Genetic history of hepatitis C virus genotype 6 in Taiwan.

Unlike hepatitis C virus (HCV) genotype (GT) 6, which is widely circulated in Southeast Asia and South China, GT 6 was not reported in Taiwan until 2006. GT 1b and 2a, also known as global HCV subtypes, have been reported as major GTs circulating in Taiwan. Because of improvement in genotyping kits and sequencing techniques for the subtyping of HCV, an increasing number of GT 6 subtypes have been reported, especially subtype 6a among intravenous drug users with human immunodeficiency virus infection after an outbreak since 2003. Thus, HCV GT 6 infection is regarded to be closely associated with injection drug use. However, recently, we found an unexpectedly high GT 6 prevalence in the general population in Tainan, southern Taiwan. Most of these GT 6 samples belonged to a putative novel subtype closely related to 6g and 6w instead of 6a. Phylogenetic analyses indicated that this putative 6g-related novel subtype and 6w could be indigenous in southern Taiwan for centuries. Southern Taiwan could be the origin of HCV subtype 6w. This finding might change the perspective of HCV epidemiology in Taiwan.

Real-world effectiveness and safety of sofosbuvir/velpatasvir and glecaprevir/pibrentasvir for genotype 6 chronic hepatitis C.

BACKGROUND: Hepatitis C virus (HCV) genotype 6 mainly distributes in Southeast Asia and South China. Because of the low prevalence in developed countries, optimal treatment for HCV genotype 6 in real-world setting remains to be determined. We aimed to evaluate the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) and glecaprevir/pibrentasvir (GLE/PIB) for patients with HCV genotype 6 infection in Taiwan. METHODS: A total of 286 patients with chronic hepatitis C (CHC) genotype 6, 161 receiving 12-week SOF/VEL and 125 receiving 8-week GLE/PIB, were enrolled. All patients were followed up for 12 weeks after treatment completion. Demographic information, HCV viral load (VL), profiles of lipid and sugar, and adverse events were recorded and reviewed. RESULTS: Sustained virological response (SVR) rates of SOF/VEL and GLE/PIB evaluated by intention-to-treat analysis were 99.38% and 100%, respectively. SVR achieved 100%, regardless of cirrhosis or viral load (cutoff: 6 MIU/mL), of both regimens by per-protocol analysis. Skin itching was the most common adverse event, with an overall incidence of 6.64% which was more prevalent in GLE/PIB (12.0%) than SOF/VEL (2.48%). A significant decrease in the estimated glomerular filtration rate was observed in patients receiving SOF/VEL but not in those receiving GLE/PIB at the time of SVR. No patient discontinued treatment due to adverse event. CONCLUSION: The high SVR and excellent safety of SOF/VEL and GLE/PIB in real-world setting reveals that the two DAA regimens are favorable options for treatment of HCV genotype 6 in Taiwan and Asia.

Real-world effectiveness and safety of ledipasvir/sofosbuvir for genotype 6 chronic hepatitis C patients in Taiwan.

BACKGROUND AND AIM: Infection with hepatitis C virus (HCV) genotype (GT) 6 is uncommon in Taiwan, and reports of ledipasvir/sofosbuvir (LDV/SOF) treatment for GT6 are few. This study evaluates the effectiveness and safety of LDV/SOF in treating chronic hepatitis C (CHC) patients with GT6 infection. METHODS: CHC patients that were infected with GT6 and treated for 12 weeks with LDV/SOF at two hospitals were enrolled. All patients were followed for an additional 12 weeks after the completion of LDV/SOF treatment. Demographics, HCV viral load, lipid and sugar profiles, and adverse events were recorded and reviewed. RESULTS: A total of 127 patients were enrolled. Cirrhosis was found in 68.2% of them. Sustained virological response (SVR), determined by per-protocol analysis, was 97.6%. The SVR rates for cirrhosis versus non-cirrhosis (96.5% vs 100%, P = 0.229) and low versus high viral load (cutoff value: 106  IU/mL; 100% vs 95.6%, P = 0.108) were similar. Following HCV clearance, significantly lower glycosylated hemoglobin was present both in patients with or without diabetes mellitus. Twenty-three (18.1%) patients exhibited adverse events, and each adverse event presented with an incidence of 0.8% to 3.1%. Neuropsychiatric symptoms were the most common. During treatment, 18 patients (14.2%) had alanine aminotransferase elevations consistent with more than grade 1 abnormalities, and none had signs of decompensation. Renal function remained unchanged. CONCLUSION: The high SVR and excellent safety of LDV/SOF treatment for GT6 CHC patients suggest that LDV/SOF is a favorable option for treating GT6 CHC patients in Taiwan and Asia.

Geographic variation of genotype 6 hepatitis C virus infection in an endemic area of southern Taiwan.

Taiwan is a hepatitis C virus (HCV) endemic country with geographic variation of prevalence and main genotypes(GTs) are 1 b and 2a. We recently reported high GT6 prevalence in Tainan of southern Taiwan. To clarify this special genotype as a local endemic disease and its geographic variation, the prevalence rates of HCV GTs of 37 districts of Tainan were analyzed. A total of 3040 patients with HCV viremia were enrolled. The prevalence rates of HCV GT 1a, 1 b, 2, 3, 4, 6 and mixed types were 3.9%, 31.6%, 45.9%, 0.6%, 0.2%, 17.1% and 0.5% respectively. GT6 prevalence showed marked variation from 0 to 39.2%. Four districts with GT6 prevalence >30% are located between Jishui and Zengwen rivers. Preliminary subtyping data were 6 g/a/w. This geographic variation with spatial restriction by two rivers with 6 g/w is suggestive of local endemic infection of preexisting GT 6 HCV for centuries.

High prevalence of genotype 6 hepatitis C virus infection in Southern Taiwan using Abbott genotype assays.

BACKGROUND/PURPOSE: Abbott RealTime Genotype II assay can effectively identify hepatitis C virus (HCV) genotypes (GTs), but some GT 6 subtypes might not be differentiated from GT 1. Abbott RealTime Genotype II PLUS and sequencing might be needed to resolve these ambiguous results. Unlike the high prevalence of GT 6 in Southeast Asia, GT 6 had rarely been reported in Taiwan except in intravenous drug abusers (IDU). But the prevalence of GT 6 in Taiwan might be underestimated. We conducted this study to determine the GTs in a HCV endemic area in Southern Taiwan. METHODS: A total of 1147 patients with hepatitis C viremia for direct acting antivirals (DAA) treatment at the Chi Mei medical system in Tainan were enrolled. Genotype was determined using a working flow consisted of Abbott GT II, PLUS assays and 5' untranslated region (5' UTR)/core sequencing. RESULTS: Among the 1147 patients, 883 (77.0%) obtained GT results by GT II, 264 (23.0%) samples with ambiguous results by GT II assay received further tests, including 194 (73.5%) with PLUS assay and 70 (26.5%) with 5'UTR/core sequencing. Nearly three-quarters (73.5%) of ambiguous results by GT II assay were GT 6. Overall, 18.3% of samples were GT 6. Phylogenetic study of 11 samples of GT 6 subtypes showed 7 (63.6%) were 6 g. CONCLUSION: GT 6 is the major factor for high ambiguous rate by GT II. Unexpected high prevalence of GT 6 (18.3%) in Southern Taiwan, especially subtype 6 g, closely related to Indonesian strains, is first reported.

Chronic hepatitis C infection is associated with insulin resistance and lipid profiles.

BACKGROUND AND AIM: Chronic hepatitis C virus (HCV) infection has been suggested to be associated with non-insulin-dependent diabetes mellitus and lipid profiles. This study aimed to investigate the possible relationships of insulin resistance (IR) and lipid profiles with chronic hepatitis C (CHC) patients in Taiwan. METHODS: We enrolled 160 hospital-based CHC patients with liver biopsy and the 480 controlled individuals without CHC and chronic hepatitis B from communities without known history of non-insulin-dependent diabetes mellitus. Fasting plasma glucose, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), alanine aminotransferase, and serum insulin levels, and homeostasis model assessment (HOMA-IR) were tested. RESULTS: When comparing factors between CHC patients, and sex- and age-matched controls who had no HCV infection, patients with HCV infection had a significantly higher alanine aminotransferase level, fasting plasma glucose level, insulin level, and HOMA-IR (P < 0.001, P = 0.023, P = 0.017, and P = 0.011, respectively), and significantly lower TG level (P = 0.023), total cholesterol, and HDL-C and LDL-C levels (all P < 0.001) than 480 controls. In multivariate logistic regression analyses, a low total cholesterol, a low TGs, and a high HOMA-IR are independent factors significantly associated with chronic HCV infection. In the 160 CHC patients (41 patients with high HOMA-IR [> 2.5]), a high body mass index, TGs, and HCV RNA level are independent factors significantly associated with high HOMA-IR in multivariate logistic analyses. CONCLUSIONS: Chronic HCV infection was associated with metabolic characteristics including IR and lipid profile. IR was also associated with virological characteristics.

Bile Duct Stone Size May Influence the Efficacy of Endoscopic Sphincterotomy With or Without Large-Balloon Dilation: A Meta-Analysis.

Purpose: Endoscopic sphincterotomy (EPT) combined with endoscopic papillary large balloon dilatation (EPBD) are used to remove large common bile duct (CBD) stones. This meta-analysis compared the efficacy and safety of EPT+EPBD versus EPT alone in the removal of stones based on stone size. Materials and Methods: Twenty-two studies (11 randomized control trials [RCTs] and 11 non-RCTs) were identified and reviewed based on searches of Embase, PubMed, and Web of Science. CBD stone's size was measured with reference to diameter of the duodenoscope (13 mm) and size of the large dilatation balloon (17 mm) seen on cholangiogram. The stone clearance rate, required mechanical lithotripsy (ML), procedure time, and pancreatitis were compared according to the mean stone size, and further divided into Groups A (small) 10-13 mm, B (medium) 13-17 mm, and C (large) >17 mm. Results: Subgroup analysis according to CBD stone size showed EPT + EPBD had a significantly better initial stone clearance rate than EPT in Groups B (odds ratio [OR] = 2.39, 95% confidence interval [CI]: 1.20-4.77) and C (OR = 3.05, 95% CI: 1.86-5.03), but not for Group A (OR = 1.41, 95% CI: 0.90-2.21). EPT+EPBD also required significantly less ML than EPT in Groups B (OR = 0.34, 95% CI: 0.15-0.77) and C (OR = 0.31, 95% CI: 0.13-0.73). EPT+EPBD had significantly shorter procedure time than EPT in Group B (standardized mean difference = -1.20, 95% CI: -2.08 to 0.32). In meta-regression analysis, Group B had a better OR in initial stone clearance rate and less ML usage rate correlation with the size of CBD stone, but not for Group C with larger stones. Conclusions: EPT+EPBD had a significantly better initial stone clearance rate, and required less ML with shorter procedure time than EPT for removing medium-sized CBD stones, but the efficacy was limited to large CBD stones. The study protocol and trial registration had been registered in PROSPERO (Registration No. CRD42020171689).

Sofosbuvir/velpatasvir/voxilaprevir for patients with chronic hepatitis C virus infection previously treated with NS5A direct-acting antivirals: a real-world multicenter cohort in Taiwan.

BACKGROUND: Real-world data are scarce about the effectiveness and safety of sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) for retreating East Asian patients with hepatitis C virus (HCV) infection who previously received NS5A direct-acting antivirals (DAAs). We conducted a multicenter study to assess the performance of SOF/VEL/VOX in patients who were not responsive to prior NS5A inhibitors in Taiwan. METHODS: Between September 2021 and May 2022, 107 patients who failed NS5A inhibitor-containing DAAs with SOF/VEL/VOX salvage therapy for 12 weeks were included at 16 academic centers. The sustained virologic response at off-treatment week 12 (SVR12) was assessed in the evaluable (EP) and per-protocol (PP) populations. The safety profiles were also reported. RESULTS: All patients completed 12 weeks of treatment and achieved an end-of-treatment virologic response. The SVR12 rates were 97.2% (95% confidence interval (CI) 92.1-99.0%) and 100% (95% CI 96.4-100%) in EP and PP populations. Three (2.8%) patients were lost to off-treatment follow-up and did not meet SVR12 in the EP population. No baseline factors predicted SVR12. Two (1.9%) not-fatal serious adverse events (AE) occurred but were unrelated to SOF/VEL/VOX. Sixteen (15.0%) had grade 2 total bilirubin elevation, and three (2.8%) had grade 2 alanine transaminase (ALT) elevation. Thirteen (81.3%) of the 16 patients with grade 2 total bilirubin elevation had unconjugated hyperbilirubinemia. The estimated glomerular filtration rates (eGFR) were comparable between baseline and SVR12, regardless of baseline renal reserve. CONCLUSIONS: SOF/VEL/VOX is highly efficacious and well-tolerated for East Asian HCV patients previously treated with NS5A inhibitor-containing DAAs. CLINICAL TRIALS REGISTRATION: The study was not a drug trial. There was no need for clinical trial registration.

Hepatitis C Virus Subtypes Novel 6g-Related Subtype and 6w Could Be Indigenous in Southern Taiwan with Characteristic Geographic Distribution.

Hepatitis C virus (HCV) genotype (GT) 6 is the most genetically diverse GT and mainly distributed in Southeast Asia and south China but not Taiwan. Earlier studies showed the major HCV GTs in Taiwan were GT 1b and 2 with very rare GT 6 except in injection drug users (IDUs), and subtype 6a is the main GT 6 subtype among IDUs. Recently, we reported a much higher prevalence (18.3%) of GT 6 in Tainan City, southern Taiwan. This study was designed to clarify the subtypes of GT 6 in this endemic area. A total of 3022 (1343 men and 1679 women) HCV viremic patients were enrolled. Subtypes of GT 6 were determined by sequencing of core/E1 and nonstructural protein 5B in 322 of 518 GT 6 patients. The overall GT 6 prevalence rate was 17.1% (518/3022), with higher prevalence districts (>25%) located in northern Tainan. A novel 6g-related subtype is the most prevalent subtype (81.0%), followed by 6w (10.8%), 6a (7.5%), and 6n (0.7%). The high GT 6 prevalence in Tainan was mainly due to a novel 6g-related subtype and 6w. These two subtypes could be indigenous in Tainan with characteristic geographic distribution.

Neither diabetes mellitus nor overweight is a risk factor for hepatocellular carcinoma in a dual HBV and HCV endemic area: community cross-sectional and case-control studies.

OBJECTIVES: Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are well-known risk factors for hepatocellular carcinoma, and diabetes mellitus (DM) and overweight have also been reported as risk factors for hepatocellular carcinoma (HCC). We tried to elucidate the roles of DM and overweight in HCC development in a dual HBV and HCV endemic area of southern Taiwan. METHODS: In 2004, a community-based comprehensive screening program was conducted in Tainan County. Hepatitis B surface antigen (HBsAg), anti-HCV, alpha-fetoprotein, complete blood counts, triglyceride, cholesterol, and glucose levels were examined. DM was defined as fasting blood sugar >126 mg per 100 ml, and overweight was defined as a body mass index >24 kg m(-2). Subjects with thrombocytopenia (platelet count <150 x 10(9) l(-1)) and elevated alpha-fetoprotein (>20 ng ml(-1)) underwent ultrasonographic screening for HCC. A total of 56,307 adults (>40 years old) participated, and 72 new HCC cases were detected and confirmed. RESULTS: In comparisons of all 72 HCC cases with the other 144 individual age-, sex-, residency-, HBsAg-, and anti-HCV-matched controls, only thrombocytopenia and high alanine transaminase (ALT) levels were shown to be independent risk factors. Neither DM nor overweight was shown to be significant in any of the analyses. CONCLUSIONS: On the basis of the community-based cross-sectional and case-controlled studies, neither DM nor overweight was a risk factor for HCC in a dual HBV and HCV endemic area. However, male gender, age (> or =65 years), HBsAg, anti-HCV, thrombocytopenia, and high ALT levels were independent risk factors for HCC.

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.

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.

Aflatoxin exposure and hepatitis C virus in advanced liver disease in a hepatitis C virus endemic area in Taiwan.

This community-based study evaluated the role of aflatoxin exposure in advanced liver disease in hepatitis C virus (HCV)-endemic townships. Preventive health examination was performed on 314 adults > or = 40 years of age recruited from HCV-endemic townships in Tainan, Taiwan. Aflatoxin-albumin in serum was quantified by a new enzyme-linked immunosorbent assay method. After adjusting serum albumin levels and platelet counts, aflatoxin-Bi albumin adducts was still an independent risk factor for advanced liver disease among all 314 residents (> 8 versus < or = 8 (AFBi)-albumin/albumin; OR = 2.29, 95% CI = 1.23-4.27, P = 0.009) and particularly in anti-HCV-positive subjects (OR = 2.09, 95% CI = 1.09-4.0, P = 0.026). Levels of AFB1-albumin/albumin were significantly related to ultrasonographic parenchyma scores (P < 0.001, one-way ANOVA) in all and anti-HCV-positive subjects. The findings indicated aflatoxin exposure may be associated with advanced liver disease in chronic hepatitis C patients in HCV-endemic regions in Taiwan.

Hepatitis C virus genotypes in southern Taiwan: prevalence and clinical implications.

The role of hepatitis C virus (HCV) genotypes in the development of hepatocellular carcinoma (HCC) is still controversial. To determine the distribution and clinical implications of HCV genotypes in southern Taiwan, we analysed 418 patients with chronic HCV infections. HCV genotypes were determined using an HCV Line Probe Assay. The predominant HCV genotype was 1b (45.5%), followed by 2a/2c (30.9%) and 2b (6.9%). The prevalence of genotype 1b in HCC patients (60.3%) was significantly higher than in those with liver cirrhosis (38.7%) and chronic hepatitis (38.7%) (P=0.003 and P<0.001, respectively). Patients with chronic HCV 2a/2c infection had higher alanine aminotransferase (ALT) levels than those with chronic HCV 1b infection (P<0.001). Univariate analysis revealed that disease severity was significantly correlated with older age, genotype 1b, lower ALT levels and lower viral load. Based on multiple logistic regression analysis, after adjusting for age and serum HCV RNA levels, HCV 1b infection was still a significant risk factor for HCC. In conclusion, the predominant genotypes in southern Taiwan were 1b and 2a/2c, and disease severity was associated with genotype 1b.

Prediction of viremia for cases of hepatitis C virus (HCV) infection using a third-generation anti-HCV enzyme immunoassay test.

BACKGROUND/AIMS: Positive results for anti-hepatitis C virus (HCV) testing reveal subjects are infected by HCV, with presence of HCV RNA indicating persistent infection. In this study, we attempted to evaluate the validity of the HCV viremia using a commercially available, third-generation anti-HCV test. METHODOLOGY: Sample rate/cut-off rate (S/CO) ratios for 1,907 anti-HCV-positive tests (S/CO >1, AxSYM HCV 3.0; Abbott, IL, USA), which had been performed during the last three years, were retrospectively analyzed. Cases with S/CO values between 1 and 100 were divided into 20 groups according to S/CO range (in increments of 10) and ALT (normal or elevated). Ten random cases were obtained for each of the 20 groups. If cases in any group numbered < or =10, all were recruited. Totally, 193 cases were enrolled for HCV RNA detection (COBAS Amplicor; Roche Diagnostics, NJ, USA). RESULTS: The S/CO distribution was biphasic, with two S/CO peaks in the ranges 1-10 (10.7%) and 81-90 (24.2%). Regardless of the ALT level, all samples with S/COs < or =10 were negative for HCV RNA. Of the samples with S/CO values >10, the optimal cut-off was 40 with sensitivity and specificity for both of 81%. In conclusion, subjects with S/CO values < or =10 (10.7%) were more likely to be cases of past infection or of non-specific reaction. Most (90%, 108/120) of the subjects with S/COs >40 represent current or persistent infection. To predict viremia in subjects with S/COs between 10 and 40, 6.7% of all anti-HCV-positive subjects was invalid by a cross-sectional observation. CONCLUSIONS: Follow-up or further study is recommended. The third-generation EIA test plays a semiquantitative role for the prediction of viremia in HCV infection.

Predicting the prevalence of antibody to hepatitis C virus (HCV) in a community by the prevalence of elevated levels of alanine aminotransferase: a method to identify areas endemic for HCV.

To identify areas endemic for hepatitis C virus (HCV), we attempted to predict the prevalence of antibody to HCV (anti-HCV) in a community by the prevalence of elevated levels of alanine aminotransferase (ALT). The results of health examinations of 2,273 women > or = 40 years old in five townships in central Taiwan were analyzed. The overall prevalence of elevated ALT levels was 11.6%. A township (20.3%) and 10 villages were identified as having a high prevalence (17.9-40.0%) of elevated ALT levels. Five communities with variant rates of elevated ALT levels, which ranged from 8.0% to 27.3%, were selected for correlation with the prevalence of anti-HCV among adults (> or = 40 years old). The prevalence of anti-HCV, which ranged from 10.1% to 72.1%, were obtained by community screenings and/or hospital-based studies. The correlation equation used was the prevalence of anti-HCV (%) = 3.33 x (prevalence of elevated ALT levels (%) - 5.7%) (r2 = 0.94, P < 0.01). Using this method, areas endemic for HCV can be identified by determining the community prevalence of elevated ALT levels.

A higher than expected recovery rate from hepatitis C infection amongst adolescents: a community study in a hepatitis C-endemic township in Taiwan.

This study investigated the prevalence of antibody to hepatitis C virus (anti-HCV), evaluated clinical manifestations of hepatitis C, and explored the risk factors amongst adolescents in an HCV-hyperendemic area in Taiwan. In December 1999, 713 students aged 13-16 years from Taishi township, in central Taiwan, were enrolled in a screening program for anti-HCV and alanine transaminase (ALT) status. Fourteen participants (M/F = 6/8) were positive for anti-HCV. Eight of the 14 later proved to be negative for HCV RNA, and they demonstrated relatively low sample rate/cut-off rate (S/CO) ratios (1.05-11.83) for anti-HCV tests. All HCV RNA negative cases had normal serum ALT levels. The other six (43%) seropositive students demonstrated HCV viraemia and greater S/CO ratios (25.66-77.49). Two of these six participants had elevated serum ALT levels. Compared to anti-HCV-negative subjects, anti-HCV-positive students exhibited significantly greater rates of exposure to one or more of the following: blood transfusion, tattooing, and earlobe piercing. This study group has a greater prevalence (2%) of anti-HCV than the general Taiwanese population at the same age. The study also reveals a lower rate (43%) of chronicity of HCV infection than that reported in the literature.

Correlation between ultrasonographic and pathologic diagnoses of hepatitis B and C virus-related cirrhosis.

UNLABELLED: BACKGROUND. We aimed to evaluate the validity of ultrasonography (US) in the diagnosis of cirrhosis in patients with chronic hepatitis B virus (HBV) or C virus (HCV) infection. METHODS: A total of 210 patients, 67 with chronic HBV and 143 with HCV infection, were evaluated for the cirrhotic status of liver by both needle biopsy and US. According to the pathological findings, a fibrosis score 4 on the histology activity index was the gold standard for the diagnosis of cirrhosis. A US scoring system consisting of liver surface, parenchyma, vascular structure, and splenic size was used to describe the severity of hepatic parenchymal damage. RESULTS: Cirrhosis was found in 27 (40%) of the 67 HBV patients and in 51 (36%) of the 143 HCV patients pathologically. The mean fibrosis scores were 0.95, 1.24, 2.35, 2.95, 3.8 and 3.7 in patients with US scores of 4, 5, 6, 7, 8, and 9 or more, respectively. The US scores were significantly correlated with the hepatic fibrosis scores (P < 0.05). Based on the receiver operating characteristic (ROC) curve, a US score of 7 was the best cutoff point for the prediction of HBV-related cirrhosis, with sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 77.8%, 92.5%, 87.5%, 86.0%, and 86.6%, respectively. In HCV-related cirrhosis, a US score of 6 provided results of 82.4%, 70.7%, 60.9%, 87.8%, and 74.8%, respectively. The specificity, positive predictive value, and accuracy were significantly higher in patients with HBV than in those with HCV infection (P = 0.012, P = 0.032, and P= 0.079, respectively). CONCLUSIONS: Cirrhosis can be predicted well by US, especially in patients with HBV infection.

Correlation of quantitative assay of hepatitis B surface antigen and HBV DNA levels in asymptomatic hepatitis B virus carriers.

OBJECTIVE: This study was to elucidate the correlation between quantity of hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA levels in asymptomatic carriers. METHODS: Based on the presence of the hepatitis B e antigen (HBeAg) and HBV DNA levels, 67 asymptomatic carriers were divided into four groups. HBV DNA was determined by hybridization (sensitivity 141 500 copies/ml) and polymerase chain reaction (PCR, sensitivity < 10 copies/ml). Cases of groups I (n = 18), II (n = 17) and III (n = 16) were negative for HBeAg and had HBV DNA levels of < 10 (PCR undetectable), 10 to 10 (PCR detectable) and > 10 copies/ml (hybridization detectable), respectively. Cases of group IV (n = 16) were positive for HBeAg and high HBV DNA levels (> 2 x 10 copies/ml). HBsAg was determined quantitatively by the ARCHITECT HBsAg assay. RESULTS: Our data showed HBsAg levels were correlated with HBV DNA (r = 0.709; P < 0.001) on a log scale. The mean log HBsAg (IU/ml) of groups I, II, III and IV were 2.68 +/- 0.8, 2.93 +/- 1.03, 3.22 +/- 0.45, 4.83 +/- 0.19, respectively. That of group IV was significantly higher than the mean log HBsAg of any other group (P < 0.001). The best cut-off for HBsAg in differentiating group IV from other groups was 15 000 IU/ml with both sensitivity and specificity of 100%. That of group I was significantly lower than those of group III (P = 0.035) and IV (P < 0.001). The best cut-off in differentiating group I from the other groups was 1600 IU/ml with a sensitivity of 69.4% and a specificity of 66.7%. CONCLUSION: Quantitative measurement of HBsAg titres may be an easy and economical reference for HBV replication in HBV carriers.

Liver abscess complicating transcatheter arterial embolization: a rare but serious complication. A retrospective study after 3878 procedures.

OBJECTIVES: Liver abscess is one of the complications of transcatheter arterial embolization (TAE) for hepatocellular carcinoma. We studied the clinical features and analysed the incidence, risk factors, helpful clinical clues, culture profiles and predictive factors of post-TAE liver abscess. The influence of abscess development on the evolution of the tumour process was also studied. METHODS: We retrospectively reviewed records of 3878 TAE procedures performed over a 6 year period. RESULTS: Ten cases of liver abscess developed in nine patients (eight males and one female). The incidence was 0.26% (10 episodes/3878 procedures). The main clinical presentations included fever (91.7%), chills (50%) and abdominal pain (33.3%). All but one febrile patient presented fever in a recurrent form. The positive culture rates were 41.7% for blood and 83.3% for pus. Gram negative bacteria were found in 80% of blood cultures and 68% of pus cultures. Polymicrobial infections were encountered in 60% of the blood cultures and 70% of pus cultures. Management included antibiotics, drainage and operation. Four patients died due to the direct complications of liver abscess. One patient experienced total tumour resolution after successful treatment for liver abscess. Patients with larger liver abscesses and patients with greater age carried higher mortality rates. CONCLUSIONS: Liver abscess is a rare complication after TAE for hepatocellular carcinoma. Recurrent fevers after an initial symptom free interval should arouse suspicion of an abscess. The mortality is high and a large abscess and higher age predict an unfavourable outcome. Abscess formation can lead to complete tumour resolution.