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Although current evidence suggests potential antitumor activity of proton pump inhibitors (PPIs), there is no population-based evidence of an association between PPI use and subsequent breast cancer risks. We used an observational case-control study to examine the association between prior PPI use and breast cancer occurrence. Additional analysis examined dose-response and age-stratified associations of PPIs with breast cancer. This study used data from the Taiwan National Health Insurance Research Dataset. A total of 64,234 women diagnosed with breast cancer between 2004 and in 2013 were selected as cases. Controls were 64,234 women without cancer who were selected by matching them with cases on the basis of sociodemographic characteristics and widely prevalent comorbidities. Each study subject's claims data were tracked back for 5 years to determine precancer prescriptions of PPIs. Logistic regression modeling was used for the analysis. A total of 11,871 (9.24%) women had used PPIs within the prior 5 years, 8.06% and 10.42% among cases and controls, respectively. Breast cancer patients were 25% less likely to have had prior PPI exposure after adjustment for comorbidities that predispose to PPI exposure (95%CI 0.72-0.78) in the risk of breast cancer occurrence. A dose-response effect was also detected, with the highest effect, 35% lower PPI odds (95%CI 0.61-0.70) among patients in the highest exposure category. Our findings may suggest that women at a higher-than-average risk of breast cancer may benefit from PPI prescriptions if they have medical conditions that could benefit from PPIs.

Introduction: This study aimed to examine the association between chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and receipt of a prior colonoscopic examination using a populationbased database.Methods: We used the Taiwan Longitudinal Health Insurance Database 2005 to retrieve the study sample. This study included 3933 patients with CP/CPPS and 3933 age-matched controls. We designated the date of receiving the first diagnosis of CP/CPPS as the index date for cases. We defined the first an ambulatory care visit occurring in the matched year as the index date for the controls. Conditional logistic regressions was used to calculate the odds ratio (OR) and 95% confidence interval (CI) for having previously received colonoscopy between cases and controls.Results: We found that 349 (4.44%) of the 7866 sampled patients had previously undergone colonoscopy, including 223 (5.67%) cases and 126 (3.20%) controls (p

The purpose of this study was to investigate the relationship between perforated appendicitis and patient with diabetes using a population-based data set.This study used data from the Longitudinal Health Insurance Database 2005 in Taiwan. We identified 4,806 patients hospitalized with acute appendicitis. The independent variable was whether a patient had ever received a diagnosis of diabetes before the index hospitalization. We performed a conditional logistic regression model to explore the odds ratio and its corresponding 95% confidence interval of perforated appendicitis.Rates of perforated appendicitis for patients with and those without diabetes were 46.2% and 28.3%, respectively. A chi-square test revealed that there was a significant difference in rates of perforated appendicitis between patients with and those without diabetes (P.001). The conditional logistic regression model revealed that the adjusted odds ratio of perforated appendicitis for patients with diabetes was 1.35 (95% confidence interval = 1.11 to 1.65) compared with patients without diabetes.Our study demonstrated that a history of diabetes is an important factor with regard to the rate of perforated appendicitis.

This study demonstrates an association between sialolithiasis and nephrolithiasis. The results call for more awareness of this association among physicians and patients with nephrolithiasis.Very few empirical studies have been conducted to explore the potential association between sialolithiasis and nephrolithiasis. As such, the association between sialolithiasis and nephrolithiasis still remains unclear. This study aimed to explore the possible association between sialolithiasis and nephrolithiasis using a population-based dataset.Using data from the Taiwan Longitudinal Health Insurance Database 2005, this case-control study identified 966 patients with sialolithiasis as cases and 2898 sex- and age-matched subjects without sialolithiasis as controls. Conditional logistic regressions were conducted to examine the association of sialolithiasis with previously diagnosed nephrolithiasis.Out of 3864 sampled patients, 165 (4.27%) had prior nephrolithiasis. Using Chi-square test, it was found that there was a significant difference in the prevalence of prior nephrolithiasis between the cases and controls (10.25% vs 2.28%, p0.001). Moreover, by conditional logistic regression analysis, the odds ratio of prior nephrolithiasis for cases was 4.74 (95% CI = 3.41-6.58, p0.001) when compared to controls after adjusting for monthly income, geographic location, urbanization level of residence, diabetes, hypertension, heart failure, chronic renal disease, and tobacco use.

Objective: To determine whether hepatitis C virus (HCV) infection is a risk factor for developing Parkinson disease (PD). Methods: This nationwide population-based cohort study was based on data obtained from a dataset of the Taiwan National Health Insurance Research Database for the period 2000 to 2010. A total of 49,967 patients with viral hepatitis were included for analysis. Furthermore, 199,868 people without viral hepatitis were included for comparisons. Patients with viral hepatitis were further grouped into 3 cohorts: hepatitis B virus (HBV) infection, HCV infection, and HBV-HCV coinfection. In each cohort, we calculated the incidence of developing PD. A Cox proportional hazards model was applied to estimate the risk of developing PD in terms of hazard ratios (HRs) and 95% confidence intervals (CIs). Results: The crude HRs for developing PD was 0.66 (95% CI = 0.55–0.80) for HBV infection, 2.50 (95% CI = 2.07–3.02) for HCV infection, and 1.28 (95% CI = 0.88–1.85) for HBV-HCV coinfection. The association between HCV and PD remained statistically significant after adjustments for age, sex, and comorbidities (adjusted HR = 1.29, 95% CI = 1.06–1.56). Conclusions: We conducted a large nationwide population-based study and found that patients with HCV exhibit a significantly increased risk of developing PD.

Background Although the appendix may not be considered vital, recent studies have noted adverse health consequences after appendectomy. This study aimed to use a population-based data set to explore whether appendectomy increases the risk for subsequent ischemic heart disease (IHD) in a 3-y follow-up period. Materials and methods This study used data from the Longitudinal Health Insurance Database 2000 in Taiwan. The study cohort included 5413 patients who underwent appendectomies. The comparison cohort was selected by randomly recruiting 16,239 enrollees matched with the study group in terms of sex, age, hypertension, hyperlipidemia, and diabetes. Each individual was tracked for 3 y to identify whether he and/or she developed IHD during the follow-up period. Cox proportional hazard regressions were performed for analysis. Results During a 3-y follow-up, 196 (3.62%) and 375 (2.31%) IHD incidents developed in the study and the comparison cohorts, respectively. For adults aged ≥18 y, experiencing an appendectomy was independently associated with a 1.54-fold increased risk of IHD during the 3 y of follow-up (95% CI = 1.29–1.84). The association persisted in further analyses stratified by age. Conclusions There is an increased risk of subsequent IHD within 3 y after appendectomy, and this underscores the need for more serious clinical decision-making in removing the appendix. Regular monitoring for IHDs is also recommended for patients who have undergone an appendectomy.

ObjectiveGastro-oesophageal reflux disease (GORD) is a common comorbidity among patients with rheumatoid arthritis (RA). While GORD has been attributed to the antirheumatic medications, no studies of human cohorts have investigated a link between GORD and RA. This study investigates whether GORD is associated with a subsequent RA diagnosis over a 5-year follow-up using a population-based dataset.SettingTaiwanParticipantsWe used data from the Taiwan Longitudinal Health Insurance Database. The study group consisted of 13 645 patients with an ambulatory claim showing a GORD diagnosis. We used propensity score matching to select 13 645 comparison patients (one per study patient with GORD).InterventionWe tracked each patient’s claims over a 5-year period to identify those who subsequently received a diagnosis of RA. Cox proportional hazard (PH) regression modelling was used for analysis.ResultsOver 5-year follow-up, RA incidence rate per 1000 person-years was 2.81 among patients with GORD and 0.84 among the comparison group. Cox PH modelling showed that GORD was independently associated with a 2.84-fold increased risk of RA (95% CI 2.09 to 3.85) over 5-year follow-up, after adjusting for the number of ambulatory care visits within the year following the index date (to mitigate surveillance bias).ConclusionsWe observed that GORD might associate with subsequent RA occurrence. Because current treatment guidelines for RA emphasise early diagnosis and prompt treatment, the observed association between GORD and RA may help acquaint clinicians to patients with GORD with higher RA risk and facilitate early diagnosis and treatment.

AIM: To investigate variations in the incidence of peptic ulcers (PUs) in Taiwan by day of the week within age subgroups. METHODS: Ambulatory care data were retrieved from the Longitudinal Health Insurance Database 2000. There were 7204 subjects ≥ 18 years-old with an emergency room admission claim for the treatment of PUs, resulting in a total of 9234 emergency room visits for PUs between 2009 and 2011. Data was divided into the seven days of the week and an additional variable for holidays. One-way analysis of variance was used to examine associations among the daily mean number of PU emergency room admissions and holidays/weekends/weekdays. RESULTS: One-way analysis of variance showed that there was a significant difference in emergency room admissions for PUs by the day of the week (P < 0.001), with admission more likely to occur on Sundays or holidays than weekdays within the total and working populations. The weekday patterns of admission were similar for the patients aged 18-64 years and ≥ 65 years of age. Holidays, followed by Sundays, had higher PU admissions than the mean daily PU emergency room admissions. Furthermore, inclusion of only those treated for PUs with hemorrhage or perforation, Sundays and holidays had higher mean emergency room admissions than other days. Inclusion of patients who diagnosed with Helicobacter pylori infection, only holidays had higher mean emergency room admissions than other days. Inclusion of patients who had been prescribed non-steroidal anti-inflammatory drugs (NSAIDs) for over 30 d, Sundays and holidays had higher mean PU ER admissions than other non-holiday weekdays. CONCLUSION: There is a higher incidence of emergency room admission for PUs on weekends than on weekdays for the total and working populations.

SummaryObjective Ulcerative colitis (UC) is a chronic relapsing inflammatory disease with significant clinical diversity. However, the aetiology, pathogenesis and optimal treatment of UC remain unclear. The purpose of this case-control study was to investigate the association between previously diagnosed hyperthyroidism and UC using a large population-based data set in Taiwan. Methods The data for this population-based case-control study were retrieved from the Taiwan Longitudinal Health Insurance Database 2005. We included 2709 patients with UC as cases and 8127 sex- and age-matched patients without UC as controls. A conditional logistic regression analysis was conducted to compute the odds ratio (OR) and corresponding 95% confidence interval (CI) for the association between UC and prior hyperthyroidism. Results We found that, in total, 327 of the 10 836 sampled patients (3.02%) had previously been diagnosed with hyperthyroidism. There was a higher proportion of prior hyperthyroidism among cases than controls (4.10% vs 2.66%, P

This retrospective cohort study examined the relationship between a cholecystectomy and the subsequent risk of peptic ulcers using a population-based database. Data for this study were retrieved from the Taiwan Longitudinal Health Insurance Database 2005. This study included 5209 patients who had undergone a cholecystectomy for gallstones and 15,627 sex- and age-matched comparison patients. We individually tracked each patient for a 5-year period to identify those who subsequently received a diagnosis of peptic ulcers. We found that of the 20,836 sampled patients, 2033 patients (9.76%) received a diagnosis of peptic ulcers during the 5-year follow-up period: 674 from the study group (12.94% of the patients who underwent a cholecystectomy) and 1359 from the comparison group (8.70% of the comparison patients). The stratified Cox proportional hazard regressions showed that the adjusted hazard ratio (HR) for peptic ulcers during the 5-year follow-up period was 1.48 (95% CI = 1.34~1.64) for patients who underwent a cholecystectomy than comparison patients. Furthermore, the adjusted HRs of gastric ulcers and duodenal ulcers during the 5-year follow-up period were 1.70 and 1.71, respectively, for patients who underwent a cholecystectomy compared to comparison patients. This study demonstrated a relationship between a cholecystectomy and a subsequent diagnosis of peptic ulcers.

Background This retrospective cohort study examined whether diabetic patients have a higher risk for recurrent appendicitis during a 1-year follow-up period after successful antibiotic treatment for patients with acute uncomplicated appendicitis than nondiabetic patients using a population-based database. Methods We included 541 appendicitis patients who received antibiotic treatment for acute appendicitis. We individually tracked each patient for a 1-year period to identify those who subsequently underwent an appendectomy during the follow–up period. Results Cox proportional hazard regressions suggested that the adjusted hazard ratio of an appendectomy during the 1-year follow-up period was 1.75 for appendicitis patients with diabetes than appendicitis patients without diabetes. We found that among females, the adjusted hazard ratio of an appendectomy was 2.18 for acute appendicitis patients with diabetes than their counterparts without diabetes. However, we failed to observe this relationship in males. Conclusions We demonstrated a relationship between diabetes and a subsequent appendectomy in females who underwent antibiotic treatment for noncomplicated appendicitis.

Appendicitis and gastroesophageal reflux disease (GERD) are both prevalent diseases and might share similar pathological mechanisms. The aim of this study was to investigate the association between GERD and appendicitis using a large population-based dataset. This study used administrative claims data from the Taiwan Longitudinal Health Insurance Database 2005. We identified 7113 patients with appendicitis as cases, and 28452 matched patients without appendicitis as controls. This study revealed that GERD was found in 359 (5.05%) cases and 728 (2.56%) controls (p

Background and Aim: Hepatocellular carcinoma (HCC) is the leading cause of cancer-related deaths in Taiwan. HCC with duodenal involvement are rare and are associated with a poor prognosis. The purpose of this retrospective study was to collect clinical information and data regarding survival following various treatments. Methods: Between 1996 and 2009, 21 cases (17 men) were diagnosed with HCC and duodenal invasion and metastases by diagnostic imaging, endoscopy with biopsy, or surgically collected specimens sent to pathology. The clinical course was analyzed from the patients' medical records. Results: Gastrointestinal bleeding was reported in 18/21 patients. Diagnostic imaging showed that the majority of cases involved direct tumor invasion (predominantly from the right liver lobe) and six cases from metastasis. Tumor mass and ulcerations were the most common features noted on endoscopy. In addition to the component therapy and medication treatment, panendoscopic hemostasis, surgery, transcatheter arterial embolization, and radiotherapy were performed for the management of duodenal involvement and gastrointestinal bleeding. Survival duration after duodenal involvement ranged from 0.2 to 57.8 months (mean 10.5 months). Conclusions: Gastrointestinal bleeding in advanced HCC should raise suspicions of duodenal involvement. HCC can involve the duodenum by direct invasion (from either the left or right liver lobes) or metastasis. The prognosis for HCC patients with duodenal involvement is poor, but is improved by supportive care and application of various treatment modalities.

Despite some studies having indicated a possible association between appendicitis and duodenal ulcers, this association was mainly based on regional samples or limited clinician experiences and as such, did not permit unequivocal conclusions. In this case-control study, we examined the association of acute appendicitis with peptic ulcers using a population-based database. We included 3574 patients with acute appendicitis as cases and 3574 sex- and age-matched controls. A Chi-squared test showed that there was a significant difference in the prevalences of prior peptic ulcers between cases and controls (21.7% vs. 16.8%, p p pared to controls. The results further revealed that younger groups demonstrated higher ORs for prior peptic ulcers among cases than controls. In particular, the adjusted OR for cases p

Hepatitis delta virus (HDV) encodes two isoforms of delta antigens (HDAgs). The small form of HDAg (SHDAg) is required for HDV RNA replication, while the large form of HDAg (LHDAg) is required for viral assembly. Using tandem affinity purification method combined with mass spectrometry, we found that linker histone H1e bound to SHDAg. The binding domain of SHDAg to histone H1e was mapped to the N-terminal 67 amino acids. Oligomerization of SHDAg was required for its interaction with histone H1e. LHDAg barely bound to histone H1e and was masked at N-terminus. The binding domain of histone H1e to SHDAg was mapped to its central globular domain. HDV replication was inhibited by N- or C-terminal deletion mutants of histone H1e and was rescued by wild-type histone H1e. We conclude that histone H1e plays a significant role in HDV replication through forming protein complex with SHDAg.

Genomic heterogeneity has been shown to be associated with Klebsiella pneumoniae strains causing pyogenic liver abscesses (PLA) and metastatic infections. In order to explore the mechanism responsible for genomic heterogeneity in K. pneumoniae , we compared the complete genomic sequences of strains NTUH-K2044 and MGH78578. An ∼76-kbp DNA fragment located adjacent to an asparagine ( asn ) tRNA gene was present in NTUH-K2044 but not in MGH78578. This fragment could be divided into three regions with different functions, and structurally it resembled a functional integrative and conjugative element (ICE), ICE Ec1 , in Escherichia coli . The 5′ region of this fragment contained genes similar to a high-pathogenicity island (HPI) of Yersinia pestis and Yersinia pseudotuberculosis . The middle region was similar to part of a large plasmid in K. pneumoniae , and the 3′ region contained genes responsible for DNA conjugative transfer. Therefore, this DNA fragment was designated ICE Kp1 . Precise excision and extrachromosomal circularization of ICE Kp1 were detected in K. pneumoniae wild-type strain NTUH-K2044. ICE Kp1 could integrate into the asn tRNA loci of the chromosome of another K. pneumoniae isolate. The prevalence of ICE Kp1 was higher in PLA strains (38 of 42 strains) than in non-tissue-invasive strains (5 of 32 strains). Therefore, ICE Kp1 may contribute to the transmission of the HPI and result in K. pneumoniae PLA infection-associated genomic heterogeneity.

To evaluate whether the tumour suppressor gene, PPP2R1B, is involved in pathogenesis of hepatocellular carcinoma (HCC), reverse transcription-polymerase chain reaction (RT-PCR) and cDNA sequencing were performed. Eleven of 38 (29%) tumours and 1 of 34 (3%) corresponding non-tumour tissues showed coexpression of wild-type and aberrant mRNA. Various deletions were found in aberrant transcripts. Southern blot analysis did not show gene deletion in tumours, suggesting abnormal RNA splicing may be involved. These data suggest the possibility that aberrant transcripts of PPP2R1B might be associated with the development of HCC.

Background This study aimed to compare clinical outcome between laparoscopic and open right hemicolectomy. Methods The data were sourced from Taiwan’s National Health Insurance Research Database. This study included 14,320 and 1313 patients who underwent open and laparoscopic right hemicolectomies, respectively. The study outcome included “intensive care unit (ICU) admission,” “over 2 h of general anesthesia,” “use of mechanical ventilation,” “acute respiratory failure,” “in-hospital death,” and “hospitalization for pneumonia.” Separate conditional logistic regressions were performed for each clinical outcome. Results The results showed that patients who underwent an open right hemicolectomy had significantly higher likelihood of ICU admission (31.4 vs. 13.4 %, p

Background Prior studies indicate a possible association between depression and cholecystectomy, but no study has compared the risk of post-operative depressive disorders (DD) after cholecystectomy. This retrospective follow-up study aimed to examine the relationship between cholecystectomy and the risk of DD in patients with gallstones in a population-based database. Methods Using ambulatory care data from the Longitudinal Health Insurance Database 2000, 6755 patients who received a first-time principal diagnosis of gallstones at the emergency room (ER) were identified. Among them, 1197 underwent cholecystectomy. Each patient was then individually followed-up for two years to identify those who were later diagnosed with DD. Cox proportional hazards regressions were performed to estimate the risk of developing DD between patients with gallstone who did and those who did not undergo cholecystectomy. Results Of 6755 patients with gallstones, 173 (2.56%) were diagnosed with DD during the two-year follow-up. Among patients who did and those who did not undergo cholecystectomy, 3.51% and 2.36% later developed depressive disorder, respectively. After adjusting for the patient’s sex, age and geographic location, the hazard ratio (HR) of DD within two years of gallstone diagnosis was 1.43 (95% CI, 1.02–2.04) for patients who underwent cholecystectomy compared to those who did not. Females, but not males, had a higher the adjusted HR of DD (1.61; 95% CI, 1.08–2.41) for patients who underwent cholecystectomy compared to those who did not. Conclusions There is an association between cholecystectomy and subsequent risk of DD among females, but not in males.

Background Physicians are considered to be the most informed consumers in the use of medical services since they have more information about diseases or medical technology. However, although plenty of researchers have suggested that different medical seeking behavior exists among physicians, very few empirical studies have been conducted to investigate differences in medical utilization between physicians and the general population. Objective We explored differences in the utilization of healthcare services between physicians and the general population using a population-based dataset. Design A cross-sectional study. Participants Data for this study were sourced from the Taiwan Longitudinal Health Insurance Database 2000. We included 1426 physicians and 1426 sex- and age-matched comparison subjects. Methods We used Wilcoxon-Mann-Whitney tests to explore differences in variables of healthcare resource utilization between physicians and comparison subjects. We further used Kruskal-Wallis tests to examine differences in variables of healthcare resource utilization between physician practice location and comparison subjects. Results We found that physicians had significantly fewer outpatient visits (13.2 vs. 15.7, p

Background Altered immune function after appendicectomy has been associated with autoimmune disease, even though the mechanisms are not clearly elucidated. This study aimed to investigate whether the frequency of new-onset type II diabetes was increased after appendicectomy in a case–control study. Methods This was a retrospective cohort study from the Taiwan Longitudinal Health Insurance Database 2000. The relative risk was compared with that in the general population using population-based data. Each patient was tracked for a 3-year interval to identify those who developed type II diabetes. Cox proportional hazard regression analysis was used to assess the risk of type II diabetes during follow-up. Results A total of 31 512 patients were included in the study, of whom 5252 had an appendicectomy (study cohort) and 26 260 were matched for comparison. Some 714 patients (2·3 per cent) developed type II diabetes during the 3-year follow-up, 161 in the study cohort (3·1 per cent) and 553 in the comparison cohort (2·1 per cent). The adjusted hazard ratio (HR) for type II diabetes in the study cohort was 1·45 (95 per cent c.i. 1·22 to 1·74). This increased risk was most pronounced in men (adjusted HR 1·47, 1·16 to 1·88) and in those with a perforated appendix (adjusted HR 2·28, 1·71 to 3·03), and applied only to patients younger than 65 years of age. Conclusion An increased risk of new-onset type II diabetes within 3 years after appendicectomy was found in patients aged less than 65 years. The risk was highest in men and in those with complicated appendicitis.

Aims The study was designed to survey the change of adiponectin levels before and after interferon-alpha (IFN-alpha) therapy in patients with chronic hepatitis B and C infections. Methods Twenty-one biopsy-proved patients with chronic hepatitis B (10 cases) and hepatitis C (11 cases) were given IFN-alpha for a total of 24 weeks. Fasting plasma glucose, insulin and adiponectin levels were obtained before and 12 weeks after completion of IFN-alpha therapy. Insulin suppression test was conducted before and within 1 week after IFN-alpha therapy. Results The change of adiponectin levels differed significantly between responders (eight cases) and non-responders (13 cases) to IFN-alpha treatment (-4.8+/-2.2 vs. 0.5+/-1.0 microg/ml, P=0.03). After adjusting for age, gender and change in body mass index, the study found the change of adiponectin levels still significantly related to the response to IFN-alpha (P=0.04). When hepatitis B virus (HBV) and hepatitis C virus (HCV)-infected patients were separately analyzed, the adiponectin levels reported a trend to decrease in HCV responders (11.9+/-3.2 vs. 10.8+/-3.0 microg/ml, P=0.02, n=4) and HBV responders (17.7+/-4.1 vs. 9.2+/-1.0 microg/ml, P=0.10, n=4). In addition, a significant decrease of steady-state plasma glucose in insulin suppression test was noted in responders (13.6+/-1.8-11.7+/-1.2 mmol/l, P=0.03), but not in non-responders (12.3+/-1.1-11.0+/-1.0 mmol/l, P=0.20), after IFN-alpha therapy. Conclusions IFN-alpha resulted in a decrease of serum adiponectin levels but an improvement of insulin resistance in responders to the treatment. The result contradicts previous concept of the relationship between insulin resistance and adiponectin levels. Whether and how the augmented immune response, which was supposed to result from the disappearance or the profound down-regulation of the virus or viral antigens in responders to IFN-alpha treatment, contributes to the lowering of adiponectin levels needs to be further investigated.

Klebsiella pneumoniae liver abscess with metastatic complications is an emerging infectious disease in Taiwan. To identify genes associated with liver infection, we used a DNA microarray to compare the transcriptional profiles of three strains causing liver abscess and three strains not associated with liver infection. There were 13 clones that showed higher RNA expression levels in the three liver infection strains, and 3 of these 13 clones contained a region that was absent in MGH 78578. Sequencing of the clones revealed the replacement of 149 bp of MGH 78578 with a 21,745-bp fragment in a liver infection strain, NTUH-K2044. This 21,745-bp fragment contained 19 open reading frames, 14 of which were proven to be associated with allantoin metabolism. The K2044 (Δ allS ) mutant showed a significant decrease of virulence in intragastric inoculation of BALB/c mice, and the prevalence of this chromosomal region was significantly higher in strains associated with liver abscess than in those that were not (19 or 32 versus 2 of 94; P = 0.0001 [χ 2 test]). Therefore, the 22-kb region may play a role in K. pneumoniae liver infection and serve as a marker for rapid identification.

BACKGROUND : By NAT, HBV DNA is occasionally detectable in blood donors with past HBV infection but negative for HBsAg. Whether or not these donors can cause transfusion-transmitted HBV infections is uncertain. STUDY DESIGN AND METHODS : To determine whether or not donors with past HBV infection but negative for HbsAg can cause HBV transfusion-transmitted infections, recipients followed for blood transfusion in a university medical center in Taiwan were studied. HBV DNA and serologic markers were tested in donors and recipients. RESULTS : Of 1038 enrolled recipients, 910 completed the 6-month post-transfusion follow-up visit. Of these, only 39 patients (4.3%) tested negative on the pretransfusion sample for HBsAg, anti-HBs, anti-HBc, and HBV DNA by PCR. These 39 HBV-naive recipients had been transfused with blood from 147 donations for which stored samples were available for HBV DNA testing by PCR; 11 of these HBsAg-negative samples tested positive for HBV DNA and anti-HBc. Two of the 11 patients who received the HBV-DNA-positive donations (18%) became positive for HBV DNA, and one seroconverted to anti-HBc and finally to anti-HBs, with a mild transient elevation of serum ALT activities. Based on the one confirmed case of HBV transmission, a projection was made that approximately 200 post-transfusion HBV infections could occur in one million units of transfused blood in Taiwan. CONCLUSIONS : In HBV-endemic areas like Taiwan, where blood donors are screened for HBsAg only, the risk of transfusion-transmitted HBV appears to be substantial. Implementation of NAT for blood screening in these settings warrants consideration.

Aim: We sought to evaluate whether serum HBV DNA levels correlates with the liver free HBV DNA levels in chronic hepatitis B. Methods: Thirty-three consecutive chronic hepatitis B patients with cirrhosis were included in this study. Twenty cases had detectable serum HBV DNA (> 1.8 pg/ml). All had detectable free liver HBV DNA. Results: There was a strong correlation between the serum and liver HBV DNA levels (P = 0.0018, r = 0.717). Thirteen cases had undetectable serum HBV DNA. Among them, six cases still had detectable liver free HBV DNA. Eight cases were HBeAg-positive. Among them, seven cases were positive for both serum and liver HBV DNA, and one case was negative for both serum and liver HBV DNA. Twenty-five cases were HBeAg-negative and anti-HBe-positive. Among them, 13 cases were positive for serum HBV DNA, and 19 cases were positive for liver HBV DNA. No significant difference was noted for positivity of serum HBV DNA or liver free HBV DNA between HBeAg-positive and HBeAg-negative groups. The level of serum HBV DNA(491 ± 772 pg/ml versus 203 ± 447 pg/ml, p = 0.07) and liver free HBV DNA (33 ± 81 pg/µg versus 6 ± 15 pg/µg, p = 0.13) was also not statistically different. Conclusion: In conclusion, serum HBV DNA levels is strongly correlated with liver HBV DNA levels in chronic hepatitis B with cirrhosis. Liver free HBV DNA can still be detected in about half of the cirrhotic patients with undetectable serum HBV DNA. Serum HBeAg is not a good predictor of serum or liver HBV DNA levels in cirrhotic patients.

BackgroundPsoriasis is a prevalent autoimmune disorder. Various studies have reported on the relationship between psoriasis and chronic diseases but very few have explored the association between psoriasis and subsequent acute infection. This retrospective cohort study aimed to compare the risk of pneumonia between subjects with and those without psoriasis.MethodsThe medical records of 14,022 patients with psoriasis and 14,022 without psoriasis were obtained from the Taiwan Longitudinal Health Insurance Database 2000. Each patient was followed-up for a three-year period. Cox proportional hazard regressions were performed to compare difference of subsequent pneumonia incidence between subjects with and those without psoriasis.ResultsThere were 206 (1.47%) subjects with psoriasis and 138 (0.98%) without psoriasis hospitalized for pneumonia. By Cox proportional hazard regressions analysis, the HR (hazard ratio) of pneumonia requiring hospitalization for patients with psoriasis was 1.50 (95% confidence interval [CI]: 1.21-1.86) compared to patients without psoriasis. The adjusted HR was 1.40 (95% CI: 1.12-1.73). The adjusted HR of pneumonia hospitalization for subjects with mild and severe psoriasis was 1.36 (95% CI: 1.09-1.70) and 1.68 (95% CI: 1.12-2.52), respectively, compared to those without psoriasis.ConclusionsPatients with psoriasis have significantly higher incidence of pneumonia compared to those without psoriasis.

Helicobacter pylori is the causative agent of chronic superficial gastritis in humans, and the presence of this organism increases risk of development of peptic ulcer disease and adenocarcinoma and mucosa-associated lymphoid tissue lymphoma of the distal stomach (2, 3, 10, 19, 21). The mechanism of pathogenesis remains largely unknown. The ability to survive under acidic stomach conditions might be one of the virulence mechanisms. Monitoring the response of H. pylori genes during acid stress may be helpful to understand the pathogenesis. Expression of many bacterial genes is induced in response to environmental stimuli (17). For technical reasons, only a limited subset of genes could be simultaneously analyzed until recently. Differential display of subsets of mRNA on a sequencing gel allows a broad search for expression differences (11, 15), but the method has been difficult to standardize. An rRNA subtraction approach has been used to identify differentially expressed genes in Mycobacterium avium (23); however, removal of rRNA by subtraction caused loss of mRNA. Chuang et al. (6) have analyzed differentially expressed genes in Escherichia coli by a method based on hybridization to spot overlapping λ clones. This method required subcloning and subsequent sequencing for the identification of relevant genes. Recently, a system for monitoring of a large number of gene expressions has been developed in eukaryotes using DNA microarray (5, 23, 24) or oligonucleotide microarray (16, 22, 29). Labeled cDNA, or in vitro-transcribed mRNA, was hybridized to the high-density probe microarray. Microarrays are able to analyze the expression of hundreds of genes in a single hybridization experiment. DNA array has also been recently adopted for monitoring gene expressions in bacteria. Unfortunately, since bacterial mRNA could not be separated from rRNA, large amounts of total RNAs are needed for probe labeling, and confocal microscopy is usually necessary for result interpretation (8, 28). A method of “differential expression using customized amplification libraries” that needs only small amounts of total RNA for analysis has been developed (1). However, the optimal restriction enzyme for cosmid library construction, one that would exclude contamination by all the rRNA clones, was difficult to select. We adopted a catalyzed amplification of reporter deposition (CARD) method to explore the gene expression of H. pylori in genomic scale (5).

This study attempted to identify a possible antibody response to Helicobacter pylori, which is associated with patients with adeno-carcinoma of the stomach. By using proteins of H. pylori as the antigen, pooled sera from gastric cancer and non-cancer patients were used as the first antibody for Western blot analysis. Antibody responses to a 26 kD secreted protein were observed in pooled cancer sera, but not in pooled sera from non-cancer patients. The protein was purified, while amino acid sequences revealed that it was a H. pylori species specific protein. The gene of this protein was cloned and a recombinant protein was expressed in E. coli. In addition, an antibody to the recombinant protein was tested in each individual patient using Western blot analysis. None of the forty non-gastric cancer patients were positive for the antibody to the recombinantly expressed 26 kD species specific protein. Meanwhile, six of the twenty four cancer patients tested positive (0/40 vs 6/24, p0.01). Results presented herein demonstrate that the species specific protein of H. pylori can be useful in detecting H. pylori associated with adenocarcinoma of the stomach.

To study the incidence and outcome of GB virus C (GBV-C) infection in blood recipients. Serum samples collected in a prospective study were examined for GBV-C RNA by a nested polymerase chain reaction assay. Among the 400 adults who underwent cardiac surgery, 40 were positive for GBV-C RNA, including six whose pretransfusion sera were already positive and seven coinfected with hepatitis C virus (HCV) during transfusion. The risk of transmission was estimated to be approximately 0.46% per donor. GBV-C viremia was detectable 1 week after transfusion and could persist for 8 years. However, no evident symptoms or signs were noted in the 25 patients infected by GBV-C alone, and the average peak serum alanine aminotransferase activity was 31 IU/L only (range, 12 to 123), with persistently normal levels in 20 patients. In the seven patients coinfected with HCV, the clinical courses of posttransfusion hepatitis were similar to those infected by HCV alone. In eight patients with posttransfusion non-A approximately E hepatitis, only one was positive for GBV-C RNA. Sixty samples were chosen to test hepatitis G virus (HGV) sequences, 26 of the 30 GBV-C positives were positive for HGV RNA in contrast to none of the 30 GBV-C negative samples. In conclusion, GBV-C can be transmitted by transfusion in approximately 9% of patients who underwent cardiac surgery. Nevertheless, this virus does not seem to cause classic hepatitis in most instances.

Hepatitis delta virus (HDV) encodes two proteins, the small delta antigen (SHDAg) and large delta antigen (LHDAg). The latter is identical to the former except for the presence of additional 19 amino acids at the C terminus. While SHDAg is required for HDV replication, LHDAg inhibits replication and, together with hepatitis B surface antigen (HBsAg), is required for the assembly of HDV. The last 19 C-terminal amino acids of LHDAg are essential for HDV assembly. Most of LHDAg (amino acids 19 to 146 and 163 to 195) had been shown to be dispensable for packaging with HBsAg. To discern whether the last 19 C-terminal amino acids solely constitute the signal for packaging with HBsAg, we constructed two LHDAg deletion mutants and tested their abilities to be packaged with HBsAg in cotransfection experiments. We found that deletion of amino acids 2 to 21 and 142 to 165 did not affect LHDAg packaging. This result suggested that only the last 19 C-terminal amino acids of LHDAg are required for packaging. We further constructed two plasmids which expressed c-H-ras with or without additional 19 C-terminal amino acids identical to those in LHDAg. Only c-H-ras with additional 19 amino acids could be cosecreted with HBsAg in the cotransfection experiment. This result confirmed that the C-terminal 19 amino acids are the packaging signal for HBsAg. We also tested the trans activation activity and trans-dominant inhibitory activity of the deletion mutants of SHDAg and LHDAg, respectively. In contrast to deletion of amino acids 142 to 165, deletion of amino acids 2 to 21 impaired the trans-dominant inhibitory activity of LHDAg. Deletion of amino acids 2 to 21 and 142 to 165 did not affect the trans activation activity of SHDAg. This result suggested that a functional domain which is important for the trans-dominant inhibitory activity of LHDAg exists in the amino terminus of HDAg.

A national screening programme for antibody to hepatitis C virus (HCV) in blood donors in Taiwan began in July 1992 using a second-generation immunoassay. To study the impact of this screening on post-transfusion hepatitis in Taiwan, a prospective study on post-transfusion hepatitis, that was started in 1987, was continued. As of June 1994, 245 patients who received a blood transfusion after July 1992 had completed a follow-up period for more than 6 months post-transfusion. Of them, seven (2.8%) recipients developed acute post-transfusion hepatitis. The hepatitis in six cases could not be attributed to infection by hepatitis A, B, C, D, E viruses or cytomegalovirus (CMV) or Epstein-Barr virus (EBV). The remaining patient seroconverted to both IgG and IgM anti-CMV. All seven patients recovered in 6 months without development of chronicity, and the mean peak alanine aminotransferase level was lower compared with that of the cases before anti-HCV screening (i.e. pre-July 1992). These results indicate that the current anti-HCV screening has effectively interrupted HCV transmission through blood transfusion in Taiwan.

Hepatitis delta virus (HDV) encodes two proteins, the small hepatitis delta antigen (SHDAg) and large hepatitis delta antigen (LHDAg). Both proteins are identical except for the presence of additional 19 amino acids at the C terminus of LHDAg. While SHDAg is required for HDV RNA replication, LHDAg inhibits replication and is required together with hepatitis B surface antigen for the assembly of HDV. The C-terminal last 4 amino acids of LHDAg (Cys-Arg-Pro-Gln) is an isoprenylation motif. It has previously been shown that the mutation of the Cys inhibited the assembly of HDV. In order to discern whether this effect is due to change of amino acid residue or abolition of isoprenylation, we constructed several LHDAg mutants of the terminal three amino acid residues and tested their abilities to be packaged with HBsAg by cotransfection experiments. We also made GST-fusion proteins of these mutants and tested their abilities to be isoprenylated in rabbit reticulocyte lysate system. We found that some, but not all, of the substitutions of the amino acid residues other than the Cys also inhibited isoprenylation and that the status of isoprenylation of these mutant proteins correlated well with their abilities to be packaged with HBsAg into virions. This result indicates that isoprenylation, rather than the primary amino acid sequence, is required for LHDAg packaging. Furthermore, we found that the attachment of an isoprenylation motif to SHDAg did not enable it to be packaged with HBsAg and that the deletions of any 5 amino acids in the last 15 amino acids (amino acids 196 to 210) unique to the LHDAg abolished the packaging ability. In contrast, the deletion of 33 amino acids (amino acids 163 to 195) upstream of the last C-terminal 19 amino acids of LHDAg did not interfere with its packaging ability. Therefore, we conclude that the 15 amino acids upstream of the isoprenylation site of LHDAg are also essential for HDV assembly, and a large portion of the alleged C-terminal Pro/Gly-rich region (amino acids 146 to 195) is not required for the assembly process.

Hepatocellular carcinoma (HCC) is the leading cause of cancer-related deaths in Taiwan. HCC with duodenal involvement are rare and are associated with a poor prognosis. The purpose of this retrospective study was to collect clinical information and data regarding survival following various treatments.Between 1996 and 2009, 21 cases (17 men) were diagnosed with HCC and duodenal invasion and metastases by diagnostic imaging, endoscopy with biopsy, or surgically collected specimens sent to pathology. The clinical course was analyzed from the patients' medical records.Gastrointestinal bleeding was reported in 18/21 patients. Diagnostic imaging showed that the majority of cases involved direct tumor invasion (predominantly from the right liver lobe) and six cases from metastasis. Tumor mass and ulcerations were the most common features noted on endoscopy. In addition to the component therapy and medication treatment, panendoscopic hemostasis, surgery, transcatheter arterial embolization, and radiotherapy were performed for the management of duodenal involvement and gastrointestinal bleeding. Survival duration after duodenal involvement ranged from 0.2 to 57.8 months (mean 10.5 months).Gastrointestinal bleeding in advanced HCC should raise suspicions of duodenal involvement. HCC can involve the duodenum by direct invasion (from either the left or right liver lobes) or metastasis. The prognosis for HCC patients with duodenal involvement is poor, but is improved by supportive care and application of various treatment modalities.

Hepatitis delta virus (HDV) encodes only one protein, the hepatitis delta antigen (HDAg). Two forms of HDAg, a large (27 kDa) and a small (24 kDa) one, participate in the various steps of HDV replication. To further understand the properties of HDAg, we have constructed recombinant baculoviruses and expressed both forms of the HDAg in insect cells. The gene encoding HDAg was placed under the control of the polyhedrin promoter of Autographa Californica nuclear polyhedrosis virus (AcNPV) by homologous recombination. When Spodoptera frugiperda (Sf9) cells were infected with the recombinant viruses, both the small HDAg and the large HDAg were expressed at high levels. The HDAgs produced by the recombinants were similar in size and antigenic properties to those of the proteins produced in mammalian hepatoma cell lines. It was also localized exclusively in the nuclei. In addition, both proteins bound to HDV RNA in an in vitro assay. No difference in the RNA-binding affinity was noted between the two forms of HDAg, suggesting that the trans-dominant inhibitory activity of the large HDAg on HDV replication is not due to its competition with the small HDAg for RNA binding. Two RNA-protein complexes could be detected, suggesting either that there are at least two binding sites on the HDV RNA or that HDAg binds to HDV RNA in two multimeric forms. We have further shown that both the large and the small HDAgs are phosphoproteins, with the former having an approximately sixfold higher level of phosphorylation. Finally, it was demonstrated that the large HDAg was isoprenylated, while the small one was not. These differences in post-translational modifications are the first differences in biochemical properties demonstrated between the two forms and may explain the differential effects of the large and small HDAgs on HDV RNA replication and virus packaging.

Liver progenitors, so-called oval cells, proliferate remarkably from periportal areas after severe liver injury when hepatocyte regeneration is compromised. These cells invade far into the liver parenchyma. Molecular mechanisms underlying these behaviors of oval cells remain poorly understood. In this study, we treated rats with 2-acetylaminofluorene/carbon tetrachloride to induce hepatic oval cells. By expression microarray analysis, we investigated global gene expression profiles in liver tissue, with an emphasis on adhesion molecules, extracellular matrix proteins, matrix metalloproteinases (MMPs), growth factors/cytokines, and receptors that might contribute to the distinct behaviors of oval cells. Genes upregulated at least twofold were selected. We then performed immunostaining to verify the microarray results and identified expression of MMP-7 and CD44 in oval cells. Staining of cytokeratin (CK)-19, an oval-cell marker, was similar between oval cells located next to periportal areas and those located far within the parenchyma. In contrast, CD44 staining was more intense in the parenchyma than in periportal areas, suggesting a role of CD44 in oval-cell invasion. Moreover, newly differentiated CK-19+ hepatocytes within foci did not show CD44 staining, suggesting that CD44 is related to the undifferentiated oval-cell phenotype. We then investigated oval-cell reactivity in CD44-deficient mice fed an oval cell-inducing diet of 3,5-diethoxycarbonyl-1,4-dihydrocollidine. Results showed significantly reduced oval-cell reactivity in CD44-deficient mice. Thus, oval cells express MMP-7 and CD44, and CD44 appears to play critical roles in the proliferation, invasion, and differentiation of hepatic oval cells in rodents.

Background Klebsiella pneumoniae has become the predominant pathogen causing primary pyogenic liver abscess (PLA). Methods K. pneumoniae was stimulated by human serum, and gene expression was analyzed by microarray. Results Three putative iron acquisition systems, Yersinia high-pathogenicity island (HPI), iucABCDiutA, and iroA(iroNDCB), that increased in expression and predominated in PLA-associated K. pneumoniae strains were identified. By use of siderophore uptake assays, these 3 systems were confirmed to be siderophore-dependent iron acquisition systems. Only the irp2-iuc-iroA triple mutant showed decreased virulence in mice. Full-genome analysis of K. pneumoniae strain NTUH-K2044 identified 10 putative iron uptake systems. Seven of these 10 systems were TonB dependent, including Yersinia HPI, iucABCDiutA, and iroA. A tonB deletion mutant was demonstrated to have profound attenuation of virulence. Immunization with the tonB mutant resulted in seroconversion of extracellular polysaccharide antibodies and protective efficacy against subsequent exposure to the parental strain. Conclusions Iron uptake systems were the genes in K. pneumoniae that were highly up-regulated in response to sera. Although there are multiple iron transporter systems in NTUH-K2044, a mutation in all 3 loci (irp2, iuc, and iroA) is necessary to decrease virulence. The tonB mutant is a potential vaccine candidate because it can induce a significant protective immune response against challenge with a wild-type strain.

Hepatocellular carcinoma (HCC) is prevalent in Southeast Asia and sub-Saharan Africa.1 With the widespread use of alpha fetoprotein (AFP), ultrasound, and other diagnostic modalities as screening tools, many small HCC tumors are detected before symptoms develop and are treated effectively.2,3 Surgical resection is considered the standard treatment of small HCCs, and results have been promising.4 Initially, percutaneous ethanol injection therapy (PEIT) was considered an alternative treatment of patients with small HCC and poor liver reserve for whom resection posed the risk of liver failure. However, several studies have shown similar or even better results with PEIT than with surgical resection.5–7 In Taiwan, HCC is the leading cause of cancer mortality. Many small HCCs are detected by surveillance, and routine surveillance of at-risk groups has been common in daily practice for at least a decade.2,3 Resection and PEIT are both widely used for the treatment of small HCCs,4,8 and the Taiwan National Health Insurance covers both treatments. Because the existing literature does not contain objective comparisons of these 2 treatment modalities9 and a prospective randomized comparative trial has been suggested repeatedly,9–11 we performed a randomized study comparing surgicalresection with PEIT for the treatment of small HCC.

Klebsiella pneumoniae liver abscess with metastatic complications is an emerging infectious disease in Taiwan. The present study aimed to identify virulence genes involved in the pathogenicity of K. pneumoniae.The closely related Escherichia coli genome array was employed to study the expression of the putative genome of K. pneumoniae. Total mRNA expression levels of a K. pneumoniae strain (designated National Taiwan University Hospital [NTUH]-K2044), isolated from a patient with liver abscess, and another strain (designated NTUH-K9), from a patient with sepsis only, were compared on the E. coli array. RNA blot was used to reconfirm mRNA expression in NTUH-K9, K2044 and in 9 other sepsis strains and 9 other liver abscess strains.One of the genes which was found to be highly expressed in NTUH-K2044, designated aldA, was selected for further study. The aldA gene codes for the enzyme aldehyde dehydrogenase (aldehyde:NAD[P](+) oxidoreductase; ALDH). Kinetic properties of ALDH isolated from the 2 strains, designated K2044 ALDH and K9 ALDH respectively, were characterized. The isolated recombinant K2044 ALDH and K9 ALDH, both with subunit molecular weight 55 kDa, exhibited similar substrate specificity and coenzyme preference with glycolaldehyde (V(max)/K(m) = 27 and 17 U/mg/mM, respectively) and glyceraldehyde (maximum velocity [V(max)]/ Michaelis constant [K(m)] = 42 and 30 U/mg/mM, respectively) being the much better substrates and NAD(+) being the preferred coenzyme (K(m) = 0.28 and 0.23 mM, respectively). Unlike K9 ALDH, K2044 ALDH displayed inhibition at high concentrations of glycolaldehyde (substrate inhibition constant [K(i)] = 7.4 mM) and glyceraldehyde (K(i) = 2.6 mM).The expression of the aldA gene is higher in K. pneumoniae strains from patients with liver abscess. The aldA gene encodes functional ALDH and can use glycolaldehyde and glyceraldehydes as substrates.

The effectiveness of antiviral therapy in preventing disease progression in patients with chronic hepatitis B and advanced fibrosis or cirrhosis is unknown.Patients with chronic hepatitis B who had histologically confirmed cirrhosis or advanced fibrosis were randomly assigned in a 2:1 ratio to receive lamivudine (100 mg per day) or placebo for a maximum of five years. Of 651 patients, 436 were assigned to receive lamivudine and 215 to receive placebo. The primary end point was time to disease progression, defined by hepatic decompensation, hepatocellular carcinoma, spontaneous bacterial peritonitis, bleeding gastroesophageal varices, or death related to liver disease. An independent data and safety monitoring board monitored the progress of the study and performed interim analyses of the data.We randomly assigned 651 patients (98 percent Asian and 85 percent male) to receive lamivudine or placebo. The study was terminated after a median duration of treatment of 32.4 months (range, 0 to 42) owing to a significant difference between treatment groups in the number of end points reached. End points were reached by 7.8 percent of the patients receiving lamivudine and 17.7 percent of those receiving placebo (hazard ratio for disease progression, 0.45; P=0.001). The Child-Pugh score increased in 3.4 percent of the patients receiving lamivudine and 8.8 percent of those receiving placebo (hazard ratio, 0.45; P=0.02), whereas hepatocellular carcinoma occurred in 3.9 percent of those in the lamivudine group and 7.4 percent of those in the placebo group (hazard ratio, 0.49; P=0.047). Genotypic resistance YMDD mutations developed in 49 percent of the patients treated with lamivudine, and the Child-Pugh score was more likely to increase in patients with these mutations than in the other patients treated with lamivudine (7 percent vs.1 percent). Overall, 12 percent of the patients in the lamivudine group and 18 percent of the patients in the placebo group reported serious adverse events.Continuous treatment with lamivudine delays clinical progression in patients with chronic hepatitis B and advanced fibrosis or cirrhosis by significantly reducing the incidence of hepatic decompensation and the risk of hepatocellular carcinoma.

We sought to evaluate whether serum HBV DNA levels correlates with the liver free HBV DNA levels in chronic hepatitis B.Thirty-three consecutive chronic hepatitis B patients with cirrhosis were included in this study. Twenty cases had detectable serum HBV DNA (1.8 pg/ml). All had detectable free liver HBV DNA.There was a strong correlation between the serum and liver HBV DNA levels (P = 0.0018, r = 0.717). Thirteen cases had undetectable serum HBV DNA. Among them, six cases still had detectable liver free HBV DNA. Eight cases were HBeAg-positive. Among them, seven cases were positive for both serum and liver HBV DNA, and one case was negative for both serum and liver HBV DNA. Twenty-five cases were HBeAg-negative and anti-HBe-positive. Among them, 13 cases were positive for serum HBV DNA, and 19 cases were positive for liver HBV DNA. No significant difference was noted for positivity of serum HBV DNA or liver free HBV DNA between HBeAg-positive and HBeAg-negative groups. The level of serum HBV DNA(491 +/- 772 pg/ml versus 203 +/- 447 pg/ml, p = 0.07) and liver free HBV DNA (33 +/- 81 pg/microg versus 6 +/- 15 pg/microg, p = 0.13) was also not statistically different.In conclusion, serum HBV DNA levels is strongly correlated with liver HBV DNA levels in chronic hepatitis B with cirrhosis. Liver free HBV DNA can still be detected in about half of the cirrhotic patients with undetectable serum HBV DNA. Serum HBeAg is not a good predictor of serum or liver HBV DNA levels in cirrhotic patients.