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Background: Evidence for mitigation of transfusion-transmitted dengue informed by surveillance data is lacking. In this study, we evaluated the risk of positive dengue viral (DENV) ribonucleic acid (RNA) from blood transfusions during a large outbreak in Taiwan.Methods: Serum collected from blood donors living in districts experiencing the dengue epidemic were tested for DENV RNA using a qualitative transcription-mediated nucleic acid amplification assay (TMA). The TMA-reactive specimens were further tested for immunoglobulin (Ig)M and IgG antibodies, nonstructural protein 1 (NS1) antigen, and viral RNA by reverse-transcription polymerase chain reaction. We estimated DENV RNA prevalence and the number of DENV infections among blood donors.Results: A total of 4976 specimens were tested for DENV RNA, and 21 were TMA-reactive. The detection rate was 0.84 (95% confidence interval [CI], 0.15-4.73), 3.36 (95% CI, 1.31-8.60), and 6.19 (95% CI, 3.14-12.17) per 1000 donors in districts where the weekly dengue incidence was 5-50, 50-200, and 200 or more per 100 000 residents, respectively. Alanine aminotransferase screening only detected 4.4% of TMA-reactive donations. A total of 143 transfusion-transmitted DENV infections probably occurred during this outbreak, accounting for 9.2 in 10 000 dengue infections.Conclusions: Approximately 0.5%-1% of blood donations were DENV RNA positive in epidemic districts. The correlation of DENV RNA rates with dengue incidence may inform the design of effective control measures. [ABSTRACT FROM AUTHOR]

Background: Prophylaxis with nucleos(t)ide analogue (NA) is recommended to prevent hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)-positive patients receiving rituximab-based B-cell depletion therapy. However, little is known about the risk of clinical relapse after withdrawal of NA.Methods: We retrospectively analyzed 77 noncirrhotic HBsAg carriers with hematological cancer who received rituximab-containing chemotherapy. All of them received either prophylactic entecavir or tenofovir therapy. The risk of clinical relapse and hepatic decompensation after cessation of NA was explored.Results: Clinical relapse and hepatic decompensation developed in 25 (32.5 %) and 11 (14.3 %) of the patients, respectively, and 2 patients died of hepatic decompensation. Most of the hepatic events occurred within 1 year (20 of 25; 80.0%) after stopping NA. A higher pretreatment viral load (≥2000 vs <2000 IU/mL) was associated with increased risks of clinical relapse (hazard ratio, 3.47; 95% confidence interval, 1.56-7.73) and hepatic decompensation (9.91; 2.14-45.92). Of 51 patients with pretreatment viral load <2000 IU/mL, clinical relapse occurred in 10 (19.6 %) and hepatic decompensation in 2 (3.9%).Conclusions: Pretreatment HBV DNA ≥2000 IU/mL is associated with increased risk of liver-related disease after cessation of prophylactic NA therapy in patients who received rituximab-containing chemotherapy. [ABSTRACT FROM AUTHOR]

Background To investigate serum Mac-2-binding protein glycosylation isomer (M2BPGi) levels in predicting hepatocellular carcinoma (HCC) and mortality at virological remission (VR, HBV DNA <20 IU/mL) following antiviral therapy in chronic hepatitis B (CHB) patients with cirrhosis. Methods This retrospective cohort study included patients with CHB-related Child-Pugh A cirrhosis undergoing long-term antiviral therapy. Serum M2BPGi levels were quantified and multivariable Cox proportional hazards regression models were used to identify risk predictors for HCC and death. Results A total of 126 and 145 patients were included in the derivation and validation cohorts, respectively. The mean age was 56, and the mean M2BPGi level was 1.86 cut-off index (COI) in the derivation cohort. After adjustment for confounders, a higher M2BPGi level at VR significantly predicted HCC (hazard ratio [HR]: 1.58, 95% confidence interval [CI]: 1.19-2.10, P=0.002) and death (HR: 2.17, 95% CI: 1.02-4.62, P=0.044). The M2BPGi ≥3 COI significantly increased the risk of HCC and death in the derivation and validation cohorts. Serial M2BPGi levels declined significantly (P=0.0001) in non-HCC patients only, and remained significantly lower than those who developed HCC afterwards (P=0.039). Conclusions Serum M2BPGi levels at antiviral therapy-induced VR predict HCC development and death in patients with CHB-related Child-Pugh A cirrhosis. [ABSTRACT FROM AUTHOR]

Background: We investigated the patterns and predictors for virological relapse (VR), clinical relapse (CR), and sustained clinical response (SCR) and the outcomes of retreatment after nucleos(t)ide analogue (NUC) therapy discontinuation.Methods: Patients with chronic hepatitis B who were discontinuing NUC therapy were prospectively enrolled. Viral and host predictors of relapse were evaluated, including hepatitis B virus (HBV) surface antigen (HBsAg) level, anti-HBV core antibody level, and presence of single-nucleotide polymorphisms in the genes encoding the receptors NTCP (rs2296651) and CTLA4 (rs231775) and in the 3' untranslated regions of the genes encoding HLA-DPA1 (rs3077) and HLA-DPB1 (rs9277535); posttherapy predictors of relapse were also investigated. Information about NUC retreatment and outcomes were recorded.Results: Overall, 100 patients discontinuing 3-year entecavir (ETV) or tenofovir (TDF) therapy were enrolled. Patients discontinuing TDF exhibited significantly higher rates of VR (52.9% vs 6.1%; P < .001) and CR (15.2% vs. 1.5%, P = .007) at 3 months than those discontinuing ETV, but relapse rates at 12 months were comparable. The end-of-therapy HBsAg levels predicted VR (hazard ratio [HR], 1.62; 95% confidence interval [CI], 1.19-2.21), CR (HR, 1.78; 95% CI, 1.13-2.81), and SCR (OR, 0.57; 95% CI, .35-.94). The CTLA4 (rs231775) non-GG genotype predicted VR (HR, 1.74; 95% CI, 1.01-3.00) and CR (HR, 2.06; 95% CI, 1.04-4.11), while the HLA-DPA1 (rs3077) AA genotype predicted SCR (OR, 10.84; 95% CI, 1.12-105). The HBV DNA 1 month after NUC treatment cessation was an early predictor of subsequent relapse.Conclusions: Discontinuation of tenofovir disoproxil fumarate treatment rather than entecavir treatment is associated with earlier relapse, and NUC-specific posttherapy monitoring is necessary. [ABSTRACT FROM AUTHOR]

Background. The serum hepatitis B virus (HBV) surface antigen (HBsAg) level can predict hepatocellular carcinoma (HCC) development in hepatitis B e antigen (HBeAg)-negative patients with an HBV DNA level of <2000 IU/mL. However, little is known regarding how well the combination of both viral biomarkers stratifies HCC risk. Methods. A total of 2165 Taiwanese HBeAg-negative noncirrhotic patients were followed for 14.9 years. The predictive power of the HBsAg level for HCC was analyzed for different viral load ranges. Results. In patients with HBV DNA levels of 2000-19 999 IU/mL (intermediate viral load), a positive correlation between HBsAg level and HCC development was identified after adjustment for other risk factors (P = .002). In contrast, no association was found between HBsAg level and HCC in patients with higher viral loads. HBsAg level was subsequently included to stratify HCC risk in patients with low and intermediate viral loads. Receiver operating characteristic curve analysis showed that combining HBV DNA and HBsAg level better predicts 10-year HCC development as compared to using HBV DNA level alone in the overall cohort (P = .028). Conclusions. Serum HBsAg level helps stratify HCC risk in patients with intermediate viral loads. Combining HBV DNA and HBsAg levels better predicts HCC risk. [ABSTRACT FROM AUTHOR]

Background. The long-term evolution and outcomes of infection with a hepatitis B virus (HBV) surface antigen (HBsAg) gene mutant (hereafter, “HBsAg-mutant HBV”) among immunized children remain unclear.Methods. Ninety-five HBsAg-positive children aged 0.5–18.4 years (mean age, 5.8 years) who did not respond to postnatal immunoprophylaxis were prospectively followed for 1–22.8 years (mean follow-up, 8.5 years). Clinical, serologic, and virologic features were compared between 38 untreated HBV e antigen (HBeAg)–positive children carrying HBsAg-mutant HBV (group 1) and 49 children carrying wild-type HBV (group 2). HBsAg-mutant HBV was examined in 20 immunized children presenting with HBV-related hepatocellular carcinoma (HCC).Results. The initial alanine aminotransferase (ALT) level, the maximal ALT level during the HBeAg-positive phase of HBV infection, the cumulative incidence of HBeAg seroconversion (P = .0018), and the rate of low serum HBV DNA load (defined as <104 copies/mL) at the last visit (P = .006) were higher in group 1 than in group 2. A higher frequency of HBV genotype C and a higher ALT level during surface mutant viremia were observed in codon 110–129 mutants than in codon 144–145 mutants. None of the 95 patients developed cirrhosis or HCC. HBsAg-mutant HBV was detected in 3 of 8 (38%) HBV DNA-positive children with HCC.Conclusions. HBeAg-positive immunized children carrying HBsAg-mutant HBV may develop hepatitis activity, HBeAg seroconversion, and a low viremic state earlier than those carrying wild-type HBV. Continuous monitoring of children with wild-type HBV infection and those with HBsAg-mutant HBV for possible development of HCC is needed. [ABSTRACT FROM PUBLISHER]

Background. It is unclear whether hepatitis B e antigen (HBeAg) seroconversion induced by nucleos(t)ide analogues (NUC) has a prognosis that is similar to that of spontaneous HBeAg seroconversion.Methods. A total of 148 noncirrhotic NUC-induced HBeAg seroconverters were consecutively enrolled. A historical control of 407 noncirrhotic spontaneous HBeAg seroconverters was also recruited. We compared the rates of HBeAg seroreversion and HBV reactivation between these 2 cohorts.Results. There were 1652.8 and 465.2 person-years of follow-up for spontaneous and NUC-induced HBeAg seroconverters, respectively. Compared with NUC-induced seroconverters, spontaneous seroconverters were younger when achieving HBeAg seroconversion. We thus compared these 2 cohorts according to their age at HBeAg seroconversion. In patients achieving HBeAg seroconversion before 30 years of age, NUC-induced seroconverters had a higher 2-year HBeAg seroreversion rate than spontaneous seroconverters (12.0% vs 2.9%; P = .004) and were at a higher risk of HBV reactivation (hazard ratio, 4.6; 95% confidence interval, 1.5–14.4). Using multivariate analysis, NUC-induced HBeAg seroconversion remained a risk factor of both endpoints in young HBeAg seroconverters.Conclusion. NUC-induced HBeAg seroconverters may not have durable response after stopping therapy. For patients achieving HBeAg seroconversion before 30 years of age, the risk of HBeAg seroreversion and HBV reactivation is higher in NUC-induced seroconverters than spontaneous HBeAg seroconverters. [ABSTRACT FROM AUTHOR]

To study mother-to-infant transmission of GB virus C/hepatitis G virus (GBV-C/HGV), blood samples of infants born to carrier mothers were collected beginning 3 months after birth and were tested for GBV-C/HGV RNA until 1 year of age. Of 2046 mothers, 2.1% were positive for GBV-C/HGV RNA, and 25 of their infants were followed for a median of 12 months. Thirteen infants (52%) were viremic, and infection became persistent in all. Maternal GBV-C/HGV RNA levels of this group were >107 copies/mL. Nucleotide sequence comparison in 5 viremic mother-infant pairs revealed a homology of 93%–98.2%, and none delivered by elective cesarean section. In comparison, of the 12 uninfected infants' mothers, 10 had lower GBV-C/HGV RNA levels (mean, 5 × 104 copies/mL), and the remaining 2 high-titered mothers had elective cesarean section. Thus, high-titered maternal viremia and mode of delivery are closely associated with the mother-to-infant transmission of GBV-C/HGV to infants, and the infection usually becomes persistent. [ABSTRACT FROM PUBLISHER]

A group of flavi-like GB viruses (GBV-A, -B, and -C) has been discovered and partially characterized. Only GBV-C is found in humans. Nucleotide sequences of the putative helicase gene of the GBV-C genome were determined in 21 Taiwanese patients and compared with isolates from Africa and North America by phylogenetic analysis. The average similarities of Taiwanese isolates to those from West Africa, East Africa, Canada, and United States were 83%, 85%, 78%, and 82%, respectively. Phylogenetic analysis of the NS3 region showed that 81% of the Taiwanese isolates were more closely related to the East African isolate. GBV-C isolates from Taiwan could be classified into at least 3 groups. These data suggest that GBV-C isolates cloned from different geographic areas have genetic heterogeneity. [ABSTRACT FROM PUBLISHER]

Immunoblot analysis on serum samples from 90 patients with chronic hepatitis C virus infection revealed four putative immunogenic regions within the NS3 protein of the virus: E (around aa 1250/1251), A (within aa 1250-1334), A/B (around aa 1323 and 1334), and B/C (around aa 1407 and 1412). Among them, region E was most immunodominant, and region A was recognized much less frequently by patients with cirrhosis than by those with chronic hepatitis (10% vs. 46%, x2 = 12.05, P < .01). The results suggest that region A might be a potential prognostic marker to differentiate chronic hepatitis from cirrhosis. [ABSTRACT FROM PUBLISHER]

Serum HBV DNA from infants and children with fulminant hepatitis B (FHB) or acute selflimiting hepatitis B (AHB) and patients believed to be contamination sources was amplified by polymerase chain reaction (Pf.R) followed by direct sequencing of the precore region. A precore mutation from G to A at nucleotide 1896 was found in 5 of 14 FHB patients and in 3 of 10 AHB patients. Among the 10 infants who developed hepatitis during the first 6 months of age, the precore mutation was detected in only 2 of 7 with FHB and in 1 of 3 with AHB. In 1 infant with FHB, a shift from wild type to precore mutant predominance occurred in the serum virus population during the incubation period. Thus, the precore mutation is neither necessary nor sufficient to cause FHB in childhood, although its contributory role cannot be excluded. Factors other than precore mutations may be important in the pathogenesis of FHB. [ABSTRACT FROM PUBLISHER]

Twenty patients with chronic hepatitis C virus (HCV) infection and acute exacerbations (group A) were studied by polymerase chain reaction with genotype-specific primers to explore the role of mixed infections of HCV in acute exacerbations of chronic type C hepatitis. Another 26 patients who did not have acute exacerbation were matched controls (group B). Eleven (55%) of the group A patients had heterologous HCV, and their mean age was significantly younger than that of the 9 without heterologous infection (55 vs. 67 years, P < .05). In contrast, only 2 group B patients (7.7%) had heterologous HCV infection. In 10 of 13 patients with heterologous HCV infection, type III/2a virus emerged on type II/1b HCV, and viral interference was observed in half of them. The results support that mixed infections of HCV may be important in acute exacerbations of chronic type C hepatitis. [ABSTRACT FROM PUBLISHER]

To study perinatal transmission of hepatitis C virus (HCV), 15 anti-HCV-positive carrier mothers without human immunodeficiency virus coinfection were recruited. At delivery, maternal blood was taken and anti-HCV titer was determined and HCV RNA measured in each serum sample by reverse transcription polymerase chain reaction (PCR). A competitive PCR was used in selected samples to quantitate HCV concentration. The 15 neonates were followed regularly for 1 year and their sera were also assayed for anti-HCV and for HCV RNA by reverse transcription PCR. All the mothers were positive for HCV RNA. Only one normal spontaneously delivered neonate of a mother with extremely high titer of anti-HCV (1:20,000) and HCV concentration (1010 copies/ml.) had both anti-HCV and HCV RNA in serum for up to 6 months of age. In contrast, none of the remaining 14 neonates born to mothers with low- to high-titer anti-HCV (1:4-1:1000) and moderate amounts of HCV RNA (105-106 copies/ml.) contracted HCV infection. The results imply that high-titer maternal viremia and normal spontaneous delivery may allow more HCV to infect the neonate intrapartum, therefore establishing perinatal transmission. [ABSTRACT FROM PUBLISHER]

To investigate the intrafamilial transmission of hepatitis C virus (HCV) and related risk factors, anti-HCV antibodies in 186 family members of 48 index patients were studied. The index patients were anti-HCV-positive and had chronic liver disease. Overall, 10 family members (5.4%) were positive for anti-HCV, indicating a higher prevalence of anti-HCV among family members than among the Taiwanese general population. Spouses had the highest prevalence (21%) of anti-HCV, with older age and longer duration of marriage of index patients the most evident risk factors. HCV RNA, recovered from the infected couples by reverse transcription-nested polymerase chain reaction and subsequently sequenced directly, was identical at the nucleotide level in 3 of the 4 couples studied, and the remaining couple had a homology of >96%. These results strongly support that interspousal transmission may be the most important route of intrafamilial spreading of HCV, and thus sexual transmission, although with low efficiency, should be considered important in HCV infection. [ABSTRACT FROM PUBLISHER]

To assess the contribution of hepatitis C virus (HCV) in liver disease in Taiwan, antibody to HCV (anti-HCV) was studied by radioimmunoassay in 392 patients with chronic liver disease and in 440 healthy adults and 444 subjects at risk. The anti-HCV prevalence was 0.95% in 420 volunteer blood donors, 90% in 100 hemophiliacs, and 81% in 58 parenteral drug abusers. AntiHCV was present in 6 (7.7%) of 78 hepatitis B surface antigen (HBsAg)-positive and 28 (65%) of 43 HBsAg-negative patients with chronic hepatitis, 3 (10%) of 31 HBsAg-positive and 13 (43%) of 30 HBsAg-negative cirrhotics, and 7 (17%) of 42 HBsAg-positive and 15 (63%) of24 HBsAgnegative patients with hepatocellular carcinoma (HCC). An outbreak of non-A, non-B hepatitis revealed 18% of 57 patients to bepositive for anti-HCV, and in 29 patients with posttransfusion hepatitis prospectively followed, 7 (24%) developed anti-HCV. Thus, HCV infection appears to playa relatively minor role in HBsAg-positive liver disease in Taiwan but is strongly associated with HBsAg-negative chronic liver disease and HCC. The infection is extremely common in hemophiliacs and parenteral drug abusers. [ABSTRACT FROM PUBLISHER]

To examine the replication of hepatitis D virus (HDV) and its interactions with helper hepatitis B virus (HBV), the RNA of both viruses was analyzed in liver biopsy tissue obtained from six patients with past or present hepatitis. In four of five hepatitis B surface antigen (HBsAg) carriers, the RNA genome of HDV was found in the liver. Further, the complementary RNA species as replication templates of HDV genomes documented in previous animal studies were confirmed. Within the livers of four HBsAg carriers, the transcription of HBV was absent or incomplete, however, in the patient without HDV RNA, the HBV genes expressed accurately and actively. This may account for the previously observed HBV suppression by concomitant HDV infection. [ABSTRACT FROM PUBLISHER]

Background: To investigate serum Mac-2-binding protein glycosylation isomer (M2BPGi) levels in predicting hepatocellular carcinoma (HCC) and mortality at virological remission (VR, HBV DNA <20 IU/mL) following antiviral therapy in chronic hepatitis B (CHB) patients with cirrhosis.Methods: This retrospective cohort study included patients with CHB-related Child-Pugh A cirrhosis undergoing long-term antiviral therapy. Serum M2BPGi levels were quantified and multivariable Cox proportional hazards regression models were used to identify risk predictors for HCC and death.Results: A total of 126 and 145 patients were included in the derivation and validation cohorts, respectively. The mean age was 56, and the mean M2BPGi level was 1.86 cut-off index (COI) in the derivation cohort. After adjustment for confounders, a higher M2BPGi level at VR significantly predicted HCC (hazard ratio [HR]: 1.58, 95% confidence interval [CI]: 1.19-2.10, P=0.002) and death (HR: 2.17, 95% CI: 1.02-4.62, P=0.044). The M2BPGi ≥3 COI significantly increased the risk of HCC and death in the derivation and validation cohorts. Serial M2BPGi levels declined significantly (P=0.0001) in non-HCC patients only, and remained significantly lower than those who developed HCC afterwards (P=0.039).Conclusions: Serum M2BPGi levels at antiviral therapy-induced VR predict HCC development and death in patients with CHB-related Child-Pugh A cirrhosis. [ABSTRACT FROM AUTHOR]

Background: We investigated the patterns and predictors for virological relapse (VR), clinical relapse (CR), and sustained clinical response (SCR) and the outcomes of retreatment after nucleos(t)ide analogue (NUC) therapy discontinuation., Methods: Patients with chronic hepatitis B who were discontinuing NUC therapy were prospectively enrolled. Viral and host predictors of relapse were evaluated, including hepatitis B virus (HBV) surface antigen (HBsAg) level, anti-HBV core antibody level, and presence of single-nucleotide polymorphisms in the genes encoding the receptors NTCP (rs2296651) and CTLA4 (rs231775) and in the 3' untranslated regions of the genes encoding HLA-DPA1 (rs3077) and HLA-DPB1 (rs9277535); posttherapy predictors of relapse were also investigated. Information about NUC retreatment and outcomes were recorded., Results: Overall, 100 patients discontinuing 3-year entecavir (ETV) or tenofovir (TDF) therapy were enrolled. Patients discontinuing TDF exhibited significantly higher rates of VR (52.9% vs 6.1%; P < .001) and CR (15.2% vs. 1.5%, P = .007) at 3 months than those discontinuing ETV, but relapse rates at 12 months were comparable. The end-of-therapy HBsAg levels predicted VR (hazard ratio [HR], 1.62; 95% confidence interval [CI], 1.19-2.21), CR (HR, 1.78; 95% CI, 1.13-2.81), and SCR (OR, 0.57; 95% CI, .35-.94). The CTLA4 (rs231775) non-GG genotype predicted VR (HR, 1.74; 95% CI, 1.01-3.00) and CR (HR, 2.06; 95% CI, 1.04-4.11), while the HLA-DPA1 (rs3077) AA genotype predicted SCR (OR, 10.84; 95% CI, 1.12-105). The HBV DNA 1 month after NUC treatment cessation was an early predictor of subsequent relapse., Conclusions: Discontinuation of tenofovir disoproxil fumarate treatment rather than entecavir treatment is associated with earlier relapse, and NUC-specific posttherapy monitoring is necessary.

Background: Hepatitis B virus (HBV) surface antigen (HBsAg) seroclearance is the ultimate serological end point in chronic hepatitis B. This study aimed to develop and validate a prediction score for spontaneous HBsAg seroclearance in HBV e antigen (HBeAg)-negative patients with chronic hepatitis B due to HBV genotype B or C., Methods: The development cohort included 2491 untreated participants from the community-based REVEAL-HBV study, who were HBeAg negative, anti-hepatitis C virus negative, and cirrhosis free. The independent validation cohort consisted of 1934 hospital-based individuals from the National Taiwan University Hospital. Clinical markers included in the model were age and serum HBV DNA and HBsAg levels. Cox proportional hazards regression models were used to create the prediction model., Results: A prediction score ranging from 0 to 27 was developed. Predicted probabilities of 5- and 10-year HBsAg seroclearance ranged from 0.95% to 30.49% and from 2.58% to 62.52%, respectively. When applied to the independent validation cohort, the areas under the receiver operating characteristic curves for the 5- and 10-year prediction of HBsAg seroclearance in the validation cohort were 0.82 (95% confidence interval [CI], .76-.88) and 0.74 (95% CI, .70-.78). Model fit was still adequate, according to Hosmer-Lemeshow goodness of fit tests., Conclusions: A clinically applicable prediction score for HBsAg seroclearance was developed and externally validated. This model can assist clinicians in further stratifying risk groups., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Clinical implications of persistent alanine aminotransferase (ALT) elevation and associated factors in chronic hepatitis C (CHC) patients who achieved undetectable hepatitis C virus (HCV) RNA during pegylated interferon plus ribavirin (peg-IFN/RBV) therapy remain unknown., Methods: A total of 1113 CHC patients with undetectable HCV RNA during peg-IFN/RBV therapy were enrolled. Baseline characteristics associated with persistent on-treatment ALT elevation (POAE), and its impact on treatment outcomes, were investigated., Results: Of 1113 CHC patients, 254 (22.8%) had POAE. Among patients with HCV genotype 1 (HCV-1) who had complete early virologic response (EVR) and received 48 weeks of therapy, patients with POAE had a lower rate of sustained virologic response (SVR) than those without POAE (44.1% vs 74.0%; P = .0002). Multivariate analyses showed that body mass index ≥ 27 kg/m(2), ALT level ≥3 times the upper limit of normal, aspartate aminotransferase to platelet ratio index score ≥1.5, hepatic fibrosis ≥F3, and hepatic steatosis ≥S2 were independent factors associated with POAE after viral clearance., Conclusions: POAE is common in CHC patients during therapy. HCV-1 patients with POAE have a lower SVR rate to 48-week therapy if they achieve complete EVR. Advanced hepatic fibrosis, obesity, and steatosis are factors associated with POAE in these patients., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Hepatitis B e antigen (HBeAg) status and serum hepatitis B virus (HBV) DNA levels are major factors affecting the prognosis of adult HBV carriers; however, the impact of viral load on long-term outcomes after spontaneous HBeAg seroconversion remains unclear., Methods: A total of 390 spontaneous HBeAg seroconverters with a long-term follow-up were enrolled. Serum HBV-DNA levels at 1 year after HBeAg seroconversion were determined, and their correlation with long-term adverse outcomes was explored., Results: In a mean follow-up of 6.8 years, the average annual incidence rates were 4.4% and 1.9% for HBeAg-negative hepatitis and hepatitis flare, respectively. Compared with patients with HBV-DNA levels <200 IU/mL, the adjusted hazard ratios of HBeAg-negative hepatitis were 2.4 (95% confidence interval, 1.3-4.4), 3.6 (1.8-7.2), and 5.3 (2.8-10.0), respectively, for serum HBV-DNA level of 2000 -2 × 10(4), 2 × 10(4) -2 × 10(5), and ≥2 × 10(5) IU/mL. In addition, serum HBV-DNA levels were independently associated with HBeAg-negative hepatitis flare, which confirmed their impact on the immune active hepatitis after HBeAg seroconversion., Conclusions: HBeAg seroconversion may not always confer favorable outcomes. Serum HBV-DNA levels ≥2000 IU/mL at 1 year post HBeAg seroconversion correlate with increased risk of HBeAg-negative hepatitis and hepatitis flare.

To clarify the influence that a recently identified SEN virus (SENV) has on hepatitis C virus (HCV) response to therapy with interferon plus ribavirin, 2 SENV variants, SENV-D and SENV-H, were studied in 100 patients with chronic hepatitis C; 57 of these patients were positive for SENV-D/H DNA, and there were no differences, in clinicopathological features, between patients with and without SENV coinfection. However, patients with SENV coinfection had a higher prevalence of HCV genotype 2a than did those without it. The sustained HCV response rate after combination therapy was comparable between patients with and without SENV coinfection. Of the 57 patients with SENV coinfection, 18 (32%) had a sustained SENV response to combination therapy, and SENV-D had a higher sustained response rate than did SENV-H. These results suggest that SENV has a specific link to HCV genotype 2a and that SENV infection has no apparent effect on coexisting chronic hepatitis C.

To investigate the prevalence and clinical relevance of a recently identified SEN virus (SENV) in Taiwan, 2 SENV variants (SENV-D and SENV-H) were studied in high-risk persons, patients with liver disease, and healthy adults. SENV-D and/or SENV-H (SENV-D/H) infections were more frequent in high-risk groups (54%-90%) and in patients with chronic hepatitis B (41%), hepatitis B-related hepatocellular carcinoma (HCC) (54%), chronic hepatitis C (67%), and hepatitis C-related HCC (76%) than in healthy adults (15%). The prevalence of SENV-D/H infection was comparable between patients with non-A to E fulminant hepatitis (30%) and healthy adults. Most subjects with SENV-D/H infection alone had no or mild hepatitis, and coinfection of SENV-D/H with chronic hepatitis B or C was not associated with increased evidence of liver disease and the risk of HCC. These results suggest that SENV-D/H infection is common in high-risk groups in Taiwan but that SENV-D/H infection is not associated with hepatitis.