The median (range) follow-up was 190 (05-621) months after ini

The median (range) follow-up was 19.0 (0.5-62.1) months after initial presentation and 16.8 (0.0-46.1) months after initiation of treatment. Serum concentrations of IgG subclass 4 were measured by automated nephelometry (Behring Nephelometer II; Dade Behring,

Newark, DE).12 Tissue immunostaining using monoclonal antihuman IgG4 antibody was performed as reported.3 AUY-922 in vivo The number of IgG4-positive plasma cells per high-power field (hpf) was counted in each specimen (Nikon E 600, field diameter 0.625 mm; Nikon, Tokyo, Japan). Moderate (11-30 cells/hpf) to severe (>30 cells/hpf) infiltration with IgG4-positive cells in the presence of characteristic histology was considered diagnostic of AIP. Scores were assigned as negative (0-1) or positive.2, 3 All histologic specimens were reviewed by a single pathologist (L.Z.). IAC was diagnosed histologically from a resection specimen or core biopsy if there was a lymphoplasmacytic infiltrate within and around bile ducts with associated obliterative phlebitis and storiform fibrosis leading to sclerosis of the bile duct.25-27 EPZ-6438 Available cholangiograms, computerized tomography,

magnetic resonance imaging, and magnetic resonance cholangiopancreatography scans from the 31 patients with CCA-PSC in the test cohort were reviewed by a single radiologist (N.T.) for features of AIP. Data were analyzed using JMP v. 8.0.0 (SAS Institute, Cary, NC). Differences between groups were evaluated using the chi-square or Fisher’s exact test for qualitative variables and the rank sum test for quantitative variables. Receiver operator characteristic (ROC) curves were used to judge the diagnostic utility of sIgG4

levels. IgG4 values (mg/dL) are represented as median and interquartile range, and a two-tailed P value of less than 0.05 was considered significant. Spearman’s correlation coefficient analysis was used to determine the relationship between CA19-9 and sIgG4 level in CCA patients. Survival of CCA patients was defined as the time from diagnosis to death or last follow-up visit date. Median survival of CCA patients with elevated IgG4 > upper limit of normal (ULN) was compared Phosphatidylethanolamine N-methyltransferase to that of CCA patients with normal sIgG4 levels by the Kaplan-Meier method. For the test cohort, we used frozen serum collected at the time of diagnosis from 126 patients with CCA (82 hilar or extrahepatic CCA and 44 intrahepatic CCA). We compared the sIgG4 level and other clinical and laboratory characteristics in these patients to those of 50 patients with known IAC. As expected, the median sIgG4 levels in the 50 IAC patients were significantly higher than the levels in the 126 patients with CCA (irrespective of PSC status) (261.0 mg/dL vs 37.5 mg/dL, P < 0.0001, rank sum test) (Table 1A). The individual sIgG4 levels in each group are shown in the scatterplot (Fig. 2).

Radiation esophagitis is usually diagnosed clinically, based on p

Radiation esophagitis is usually diagnosed clinically, based on patient symptoms and radiation dose exposure of the esophagus. Treatment includes acid suppression, diet modification, analgesics,

empiric treatment for candidiasis, and aggressive nutritional support. Esophageal stricture is the most common late effect of radiation on the esophagus, presenting as progressive dysphagia. Endoscopic dilatation is successful therapy in the majority of patients. “
“A 34-year-old Malaysian man presented with esophageal variceal bleeding, which was successfully treated with sclerotherapy. Investigations at that time showed evidence of portal hypertension with prominent portosystemic collateral vessels and splenomegaly. Hepatic synthetic function was normal. A liver biopsy Gemcitabine ic50 revealed minimal fibrosis of nonspecific etiology and a diagnosis of noncirrhotic portal hypertension (NCPH) was made. Five years later he presented with increasing exertional breathlessness. On examination he had developed finger clubbing and was cyanotic. O2 saturation and PaO2 on room air were reduced at 91% and 60 mmHg, respectively. The PO2 rose to 576 mmHg on 100% O2. Pulmonary angiography showed no evidence of discrete AV malformations;

however, hepatic vein wedge pressure was measured at the time and was elevated at 30 mmHg, in keeping with marked portal hypertension. Doppler studies of the hepatic vasculature showed patent vasculature. A repeat liver biopsy revealed hepatoportal

sclerosis, in keeping with the MG132 original diagnosis of NCPH. Subsequently, a contrast-enhanced echocardiogram was performed which demonstrated delayed appearance of echo-contrast in the left atrium indicating an intrapulmonary shunt confirming the diagnosis of Acetophenone hepatopulmonary syndrome (HPS). The patient’s respiratory symptoms insidiously worsened. By 4 years later his PaO2 on room air had fallen to 49 mmHg. A technetium-labeled macroaggregated albumin (99mTcMAA) lung perfusion scan revealed markedly abnormal brain uptake of radioactivity tracer and a shunt fraction of 15.25% (normal <6%) was calculated using standard methods.[1] The patient was listed for orthotopic liver transplantation (OLT) and the surgery was successfully performed 6 months later. Examination of the explanted liver was again consistent with hepatoportal sclerosis with no evidence of cirrhosis or active liver disease. Following OLT his breathlessness improved steadily over several months. By 3 months post-OLT his O2 saturation on room air was 96% and PO2 was 90 mmHg. Three years post-OLT he presented with right upper quadrant discomfort and worsening dyspnea associated with the redevelopment of hypoxia. At rest, in the supine position his O2 saturation on room air was 93% with a PaO2 of 64 mmHg. A liver biopsy revealed no evidence of significant graft pathology and a computed tomography (CT) chest was unremarkable. A 99mTcMAA lung perfusion scan was repeated and indicated 8.

Radiation esophagitis is usually diagnosed clinically, based on p

Radiation esophagitis is usually diagnosed clinically, based on patient symptoms and radiation dose exposure of the esophagus. Treatment includes acid suppression, diet modification, analgesics,

empiric treatment for candidiasis, and aggressive nutritional support. Esophageal stricture is the most common late effect of radiation on the esophagus, presenting as progressive dysphagia. Endoscopic dilatation is successful therapy in the majority of patients. “
“A 34-year-old Malaysian man presented with esophageal variceal bleeding, which was successfully treated with sclerotherapy. Investigations at that time showed evidence of portal hypertension with prominent portosystemic collateral vessels and splenomegaly. Hepatic synthetic function was normal. A liver biopsy LY2835219 revealed minimal fibrosis of nonspecific etiology and a diagnosis of noncirrhotic portal hypertension (NCPH) was made. Five years later he presented with increasing exertional breathlessness. On examination he had developed finger clubbing and was cyanotic. O2 saturation and PaO2 on room air were reduced at 91% and 60 mmHg, respectively. The PO2 rose to 576 mmHg on 100% O2. Pulmonary angiography showed no evidence of discrete AV malformations;

however, hepatic vein wedge pressure was measured at the time and was elevated at 30 mmHg, in keeping with marked portal hypertension. Doppler studies of the hepatic vasculature showed patent vasculature. A repeat liver biopsy revealed hepatoportal

sclerosis, in keeping with the BGB324 original diagnosis of NCPH. Subsequently, a contrast-enhanced echocardiogram was performed which demonstrated delayed appearance of echo-contrast in the left atrium indicating an intrapulmonary shunt confirming the diagnosis of Glutathione peroxidase hepatopulmonary syndrome (HPS). The patient’s respiratory symptoms insidiously worsened. By 4 years later his PaO2 on room air had fallen to 49 mmHg. A technetium-labeled macroaggregated albumin (99mTcMAA) lung perfusion scan revealed markedly abnormal brain uptake of radioactivity tracer and a shunt fraction of 15.25% (normal <6%) was calculated using standard methods.[1] The patient was listed for orthotopic liver transplantation (OLT) and the surgery was successfully performed 6 months later. Examination of the explanted liver was again consistent with hepatoportal sclerosis with no evidence of cirrhosis or active liver disease. Following OLT his breathlessness improved steadily over several months. By 3 months post-OLT his O2 saturation on room air was 96% and PO2 was 90 mmHg. Three years post-OLT he presented with right upper quadrant discomfort and worsening dyspnea associated with the redevelopment of hypoxia. At rest, in the supine position his O2 saturation on room air was 93% with a PaO2 of 64 mmHg. A liver biopsy revealed no evidence of significant graft pathology and a computed tomography (CT) chest was unremarkable. A 99mTcMAA lung perfusion scan was repeated and indicated 8.

Cholangioscope-directed forceps biopsies have a much higher sensi

Cholangioscope-directed forceps biopsies have a much higher sensitivity in most reports, but are usually negative in some cases of sclerosing-type cholangiocarcinoma. EUS-FNA is the best method for cytologic diagnosis of distal tumors, however for proximal tumors, specially those that are not mass-forming, traditionally the sensitivity is much lower Methods: As part of a prospective study to compare methods for the diagnosis of indeterminate biliary strictures in a stepwise-fashion, EUS-FNA

is performed initially when technically feasible, followed by ERCP with brushings and cholangioscopy with forceps biopsies. Only when FNA is inadequate or unknown during the procedure (no cytologist present), the other procedures are performed www.selleckchem.com/products/poziotinib-hm781-36b.html during ERCP. Results: 42 patients have been included, of which 19 had proximal strictures. Of these, EUS-FNA was performed in 17 with a 94% sensitivity (in two it was technically impossible, for brush cytology the sensitivity was 55% (5/9) and 30% for cholangioscopy directed biopsies (2/6). 18 tumors were of the sclerosing, non-mass forming type, seen by EUS only as diffuse thickening of the wall and no intralumenal mass bu cholangioscopy. Conclusion: An approach LY294002 datasheet starting with EUS-FNA seems highly sensitive in cases of non-mass forming proximal strictures and obviates the need for other procedures; this is a change in the traditional Metalloexopeptidase paradigm

in these patients. Key Word(s): 1. cholangiocarcinoma; 2. EUS-FNA; 3. cholangioscopy; 4. cytology; Presenting Author: HUIJER HWANG Additional Authors: RAUL MATANO, MARTIN GUIDI, JULIO DE MARIA, ESTEBAN PROMENZIO, FERNANDO RAGONE, JUAN VISCARDI Corresponding Author: HUIJER HWANG Affiliations: El Cruce Hospital Objective: Approximately 10-15% of the choledocal stones extraction can be difficult with ERCP conventional sphincterotomy. In the past decade it has begun to use a new technique combining sphincterotomy with large balloon dilation of 12-20 mm in diameter in such cases: larger than 20 mm stones extraction , multiple stones, large periampullary diverticulum and / or thin distal common bile duct.

Several studies have demonstrated increased therapeutic efficacy and lower complication rates. Aim:To compare the effectiveness and complications of sphincterotomy followed by large balloon dilation with sphincterotomy alone in the management of difficult bile duct stones (giants and / or multiple calculies). Methods: A retrospective comparative analysis of managing difficult stones (stones &gt 20 mm in diameter and / or multiple) by ERCP for 26 months. Comparison of the first treatment with conventional ERCP between sphincterotomy (group A) and sphincterotomy plus large balloon dilation (group B) was made, and the following variables were analized: procedural success, successful complete removal of the stones, use of mechanical lithotripsy and complications.

2012b) and gut content and stable isotope data indicate that macr

2012b) and gut content and stable isotope data indicate that macroalgal-associated, grazing amphipods from nature are consuming epiphytic diatoms (Aumack 2010), but our other evidence for benefits to the macroalgae comes from laboratory or mesocosm experiments (Amsler et al. 2009b, Aumack et al. 2011b). In recent field experiments in lower latitude communities, investigators selleck kinase inhibitor have used slow-release toxins to kill amphipods

associated with macroalgae or seagrasses (e.g., Poore et al. 2009, Cook et al. 2011, Whalen et al. 2012, Myers and Heck 2013) and found that while this often benefits the associated macrophytes, it is not always true. For example, Myers and Heck (2013) observed benefits to seagrasses only in areas where amphipod densities were relatively high. Release of toxins into the Antarctic environment is banned by The Antarctic Treaty of which the United States is one of 48 current Parties so such an experiment would be illegal to perform there. However, considering the very high amphipod densities on WAP macroalgae in combination with the laboratory, mesocosm, and field observations we have been able to accumulate, an EX-527 assumption that amphipod and probably gastropod mesograzers are benefiting their host macroalgae by consuming light-competing epiphytes in nature is justified. As discussed previously, the Hay and Duffy et al. hypothesis predicts that selection should favor the evolution

of mesograzer tolerance to the chemical defenses elaborated by their hosts and there are a number of examples of this in amphipods and other mesograzers from lower latitudes (Hay 1992, 1996, 2009). Erastin cost A fundamental tenet of our idea of a community-wide mutualism between Antarctic macroalgae and amphipods is that the amphipods are unable to eat the living macroalgae. If they did, or at least if they did so to an extent that surpassed any benefits from also eating epiphytes on the host, clearly, the relationship could not be considered mutualistic. To date, with one exception, we have seen no evidence that amphipods are specializing on specific host macroalgal species either

for food or shelter, at least among the more common amphipod species. Other than the exception, all of the moderately to very common amphipods utilize a range of macroalgal hosts (Huang et al. 2007) and there is no evidence from gut content or stable isotope analyses (Aumack 2010) for feeding specialization on macroalgae even in general, let alone on any macroalgal species or group of species. The exception is the amphipod Paradexamine fissicauda, which Aumack (2010) found to have a stable isotope signature that was unique in being close to many chemically defended red algae as well as having macroalgal thalli as important components of their gut contents, and which Huang et al. (2007) observed to be two to three orders of magnitude more abundant on the chemically defended red alga P.

Viral breakthrough was defined as an HCV RNA increase of ≥1 log10

Viral breakthrough was defined as an HCV RNA increase of ≥1 log10 IU/mL from the lowest level reached during treatment, or HCV RNA >100 IU/mL in patients who previously had <25 IU/mL during treatment. Relapse was defined as detectable HCV RNA during the follow-up period after having undetectable HCV RNA at the end of treatment. On the basis of previous studies,13, 15 commonly observed substitutions in NS3 after treatment failure considered to confer lower-level in vitro resistance to telaprevir (3- to 25-fold increase in replicon 50% inhibitory concentration

[IC50]) were: V36A/M, T54A/S, R155I/K/M/T, and A156S. Substitutions considered to confer higher-level in vitro resistance to telaprevir (>25-fold increase in replicon IC50) were ABT-199 cell line A156T/V and the combination of V36M+R155K.16 Other changes within the NS3·4A region were also investigated. Following sequencing, amino acid positions were assigned with hidden Markov models using HMMer2 software (Howard Hughes Medical Institute, Chevy Chase, MD), which was trained on multiple sequence alignments of HCV reference sequences from the Los Alamos National Laboratory database.17 Pretreatment sequence and sequence at time of failure were compared for all patients with on-treatment virologic failure or relapse. MDV3100 in vitro Potential new resistance-associated mutations were identified as amino acid states whose

frequencies were significantly different between pretreatment and failure sequences. Aspartate Statistical significance was defined as a one-tailed P < 0.05 using Fisher's exact test for unpaired pretreatment and failure sequences, and Liddell's exact test18 for paired sequences. A Bonferroni correction was applied for multiple comparisons. For each patient not achieving an SVR, any nonwildtype variants at positions known to be associated with telaprevir treatment failure (36, 54, 155, and 156)

were indexed from the failure visit. The proportion of patients losing these variants was recorded until the end of study visit (i.e., last available sequence during the study). To ascertain the median time to loss of variants as compared to time of failure at each position, nonparametric (Kaplan-Meier) survival analyses were performed. P-values for other analyses mentioned in this article were generated using the chi-squared test and were not calculated where sample sizes were low. The disposition of patients in the REALIZE trial, and the baseline characteristics of the two telaprevir treatment arms included in this virologic analysis, have been published elsewhere.4 Briefly, 662 patients were randomized: 266 to the T12/PR48 arm, 264 to the lead-in T12/PR48 arm, and 132 to the PR48 control arm. Regarding previous peginterferon/ribavirin response, 53% were prior relapsers, 19% were prior partial responders, and 28% were prior null responders.

Some liver cancers are not even typical HCC, but are composed pri

Some liver cancers are not even typical HCC, but are composed primarily of small spindled cells, are difficult to characterize as epithelial by conventional immunohistochemical markers for

HCC, and best labeled simply as “primary liver cancer”, and their outcome may be considered similar to that of other undifferentiated primary carcinomas. We now recognize liver carcinomas can also be characterized as having arisen from the Hering canal (progenitor) cells (so-called cholangiolocarcinoma). These tumors Afatinib research buy have a striking histologic appearance of altered cord-like and antler-shaped structures within a dense stromal background, often reminiscent check details of an aberrant ductal plate, and differ in many ways from conventional cholangiocarcinoma. If these tumors

and their stromal components are never carefully documented histologically, results of the sophisticated molecular -omics, micro-RNA studies will continue to be heterogenous, unfocused, and essentially irreproducible. We are, we fear, losing a valuable opportunity to correlate genotypic information with histopathologic phenotype of the plethora of cancers in these studies. In most published manuscripts on molecular signatures of HCC, the cancer phenotype presented is limited to size and number of lesions, presence of microvascular invasion, serum alpha-fetoprotein levels, and, of course, very disease recurrence or survival. Detailed histopathology is commonly missing from such articles and, yet, has much to offer. An example of this lack of attention to details of histopathology at the recent ILCA meeting was the luncheon workshop for Molecular Markers of HCC. Both moderators made

a point of stating early on in the meeting that “liver biopsies need to be done on all liver cancer”. Why, they asked? They went on to answer: To be able to study predictors (molecular), as well as prognosis (molecular). Also noted, however, in the seminar was the diversity of (molecular) platforms for these highly sophisticated studies, the plethora of genetic, inflammatory, metabolic pathways and data being generated, and our current need, therefore, for highly sophisticated, costly, and center-specific techniques for analysis of large numbers of cases and datasets. Yet, no discussion whatsoever occurred of the possible presence or significance of correlations or differentiating histopathologic subtypes. It seems unfortunate that the history of our discipline in hepatology is rapidly being lost to the memories of the young generation.

We also compared the interval between first IFX induction dose an

We also compared the interval between first IFX induction dose and the first escalated IFX dose. The primary endpoint was the pharmacological costs derived from the IFX administration (patient per kg/year) (IFX, pre-medication, and day hospital cost) in patients of each cohort who were in treatment

for at least 1 year. Results: Seventy-nine patients were in treatment for at least 1 year 51 CD and 28 UC). The rate per month of patients who needed intensification was 1.5% vs 3.6% (p = 0.008) respectively. In patients who underwent IFX optimization, median time between the first IFX induction dose and the first escalated IFX dose was 10 months vs 6 months (p = 0.021) for CD patients and UC patients, respectively. In the survival analysis, the cumulative probability of avoiding IFX dose intensification was significantly higher in CD patients (p = 0.006). In RXDX-106 supplier the multivariate analysis, disease (UC vs CD) was the only factor significantly associated

with dose intensification. The costs per patient per kg were significantly higher in UC patients than in EC (p < 0.001). In the multivariate analysis, only the need for IFX dose intensification was associated learn more with increased cost (p = 0.001). Conclusion: Direct (one-year) cost of IFX is significantly higher in patients with UC compared with CD patients. The increased costs of IFX in the UC cohort was driven by the higher rate per month of UC patients who needed IFX dose intensification. Our data provide a rational basis for economic planning in patients with ulcerative colitis selected for IFX therapy. Key Word(s): 1. infliximab; 2.

Crohn′s disease; 3. costs; 4. intensification; Presenting Author: CARLOS TAXONERA Additional Authors: IGNACIO FERNÁNDEZ-BLANCO, MANUEL BARREIRO-DE ACOSTA, GUILLERMO BASTIDA, JAVIER MARTINEZ-GONZALEZ, OLGA MERINO, VALLE GARCÍA-SÁNCHEZ, JAVIERP GISBERT, IGNACIO MARÍN-JIMÉNEZ, PILAR LÓPEZ-SERRANO, EVA IGLESIAS, ANTONIO LÓPEZ-SANROMÁN, MARIA CHAPARRO, CRISTINA SARO, FERNANDO BERMEJO, LETICIA PÉREZ-CARAZO, ROCIO PLAZA, JUANL MENDOZA, ENRIQUE REY Corresponding Author: CARLOS TAXONERA Affiliations: Hospital Clinico San Carlos; Hospital La Moncloa; Hospital Santiago; Hospital La Fe; Hospital Ramon y Cajal; Hospital de Cruces; Hospital Methocarbamol Reina Sofia; Hospital La Princesa; Hospital Gregorio Marañon; Hospital de Alcorcon; Hospital Ramón y Cajal; Hospital Fuenlabrada; Hospital Infanta Leonor Objective: The success of medical treatment for entero-urinary fistulas (EUFs) in Crohn’s disease (CD) has so far been modest and surgery is the standard treatment. The advent of anti-tumour necrosis factor (TNF) therapy has provided a powerful new potential treatment option. The aim of this study was to evaluate the effectiveness and predictors of response of anti-TNF therapy for inducing remission of EUF in CD patients and avoiding the need for surgery.

Thus, the prediction

of the rate of disease progression a

Thus, the prediction

of the rate of disease progression at an individual level is still quite inaccurate, often making impossible the selection of patients selleckchem for anti-HCV treatment on the basis of the risk to progress to the advanced stages of hepatitis. Some evidences exist on the role of host genetics in modifying disease progression, because several single-nucleotide polymorphisms (SNPs) located in various genes, including interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), and transforming growth factor beta (TGF-β), among others, have been associated with progression of liver fibrosis.2 A recent article supported these findings, providing evidence that a seven-SNP signature was associated with fibrosis progression in a large cohort of HCV-infected patients in Italy.5 Among the SNPs identified to play a major role in HCV infection, those located in the IL28B region on chromosome 19 have been strongly associated with spontaneous and treatment-induced viral clearance in patients of different ethnicity.6-10 Thus, patients

with the T/T and C/T genotype at the rs12979860 SNP (nonresponder genotype) have been shown to exhibit a slower viral decline after pegylated interferon plus ribavirin (PEG-IFN/RBV) therapy, with the sustained virologic response (SVR) rates being significantly lower, compared to patients with the favorable C/C genotype.11 Although this discovery has radically changed the landscape of antiviral treatment for HCV patients, providing insights into the mechanisms of IFN hyporesponsiveness, the

precise mechanisms behind PD332991 this association still needs to be unraveled. In addition, whether there is a link between the clinical manifestation of chronic HCV infection and oxyclozanide the patient IL28B genotype is still an open question. Here, we asked whether a correlation between IL28B SNPs and fibrosis progression exists. To test this hypothesis, we studied 247 consecutive patients with a known date of HCV infection, whose liver fibrosis was staged by a percutaneous liver biopsy. We studied the effect of host and external factors on both fibrosis progression rate and advanced fibrosis stage. ALT, alanine aminotransferase; BMI, body mass index; CI, confidence interval; EDTA, ethylenediaminetetraacetic acid; FPR, fibrosis progression rate; gDNA, genomic DNA; HCV, hepatitis C virus; HIV, human immunodeficiency virus; IFN-γ, interferon gamma; IL28B, interleukin-28B; PEG-IFN/RBV, pegylated interferon plus ribavirin; SNPs, single-nucleotide polymorphisms; SVR, sustained virologic response; TGF-β, transforming growth factor beta; TNFα, tumor necrosis factor alpha. A total of 247 participants with chronic HCV infection were included in this study. All participants were consecutively selected at the Center for Liver Disease at Maggiore Hospital (Milan, Italy).

Some of the patients had liver stiffness

Some of the patients had liver stiffness GSK458 mw measurement assessed by transient elastography in our previous study and the last visit was taken as the day of transient elastography.14 Otherwise, the last visit was taken as the last follow-up visit with serum sample available. Detailed analyses were also performed to investigate the changes of HBsAg levels at the time of HBeAg seroconversion and hepatitis flare. For Group 3 patients, the HBsAg levels immediately before and after HBeAg seroconversion were measured and compared. Hepatitis flare was defined as an abrupt elevation of ALT to > 200 IU/L or >3 times the baseline level,

whichever was higher.15 HBsAg levels were determined in the available serum samples at the visits immediately before the flare, at the flare, and immediately after the flare. HBsAg was quantified by Architect HBsAg QT (Abbott Diagnostic, Germany) according to the manufacturer instructions.16 The sensitivity of Architect assay ranged from 0.05 to 250 IU/mL. Samples with HBsAg titer higher than 250 IU/mL were diluted to 1:500 to 1:1000 to bring the reading within the range

of the calibration curve. HBV DNA was quantified by TaqMan real-time polymerase chain reaction assay as described.17 This assay was standardized by serial dilution of EUROHEP genotype D HBV standard, which contained 2.7 × 109 viral copies per mL and was validated by the World Health Organization HBV standard. The range of HBV DNA detection was from 102 to 109 copies/mL with correlation coefficient of the standard curve routinely greater than 0.990. For samples with HBV DNA > 109 copies/mL, BVD-523 clinical trial HBV DNA assay would be repeated after dilution to 1:100. In this assay, 4.86 copies/mL equaled 1 IU/mL. HBV genotyping was determined by restriction fragment length polymorphism and was confirmed by direct sequencing in case of doubt in the residual serum sample at initial visit, as described.18 Statistical analysis was performed by SPSS (version 15.0; SPSS, Inc., Chicago, IL). Continuous variables were expressed as mean ± standard deviation Adenosine or median (range) as appropriate. HBV DNA (IU/mL) and HBsAg

(IU/mL) were logarithmically transformed for analysis. For patients with undetectable HBV DNA and negative HBsAg, the results were taken as the lower limit of detection (20.6 IU/mL for HBV DNA and 0.05 IU/mL for HBsAg) for calculation. Ratio of HBsAg (log IU/mL) to HBV DNA (log IU/mL) was determined to reflect the proportion of subviral particles to virions. Continuous variables including HBV DNA and HBsAg were compared by Student t test or Mann-Whitney U test as appropriate. Wilcoxon signed rank test was used to compare the reduction in log HBV DNA and log HBsAg levels during the longitudinal follow-up. The annual decline of HBsAg was computed by dividing the HBsAg decline from the first to the last follow-up visit by the total duration of follow-up.