Did AFP-L3 save ultrasonography in community screening?

In the community screening, those subjects with elevated serum alpha-fetoprotein (AFP) required further abdomen ultrasonography (US) to detect hepatocellular carcinoma (HCC). However, some chronic hepatitis patients might have elevated AFP. AFP-L3, has been proposed to differentiate HCC and hepatitis in elevated AFP cases in Japan for decades, but the utility is limited outside Japan. We conducted this study to elucidate the role of AFP-L3 in the community and the possibility of saving unnecessary US. A total of 56,702 subjects underwent a large-scale healthcare screening in Tainan county in 2004. Among them, 286 residents with AFP more than 20 ng/ml further received US and 169 (59%) had stored baseline sera were enrolled into this study in 2013. Their AFP and AFP-L3 levels were further detected. HCC patients were initially identified through US and personal history. Among 169 studied sera, only 148 (87.6%) samples still had AFP level more than 20 ng/ml after a 10-years frozen period. The decrease of AFP level was significant (481.3 ± 2093.8 ng/ml and 456.1 ± 2095.3 ng/ml in paired-T test, p < 0.001). Focusing on these 148 cases, 23 (15.5%) HCC cases were diagnosed at the baseline screening. There was no difference of AFP-L3 level between HCC and non-HCC cases. Using AFP-L3 to predict HCC, the area under Receiver Operating Characteristic curve was as low as 52%, p = 0.757. Too long frozen period might lower the quality of stored sera. Additionally, AFP-L3 might not provide more information for HCC identification to save advanced US examinations in the community screening.

Comparison Stratagems of Post-Screening Management of Anti-HCV-Positive Community Residents: Simple Notification, Active Referral, or Accessible Medical Care.

To elucidate the results of post-screening care stratagems for anti-hepatitis C virus (HCV)-positive subjects in the community. Part I methods: The intervention program: A total of 151,790 subjects underwent a large-scale healthcare screening. Subjects aged less than 65 years, with anti-HCV-positive and alanine aminotransferase (ALT) level more than 80 IU/L were followed-up to answer a structured questionnaire. Those responders who met the reimbursement criteria of Taiwan's National Health Insurance for anti-HCV treatment were referred for treatment. Part II: The accessible medical care program: In Yujing township, 271 HCV residents who have been screened before were invited to a bi-weekly hepatitis clinic in Yujing health center. Part-I results: A total of 907 anti-HCV-positive subjects responded and 197(21.7%) were advised the treatment, but only 83(9.2%) did. Finally, 47 patients achieved a sustained virological response (SVR). After this intervention program, 96(10.6%) additional patients were encouraged to be referred, 33(3.6%) received treatment and 20 obtained a SVR. Part II: A total of 140(51.7%) subjects responded and 112 were anti-HCV-positive including 31(27.7%) HCV RNA-negative, 49(43.8%) HCV RNA-positive plus ALT less than 40 IU/L and 32(28.5%) HCV RNA-positive plus ALT more than 40 IU/L. During the follow-up, 14 of 49 patients had ALT more than 40 IU/L. Among 46 eligible HCV patients, 15(32.6%) received treatment and 10 achieved a SVR. Simple notification only made 9.2% of the screened HCV patients treat. Active referral could encourage additional 3.6% to be treated. Additionally, accessible medical care program could result in treatment of 32.6% elderly eligible patients.

Diabetes mellitus, metabolic syndrome and obesity are not significant risk factors for hepatocellular carcinoma in an HBV- and HCV-endemic area of Southern Taiwan.

A prominent factor in hepatocellular carcinoma (HCC) is chronic infection with hepatitis B virus (HBV) and hepatitis C virus (HCV). Diabetes mellitus (DM), metabolic syndrome (MetS), and obesity have also been implicated in HCC development, but these associations are not observed in all HBV- and HCV-endemic areas. We attempted to clarify the role of these factors in HCC development in an HBV- and HCV-endemic area in southern Taiwan. A community-based health examination was conducted in 2004 in Tainan County. After individuals with incomplete data and those with known HCC were excluded, there were 56,231 participants who were over 40 years of age. A further 262 HCC cases were identified from the National Cancer Registration Database records from 2005 to 2007. The hepatitis B surface antigen (HBsAg) seropositivity, anti-HCV seropositivity, platelet count, serum biochemical data, blood pressure, sociodemographic information, and anthropometric measurements were analyzed. Survival analyses were used to identify the associations between these factors and HCC. For the 262 HCC cases, male gender and age greater than 65 years were risk factors. Furthermore, a high alanine aminotransferase level, chronic HBV and/or HCV infection, and liver cirrhosis were also risk factors for HCC. However, DM, MetS and obesity were not associated with HCC development in the non-HBV-/non-HCV-infected, HBV, HCV, or dual B/C groups. In this HBV- and HCV- endemic area, DM, MetS and obesity were not risk factors for developing HCC.

Hepatocellular carcinoma surveillance at 4- vs. 12-month intervals for patients with chronic viral hepatitis: a randomized study in community.

OBJECTIVES: To compare the efficacy of hepatocellular carcinoma (HCC) surveillance at 4- and 12-month intervals in a community for patients with chronic viral hepatitis and thrombocytopenia. METHODS: In 10 townships, adults (≥ 40 years) with platelet ≤ 150 (× 10(9))/l, positive hepatitis B surface antigen, or antibody to hepatitis C virus were invited to this study. These townships were randomized into 4- (group A) and 12-month (group B) interval surveillance groups. Seven hundred and eighty-five and 796 residents met the study criteria in groups A and B. Ultrasonography (US) was the surveillance method. RESULTS: A total of 744 residents (group A: 387; group B: 357) were enrolled. In the study period, HCC was diagnosed in 39 residents (group A: 24; group B: 15). There was no difference in cumulative 3-year HCC incidence between the two groups. The tumors were smaller in group A than in group B, though group A had more patients with tumor ≤ 2 cm (P = 0.003) who were in Barcelona Clinic Liver Cancer (BCLC) very-early stage (P = 0.017) and had undergone curative treatments (P = 0.049). Male gender, cirrhosis, and platelet ≤ 100 (× 10(9))/l were associated factors of HCC occurrence. There was no difference in 4-year overall survival between the two groups. Patients undergoing recommended treatments had better 4-year survival rates. CONCLUSIONS: Compared with 12-month interval, US surveillance at 4-month interval detected more patients with HCC ≤ 2 cm who were in BCLC very-early stage and were fit for curative treatments. Up to 4-year follow-up, however, the overall survival was not different.

Community-based cross-sectional study: the association of lipids with hepatitis C seropositivity and diabetes mellitus.

BACKGROUND AND AIMS: Hepatitis C virus (HCV) infection is reported to be associated with or to cause type 2 diabetes mellitus (T2DM). Our study aimed to elucidate the role of triglyceride (TG) and cholesterol (CHOL) levels in the association between anti-HCV seropositivity and T2DM in an HCV-endemic area. METHODS: We analyzed a computerized dataset of 56 338 residents from a community-based comprehensive screening program in Tainan County in southern Taiwan. Fasting glucose, anti-HCV status, hepatitis B surface antigen (HBsAg) status, platelet counts, TG levels, CHOL levels, age, gender, and body mass index were included in the analyses. Multivariate logistic analysis was used to identify factors independently associated with T2DM. RESULTS: Older age, being overweight, thrombocytopenia, hypertriglyceridemia, hypercholesterolemia, anti-HCV seropositivity, and HBsAg seronegativity were common factors independently associated with diabetes. Among all models of multiple logistic regression analysis used for identifying factors independently associated with T2DM, anti-HCV seropositivity was only identified in the models that included either hypertriglyceridemia or hypercholesterolemia. When subjects were divided into hyperlipidemia (CHOL, > 200 or TG, > 150 mg/dL; n = 33 393) or non-hyperlipidemia subgroups (CHOL, < 200 and TG, < 150 mg/dL; n = 22 945), anti-HCV seropositivity was identified as an independent factor only in the non-hyperlipidemia subgroup. The odds ratio was 1.35, with a 95% confidence interval of 1.17-1.55. CONCLUSIONS: This study demonstrates that the lipid level is associated with the relationship between T2DM and anti-HCV seropositivity in non-hyperlipidemic individuals. However, the relationship between HCV and T2DM did not exist when the lipid level was not included in the analysis.

Lower prevalence of hypercholesterolemia and hyperglyceridemia found in subjects with seropositivity for both hepatitis B and C strains independently.

BACKGROUND AND AIM: To evaluate the association of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection with hypercholesterolemia and hypertriglyceridemia. METHODS: We analyzed the computerized health datasets of 56,336 residents from a community-based comprehensive screening in Tainan County in southern Taiwan. The overall prevalence rates of HBV surface antigen (HBsAg) and anti-HCV were 10.9% and 10.2%, respectively. Anti-HCV, HBsAg, platelet counts, albumin/globulin ratio (A/G ratio), fasting glucose, triglyceride, cholesterol levels, and body mass index (BMI) were abstracted for analyses. Multivariate logistic analysis was used for identification of the independent factors of hypercholesterolemia and hypertriglyceridemia. RESULTS: The prevalence of hypercholesterolemia and hypertriglyceridemia were 48.9% and 28.0%, respectively. Hypercholesterolemia and hypertriglyceridemia were associated with each other. Older age, negativity for HBsAg and anti-HCV, normal platelet counts, A/G ratio ≥ 1, higher BMI, and being diagnosed as diabetic were common independently associated factors of both hypercholesterolemia and hypertriglyceridemia. Men had higher risk for hypertriglyceridemia, while women had higher risk for hypercholesterolemia. CONCLUSIONS: This large scale community-based study demonstrated that subjects with seropositivity for Hepatitis C not only had lower prevalence of hypercholesterolemia and hypertriglyceridemia but subjects with seropositivity for Hepatitis B had the same trend.

Optimal treatment increased survival of hepatocellular carcinoma patients detected with community-based screening.

BACKGROUND AND AIM: The early detection of hepatocellular carcinoma (HCC) and opportunity to select appropriate treatment are important benefits of HCC screening. Our aim in the present study was to investigate the survival rate, prognostic factors and treatment effects in HCC patients of community-based screening. METHODS: Community-based ultrasound (US) screening for HCC in adults with platelet counts (< 150 x 10(3)/mm(3)) and/or alpha fetoprotein (AFP) > 20 ng/mL was conducted in 2002 and 2004. As per the Barcelona Clinic Liver Cancer (BCLC) stage, 90 cases of intermediate or earlier stage HCC were detected and 88 cases had sufficient information for analysis (49 men and 39 women, aged 65.8 +/- 9.6 years). The tumor diameter was mostly less than 5 cm (76.1%). The follow up was continued until June 2008. RESULTS: The 4-year overall survival rate was 46.8%. Old age (> or = 70 years) (P = 0.046), later stage of HCC (intermediate vs earlier) (P = 0.012), low platelet count (< 100 x 10(3)/mm(3)) (P = 0.013) and refusal of modern treatment (P = 0.026) were independent poor prognostic factors. Curative treatment increased survival in patients of all ages. Both curative treatment and transcatheter arterial embolization (TAE) increased survival in cases of intermediate HCC. However, treatment benefits were not found for patients with (very) early stage HCC. CONCLUSIONS: Early detection and prompt treatment of HCC leads to increased survival. For elderly patients this benefit was seen only for early stage cases receiving curative treatment. Differences between treatment types for patients with (very) early stage HCC might emerge with a longer follow-up period.

Identifying hepatitis C virus: endemic areas and estimating the viral antibody prevalence based on the prevalence of ALT elevation.

To evaluate the validity of predicting the prevalence of antibodies to hepatitis C virus (anti-HCV) based on the prevalence of alanine transaminase (ALT) elevation (>40IU/l), we conducted a community-based study. In total, 56698 individuals underwent health examinations in 2004. Another 43738 subjects in 2005 were the validation set. It should be valid to predict the prevalence of anti-HCV in villages (>25 participants) by the prevalence of ALT elevation. The equation was anti-HCV (%)=(% of ALT elevation - 6%)/65% (n=487 villages, R(2)=0.58). Villages with prevalence of ALT elevation >13% had a high probability of being HCV-endemic (anti-HCV >10%). The sensitivity and specificity were 73.6 and 74.6%, respectively. By the validation set, the positive and negative predictive values were 52.0% and 79.4%, respectively. Clinical and epidemiological deductions of the equation were that baseline of ALT elevation was 6% and two-thirds of anti-HCV-positive subjects had elevated ALT.

Community-based mass ultrasonographic screening of hepatocellular carcinoma among thrombocytopenic adults.

Thrombocytopenia has been reported as a valid surrogate for liver cirrhosis and could be used to identify groups at high risk of hepatocellular carcinoma (HCC) for ultrasonographic (US) screening. We designed this two-stage community-based screening for HCC. In 2004, subjects (ages > or =40 years) were invited to undergo comprehensive health examinations, with 17,551 men (ages 63.0 +/- 11.5 years) and 39,151 women (ages 59.9 +/- 11.7 years) participating. Subjects with platelet counts <150 x 10(9)/L or alpha-fetoprotein (AFP) >20 ng/mL were enrolled for the second-stage US screening; 3,242 subjects (5.7%; male/female, 1,415/1,827; age 66 +/- 10 years) were candidates for US screening and 2,983 (92.2%) responded. Of 137 suspected cases, 124 (90.5%) complied with referral for confirmation and 72 (58.1%) were confirmed to be HCC cases (male/female, 41/31; age 68.1 +/- 8.8 years). Screening with AFP, thrombocytopenia, or both could identify 0.64% (n = 364), 5.33% (n = 3,205), and 5.7% (n = 3,242) of the high-risk subjects from the population, estimated to include 50.5%, 54.5%, and 71.3% of all HCC cases. Among confirmed patients, tumor diameters were <3 cm for the 27 (37.5%) patients and 3 to 5 cm for the 23 (31.9%) patients. Only 5 (6.9%) patients' conditions were too advanced to be actively treated. This study enrolled only 5.7% of the participants for US, which cover 64.7% to 71.3% of the HCC cases. Most (93%) of the detected cases were caught early enough to undergo effective treatment modalities. This HCC screening protocol should be feasible, economical, and effective.

Excess mortality of hepatocellular carcinoma and morbidity of liver cirrhosis and hepatitis in HCV-endemic areas in an HBV-endemic country: geographic variations among 502 villages in southern Taiwan.

AIMS: The aim of this study was to investigate excess mortality for hepatocellular carcinoma (HCC) and prevalence of hepatitis and liver cirrhosis (LC) in hepatitis C virus (HCV)-endemic areas in Taiwan, which is a hepatitis B virus (HBV)-endemic country. METHODS: Tainan County, located in southern Taiwan, consists of 533 villages in 31 townships. A total of 56 702 subjects >or= 40 years old (mean age, 60.9 +/- 11.8 years) were enrolled from 502 of the 533 villages between April and November 2004 (n >or= 20/village). Serum blood HBV surface antigen (HBsAg), antibody to HCV (anti-HCV) and alanine transaminase (ALT) levels and platelet counts were measured. Township-specific mortality for liver cancer (ICD = 155) for both sexes between 1992 and 2001 were obtained from official publications. RESULTS: The prevalence of anti-HCV in Tainan County was 10.2% (township range, 2.6-30.9%; village range, 0-90.5%). The prevalence of HBsAg was 10.9% (township range, 5.5-17.2%; village range, 0-30.8%). The prevalence of hypertransaminemia (serum ALT > 40 IU/L) was 12.8%. At township levels, prevalence of anti-HCV (r2 = 0.92, P < 0.001), HBsAg and anti-HCV (multiple r2 = 0.94) were correlated with hypertransaminemia prevalence by single and multiple linear analysis, respectively. At village levels, prevalence of anti-HCV (r2 = 0.52, P < 0.001), HBsAg and anti-HCV (multiple r2 = 0.53) were each correlated with prevalence of hypertransaminemia, respectively. The prevalence of thrombocytopenia (<150,000 platelets/microL) was 5.5%, and adopted as a surrogate prevalence for LC. At township levels, prevalence of anti-HCV (r2 = 0.58) was the only factor correlated by multivariate analysis with prevalence of thrombocytopenia. At village levels, prevalence of anti-HCV and female-to-male ratio (multiple r2 = 0.43) were each independently associated with prevalence of thrombocytopenia. At township levels, HBsAg prevalence (r2 = 0.42) was more correlated with HCC mortality than anti-HCV prevalence (r2 = 0.28) for male subjects, while anti-HCV prevalence (r2 = 0.45) was more correlated with HCC mortality than HBsAg prevalence (r2 = 0.14) for female subjects. Prevalence of HBV and HCV infection were associated by multivariate analysis with both male (multiple r2 = 0.62) and female (multiple r2 = 0.53) HCC mortality. CONCLUSIONS: Prevalence of anti-HCV showed significant correlations with prevalence of hypertransaminemia, thrombocytopenia and liver cancer mortality. The findings indicate excessive mortality due to HCC, and LC and hepatitis prevalence in HCV-endemic areas in Taiwan, an HBV-endemic country.