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The spreading of viral hepatitis among injecting drug users (IDU) is an emerging public health concern. This study explored the prevalence and the risks of hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus (HDV) among IDU-dominant prisoners in Taiwan. HBV surface antigen (HBsAg), antibodies to HCV (anti-HCV) and HDV (anti-HDV), viral load and HCV genotypes were measured in 1137(67.0%) of 1697 prisoners. 89.2% of participants were IDUs and none had HIV infection. The prevalence of HBsAg, anti-HCV, dual HBsAg/anti-HCV, HBsAg/anti-HDV, and triple HBsAg/anti-HCV/anti-HDV was 13.6%, 34.8%, 4.9%, 3.4%, and 2.8%, respectively. HBV viremia rate was significantly lower in HBV/HCV-coinfected than HBV mono-infected subjects (66.1% versus 89.9%, adjusted odds ratio/95% confidence intervals [aOR/CI] = 0.27/0.10–0.73). 47.5% anti-HCV-seropositive subjects (n = 396) were non-viremic, including 23.2% subjects were antivirals-induced. The predominant HCV genotypes were genotype 6(40.9%), 1a(24.0%) and 3(11.1%). HBsAg seropositivity was negatively correlated with HCV viremia among the treatment naïve HCV subjects (44.7% versus 72.4%, aOR/CI = 0.27/0.13–0.58). Anti-HCV seropositivity significantly increased the risk of anti-HDV-seropositivity among HBsAg carriers (57.1% versus 7.1%, aOR/CI = 15.73/6.04–40.96). In conclusion, IUDs remain as reservoirs for multiple hepatitis viruses infection among HIV-uninfected prisoners in Taiwan. HCV infection increased the risk of HDV infection but suppressed HBV replication in HBsAg carriers. An effective strategy is mandatory to control the epidemic in this high-risk group.

Background/Aims Undetectable HCV RNA 12 weeks after the end of treatment (SVR12) has been the valid efficacy endpoint in the era of direct-acting antivirals (DAAs). Its concordance with SVR4 and SVR24 and long-term durability is unknown in Taiwanese chronic hepatitis C (CHC) patients. Methods A total of 1080 CHC patients who received all-oral DAAs and an achieved end-of-treatment virological response (EOTVR), defined as undetectable HCV RNA at the end of therapy, were consecutively enrolled. HCV RNA was monitored 4, 12, and 24 weeks after EOT. Patients who achieved SVR24, defined as undetectable HCV RNA 24 weeks after EOT, were followed annually for assessing SVR durability. Results Eleven (1.02%) patients experienced HCV RNA reappearance after EOT. The most frequent timing of RNA reappearance was observed at SVR4 (n = 7), followed by SVR12 (n = 3) and SVR 24 (n = 1). The positive predictive value (PPV) and negative predictive value (NPV) of SVR4 in predicting SVR12 were 99.7% and 100%, respectively, whereas the PPV and NPV of SVR12 in predicting SVR24 were 99.9% and 100%, respectively. Pyrosequencing confirmed delayed relapse rather than reinfection for the patient who had detectable HCV RNA at SVR24. Among 978 patients who achieved SVR24, after a median follow-up period of 17.3±8.2 months, the SVR durability is 100% up to a 4-year follow-up. Conclusion Achievement of SVR12 provides excellent durability of HCV seroclearance after DAA therapy. On-demand HCV RNA beyond SVR12 should be recommended for patients with unexplainable abnormal liver function or high-risk behaviors.

Treatments with pegylated interferon/ribavirin (PEG-IFN/RBV) has been standard-of-care in patients with chronic hepatitis C virus (HCV) (CHC) infection and reimbursed in Taiwan. However, the actual cost-effectiveness remains unclear. We aimed to evaluate a real-world cost-effectiveness for CHC patients treated with PEG-IFN/RBV by using a clinical cohort with linkage to the National Health Insurance Research Database of Taiwan. The total and itemized medical-care expenses of outpatient visits of 117 treatment-naïve CHC patients with linkage to the two million sampling of the National Health Insurance Research Database were collected. Four components of costs were assessed, including antiviral agents, nonantiviral agents, laboratory testing and consultation costs. The cost per sustained virological response (SVR) achieved was calculated to evaluate the cost-effectiveness. The average cost per treatment in 117 naïve Taiwanese CHC patients was $4620. With an overall SVR rate of 78.6%, the average cost per SVR was $5878. The average medical-care cost per treatment for 52 Genotype 1 (G1) patients was $5133, including $4420 for antivirals, $380 for nonantivirals, $302 for laboratory, and $78 for consultation, compared to $4209, $3635, $317, $233, and $56 for 65 Genotype 2 (G2) patients. With an SVR rate at 67.3% for G1 and 87.7% for G2 patients, the cost per SVR achieved was significantly higher in G1 patients than those in G2 patients ($7627 vs. $4799, p = 0.001). In the current study, we provided the real-world cost-effectiveness of PEG-IFN/RBV for treatment-naïve CHC patients. The genotype-specific cost-effectiveness could enhance decision-making for policy-makers in the coming era of directly acting antiviral therapy.

The role of transcatheter arterial chemoembolization (TACE) prior to curative therapy is still unclear. The aim of our study was to elucidate the survival of single hepatocellular carcinoma (HCC) and also to clarify whether TACE plus sequential curative therapy provides benefits in single HCC. A total of 470 patients with a diagnosis of single HCC between 2005 and 2010 were studied. The factors associated with clinical outcomes were analyzed. The outcomes between patients who underwent neoadjuvant TACE and those who did not were also compared. The 1-, 3-, and 5-year overall survival (OS) rates of all patients were 92.6%, 73.3%, and 59.6%, respectively. Child-Pugh class A [HR: 2.04, 95% confidence interval (CI): 1.277–3.254, p = 0.003], very early stage Barcelona Clinic Liver Cancer (BCLC) (HR: 2.03, 95% CI: 1.021–4.025, p = 0.043), tumor size

Chronic hepatitis C virus (HCV) infection had been associated with cytokine imbalance. Cytokine dynamics in response to peginterferon/ribavirin therapy have an impact on the treatment efficacy for HCV patients. Ninety-two treatment-naive chronic hepatitis C patients were treated with 24 or 48 weeks of peginterferon/ribavirin therapy according to their viral genotypes. Sustained virologic response (SVR) is defined as undetectable HCV RNA throughout a 24-week post-treatment follow-up period. Dynamic serum levels of the following cytokines: (1) Th1-mediated cytokines: IFN-γ, interleukin-2, and TNF-alpha; (2)Th2-mediated cytokines: interleukin-4, interleukin-5, interleukin-6, and interleukin-10 and (3)immuno-modulatory cytokines: interleukin-1β, interleukin-8, and interleukin-12 were determined by Fluorescent Bead immunoassay. Serial dynamic cytokine expression demonstrated that not only elevated IFN-γ concentrations at specific time points but also the total IFN-γ amount was strongly linked to non-response in peginterferon/ribavirin therapy. IFN-γ levels could serve as an independent predictor for SVR analyzed by multivariate logistic regression test. The accuracy of discriminating responders from non-responders was acceptable when IFN-γ cut-off levels were set at 180, 120, and 40 pg/ml at the 4th week, 12th week, and end-of-treatment of therapy, respectively. Elevated on-treatment IFN-γ concentration was significantly associated with treatment failure among interleukin-28B rs8099917TT carriers and those patients failed to achieve rapid virologic response.

Diagnosis of abdominal splenosis is often undiagnosed until treatment for splenic rupture or splenectomy. This report describes a patient with splenosis mimicking hepatic tumor. The patient had a history of splenic trauma with splenectomy and chronic hepatitis C. After routine abdominal ultrasound revealed a liver nodule, further imaging studies, including magnetic resonance imaging, computed tomography and angiography, were performed. After the patient eventually underwent surgery, pathology revealed splenic tissue. Despite its distinguishable clinical features, splenosis is difficult to identify by modern imaging modalities. Therefore, accurate and timely diagnosis of this disease requires constant vigilance.

The influence of patatin-like phospholipase domain-containing 3 (PNPLA3) genetic variants in the development of liver steatosis in Asian chronic hepatitis C patients remains elusive. A total of 1018 biopsy-proven chronic hepatitis C patients were enrolled for evaluation. The proportions of PNPLA3 rs738409 GG genotype carriage were 7.8% (44/563), 15.8% (58/367) and 19.3% (17/88) in patients with no (liver fat content 66%) hepatic steatosis, respectively (trend P PNPLA3 rs738409 GG genotype (odds ratio [OR]/95% confidence intervals [CI]:2.34/1.557–3.515, P 2, carriage of the rs738409 GG genotype was the only factor associated with hepatic steatosis (OR/CI:3.44/1.824–6.500, P PNPLA3 genetic variants had minimal effects on hepatic steatosis among overweight or obese patients. Compared to patients with BMI2/non-GG genotype, those with BMI>24 kg/m2/GG genotype were more likely to have hepatic steatosis (OR/CI:3.87/2.292–6.524, P PNPLA3 genetic variants and BMI played important roles in hepatic steatosis among Asian chronic hepatitis C patients. However, the genetic effect was mainly restricted to non-obese patients.

The aim of this study is to explore the prevalence of hepatitis C virus (HCV) infection among injection drug users (IDUs) with and without human immunodeficiency virus (HIV) infection in southern Taiwan. For 562 IDUs (265 anti-HIV negative, 297 anti-HIV positive), we analyzed liver function, anti-HIV antibody, anti-HCV antibody, HCV viral loads, and hepatitis B surface antigen (HBsAg). HIV RNA viral loads and CD4 cell count for anti-HIV-seropositive IDUs and the HCV genotype for HCV RNA-seropositive IDUs were measured. The seroprevalence rates of anti-HIV, anti-HCV, and HBsAg were 52.8%, 91.3%, and 15.3%, respectively. All the anti-HIV-seropositive IDUs were positive for HIV RNA. Anti-HCV seropositivity was the most important factor associated with HIV infection (odds ratio [OR], 25.06; 95% confidence intervals [CI], 8.97–74.9), followed by male gender (OR, 6.12; 95% CI, 4.05–9.39) and HBsAg seropositivity (OR, 1.90; 95% CI, 1.11–3.34). Among IDUs positive for anti-HCV, 80.7% had detectable HCV RNA. HCV viremia after HCV exposure was strongly related to HIV infection (OR, 6.262; 95% CI, 1.515–18.28), but negatively correlated to HBsAg seropositivity (OR, 0.161; 95% CI, 0.082–0.317). HCV genotype 6 was the most prevalent genotype among all IDUs (41.0%), followed by genotypes 1 (32.3%), 3 (12.8%), and 2 (5.6%). In conclusion, about half IDUs were infected with HIV and >90% with HCV infection. Male and seropositivity for HBsAg and anti-HCV were factors related to HIV infection among our IDUs. HIV was positively correlated, whereas hepatitis B co-infection was negatively correlated with HCV viremia among IDUs with HCV exposure. Different HCV molecular epidemiology was noted among IDUs.

The clinical significance of co-infection of SENV-D among patients with chronic hepatitis C (CHC) and response of both viruses to combination therapy with high-dose interferon-alfa (IFN) plus ribavirin remain uncertain and are being investigated.Total 164 (97 males and 67 females, the mean age 48.1+/-11.4 years, range: 20-73 years, 128 histologically proved) naive CHC patients were enrolled in this study. SENV-D DNA was tested by PCR method. Detection of serum HCV RNA was performed using a standardized automated qualitative RT-PCR assay (COBAS AMPLICOR HCV Test, version 2.0). HCV genotypes 1a, 1b, 2a, 2b, and 3a were determined by using genotype-specific primers. Pretreatment HCV RNA levels were determined by using the branched DNA assay (Quantiplex HCV RNA 3.0). There are 156 patients receiving combination therapy with IFN 6 MU plus ribavirin for 24 wk and the response to therapy is determined.Sixty-one (37.2%) patients were positive for SENV-D DNA and had higher mean age than those who were negative (50.7+/-10.6 years vs 46.6+/-11.6 years, P = 0.026). The rate of sustained viral response (SVR) for HCV and SENV-D were 67.3% (105/156) and 56.3% (27/48), respectively. By univariate analysis, the higher rate of SVR was significantly related to HCV genotype non-1b (P0.001), younger ages (P = 0.014), lower pretreatment levels of HCV RNA (P = 0.019) and higher histological activity index (HAI) score for intralobular regeneration and focal necrosis (P = 0.037). By multivariate analyses, HCV genotype non-1b, younger age and lower pretreatment HCV RNA levels were significantly associated with HCV SVR (odds ratio (OR)/95% confidence interval (CI): 12.098/0.02-0.19, 0.936/0.890-0.998, and 3.131/1.080-9.077, respectively). The SVR of SENV-D was higher among patients clearing SENV-D than those who had viremia at the end of therapy (P = 0.04).Coexistent SENV-D infection, apparently associated with higher ages, is found in more than one-third Taiwanese CHC patients. Both HCV and SENV-D are highly susceptible to combination therapy with high-dose IFN and ribavirin and SENV-D co-infection does not affect the HCV response. HCV genotype, pretreatment HCV RNA levels and age are predictive factors for HCV SVR.

The subsequent maintenance therapy in chronic hepatitis B (CHB) patients after long-term viral replication suppression is still uncertain. We aim to evaluate the efficacy of lamivudine (LAM) maintenance therapy in CHB patients achieving undetectable hepatitis B virus (HBV) DNA after 3 years of entecavir (ETV) therapy. Consecutive CHB patients who received at least 3 years of ETV and achieved HBV DNA negativity were allocated either LAM switch therapy or stopped ETV therapy in a prospective, open-label study. Another group of sex- and age-matched patients with continuous ETV therapy for at least 4 years served as historical control group. The primary outcome measurement of the study was relapse of HBV DNA (defined as serum HBV DNA level ≥ 2000 IU/mL). A total of 74 patients, including 42 of LAM switch and 32 of the nonswitch group, were enrolled. There were no significant differences in demographics, except a higher proportion of patients with positive hepatitis B envelope antigen in the nonswitch group at the initiation of ETV therapy. The LAM switch group had significantly lower 1-year relapse rate of HBV within 1 year compared to the nonswitch group (14.3% vs. 75%, p

Gallbladder (GB) stones have been associated with several metabolic factors and liver diseases. This community-based study aimed at investigating the prevalence rate of GB stones and its associated factors in a hepatitis B virus (HBV)/hepatitis C virus (HCV)-endemic township in southern Taiwan. A total of 1701 residents (689 males and 1012 females; mean age: 51.2 ± 16.0 years) were enrolled in this prospectively designed screening project. Serum biochemistry tests, including testing for levels of serum aspartate aminotransferase, alanine aminotransferase (ALT), hepatitis B surface antigen (HBsAg), and antibody to HCV (anti-HCV) were conducted. In addition, a hepatobiliary ultrasonographic (US) examination was also conducted. Of the 1701 residents, 243 (14.3%) and 475 (27.9%) were found to be positive for HBsAg and anti-HCV, respectively. Results of the US examination revealed the prevalence rate of GB stone and fatty liver to be 6.8% and 55.6%, respectively. Using univariate analyses we found that significantly higher proportions of the participants with GB stone were male, over 50 years of age, positive for anti-HCV (p = 0.001, p 50 year) were identified as independent factors associated with the formation of GB stones. Anti-HCV was associated with GB stones in males but not in females in both univariate and multivariate analyses. GB stones were found to have a prevalence rate of 6.8% in this HCV/HBV hyperendemic township and are associated with higher mean age. A correlation between chronic hepatitis C and GB stones is observed only among males.

Hepatitis B and hepatitis C are highly prevalent in Taiwan. Chronic hepatitis patients are at high risk of progression to liver cirrhosis and hepatocellular carcinoma (HCC). However, HCC in association with liver abscess is very rare. Accordingly, this study analyzed the characteristics of HCC patients with liver abscess to improve the differential diagnosis of this condition. From January 2005 to July 2007, the medical records of nine HCC patients (4 females, 5 males; mean age, 65.8 years) treated for abscess formation at Kaohsiung Medical University Hospital were retrospectively reviewed. Their clinical characteristics, images, management approaches and outcomes were analyzed. Fever and highly elevated alkaline phosphatase levels were noted in all patients. All aspirate cultures revealed Klebsiella pneumoniae. All of the cases of HCC were confirmed by cytology or pathology. The imaging studies, which included abdominal ultrasonography and computed tomography, revealed liver tumors in all patients. In some cases, lead-enhanced hypervascular areas were noted. The patients were treated with antibiotic therapy, transhepatic arterial chemoembolization, or surgery. The findings of this study indicate that focal liver inflammatory changes may mimic solid neoplasms. Differential diagnosis of HCC with abscess is extremely difficult and may require aspiration cytology or pathology.

With an estimated 350–400 million people worldwide chronically infected with hepatitis B virus (HBV), and the subsequent serious complications caused by liver damage including cirrhosis, liver failure, and hepatocellular carcinoma, HBV infection remains a global health issue, particularly in Taiwan, an HBV-hyperendemic area. Sensitive and accurate quantification of HBV DNA is necessary to monitor patients with chronic hepatitis B who are receiving antiviral therapy to determine treatment response and adapt therapy. We evaluated and compared the clinical performance of two HBV DNA assays based on different technologies: the RealArt™ HBV™ PCR Kit (Abbott HBV DNA PCR kit, real-time polymerase chain reaction assay, detection limit: 27IU/mL) and the VERSANT bDNA 3.0 assay (Bayer, branched DNA signal amplification assay, detection limit: 357 IU/mL). Serum levels of HBV DNA in 173 chronic HBV carriers were determined using both the RealArt™ HBV™ PCR Kit and the VERSANT bDNA 3.0 test. Of the 173 samples analyzed for baseline viral load detection, HBV DNA was quantifiable in 147 patients (82.1%) by the RealArt™ HBV™ PCR Kit, which was significantly higher than the 92 (53.2%) samples quantified by the VERSANT bDNA 3.0 assay. A total of 86 (49.7%) samples were quantifiable by both assays, whereas 25 (14.5%) were below the detection limit of both assays. The HBV DNA quantification values measured by the RealArt™ HBV™ PCR Kit and the VERSANT bDNA 3.0 assay were positively correlated (Spearman's rank correlation coefficient r = 0.932, p < 0.001). On average, the results derived from the RealArt™ HBV™ PCR Kit were 0.67 log lower than those of the VERSANT bDNA 3.0 assay. HBV DNA concentrations were significantly higher in 63HBV e antigen (HBeAg) seropositive patients than in 110 HBeAg-seronegative patients (5.42 ± 2.34 logs vs. 3.21 ± 2.27 logs, p < 0.001). The RealArt™ HBV™ PCR Kit is more sensitive and has a wider dynamic range than the VERSANT bDNA 3.0 assay in the clinical setting of chronic hepatitis B patients. The sensitivity and wide dynamic range of the PCR assay allow optimal monitoring and timely adaptation of antiviral therapy. Nevertheless, the HBV DNA values measured by the RealArt™ HBV™ PCR Kit and the VERSANT bDNA 3.0 assay were significantly correlated.

Background Interferon-alpha monotherapy is effective in less than one-third patients with chronic hepatitis C. The dose-effect, tolerability and durability of interferon-alpha treatment and its long-term effect on the prevention of cirrhosis and hepatocellular carcinoma in naïve Taiwanese patients with chronic hepatitis C have not been well investigated. We conducted the present cohort study treated with high and standard interferon-alpha to illustrate the issues. Methods We performed a long-term virologic and histological follow-up of 214 chronic hepatitis C patients treated with interferon-alpha, 3 million units (3-MU, n = 80) or 6-MU (n = 134) thrice weekly for 24 weeks, in Taiwan between 1992 and 2001. Results There was no difference in the incidence of discontinuation between 3-MU and 6-MU groups (4/80, 5.0% versus 10/134. 7.5%). The 6-MU group had similar incidence of adverse events with the 3-MU group, except that 6-MU group had significantly higher incidence of psychological manifestations, mainly presented as irritability. The rates of sustained virological response (SVR) were significantly higher in 6-MU regimen (37.1%) than in 3-MU regimen (23.7%, p < 0.05) in per protocol analysis. Based on multivariate analysis, baseline viral load was strongly associated with SVR, followed by hepatitis C virus genotype, interferon-alpha regimen, and liver fibrosis. A histological improvement in necroinflammatory activity, but not in fibrosis was observed in the follow-up biopsy performed 0.5–5.5 years (mean: 1.9 years, n = 51) after end-of-treatment. Among patients without SVR, there was more activity improvement in 6-MU group. The durability of SVR was 100% (18/18) and 97.8% (45/46) for 3-MU and 6-MU group, respectively, in a mean follow-up period of 6.81 years (5.25–9.18 years). For 163 baseline non-cirrhotic patients, 9 of 84 (10.7%) non-responders and 3 of 79 (3.8%) sustained responders progressed to cirrhosis during a mean follow-up period of 5.52 and 5.74 years, respectively (p = 0.067, Kaplan-Meier survival analysis, log-rank test). For all 200 patients, hepatocellular carcinoma was detected in 12 of 113 (10.6%) non-responders and one of 87 (1.1%) sustained responders during a mean follow-up period of 5.67 and 5.73 years, respectively (p < 0.01, Kaplan-Meier survival analysis, log-rank test). Conclusion We confirm the dose effect of interferon-alpha in chronic hepatitis C. Six-MU regimen had better efficacy than 3-MU regimen in virologic and histological responses. Both regimens had good tolerability and durability in Taiwan. Sustained response could reduce the incidence of cirrhotic change and hepatocarcinogenesis.