that (2.0% and 17.5%, respectively) in the former (p < 0.001 and p < 0.03, respectively). There was a trend that indicated that the risk of anti-HCV positivity increased with increasing age (p < 0.001). Thirty of 76 (39.5%) donors with raised ALT level were positive for anti-HCV or HBsAg. Compared with HBsAg-positive donors, donors with anti-HCV had higher serum ALT levels (p < 0.01) and greater mean age (p < 0.01). Multivariate analysis indicated that both anti-HCV (odds ratio: 6.2; 95% confidence interval: 2.2-17.8) and HBsAg (odds ratio: 2.2; 95% confidence interval: 1.3-3.9) were significantly associated with raised serum ALT activity. The estimated population-attributable risk was 8.6% for anti-HCV, and 13.8% for HBsAg. In conclusion, although HBV and HCV infections are independent risk factors of raised ALT activity among blood donors, they play a minor role in the etiology of raised ALT activity.

Clinical evaluation of urinary transforming growth factor-beta1 and serum alpha-fetoprotein as tumour markers of hepatocellular carcinoma.

To evaluate the diagnostic application of urinary transforming growth factor-beta1 (TGF-beta1) and serum alpha-fetoprotein (AFP) levels in hepatocellular carcinoma (HCC), TGF-beta1 and AFP were determined in 94 patients with cirrhotic HCC and in 94 sex- and age-matched patients with cirrhosis alone. TGF-beta1 and AFP levels in HCC were higher than in cirrhosis alone (P = 0.0001). There is an inverse correlation between TGF-beta1 and log AFP (r = -0.292, P = 0.004). Multivariate analysis indicated that TGF-beta1 and AFP were closely associated, in a dose-related fashion, with the development of HCC. Receiver-operating characteristic (ROC) curves were used to determine the optimal cut-off values of TGF-beta1 (50 microg g(-1) creatinine) and AFP (100 ng ml(-1)). Both TGF-beta1 and AFP showed a high specificity (99%) and positive likelihood ratio. The sensitivity was 53.1% for TGF-beta1 and 55.3% for AFP. The determination of both markers in parallel significantly increased the diagnostic accuracy (90.1%) and sensitivity (84%), with a high specificity (98%) and positive likelihood ratio (40.0). In conclusion, TGF-beta1 and AFP are independent tumour markers of HCC and may be used as complementary tumour markers to discriminate HCC from cirrhosis.

Elevated urinary transforming growth factor-beta1 level as a tumour marker and predictor of poor survival in cirrhotic hepatocellular carcinoma.

To assess the clinical relevance of transforming growth factor-beta1 (TGF-beta1) in hepatocellular carcinoma (HCC), urinary TGF-beta1 and serum alpha-fetoprotein (AFP) were determined in 94 patients with cirrhotic HCC, 94 age- and sex-matched patients with cirrhosis alone and 50 healthy adults. TGF-beta1 level in HCC was higher than in cirrhosis alone or in healthy controls (each P = 0.0001). There is an inverse correlation between TGF-beta1 and AFP levels (r = -0.292, P = 0.004). Significantly higher TGF-beta1 level was found in HCC patients with worsening Child-Pugh stages, diffuse HCC, tumour size > 3 cm, multilobular tumour and AFP < or = 20 ng ml(-1). TGF-beta1 level decreased after complete treatment with transcatheter arterial chemoembolization (P = 0.0001). The median survival in HCC patients with raised TGF-beta1 was shorter than those with normal TGF-beta1 (P = 0.018). Multivariate analysis indicated that TGF-beta1 and AFP were significantly correlated with the presence of HCC. In addition, TGF-beta1 could be used as a diagnostic marker for HCC, particularly in tumours with low AFP production. In conclusion, elevated urinary TGF-beta1 level is a tumour marker and predictor of poor survival for cirrhotic HCC.

Effect of hepatitis C and B virus infection on risk of hepatocellular carcinoma: a prospective study.

To assess whether there is an additive effect between chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection on the development of hepatocellular carcinoma (HCC), 400 consecutive cirrhotic patients were followed prospectively with periodic abdominal ultrasound examination and measurement of serum alpha-fetoprotein (AFP) level every 4 months. During a follow-up of 1185 person-years, 80 (20%) patients developed HCC, with an annual incidence of 6.8%. The annual incidence was 2.0% in patients negative for hepatitis B surface antigen (HBsAg) and antibodies to HCV (anti-HCV), 6.6% in patients with HBsAg alone, 7.0% in patients with anti-HCV alone and 13.3% in patients co-infected with HBV and HCV. There was a positive linear trend in the annual incidence of HCC among patients without either marker, patients with single viral infection and patients with dual viral infection (P[for trend] < 0.0001). Cox's proportional hazard model indicated that HCV/HBV co-infection [hazard ratio (HR), 6.41; 95% confidence interval (CI), 1.80-22.80], anti-HCV alone (HR, 3.74; 95% CI, 1.07-13.07) and HBsAg alone (HR, 4.06; 95% CI, 1.23-13.34) were independently risk factors of HCC. In conclusion, there is an additive and independent effect modification of HCV and HBV infection on HCC development.

Hepatitis B surface antigen- and immunoglobulin-specific circulating immune complexes in acute hepatitis B virus infection.

For assessing the role of circulating immune complexes (CICs) in acute hepatitis B, CICs containing HBsAg, IgM, and IgG were determined, by C1q and conglutinin (K) assays, in 242 patients with acute hepatitis B and 60 healthy controls. CIC is a common feature of acute hepatitis B with 90.9% of cases having at least one abnormal test result. Patients with shorter interval (< 1 week) between onset of symptoms and patient presentation have significantly higher frequency of abnormal IgM class CIC, HBsAg-specific CIC, and higher frequency of raised alanine aminotransferase activity (> 30-fold upper limit of normal). The prevalence of raised alanine aminotransferase in patients with CIC containing HBsAg and IgM is higher than those without (P = 0.001). There is significant association between HBsAg-CIC and C1q-CIC. In conclusion, HBsAg-CIC and IgM class CIC correlate with disease activity. C1q-binding CIC is the predominant CIC that may play a role in the pathogenesis of acute hepatitis B.

Additive effect modification of hepatitis B surface antigen and e antigen on the development of hepatocellular carcinoma.

To assess the role of hepatitis B e antigen (HBeAg) and its interaction with hepatitis B surface antigen (HBsAg) on the development of hepatocellular carcinoma (HCC), this case-control study included 361 age- and sex-matched pairs of patients with histologically proven HCC and healthy control subjects. HBsAg, HBeAg and antibody to HBeAg (anti-HBe) were detected by radioimmunoassay. Antibodies to hepatitis C virus (anti-HCV) were detected by second-generation enzyme immunoassay. The prevalences of HBeAg (20.2%), HBsAg (80.3%) and anti-HCV (29.5%) in cases were higher than in controls (1.9%, 20.7%, and 2.7% respectively; each P < 0.0001). Using patients negative for HBsAg, HBeAg and anti-HBe as a referent group, univariate analysis indicated that HBsAg alone or HBsAg and HBeAg were risk factors for HCC (P for trend < 0.0001). Calculation of incremental odds ratio indicated that there was additive interaction between HBsAg and HBeAg. Multivariate analysis indicated that HCC development was strongly associated with the presence of HBeAg (odds ratio, 8.1; 95% confidence interval, 2.4-27.1), HBsAg (odds ratio, 68.4; 95% confidence interval, 20.5-227.8) and anti-HCV (odds ratio, 59.3; 95% confidence interval, 13.6-258.4). In conclusion, HBsAg, HBeAg and anti-HCV are independent risk factors for HCC. There is additive and independent effect modification between HBsAg and HBeAg on the development of HCC.

Independent and additive effect modification of hepatitis C and B viruses infection on the development of chronic hepatitis.

BACKGROUND/AIMS: This study aimed to assess the effects and interaction between hepatitis B virus and hepatitis C virus infection on the development of chronic hepatitis. METHODS: Anti-HCV and HBsAg were detected in 125 histology-proven chronic hepatitis and 250 sex-matched and age-matched healthy controls. RESULTS: The prevalences of anti-HCV (24.8%) and HBsAg (68.0%) in patients were higher than in controls (2.4% and 18.0%, respectively; each p < 0.0001). Univariate analysis showed that anti-HCV and HBsAg were strongly associated with the development of chronic hepatitis. Calculation of synergy index and Mantel extension test for trend indicated that there was additive effect modification between HCV and HBV. Multivariate analysis indicated that anti-HCV (odds ratio, 46.1; 95% confidence interval, 9.1-233.2) and HBsAg (odds ratio, 25.8; 95% confidence interval (9.3-67.2) were independent risk factors of chronic hepatitis. The population-attributable risk was estimated as 15.6% for anti-HCV alone, 52.4% for HBsAg alone and 6.8% for both anti-HCV and HBsAg. The frequency of chronic active hepatitis in patients with anti-HCV alone (100%) was higher than in patients with HBsAg alone (75%, p < 0.001). CONCLUSIONS: HCV and HBV infections are risk factors of chronic hepatitis. They act independently and probably with additive effect modification.

Increased IgM class circulating immune complexes in acute hepatitis A virus infection.

For assessing the role of circulating immune complexes (CIC) in acute hepatitis A, IgM- and IgG-specific CIC were determined, by C1q and conglutinin (K) assays, in 205 patients with acute hepatitis A and 60 healthy controls. The concentration of each type of CIC in patients was higher than healthy controls (P=0.0001). CIC was a common feature of acute hepatitis A with 95.6% of cases having at least one abnormal test result. The prevalence of abnormal IgM class CIC was significantly higher than IgG class CIC. There were significantly inverse correlations between levels of IgM class CIC and interval between onset of symptoms and patient presentation. The prevalence of abnormal IgM CIC was higher in patients with higher alanine aminotransferase (P=0.001) and patients with jaundice (P=0.0002). In conclusion, IgM class CIC is the predominant CIC in acute hepatitis A and correlated with disease activity. CIC may play a role in the pathogenesis of acute hepatitis A.

Clinical evaluation of serum alpha-fetoprotein and circulating immune complexes as tumour markers of hepatocellular carcinoma.

To evaluate the diagnostic application of serum alpha-fetoprotein (AFP) and circulating immune complexes (CICs), AFP, 3% polyethylene glycol (PEG)-CICs, 4% PEG-CICs, and C1q-CICs were determined in 101 patients with cirrhosis alone, 101 sex-matched and age-matched cirrhotic patients with hepatocellular carcinoma (HCC) and 54 healthy controls. Multivariate analysis indicated that AFP (odds ratio 1.014; 95% confidence interval 1.004-1.024) and 3% PEG-CICs (odds ratio 1.011; 95% confidence interval 1.005-1.017) are associated, in a dose-related fashion, with an increased risk for HCC. A receiver operative characteristic (ROC) curve was used to determine the optimal cut-off values of AFP (120 ng ml-1) and 3% PEG-CICs (310 micrograms aggregated IgG equivalent ml-1). The area under ROC curve was 0.875 for AFP and 0.812 for 3% PEG-CIC. Both AFP and 3% PEG-CICs show a high specificity (100%) and positive likelihood ratio. The sensitivity was 65.3% for 3% PEG-CICs and 67.3% for AFP. Determination of both markers in parallel significantly increase the diagnostic accuracy (92.1%) and sensitivity (84%), with a high specificity (100%) and positive likelihood ratio (> 84). In conclusion, both 3% PEG-CICs and AFP are independent risk factors of HCC, and may be used as complementary tumour markers to discriminate HCC from cirrhosis. Determination of 3% PEG-CICs should be performed in cirrhotics negative for AFP to improve detection of HCC.

[The re-evaluation of the prevalence of trachoma in primary school children in Kaohsiung City].

For years, trachoma screening has been a routine part of the health examination program for all primary school children. In order to ascertain the current prevalence of trachoma in primary school children, we used clinical examination, immunofluorescein-monoclonal antibody and McCoy cell culture technique to examine 771 children from 5 primary schools in Kaohsiung City. Using the results of the McCoy cell culture as a judgement standard, we found that 118 children (15.3%) had chlamydia trachomatis infections. The infection rates of children were statistically insignificant for sex, grade and location of school of children. Among the 118 infected children, most had none or mild (96.6%) conjunctival inflammation. Only 3 children (0.4%) had conjunctival cicatrization complications. These results showed that the repeated reinfections among these children were quite few. The McCoy cell culture was used to test the result of clinical diagnosis made by the senior ophthalmologists. The sensitivity of the clinical diagnosis was 50% and the predictive positive rate was 26.6%. It revealed that the diagnosis of trachoma made by clinical observation only was unreliable. The results of immunofluorescein-monoclonal antibody test showed that 120 children (15.6%) had trachomatous infections. Its sensitivity was 68.4%, and specificity was 91.7%. It revealed that more care should be taken in quality control of laboratory techniques. From these results, we conclude: 1) the trachomatous infections of primary school children in Kaohsiung City are not serious; the repeated infections among

Increased IgM-containing circulating immune complexes in patients co-infected with hepatitis C and hepatitis B.

To assess the role of circulating immune complexes (CIC) in chronic hepatitis C virus (HCV) infection, the relative frequency of CIC was determined in 60 patients with chronic hepatitis C alone, 19 patients co-infected with hepatitis B and C, 15 asymptomatic HCV carriers, and 54 healthy controls. Levels of CIC were determined with immunoglobulin-specific C1q-binding and conglutinin (K)-binding immune complex assays. Although there was no statistical difference in the levels of each type of CIC between asymptomatic HCV carriers and healthy controls, elevated levels of CIC containing IgM and IgG were common in patients with chronic HCV infection. Compared to patients with hepatitis C alone, patients co-infected with hepatitis B and C have a higher frequency of abnormal IgM-containing CIC and significantly higher levels of IgM-containing CIC. CIC levels in patients with chronic active hepatitis were significantly higher than those in patients with chronic lobular hepatitis or chronic persistent hepatitis. In conclusion, although CIC containing IgM and IgG were common in patients with chronic hepatitis C, abnormal IgM-containing CIC are the major types of CIC in patients co-infected with hepatitis B and C. An immune-mediated mechanism may play a role in the pathogenesis of chronic hepatitis C.