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.

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.

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).

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.

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.

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.

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.

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.

Comparisons of noninvasive indices based on daily practice parameters for predicting liver cirrhosis in chronic hepatitis B and hepatitis C patients in hospital and community populations.

Several noninvasive indices have been proposed for predicting liver cirrhosis (LC), particularly in chronic hepatitis C (CHC). In this study, noninvasive indices for predicting LC and hepatocellular carcinoma (HCC) were compared. A total of 119 chronic hepatitis B (CHB) patients and 240 CHC patients were evaluated in a hospital-based setting using various predictors for pathologic LC such as aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio (AAR), AAR-to-platelet ratio index (AARPRI), AST-to-platelet ratio index (APRI), age-platelet (AP) index, and platelet counts. In addition, these indices were used to predict LC [based on ultrasound (US)] in a community-based population of 201 patients with endemic hepatitis C virus (HCV). These indices were evaluated for their ability to predict HCC in CHB and CHC patients (n = 200). In CHB patients, the diagnostic performance of all indices was inadequate for predicting LC (areas under receiver operating characteristic curves < 0.7). Thrombocytopenia consistently demonstrated comparable accuracy to AARPRI ≥ 0.7 in CHB and AP index ≥ 7.0 in CHC patients. The best cut-off values for APRI, AARPRI, and AP index in predicting LC in CHC were 1.3, 0.8, and 7.0, respectively. The best cut-off values for APRI, AARPRI, and AP index in predicting LC (based on US) were 1.0, 1.2, and 8.0, respectively, in a HCV endemic community. An AAR > 1.4 might be a useful tool to identify candidates at high risk for HCC. In conclusion, platelet count was both consistent and accurate in predicting LC. An AAR > 1.4 is proposed as a possible surrogate marker for identifying patients at high risk for developing 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.

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.

Radiofrequency ablation of small hepatocellular carcinoma with intravenous pegylated liposomal doxorubicin.

PURPOSE: Synergy between radiofrequency ablation (RFA) and chemotherapy was demonstrated for liver malignancy. We assess the efficacy of intravenous pegylated liposomal doxorubicin (PLD) for RFA in patients with small hepatocellular carcinoma (HCC). METHODS: This study was designed as a non-randomized control trial. Patients received either PLD (20 mg) intravenously before RFA, or standard RFA alone. Computed tomography was performed immediately and 4 weeks after RFA to obtain ablative diameter, area and volume for each tumor. The changes in ablation size were analyzed by paired images for each tumor. All patients were followed up regularly. RESULTS: A total of 24 patients with 29 HCCs, including 12 patients with 16 tumors (mean 2.2 cm ± 0.9) in the PLD and RFA group, and 12 patients with 13 tumors (2.4 cm ± 0.5) in the RFA alone group, were enrolled. The ablative diameter, area and volume significantly decreased 4 weeks after RFA. The ablative volume decrease was significantly greater for the RFA alone group than for the combination group (26.1 vs. 12.1%, p = 0.018). The 3-year cumulative tumor progression and survival rates did not differ significantly between the two groups. CONCLUSION: Intravenous PLD before RFA reduced contraction of ablative volume and might have no impact on tumor progression and survival in patients with small HCC after RFA.

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.

Incidence of needle tract seeding and responses of soft tissue metastasis by hepatocellular carcinoma postradiotherapy.

AIM: To determine the incidence of needle tract seeding after fine needle aspiration (FNA) or percutaneous ethanol injection (PEI) and compare iatrogenic or spontaneous soft tissue metastasis (STM) by hepatocellular carcinoma (HCC) postradiotherapy (RT) in responses. METHODS: From November 1997 to January 2006, those who presented with STM by HCC after our invasive procedures or developed spontaneously were enrolled into this retrospective study. Metastatic lesions could be divided into procedure related (PR), which were located at the liver span and were related to invasive procedures, and non-procedure related (NPR), which were in extrahepatic areas. STM was treated with an electron or photon beam. RESULTS: A total of 39 HCC cases with developed STM were referred for RT, including 17 in the PR group and 22 in the NPR group. During the same period, a total of 18,227 person-times of FNA or PEI were performed on these HCC patients. The overall incidence of HCC with STM that was caused by invasive procedures was estimated at 0.13%. According to the Cox' regression model, the initial treatment modality influences the time duration after the initial diagnosis of HCC when STM has not occurred. None of these patients' soft tissue tumor increased in size during RT. The PR group had lower rates of bone metastasis (P=0.003) and coexisting extrahepatic metastasis (P=0.011) and a longer survival rate (P=0.003) than the NPR group. The estimated rates of 18-gauge and 22-gauge needle-induced HCC-related STM were 0.60% and 0.11%, respectively (P=0.064). CONCLUSION: The PR group bears a better prognosis than the NPR group post-RT.

Thrombocytopenia as a surrogate for cirrhosis and a marker for the identification of patients at high-risk for hepatocellular carcinoma.

BACKGROUND: The objective of this study was to examine the usefulness of platelet counts in the diagnosis of cirrhosis and for identifying high-risk individuals in a community-based hepatocellular carcinoma (HCC) screening program. METHODS: Pilot Study 1 determined the correlation between platelet counts and pathologic hepatic fibrosis scores among individuals with chronic hepatitis B virus (HBV) infection (n = 122 patients) and hepatitis C virus (HCV) infection (n = 244 patients). Pilot Study 2 investigated proportions of individuals with thrombocytopenia (<150 x 10(3)/mm(3)) among patients with HCC (n = 4042 patients). Pilot Study 3 demonstrated the correlation between platelet counts and ultrasonographic (US) parenchyma scores among anti-HCV-positive individuals (n = 75 patients). The core study was a 2-stage, community-based screening for HCC among residents age 40 years or older in townships with a high prevalence of anti-HCV (n = 4616 individuals) and in townships with a low prevalence of anti-HCV (n = 1694 individuals). Patients with thrombocytopenia were identified for US and alpha-fetoprotein screening. RESULTS: Among the individuals who were positive for anti-HCV, platelet counts decreased according to increased pathologic fibrosis scores or US scores for liver parenchyma disease: The best cutoff platelet count was 150 x 10(3)/mm(3) for a diagnosis of cirrhosis. The sensitivity and specificity were 68.2% and 76.4%, respectively, for pathologic cirrhosis and 76.2% and 87.8%, respectively, for US cirrhosis. Forty-eight percent of patients with HCC were thrombocytopenic. The proportion of thrombocytopenia was significantly greater in patients with HCV-related HCC (63%) than in patients with HBV-related HCC (42%). In the townships with high and low anti-HCV prevalence, the prevalence of thrombocytopenia was 17.9% and 6.1%, respectively, (P < .001), respectively. Twenty-five patients were diagnosed with HCC, and all of those patients resided in the high-prevalence township. CONCLUSIONS: Thrombocytopenia was a valid surrogate of cirrhosis and a valid marker for the identification of individuals at high-risk for HCC, especially in areas that had a high prevalence of HCV.

Flash-echo contrast sonography in the evaluation of response of small hepatocellular carcinoma to percutaneous ablation.

PURPOSE: To evaluate the use of flash-echo contrast sonography (FECS) in subtraction mode in assessing small hepatocellular carcinoma (HCC) after percutaneous local ablation therapy. METHODS: Between March 2000 and February 2002, we prospectively assessed small HCCs after percutaneous local ablation therapy using FECS in subtraction mode. Thirty-three patients (22 men, 11 women) with 35 tumors ranging in size from 1.1 to 3.0 cm (mean +/- SD, 2.0 +/- 0.5) were enrolled. Twenty-one tumors received percutaneous ethanol injection only, 13 tumors received percutaneous microwave ablation therapy only, and the remaining tumor received both treatments. CT, hepatic angiography, and follow-up were used as gold standards in analyzing the accuracy of FECS in detecting residual tumors. RESULTS: The agreements between FECS and CT, FECS and hepatic angiography, and all 3 imaging modalities were 80% (28/35), 85.7% (30/35), and 77.1% (27/35), respectively. Twenty-one patients with 23 completely ablated tumors were followed up for 5 to 39 months (mean +/- SD, 20.2 +/- 11.2). Recurrent disease was detected in 11 (52.4%) patients; local tumor recurrence occurred in 4 (17.4%) patients. The sensitivity, specificity, accuracy, and positive and negative predictive value of FECS in detecting viable tumors were 53.8% (7/13), 90.9% (20/22), 77.1% (27/35), 77.8% (7/9), and 76.9% (20/26), respectively. CONCLUSIONS: FECS in subtraction mode shows good agreement with hepatic angiography and CT in the assessment of small HCC after percutaneous local ablation therapy. The sensitivity of FECS in detecting residual tumors is suboptimal.

Thyroid dysfunction in patients with chronic hepatitis C receiving a combined therapy of interferon and ribavirin: incidence, associated factors and prognosis.

BACKGROUND AND AIMS: Interferon (IFN) plus ribavirin therapy for chronic hepatitis C (CHC) virus infection has been associated with thyroid dysfunction. The goal of our current study was to elucidate predictive factors of: (i) thyroid dysfunction associated with combination therapy; and (ii) long-term reversibility of thyroid dysfunction. METHODS: In total, 461 patients with CHC and normal baseline thyroid functions were enrolled. All patients received IFN-alpha-2b, 3 or 5 million units thrice weekly, or pegylated (PEG)-IFN-alpha-2b 80 or 100 microg weekly combined with ribavirin 1-1.2 g daily for 24-48 weeks. Assays for serum thyroid stimulating hormone (TSH) and free thyroxine were performed. RESULTS: By the end of the treatment, thyroid dysfunction (TSH <0.1 or >5 mU/L) had developed in 58 patients (12.6%). Female gender was significantly associated with thyroid dysfunction (P < 0.001 odds ratio (OR) = 2.85; 95% confidence interval (CI) = 1.6-5.1). The incidence of thyroid dysfunction was similar for standard IFN and PEG-IFN-treated patients (49/391 vs 9/70; P = 1.00). Under a nested case-control design, detailed laboratory assessment was carried out on frozen serum samples from patients and age- (+/- 5 years) and sex-matched controls (n = 58). Multivariate analysis revealed significant association between higher positive rates of pretreatment TMA and patients who developed thyroid dysfunction (OR = 5.8, 95% CI = 1.2-27.9). Ten patients ( approximately 2%) remained thyroid dysfunctional at the end of follow up (median, 26.5 months). For these patients, no risk factor can predict the reversibility of thyroid function. CONCLUSIONS: Female gender and pretreatment TMA positivity are associated with thyroid dysfunction. Long-term thyroid dysfunction may persist in a small group of patients ( approximately 2%).

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.