The miR-361–3p regulates RelA and CDX2 mRNA expression; and miR-2

The miR-361–3p regulates RelA and CDX2 mRNA expression; and miR-212–3p regulates COX-2 mRNA expression. miRNAs may contribute to the inflammation of lower esophagus with H. pylori infection, and may be involved in the development of Barrett’s Esophagus and esophageal adenocarcinoma. Key Word(s): 1. MicroRNAs; 2. COX-2; 3. CDX2; 4. Helicobacter pylori; Presenting Author: GUI-GEN TENG Additional Authors: WEI-HONG WANG, YUN DAI, SHU-JUN WANG, YUN-XIANG CHU, JIANG LI Corresponding Author: WEI-HONG WANG Affiliations: Peking University First Hospital Objective: Barrett’s esophagus (BE) is recognized as a complication of chronic gastroesophageal acid

and bile reflux, and also considered to be a precancerous state in the esophagus and may progress to esophageal adenocarcinoma (EA). H. pylori has been found to colonize the Barrett epithelium of lower esophagus. However, GS 1101 its role in the development of Barrett’s buy MK-2206 esophagus and esophageal adenocarcinoma is unclear. Here, we explored the effects of acidic deoxycholic acid and H. pylori on esophageal cell lines in vitro, with a particular focus on whether NF-kB is involved in this event. Methods: H. pylori 26695 and its cagA mutant strain were cocultured

with two esophageal cell lines (HET-1A, OE33) with or without acidic deoxycholic acid (DCA) in vitro. Cell proliferation was tested by CCK-8 assay. Apoptosis was determined by Flow Cytometry. COX-2 and CDX2 were assessed by real-time PCR and Western blot. MUC2 was determined by qPCR and immunocytochemistry. MCE公司 NF-kB phosphorylation and

DNA-binding activity were determined by Western blot and EMSA. NF-kB transcriptional activity was identified by luciferase reporter assay. The downstream genes of NF-kB, such as IL-8 were assessed by ELISA and qPCR. Results: DCA, live H. pylori and HPE (H. pylori extract) reduced proliferation and promoted apoptosis of esophageal cells. DCA, live H. pylori and HPE up-regulate the expression of COX-2, CDX2 and MUC2 in both esophageal cell lines. However, cagA mutant strain and its extract did not induce the expression of CDX2 and MUC2. NF-kB activity was induced by DCA, live H. pylori and HPE. Treatment with DCA in the presence of either live H. pylori or HPE further augmented the NF-kB phosphorylation, its DNA-binding and the transcriptional activity; and subsequently increased the expression of COX-2, CDX2, MUC2 and IL-8 as compared to DCA treatment alone. The results suggested a synergistic effect between DCA and H. pylori in esophageal cells. Both siRNA P65 and PDTC significantly inhibited NF-kB activity, and influenced the downstream genes expression in esophageal cell lines with H. pylori infection. Conclusion: The present study reveals that both H. pylori and DCA up-regulate the expression of COX-2, CDX2, MUC2 and IL-8 in esophageal cells by inducing the activation of NF-kB. These results indicate that H.

Of those 175, 16 (M=9, F=7) were included in the NKPS group The

Of those 175, 16 (M=9, F=7) were included in the NKPS group. The mean age was 64 in both groups. Successful biliary cannulation was achieved in all NKPS patients. PEP was developed in 8 of 159 (5%) in routine group and 2 of 16 (12.5%) in NKPS group (p=0.229). Bleeding was developed in 9 of 159 (5.7%), 1 of 16 (6.3%), respectively (p=1.000).

All the PEP was mild in NKPS group; however, there was a severe PEP in routine group. Mean (SD) serum amylase levels after ERCP were 194.9 (377.5) U/L in routine group and 438.2 (474.6) U/L in NKPS group (p<0.001). All PD stents were dislodged spontaneously within 7 days. Conclusion: Even though NKPS group was high risk for PEP, Pritelivir purchase the incidence of PEP was comparable to the routine group. If biliary cannulation is difficult and incidental PD cannulation is achieved, NKPS would be safe and feasible with a lower rate of post-procedure complications. Key Word(s): 1. post-ERCP pancreatitis; 2. pancreatic stent; 3. precut sphincterotomy; Presenting learn more Author: BIN XU Additional Authors: SUMEI SHA, BIN BAI, XIAOLEI SHI, YONGZHAN NIE, QINGCHUAN ZHAO Corresponding Author: YONGZHAN

NIE, QINGCHUAN ZHAO Affiliations: Fourth Military Medical University Objective: Gastric cancer (GC) is a complex disease resulting from genetic and epigenetic alterations. By using bisulfite-assisted genomic sequencing (BSP) and a novel highthroughput mass spectrometry on matrix-assisted laser desorption/ionization time-of-flight silico-chips (Mass-Array) strategies, we 上海皓元医药股份有限公司 proposed that whether DHRS3, a member of the short-chain dehydrogenases/reductases family, is a potential novel epigenetic target gene. Its biologic function and clinical significance were also investigated in gastric cancer (GC). Methods: BSP and Mass-Array were used to evaluate and quantify the promoter methylation level in 120 primary GC and matched normal mucosa tissue specimens. The mRNA and protein expression were determined by real-time PCR and immunohistochemical staining. The biological function

of DHRS3 was determined by both in vitro and in vivo assays. A two-way hierarchical cluster analysis was used to classify methylation profiles and any correlation between the methylation status of the DHRS3 promoter and clinicopathological characteristics of GC was then assessed. Results: Experiments showed that the promoter of DHRS3 was hypermethylated in GC samples compared with adjacent normal samples (p<0.0001). DHRS3 was silenced or downregulated in GC samples. In contrast, DHRS3 was high expressed in normal gastric mucosa tissues. This down-regulation was closely linked to the promoter methylation of DHRS3 as identified by BSP, Mass-Array and restored by demethylation agent 5-Aza treatment. Up-regulated the expression level of DHRS3 inhibited cell proliferation, reduced colony formation in GC MKN28 cells in vitro and decreased tumor growth in nude mice in vivo; it also induced cell early apoptosis and arrested cells in G1 phase.

[75] As summarized in Table 1, several specific miRNA have been r

[75] As summarized in Table 1, several specific miRNA have been reported to be directly regulated from their own promoters by epigenetic alterations in HCC.[76, 77] These findings indicate that specific miRNA including miR-1, miR-124 and miR-203 are PARP inhibitor tumor-suppressor miRNA that inhibit their

target oncogenes and are epigenetically silenced during hepatocarcinogenesis. Reactivation of these miRNA by chromatin-modifying drugs such as DNA methylation inhibitor and HDAC inhibitor may be a novel therapeutic strategy for HCC. RECENT STUDIES HAVE reported that some miRNA can regulate the key chromatin-modifying factors for DNA methylation and histone modifications such as DNMT1, DNMT3A, DNMT3B and EZH2 as their targets, suggesting that these miRNA have important roles in the epigenetic control of gene expression (Table 2).[78] Olaparib in vitro It has been

shown that miR-152 is downregulated in HCC and targets DNMT1.[79] miR-152 may act as a tumor suppressor via suppression of DNMT1 and it can be a new target for epigenetic therapy of HCC. PRC1 and PRC2-mediated epigenetic regulation is critical for maintaining cellular homeostasis. PRC2 mediates epigenetic gene silencing by tri-methylating histone H3 lysine 27 (H3K27me3) and is known to aberrantly silence tumor suppressor genes in cancer. EZH2, the catalytic subunit of PRC2, enhances tumorigenesis and is commonly overexpressed in several types of cancer. miR-101 is downregulated in bladder cancer, and miR-101 directly represses EZH2. This suggests that abnormal downregulation of miR-101 could lead to the overexpression of EZH2 frequently MCE seen in cancer. miR-101 may be a potent tumor suppressor by altering global chromatin structure through repression of EZH2.[80, 81] The CCCTC-binding factor, CTCF, is known to bind insulators and exhibits an enhancer-blocking and barrier function, and more recently, it also

contributes to the 3-D organization of the genome. CTCF can also serve as a barrier against the spread of DNA methylation and histone repressive marks over promoter regions of tumor suppressor genes. Recent studies have shown that CTCF is also involved in the regulation of miRNA in cancer cells and stem cells.[82] Watanabe et al.[83] have reported that CTCF plays important roles in the regulation of the cytokine genes TNF and LT in HCC cells. Figure 3 shows a model summarizing the cross-talk between epigenetics and miRNA and the link between miRNA and regulated genes. In normal hepatocytes, miR-152 is substantially expressed, and its target gene DNMT1 is suppressed. On the other hand, miR-152 is downregulated in HCC cells, resulting in overexpression of DNMT1 accompanied by aberrant DNA methylation of some tumor suppressor miRNA such as miR-1 and miR-124. Downregulation of miR-1 and miR-124 cause activation of their target oncogenes. Thus, epigenetics and miRNA are affected by each other and their cross-talk may play critical roles in the hepatocarcinogenesis.

They were treated with percutaneous ethanol infection therapy (PE

They were treated with percutaneous ethanol infection therapy (PEIT), percutaneous microwave coagulation therapy (PMCT), radiofrequency ablation

(RFA), transarterial chemoembolization (TACE), systemic chemotherapy, or radiation therapy, or received best supportive care. All patients were registered on a database, and the present study was based on data observed until the end of December 2011. From these patients, we searched patients MK0683 purchase who (i) had non-detectable serum HCV RNA by polymerase chain reaction (PCR) of recent date during the clinical course; (ii) had detectable serum HCV RNA by PCR before the treatment for HCC; (iii) were not positive for hepatitis B virus surface antigen; and (iv) had not been treated with interferon-based therapy. Hepatocellular carcinoma was diagnosed by dynamic computed tomography (CT), considering hyperattenuation in the arterial phase with washout in the late phase as a definite sign of HCC.[10] When the diagnosis of HCC was not definite on CT, ultrasound-guided tumor biopsy was performed and pathological diagnosis was made

based on Edmondson-Steiner criteria.[11] Anti-HCV antibody was examined by a chemiluminescent immunoassay (Abbott Laboratories, Chicago, IL, USA). HCV RNA was quantitatively measured by the Amplicore HCV RNA Monitor Kit Version Ixazomib mw 2.0 (Roche Diagnostics Systems, Indianapolis, IN, USA) or COBAS TaqMan HCV auto (Roche Diagnostics Systems). Seronegativity of HCV RNA was qualitatively confirmed by Amplicore HCV RNA Monitor Kit, version 2.0 or COBAS TaqMan

HCV auto. Hepatitis B virus surface antigen was examined by a chemiluminescent immunoassay (Abbott Laboratories). We examined patients’ characteristics such as age, sex, alanine aminotransferase (ALT; normal range ≤36 IU/L), γ-glutamyltranspeptidase (γ-GTP; normal range ≤68 IU/L), platelet count, liver function based on Child–Pugh classification, alcohol consumption, and the history of blood transfusion. Liver histology, tumor size, and number of tumors were also examined. Among 2407 patients with HCV related HCC, 1151 patients had no history of interferon MCE therapy. Database search identified 11 patients whose serum HCV RNA tests during the clinical course of HCC were negative without interferon therapy. Of them, HCV RNA test results before HCC treatment were not available in six patients; eventually a total of five patients met the inclusion criteria. Table 1 shows baseline characteristics of the 1145 patients and Table 2 shows demographic and clinical characteristics of these five patients. There were four men and one woman. The mean age at the time of negative HCV RNA test was 77 (range: 52–84). Three and two were infected with HCV genotype 1 and 2, respectively. The mean initial viral load was 3.7 log IU/mL (range: 3.2–4.5).

Pharmacies situated in Gothenburg, Sweden, were selected based on

Pharmacies situated in Gothenburg, Sweden, were selected based on a list from the Medical Products Agency. A request for participation was made to the regional managers of the six largest pharmacy companies in Gothenburg. One of the regional managers did not respond, which resulted in 53 eligible pharmacies from 5 pharmacy companies. Every pharmacy manager was asked for permission

to distribute the questionnaire to their staff, through an e-mail giving information Erlotinib mw about the study. Two declined participation, 5 were excluded because of no response at all from the pharmacy manager, and an additional 2 were excluded because of too few, ie, 1 or 2, employees. After approval, all pharmacy managers were e-mailed regarding a contact person at the pharmacy and a suitable date for distribution of the questionnaire. The study subjects included all pharmacy staff with permission to give advice to customers on OTC medication (pharmacists, dispensing pharmacists, pharmacy technicians, and other counseling staff). Pharmacists

have a master of science degree (5 years of university education), and dispensing pharmacists have 2–3 years of university education. Pharmacy technicians have 1–2 years of vocational training. Other counseling staff have a few weeks’ internal counseling training, conducted through educational Adriamycin mw programs implemented by the different pharmacy companies. Responsibilities differ among the different professional categories, where pharmacists and dispensing pharmacists are the only ones who have permission to dispense prescription medications.

Data were collected during the fall of 2012. A total of 326 questionnaires were distributed. The questionnaires were distributed together with response envelopes and participant information, 1 per counseling staff member at each pharmacy. The questionnaires were placed in each staff member’s personal compartment at the pharmacy or given to the contact person at the pharmacy. In addition, a box for anonymous collection of completed questionnaires was left at every pharmacy in a suitable place. After 2 weeks, new questionnaires were distributed to each pharmacy as a reminder for those who had not yet responded. The questionnaires were anonymous, medchemexpress and no single response could be identified, nor could the pharmacy company be identified. Hence, no information was collected for non-responders. The study protocol was approved by the Regional Ethical Review Board in Gothenburg (registration number 531-11). The questionnaire included background questions on sex, age, and professional category, number of years since graduation/completed education, and number of years working in a pharmacy. Pharmacy technicians and other counseling staff were merged into one group called “counseling staff.

Histopathologic examination revealed epitheloid granulomatous wit

Histopathologic examination revealed epitheloid granulomatous with caseating necrosis and presence of Langerhan’s giant cells. Therefore, postoperative diagnosis CSF-1R inhibitor was revealed tuberculosis of cholecystitis. The patient tolerated the procedure well and was discharge 1 week following surgery without any problems. The patient was started on anti tubercular treatment. Conclusion: Herein, we present a case of tuberculous cholecystitis with cholecysto-colonic fistula.

Key Word(s): 1. tuberculosis cholecystitis; 2. cholecysto-colonic fistula Presenting Author: JIN KYEONG CHO Additional Authors: Na Corresponding Author: JIN KYEONG CHO Affiliations: Seoul Medical Center Objective: Introduction After successful common bile duct (CBD) stone removal by endoscopic retrograde cholangiopancreatography (ERCP), high prolonged jaundice is very confused for the next decision (ERCP for remnant stone or other rare causes). With assurance of removal Small molecule library of CBD stone and no remnant stone, Liver biopsy may be useful for jaundice of parenchymal origin but invasive. In such cases, steroid challenge test is useful both diagnosis and treatment. Case description

A 62-year-old male presented with colicky right upper quadrant pain. Laboratory tests showed total bilirubin of 7.6 mg/dL, aspartate aminotransferase (AST) 60 IU/L, alanine aminotransferase (ALT) 15 IU/L, alkaline phosphatase (ALP) 60 IU/L and gamma-glutamyltranspeptidase

(γ-GT) 71 IU/L. At abdomen CT, There was single 1.3 cm sized distal CBD stone and diffuse dilatation of upstream bile duct and cystic duct. The patient underwent endoscopic retrograde biliary drainage (ERBD) by plastic stent because of long procedure time for cannulation. But 5 days after the ERBD, his total bilirubin increased to 18.7 mg/dL. A second ERCP was carried out, which revealed patent biliary stent and CBD stone was removed successfully. After 2 days of second ERCP, total bilirubin level increased to 19.5 mg/dL. At second abdomen CT, there was no remnant stone. It was presumed that intrahepatic cholestasis was occurred by intrahepatic bile duct inflammation from contrast agent or pethidine. 上海皓元医药股份有限公司 P rednisolone was started (30 mg/day) for three days, which caused a significant improvement of jaundice and bilirubin level. But 7 days later, his bilirubin raised up to 20.3 mg/dL. It was certain that prednisolone improved his cholestasis. Prednisolone started again and after use of 30 mg/day of prednisolone for 7 days, total bilirubin fell to 10 mg/dL, and his jaundice was progressively declined. Steroid was used and tapered off during a month. He had normal bilirubin level and normal liver function tests. Key Word(s): 1. ERCP; 2.

5 kPa (Fig 1) LSE

with IQR/M >030 (ie, with large va

5 kPa (Fig. 1). LSE

with IQR/M >0.30 (i.e., with large variability) provided lower AUROCs and a lower rate of well-classified patients when compared to LSE with <0.10 IQR/M ≤0.30, but the difference was not statistically significant (Table anti-PD-1 antibody 4). Because multivariate analyses showed a significant interaction between these two variables, we evaluated the influence of IQR/M according to LSE median. The deleterious effect of IQR/M >0.30 on LSE accuracy was amplified by the liver stiffness level: the diagnostic accuracy for cirrhosis decreased even more in patients with LSE median ≥12.5 kPa, and accuracy for significant fibrosis significantly decreased in patients with LSE median ≥7.1 kPa. Finally, LSE with IQR/M >0.30 may be considered “poorly reliable” in patients with LSE median ≥7.1 kPa and “reliable” in patients with LSE median <7.1 kPa (Fig. 1). The interaction between IQR/M and liver stiffness level is not surprising: IQR corresponds to the interval around the LSE median containing 50% of the valid measurements between the 25th and 75th percentiles, and is usually expressed as the ratio IQR/M. A

high IQR/M implies a large distribution of LSE valid measurements and thus a higher risk of an aberrant LSE median. However, by definition, a high IQR/M also implies a smaller interval in low liver stiffness levels (compared to high stiffness levels). For example, an IQR/M at 0.30 represents a 1.5 kPa interval when liver stiffness is 5.0 kPa, but a 4.5 kPa interval when liver stiffness is 15.0 kPa. Consequently, IQR/M has little impact on LSE median in low liver stiffness levels, thus explaining Enzalutamide datasheet why LSE with IQR/M >0.30 may be considered “reliable” when LSE median is <7.1 kPa (Fig. 1). Because increasing liver stiffness amplifies the deleterious effect of IQR/M >0.30 with a significant decrease in diagnostic accuracy, LSE with IQR/M >0.30 and median ≥7.1 kPa may be considered “poorly reliable” (Table 6; Fig. 1). Finally, 上海皓元医药股份有限公司 by inverting the same reasoning, one can explain why

LSE with IQR/M ≤0.10 are very accurate in high liver stiffness values (Fig. 1). The intermediate category, LSE with 0.10< IQR/M ≤0.30, may be considered “reliable” (Table 4; Fig. 1). Finally, our results permitted the establishment of new reliability criteria identifying three LSE subgroups according to IQR/M and liver stiffness level (Table 5). The accuracy of LSE for fibrosis staging was significantly different between these three subgroups, thus demonstrating the relevance of these new criteria (Table 6). Moreover, the rate of poorly reliable LSE according to the new criteria (9.1%) was significantly lower than “unreliable” LSE as defined in the previous usual criteria (24.3%). In our study, as in those of Lucidarme et al. and Myers et al.,5, 6 the ≥10 valid measurements variable had no influence on LSE accuracy (Table 3). This leads to the question: How many valid measurements are required for LSE? Kettaneh et al.

If this is enhanced to 10 IU kg−1 three times per week, this will

If this is enhanced to 10 IU kg−1 three times per week, this will then start reaching reductions in the ‘time at risk’ of ~60%. If paradigms could be changed completely and find practical and convenient ways found to administer CFC once a day then even with doses as low 5 IU kg−1 day−1 one could maintain >1% at all times with an annual dose well below 2000 IU kg−1. All the evidence suggests that any prophylaxis that reduces ABR should help improve long-term outcomes. After all, even in Western countries, prophylaxis had started with lower doses and they had already noted improvements in their patients before reaching current doses. There are

HDAC inhibitor also limited recent data that CFC doses as low as 10 IU kg−1 two to three times/week reduce joint bleeding in patients who previously received episodic replacement [36]. Such prophylaxis programmes need to be systematically initiated in different countries

[37]. Finally, everywhere in the world there is a need to assess outcomes with whatever replacement protocols that are followed. This has been a relatively ignored subject in the field around the world and needs to change, not only because modern medicine attempts to work on evidence but also because there is greater cost alertness from healthcare providers everywhere and high-cost diseases such as haemophilia are more likely to come under the scanner [10]. It is vital therefore that assessment of relevant outcomes with appropriate 上海皓元 tools becomes part of the care of PWH. This field has significantly advanced in the last 10 years as well JAK2 inhibitor drug [38]. Traditionally, the ABR into joints and other sites has been a simple and predictive indicator

of long-term outcome in haemophilia with regard to joint disease and overall musculoskeletal status. This continues to be used as a surrogate marker of both disease severity before intervention and an index of the efficacy of treatment provided. For standardizing bleeding assessment from other sites, tools have been developed in the past few years [39]. These have so far been used mainly to evaluate those conditions where bleeding is more skin and mucosal. There utility in haemophilia and related rarer bleeding disorders needs evaluation. The WFH has attempted to review and summarize the potential of the most relevant of these tools on a website to make them more easily accessible to the community for their use and comments. While data on ABRs are relatively easy to collect, there can be errors in a patient’s assessments and reporting. It is important therefore to always combine this with assessment of joints. The Hemophilia Joint Health Score is gradually replacing the WFH clinical score as a validated tool for the clinical assessment of joints [40, 41].

Thus, the CoH/ductular unit, with somewhat variable anatomy (Fig

Thus, the CoH/ductular unit, with somewhat variable anatomy (Fig. 4A) begins in the periportal parenchymal region as the first twig of the biliary tree, crosses the limiting plate, becoming a somewhat larger interlobular bile duct. The numbers, lengths, and shapes of the CoH/ductule units depend on the source and hence normalcy of the specimens and on the application of immunohistological markers, e.g., keratin 7 (K7), K19, or epithelial cell adhesion molecule (EpCAM).1, 5,6,7 Without

immunostaining, there is an average of 0.4 ductules per portal tract (range 0-4) in normal human liver,8 whereas median values of 2.5-5 ductules per portal tract were observed after application of the K7 immunostain.9,10 Historically, human DRs have been grouped on the basis of morphology selleck selleck chemical into “typical” and “atypical”, terms originally applied in and based on rodent studies.11 This terminology is discouraged, because a classification of DRs based on a quite limited set of experimental

conditions in rodents cannot readily accommodate the range of patterns seen clinically; DRs are diverse, covering a spectrum of features rather than clear subphenotypes, which will now be described (Fig. 1). DR morphologies may range from well-formed ductules with recognizable lumina to irregular counterparts without obvious lumina, sometimes merely consisting of MCE a string of cells. Variable phenotypes between both ends of this spectrum can be present concomitantly in a single specimen, depending on the etiology and evolution of the disease. Even greater complexity emerges when there are concomitant disease processes such as primary sclerosing

cholangitis (PSC) with both obstructive and regenerative DRs.12 Classification schemes suggested by Desmet12 and Turanyi et al.13 have attempted to integrate the histologic features, inciting disease, and/or immunophenotyping of DR, but these have not been subjected to a consensus-building process of review and are not (yet) recommended for DR subclassification. Biliary obstruction produces the most well-known example of DR, featuring a multiplication of small ductules at the periphery of edematous portal stroma. The ductules show variable nuclear size and contain no bile. Obstructive-type DRs may be extraordinarily prominent, seemingly replacing parenchyma with markedly expanded portal tracts, but these can rapidly resolve. When bile concretions are present in dilated ductular lumina (“cholangitis lenta” or ductular cholestasis) a superimposed septicemia should be considered, either from cholangitis or a distant source.

Changes in the S/L proteins ratio may lead to the retention of su

Changes in the S/L proteins ratio may lead to the retention of surface proteins within the hepatocytes, although this event may not affect virion secretion.18-23 Several recent studies suggest that circulating HBsAg levels might reflect intrahepatic HBV activity and that their decline under treatment might predict a response to antiviral therapies in chronic hepatitis B (CHB) patients.24-27 HBsAg titer has been proposed as a surrogate marker for HBV covalently closed circular DNA (cccDNA),24, 25, 27 the intranuclear replicative intermediate that constitutes the reservoir responsible

for viral persistence. However, studies evaluating HBsAg titers have Doramapimod nmr not considered the possible emergence of preS/S HBV mutants as dominant infecting viral populations, and in particular, they have not

taken into consideration the possible influence of preS/S gene variability on circulating levels of HBsAg. The aims of this study were to investigate whether infection with preS/S variants may influence the amounts of circulating HBsAg and HBV DNA in CHB patients and to perform a phenotypic characterization of naturally occurring preS/S variant isolates. aa, amino acid; anti-HBe, antibody to hepatitis B e antigen; BCP, basal core CHIR-99021 research buy promoter; cccDNA, covalently closed circular DNA; CHB, chronic hepatitis B; ER, endoplasmic reticulum; HBeAg, hepatitis e antigen; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; L, large; M, medium; mt, mutant; mRNA, messenger RNA; PC, precore; PCR, polymerase chain reaction; S, small; WT, wild-type. We studied 上海皓元 serum samples collected

prior to any antiviral treatment from 40 patients with HBV-related chronic liver disease (26 men and 14 women; mean age, 43 ± 14.6 years), consecutively admitted to the outpatient service of the Liver Unit of the Messina University Hospital (Italy) in 2008. All of the patients were Italian and were infected with HBV genotype D (n = 36 patients) or A (n = 4). Eleven of the patients were HBV e antigen (HBeAg)-positive, and 29 were positive for the corresponding antibody (anti-HBe). Thirteen patients had cirrhosis and 27 had CHB. The diagnosis was performed through needle liver biopsy in 17 cases and through clinical/biochemical/ultrasonographic evaluation in 23 cases (Table 1). All patients were negative for hepatitis delta virus, hepatitis C virus, and human immunodeficiency virus serum markers. The study protocol was performed according to the principles of the Declaration of Helsinki, and written informed consent was obtained from all patients. Serum HBV DNA was quantified using the COBAS AmpliPrep-COBAS TaqMan HBV test (Roche Diagnostics, Monza, Italy) with a lower limit of detection of 12 IU/mL. HBsAg was quantified on the same sera using the ARCHITECT HBsAg Assay (Abbott; Abbott Laboratories, Chicago, IL) according to the manufacturer’s instructions.