Search

BACKGROUND Hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC) worldwide. It remains incompletely understood in the real world how anti-viral therapy affects survival after HCC diagnosis. METHODS This was an international multicentre cohort study of 2518 HBV-related HCC cases diagnosed between 2000 and 2015. Cox proportional hazards models were utilised to estimate hazard ratios (HR) with 95% (CI) for anti-viral therapy and cirrhosis on patients' risk of death. RESULTS Approximately, 48% of patients received anti-viral therapy at any time, but only 17% were on therapy at HCC diagnosis (38% at US centres, 11% at Asian centres). Anti-viral therapy would have been indicated for >60% of the patients not on anti-viral therapy based on American criteria. Patients with cirrhosis had lower 5-year survival (34% vs 46%; P more...

Vesatolimod is an oral agonist of toll-like receptor 7 designed to minimize systemic exposure and side effects. We assessed the safety and efficacy of vesatolimod in viremic chronic hepatitis B (CHB) patients not currently on oral antiviral treatment (OAV) in a phase 2, multicentre, double-blind, randomized, placebo-controlled study. A total of 192 patients stratified by HBeAg status and alanine aminotransferase level were randomized 2:2:2:1 to receive oral vesatolimod (1-, 2- or 4-mg) or placebo once weekly for 12 weeks; tenofovir disoproxil fumarate (300-mg daily) was administered daily for 48 weeks. Efficacy was assessed by quantitative serum HBsAg decline at Week 24 from baseline. In addition to safety assessments, changes in whole-blood interferon-stimulated gene (ISG) transcripts and serum cytokines were explored. Most patients were male (64.1%) and HBeAg-negative (60.9%) at baseline. Among vesatolimod-treated patients, most (60.4%-69.1%) experienced ≥1 treatment-emergent adverse event; the majority were mild or moderate in severity. No clinically meaningful differences in HBsAg changes from baseline were observed between treatment groups. No patients experienced HBsAg loss, while 3 patients experienced HBeAg loss and hepatitis B e-antibody seroconversion at week 48. HBV DNA suppression rates were similar across all treatment arms at Week 24. ISG15 induction was dose-dependent and did not correlate with HBsAg changes. A small proportion of patients exhibited dose-dependent interferon-α induction that correlated with grade of influenza-like adverse events. Overall, vesatolimod is safe and well tolerated in CHB patients. Although consistent dose-dependent pharmacodynamic induction of ISGs was demonstrated, it did not result in clinically significant HBsAg decline. more...

To assess the contribution of tumor necrosis factor (TNF)β +252 polymorphisms to risk and prognosis of hepatocellular carcinoma (HCC), we enrolled 150 pairs of sex- and age-matched patients with HCC, patients with cirrhosis alone, and unrelated healthy controls. TNFβ +252 genotypes were determined by polymerase chain reaction with restriction fragment length polymorphism. Multivariate analysis indicated that TNFβ G/G genotype [odds ratio (OR), 3.64; 95%CI, 1.49-8.91], hepatitis B surface antigen (OR, 16.38; 95%CI, 8.30-32.33), and antibodies to hepatitis C virus (HCV) (OR, 39.11; 95%CI, 14.83-103.14) were independent risk factors for HCC. There was an additive interaction between TNFβ G/G genotype and chronic hepatitis B virus (HBV)/HCV infection (synergy index=1.15). Multivariate analysis indicated that factors associated with TNFβ G/G genotype included cirrhosis with Child-Pugh C (OR, 4.06; 95%CI, 1.34-12.29), thrombocytopenia (OR, 6.55; 95%CI, 1.46-29.43), and higher serum α-fetoprotein concentration (OR, 2.53; 95%CI, 1.14-5.62). Patients with TNFβ G/G genotype had poor cumulative survival (p=0.005). Cox proportional hazard model indicated that TNFβ G/G genotype was a biomarker for poor HCC survival (hazard ratio, 1.70; 95%CI, 1.07-2.69). In conclusion, there are independent and additive effects between TNFβ G/G genotype and chronic HBV/HCV infection on risk for HCC. It is a biomarker for poor HCC survival. Carriage of this genotype correlates with disease severity and advanced hepatic fibrosis, which may contribute to a higher risk and poor survival of HCC. Chronic HBV/HCV infected subjects with this genotype should receive more intensive surveillance for early detection of HCC. more...

Background In the large randomised NEPTUNE study, peginterferon alfa-2a 180 μg/wk for 48 weeks produced higher hepatitis B e antigen (HBeAg) seroconversion rates 24 weeks post-treatment (36%) than a lower dose (90 μg/wk) and/or shorter duration (24 weeks) (range 14%-26%). Aim To determine seroconversion rates 5 years after completion of treatment in NEPTUNE. Methods HBeAg-positive patients who completed 24 weeks' follow-up in NEPTUNE (with peginterferon alfa-2a 90 μg/wk × 24 weeks [group 1]; 180 μg/wk × 24 weeks [2]; 90 μg/wk × 48 weeks [3] or 180 μg/wk × 48 weeks [4]) were followed up. Results Three hundred and eighty three of the 544 patients in the original study were enrolled in the long-term follow-up study. Many patients (196 overall; more in groups 1-3 than 4) received nucleos(t)ide analogues or immunomodulators during follow-up, and more patients had missing data at year 5 in groups 2 and 4 (48 weeks, 50/112) than in groups 1 and 3 (24 weeks, 23/103), which confounds the planned per-protocol analysis. HBeAg seroconversion rates in groups 1, 2, 3 and 4 at year 5 were 47.5%, 50.7%, 52.2% and 67.1%, respectively, (odds ratio for group 4 versus 1-3: 2.02; 95% CI 1.21, 3.38), using multiple imputation methods for missing measurements. Conclusion Seroconversion rates are durable for up to 5 years after completion of peginterferon alfa-2a therapy and, consistent with NEPTUNE, the results suggest that the licensed regimen (180 μg × 48 weeks) is more efficacious for HBeAg-positive patients than a lower dose and/or shorter treatment duration. more...

The pathogenesis of hepatocellular carcinoma (HCC) related to habitual betel quid (BQ) chewing is unclear. Risk of HCCis increased with adverse hepatic fibrosis. This study aimed to assess the impact of chronic viral hepatitis on adverse hepatic fibrosis in HCC related to BQ chewing. This hospital-based case-control study enrolled 200 pairs of age- and gender-matched patients with HCC and unrelated healthy controls. Serologic hepatitis B surface antigen (HBsAg), antibodies to hepatitis C virus (anti-HCV), α-fetoprotein (AFP), and surrogate markers for significant hepatic fibrosis were measured. Information on substance-use habits was obtained with a questionnaire. By analysis of surrogate markers for hepatic fibrosis, the prevalence of significant hepatic fibrosis in patients chewing BQ was between 45.8% and 91.7%, whereas that for patients without BQ chewing was between 18.4% and 57.9%. The difference was significant (P0.05 for each surrogate marker). Multivariate analysis indicated that cirrhosis with Child-Pugh C (odds ratio (OR) = 3.28; 95% confidence interval (CI), 1.29- 8.37), thrombocytopenia (OR = 3.92, 95% CI, 1.77-8.68), AFP400 mg/L (OR = 2.21, 95% CI, 1.05-4.66) and male gender (OR = 4.06, 95% CI, 1.29-12.77) were independent factors associated with habitual BQ chewing. In conclusion, adverse hepatic fibrosis and severe liver damage play important roles in the pathogenesis of BQ- related HCC, which could be aggravated by chronic hepatitis B and hepatitis C. BQ-cessation programs and prevention of chronic HBV/HCV infection are needed to prevent HCC related to BQ chewing. more...

We conducted a case-control study to assess the roles of tumor necrosis factor (TNF)-> polymorphisms, substance use habits, and chronic hepatitis B virus (HBV)/hepatitis C virus (HCV) infection on the risk for hepatocellular carcinoma (HCC). We enrolled 200 pairs of sex- and age-matched patients with HCC and unrelated healthy controls. TNF-> polymorphisms were detected with polymerase chain reaction and direct sequencing. Serum hepatitis B surface antigen (HBsAg) and antibodies to HCV (anti-HCV) were detected. We used a structured questionnaire to obtain information about substance use habits. Multivariate analysis indicated that TNF308.2 allele (odds ratio EOR^, 3.23; p = 0.011), habitual betel quid chewing (OR, 3.70; p = 0.011), HBsAg (OR, 23.62; p = 0.0001), and anti-HCV (OR, 38.73; p = 0.0001) were independent risk factors for HCC. Having at least 2 substance use habits was associated with risk for HCC. The more substance use habits, the higher the OR for HCC ( pfor trend = 0.0001). There were additive inter- actions among TNF308.2 allele, substance use habits, and chronic HBV/ HCV infection. Multivariate analysis indicated that TNF308.2 allele ( p = 0.001), cigarette smoking ( p = 0.0001), and alcohol drinking ( p = 0.0001) were independent risk factors for habitual betel quid chewing. Moreover, patients harboring the TNF308.2 allele and/or those with habits of substance use had low serum albumin concentration and platelet count (each p = 0.0001). In conclusion, there are independent and additive interactive effects among the TNF308.2 allele, substance use habits, and chronic HBV/HCV infection on the risk for HCC. Substance use habits or carrying the TNF308.2 allele correlates with disease severity and hepatic fibrosis, which may contribute to higher risks for HCC. (Medicine 2009;88: 349Y357) more...

We conducted a case-control study to elucidate the role of heat shock protein A1B (HSPA1B) 1267 single nucleotide polymorphism (SNP) on the risk and prognosis of hepatocellular carcinoma (HCC). Subjects enrolled included 150 pairs of sex- and age-matched HCC patients and unrelated controls. Genomic DNA was typed for HSPA1B1267 SNP using polymerase chain reaction with restriction fragment length polymorphism. The frequencies of the HSPA1B P2/P2 genotype and the HSPA1B P2 allele in HCC patients were higher than in unrelated controls (each p = 0.0001). Multivariate analysis identified the following independent risk factors for HCC: HSPA1B P1/P2 genotype (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.07-5.11), HSPA1B P2/P2 genotype (OR, 12.06; 95% CI, 4.43-32.79), hepatitis B surface antigen (HBsAg) (OR, 25.95; 95% CI, 11.88-56.68), and antibodies to hepatitis C virus (anti-HCV) (OR, 70.43; 95% CI, 21.89-226.64). There was an additive interaction between HSPA1B P2 allele carriers and the presence of either HBsAg (synergy index = 2.48) or anti-HCV (synergy index = 1.52). However, as HSPA1B1267 SNP is a silent mutation, it is a surrogate genetic marker for increasing risk of HCC. Our findings indicate that patients with chronic hepatitis B/hepatitis C virus infection who harbor this SNP represent a high-risk group for HCC. They should receive more intensive surveillance for early detection of HCC. Moreover, patients with the HSPA1B P2 allele had significantly longer survival (p = 0.002). The limitations of this study include the unknown functional significance of the HSPA1B1267 polymorphism, the relatively small sample size, the fact that this was not a prospective study of cases and controls, and the questionable generalizability of the findings given the specific ethnic composition of the population studied. more...

Background: In patients with chronic hepatitis B, tenofovir disoproxil fumarate (TDF) plus pegylated interferon (PEG-IFN) for 48-weeks results in higher rates of hepatitis B surface antigen (HBsAg) loss than either monotherapy. Aim: To identify baseline and on-treatment factors associated with HBsAg loss at Week 72 and provide a model for predicting HBsAg loss in patients receiving combination therapy for 48 weeks. Methods: A secondary analysis of data from an open-label study where patients were randomised to TDF (300 mg/day, oral) plus PEG-IFN (PI, 180 μg/week, subcutaneous) for 48 weeks (TDF/PI-48w); TDF plus PEG-IFN for 16 weeks, TDF for 32 weeks (TDF/PI-16w+TDF-32w); TDF for 120 weeks (TDF-120w) or PEG-IFN for 48 weeks (PI-48w). Logistic regression methods were used to identify models that best predicted HBsAg loss at Week 72. Results: Rates of HBsAg loss at Week 72 were significantly higher in the TDF/PI-48w group (6.5%) than in the TDF/PI-16w+TDF-32w (0.5%), TDF-120w (0%) and PI-48w (2.2%) groups (P = 0.09). The only baseline factor associated with response was genotype A. HBsAg decline at Week 12 or 24 of treatment was associated with HBsAg loss at Week 72 (P < 0.001). HBsAg decline >3.5 log10 IU/mL at Week 24 in the TDF/PI-48w group resulted in a positive predictive value of 85% and a negative predictive value of 99% for HBsAg loss at Week 72. Conclusions: HBsAg decline at Week 24 of TDF plus PEG-IFN combination therapy may identify patients who, after completing 48 weeks of treatment, have a better chance of achieving HBsAg loss at Week 72. more...

Background and objectives. Virus hepatitis may lead to nephropathy as one of its multiple extrahepatic manifestations. Proteinuria by dipstick, a simple test in practice, is a useful and cardinal sign of underlying renal abnormalities. The aim of this study was to elucidate the impact of hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infections on the occurrence of proteinuria amongst adults. Designandsetting. A prospective, cross-sectional, community-based study was conducted in an HBV/HCV endemic area of southern Taiwan. Eligible subjects aged 40–65 years (n = 9934) underwent testing of hepatitis B surface antigen (HBsAg), HCV antibody (anti-HCV) and other related biochemical profiles. Urinalysis with repeated dipstick for proteinuria detection was performed. Results. Anti-HCV-positive rate amongst proteinuria subjects was significantly higher than nonproteinuria subjects (9.6% vs. 6.2%, P more...

Alpha-fetoprotein (AFP) is not a useful tumor marker for diagnosis of small hepatocellular carcinoma (HCC). There is over-expression of insulin-like growth factor (IGF)-II in HCC tissue. This study investigates the diagnostic application of IGF-II in small HCC.Serum levels of IGF-II and AFP were determined in 41 patients with small cirrhotic HCC (or = 3 cm), 41 sex- and age-matched patients with cirrhosis alone (LC), and 41 healthy adults. The optimal cut-off values for diagnosing HCC were determined with receiver operating characteristics (ROC) curve.Both IGF-II and AFP levels in HCC were higher than those in LC patients or controls (each p = 0.0001). The IGF-II levels in LC patients were lower than those in controls (p = 0.001). In HCC patients, multivariate analysis indicated that that both IGF-II (odds ratio, 4.54; 95% confidence interval, 2.15-9.55; p = 0.0001) and AFP (odds ratio, 1.05; 95% confidence interval, 1.01-1.08; p = 0.003) were found to be associated with an increased risk of presence of HCC. The optimal cut-off values of IGF-II (4.1 mg/g prealbumin) and AFP (50 ng/ml) were determined with ROC curves. The sensitivity, specificity, and diagnostic accuracy values for IGF-II were 63%, 90%, and 70%, respectively. Those for AFP were 44%, 95%, and 70%, respectively. Determination of both markers in parallel significantly increase the diagnostic accuracy (88%) and sensitivity (80%), with a high specificity (90%).Serum IGF-II level can be used as an independent serologic marker or a complementary tumor marker to AFP for diagnosis of small HCC. more...

This case-control study aimed to assess the independent and interactive role of habitual betel quid chewing and known risk factors for hepatocellular carcinoma (HCC). Subjects enrolled included 210 pairs of sex- and age-matched cirrhotic patients with HCC, patients with cirrhosis alone, and healthy controls. Information on risk factors was obtained through serologic examination of hepatitis B surface antigen (HBsAg) and antibodies to hepatitis C virus (anti-HCV), and a standardized personal interview with a structured questionnaire. Multivariate analysis indicated that betel quid chewing (odds ratio [OR], 5.81; 95% confidence interval [CI], 2.26-14.94); HBsAg (OR, 37.98; 95% CI, 19.65-73.42); and anti-HCV (OR, 47.23; 95% CI, 18.86-118.25) were independent risk factors for HCC when HCC patients were compared with healthy controls. Using patients with cirrhosis alone as a reference group, multivariate analysis indicated that only betel quid chewing (OR, 1.69; 95% CI, 1.04-2.76) and HBsAg (OR, 1.54; 95% CI, l.01-2.37) were independent risk factors for HCC. There was an additive interaction between betel quid chewing and the presence of either HBsAg (synergy index, 5.22) or anti-HCV (synergy index, 1.35). Moreover, a higher risk of HCC was associated with a longer duration of betel quid chewing and a larger amount of betel quid consumed (each p(for trend) < 0.0001). In conclusion, betel quid chewing is an independent risk factor for cirrhotic HCC. There is an additive interaction between betel quid chewing and chronic hepatitis B and/or hepatitis C virus infection. more...

Betel quid chewing, part of traditional Taiwanese culture, is common in 10%-20% of the human population worldwide. In this case-control study we assessed the independent and interactive role of habitual betel quid chewing and chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection on risk of cirrhosis. Subjects enrolled included 210 pairs of sex- and age-matched cirrhotic patients and healthy controls. Information on risk factors was obtained through serologic examination of hepatitis B surface antigen (HBsAg) and antibodies to hepatitis C virus (anti-HCV), and a standardized personal interview with a structured questionnaire. Univariate analysis indicated that betel quid chewing, HBsAg+, anti-HCV+, alcohol drinking, and smoking are significant risk factors for cirrhosis. Multivariate analysis indicated that betel quid chewing (odds ratio [OR], 3.56), HBsAg (OR 20.37), and anti-HCV (OR 31.43) are independent risk factors for cirrhosis. Most betel quid chewers habitually drink alcohol. Although our analysis indicates that betel quid chewing acts independently from alcohol as a risk factor for cirrhosis, the confounding effect of alcohol cannot be excluded entirely by our study. There was an additive effect of the interaction between betel quid chewing and the presence of either HBsAg or anti-HCV. Moreover, a higher risk of cirrhosis was associated with longer duration of betel quid chewing and greater amount of betel quid consumed (each p for trend more...

To evaluate the diagnostic application of serum insulin-like growth factor-II (IGF-II) and alpha-fetoprotein (AFP) levels in hepatocellular carcinoma (HCC), IGF-II and AFP were determined in 100 cirrhotic patients with HCC, 100 sex- and age-matched patients with cirrhosis alone and 50 healthy controls. The results indicated that IGF-II and AFP levels in patients with HCC were higher than in those with cirrhosis alone (p = 0.0001). There is an inverse correlation between IGF-II and (log)AFP (r = -0.410, p = 0.0001) in patients with HCC. Multivariate analysis indicated that IGF-II and AFP were closely associated, in a dose-related fashion, with the presence of HCC. Receiver operating characteristic curves were used to determine the optimal cutoff values of IGF-II (4.5 mg/g prealbumin) and AFP (100 ng/ml), respectively. Both IGF-II and AFP show a high specificity and positive likelihood ratio. The sensitivity was 42.0% for IGF-II and 73.0% for AFP. Determination of both markers in parallel significantly increased the diagnostic accuracy (96.5%) and sensitivity (97.9%), with a high specificity (95.1%) and positive likelihood ratio (19.9). In conclusion, IGF-II and AFP may be used as complementary tumor markers to discriminate HCC from cirrhosis. more...

This case–control study aimed to evaluate the diagnostic application of urinary transforming growth factor (TGF) α and serum α-fetoprotein (AFP) in hepatocellular carcinoma (HCC). TGFα and AFP were determined in 90 pairs of age- and gender-matched patients with cirrhotic HCC and patients with cirrhosis alone and 60 healthy controls. The results indicated that TGFα and AFP levels in patients with HCC were higher than in those with cirrhosis alone or healthy controls (each P = 0.0001). Multivariate analysis indicated that TGFα (odds ratio (OR) 1.03, 95 % confidence interval (CI) 1.05–1.16) and AFP (OR 1.03, 95 % CI 1.01–1.06) were closely associated, in a dose-related fashion, with the development of HCC. The optimal cutoff values, determined with the receiver operating characteristic (ROC) curves, were 29 μg/g creatinine for TGFα and 100 ng/ml for AFP, respectively. The areas under ROC curve (AUC) were 0.74 for TGFα and 0.78 for AFP, respectively. Both biomarkers showed the same sensitivity (52.2 %), high specificity, high positive predictive value, and moderate positive likelihood ratio. Determination of both markers in parallel significantly increased the AUC (0.91) and diagnostic accuracy (92.2 %), with a high sensitivity (86.7 %), specificity (97.8 %), positive predictive value (PPV; 97.5 %), and moderate positive likelihood ratio (PLR; 39.4). Among 31 cirrhotic HCC with AFP ≤ 20 ng/ml, the calculated AUC for TGFα was 0.79, with a sensitivity of 64.5 %, specificity of 96.7 %, PPV of 87.0 %, and PLR of 19.5. In conclusion, urinary TGFα and serum AFP are complementary tumor markers for detection of HCC with low AFP production. more...

Rare interstitial lung disease cases have been reported with albinterferon alfa-2b (albIFN) and pegylated interferon alfa-2a (Peg-IFNα-2a) in chronic hepatitis C virus (HCV) patients. Systematic pulmonary function evaluation was conducted in a study of albIFN q4wk vs Peg-IFNα-2a qwk in patients with chronic HCV genotypes 2/3. Three hundred and ninety-one patients were randomly assigned 4:4:4:3 to one of four, open-label, 24-week treatment groups including oral ribavirin 800 mg/d: albIFN 900/1200/1500 μg q4wk or Peg-IFNα-2a 180 μg qwk. Standardized spirometry and diffusing capacity of the lung for carbon monoxide (DLCO) were recorded at baseline, weeks 12 and 24, and 6 months posttreatment, and chest X-rays (CXRs) at baseline and week 24. Baseline spirometry and DLCO were abnormal in 35 (13%) and 98 (26%) patients, respectively. Baseline interstitial CXR findings were rare (4 [1%]). During the study, clinically relevant DLCO declines (≥15%) were observed in 173 patients (48%), and were more frequent with Peg-IFNα-2a and albIFN 1500 μg; 24 weeks posttreatment, 57 patients (18%) still had significantly decreased DLCO, with a pattern for greater rates with albIFN vs Peg-IFNα-2a. One patient developed new interstitial CXR abnormalities, but there were no clinically relevant interstitial lung disease cases. The risk of persistent posttreatment DLCO decrease was not related to smoking, alcohol, HCV genotype, sustained virologic response, or baseline viral load or spirometry. Clinically relevant DLCO declines occurred frequently in chronic HCV patients receiving IFNα/ribavirin therapy and commonly persisted for ≥6 months posttherapy. The underlying mechanism and clinical implications for long-term pulmonary function impairment warrant further research. more...

Background: We investigated the influence of age on intrarenal arterial resistive index (RI) measurement in 135 normal subjects (71 male, 64 female; age range = 17–68 years, median age = 37 years). Methods: Each subject underwent color Doppler measurement of the intrarenal RI from three distinct interlobar arteries in the superior, middle, and inferior parts of both kidneys. The mean of six RI values obtained from both kidneys was used for analysis. The correlation of RI with different variables was investigated by linear regression and stepwise multiple linear regression. Variables analyzed were age, systolic blood pressure, diastolic blood pressure, mean blood pressure, pulse pressure, and pulse rate. Results: The results of linear regression showed that age had a significantly positive correlation (r = 0.276, p = 0.0012) and diastolic blood pressure had a significantly negative correlation (r = −0.186, p = 0.0311) with the RI. The results of stepwise multiple linear regression showed that the combination of age and diastolic blood pressure could explain approximately 15% of the RI changes (r 2 = 0.1535). Conclusion: Although there is a statistically significant positive correlation between intrarenal RI and age, the correlation is weak. This suggests that the influence of age on RI measurement is small and may be of no clinical importance. more...

Host genetic factor and hepatic fibrosis may predispose to risk for hepatocellular carcinoma (HCC). This study aimed to assess the association between tumor necrosis factor (TNF) alpha polymorphism and hepatic fibrosis, and risk for HCC.One hundred eight pairs of gender-matched and age-matched patients with HCC and unrelated healthy controls were genotyped for TNF308.2 and TNF238.2 alleles with polymerase chain reaction and direct sequencing.The frequency of TNF308.1/TNF308.2 genotype in cases was higher than that in controls [odds ratio (OR) = 4.37]. Multivariate analysis indicated that TNF308.2 allele (OR = 3.23), hepatitis B surface antigen (OR = 17.17), and antibodies to hepatitis C virus (OR = 45.52) were independent risk factors for HCC. Surrogate markers for significant fibrosis implied that cases with the TNF308.2 allele have more advanced liver fibrosis. Moreover, multivariate analysis indicated that cirrhosis with Child-Pugh grade C, low serum albumin, and low platelet count were independent risk factors for carrying the TNF308.2 allele.TNF308.2 allele carriage and chronic hepatitis B virus/hepatitis C virus infection are independent risk factors for HCC. Carriage of the TNF308.2 allele correlates with disease severity and hepatic fibrosis, which may contribute to a higher risk for HCC. more...

Summary. The aim of this study was to investigate the association between G vs A transitions in the promoter region of the tumour necrosis factor (TNF) alpha at positions −308 (TNF308.2) and −238 (TNF238.2) and clinical features of chronic hepatitis C (CHC). These two promoter TNF-alpha variants were determined in 250 biopsy-proven CHC patients by polymerase chain reaction amplification, followed by the Restriction Fragment Length Polymorphism (RFLP) method. The distribution of −308 and −238 TNF-alpha promoter genotypes were TNF308.1/TNF308.1: 187 (74.8%), TNF308.1/TNF308.2: 57 (22.8%) and TNF308.2/TNF308.2: 6 (2.4%), respectively, and TNF238.1/TNF238.1: 247 (98.8%) and TNF238.1/TNF238.2: 3 (1.2%). The frequencies of the TNF308.2 and TNF238.2 promoter alleles were 13.8% and 0.6%. Increased TNF308.2 allele copy numbers were significantly associated with increased frequency of lower pretreatment hepatitis C virus (HCV) RNA levels ( more...

The imaging findings of multiple splenic inflammatory pseudotumors in a 45-year-old male are described. Peripheral ring enhancement on arterioportal phase and gradual enhancement from the periphery to the center on venous delay phase on contrast-enhanced dynamic magnetic resonance imaging were compatible with the pathologic findings. This result may aid in the preoperative diagnosis of these benign lesions. more...

The prevalence of TT virus (TTV) and GB virus-C/hepatitis G virus (GBV-C/HGV) infection and the association with raised liver function tests in 546 Taiwanese with negative HBsAg, anti-HCV and HCV RNA was elucidated. They were tested for serum alanine aminotransferase (ALT), GBV-C/HGV RNA, anti-envelope protein 2 antibody (anti-E2) and TTV DNA. Direct sequencing and phylogenetic analyses were performed on 58 isolates for TTV genotype determination. The prevalence of TTV DNA, GBV-C/HGV RNA, anti-E2 and over all GBV-C/HGV exposure was 24.9, 3.4, 8.2 and 11.1%, respectively. Using uni- and multi-variate analyses, male gender and TTV viremia were associated significantly with raised ALT values. Sixty-nine percent of TTV isolates were deduced to be TTV genotype 1 and they had significantly lower mean age than genotype non-1 isolates. In the population, raised ALT may be related to male gender and be attributable to TTV infection but not to GBV-C/HGV among individuals with no evidence of current HBV and HCV infection. TTV genotype 1 is the most prevalent genotype and associated with younger age. more...

The administration of interferon (IFN) could be complicated by the development of neutralizing anti-interferon antibodies (NA). This study evaluates the frequency and associated factors of NA among chronic hepatitis C patients treated with different IFNs.Ninety-five chronic hepatitis C patients were randomized to be treated with recombinant IFN-alpha2a (n = 28), IFN-alpha2b (n = 39) or lymphoblastoid IFN-alpha1 (n = 28) given intramuscularly, 3-6 million units, thrice weekly for 24 weeks. Serum samples collected before, during and after the cessation of treatment were checked for NA.Three patients were withdrawn from treatment. All patients were negative for NA before treatment and 13 (14%) patients developed neutralizing antibodies. Of the 26 patients treated with IFN-alpha2a, 6 (23.1%) developed NA. whereas NA were detected in only 6 (15.4%) of 39 and 1 (3.7%) of 27 patients treated with IFN-alpha2b and IFN-alphanl, respectively. Age, gender, HCV genotype, ALT level, IFN total dose and liver histology were not associated with the development of NA. By using multivariate logistic regression it was shown that pretreatment HCV RNA level and IFN preparation were the two major factors related to the production of NA. The response of treatment was related to pretreatment viremia but not to the presence of NA.The frequency of development of NA among Taiwanese patients with chronic hepatitis C might be related to different IFN preparations and pretreatment HCV RNA level. The response of treatment was related to pretreatment HCV RNA level but not to the presence of NA. more...