The aim of our study was to assess the use of a recently developed fully covered metal stents (FCSEMS) for the management of PFCs nationally, including learn more their ease of use compared to plastic stent insertion and its associated complications. Methods: Utilizing the Pyramid database on stent usage nationally we were able

to identify practicing endosonographers who had inserted these novel covered metal stent into PFCs. A standardized datasheet capturing patient demographics, aetiology of PFCs, technique utilized for insertion, ease of use compared with plastic stenting and early/late complications was created. End points included their ease of use compared to plastic stent insertion, rates of collection resolution, in addition to peri and post procedural complications. Results: A total of 42 stents were inserted into 39 patients over 14months. Demographics of our cohort were 27 males: 12 females, mean age 50 yrs (range 10 – 82), and aetiology of PFC were predominantly gallstone and alcohol induced pancreatitis (11 and 15 patients respectively). The mean size of PFC was buy LY2157299 11 cm (range 6–17 cm) and mean duration of cyst maturation was 16 weeks (range

3–104 weeks). Successful insertion occurred in all cases 42/42 (100%). Early complications included sepsis (2 pts), blocked stent (1 pt), bleeding requiring transfusion (1 pt), and stent migration (1 pt). Late complication was stent in growth precluding stent removal. Resolution of PFC occurred in 24/27 (88.9%) of the stents removed thus far with the remaining three patients requiring 上海皓元 surgical intervention. Conclusion: This is the largest audit of a FCSEMS to manage PFCs. Our initial findings suggest that these stents in comparison to the previous standard of pigtail stents are easier to insert, have few complications with the majority experiencing PFC resolution. NQ NGUYEN,1 L TOSCANO,1 M LAWRENCE,1 R SINGH,2 P BAMPTON,3 RH HOLLOWAY,1 MN SCHOEMAN1

1Gastroenterology, Hepatology & Colorectal Surgery, Royal Adelaide Hospital, Adelaide, SA, Australia., 2Gastroenterology, Lyell McEwin Hospital, Adelaide, SA, Australia., 3Gastroenterology, Flinders Medical Centre, Adelaide, SA, Australia. Introduction: The use of intravenous sedation with benzodiazepine and opioid for colonoscopy in subjects with morbid obesity and/or obstructive sleep apnoea (OSA) is considered unsafe with significant risk of respiratory depression. These high-risk subjects are recommended to have anaesthesia-assisted colonoscopy. Patient-controlled analgesia with portable inhaled methoxyflurane (Penthrox®) has been shown recently to be feasible and safe for colonoscopy in unselected subjects with no risk of respiratory depression. Therefore, Penthrox® may be a much more attractive alternative for colonoscopy in patients with a high risk of respiratory depression.

For these 604 patients, the estimated vCJD risk Selleck Dabrafenib is ≥1% for 595, ≥50% for 164 and 100% for 51. This is additional to background UK population risk due to dietary exposure. Of 604 patients, 94 (16%) received implicated batches linked to donors who developed clinical

vCJD within 6 months of their donations. One hundred and fifty-one (25%) had received their first dose when under 10 years of age. By 1st January 2009, none of these patients had developed clinical vCJD. The absence of clinical vCJD cases in this cohort to date suggests that either plasma fraction infectivity estimates are overly precautionary, or the incubation period is longer for this cohort than for implicated cellular blood product recipients. Further follow-up of this cohort is needed. “
“This chapter contains sections titled: Introduction Products of local and blood bank production Products of large-scale plasma fractionation Issues related to hemophilia concentrates from recombinant technology Conclusion References

“
“Summary.  To construct a cost-minimization model comparing activated prothrombin complex concentrates (APCC) vs. recombinant factor VIIa (rFVIIa) in haemophilia patients with inhibitors from a US third party payer find more perspective. A literature-based decision model was used to model inhibitor treatment costs and outcomes. As existing clinical trials fail to demonstrate differences in the relative efficacy or safety of APCC vs. rFVIIa, we assumed the same efficacy for both products in the base-case. Regimens of APCC (75 IU kg−1 × 2 doses) and rFVIIa (90 μg kg−1 × 3 doses) were assumed according to manufacturer recommendations. If the first-line treatment failed, patients chose to continue the current treatment or switch MCE to another drug. All costs were adjusted to 2009 US dollars. Sensitivity analyses on the infusion frequency, efficacy, unit price, switch rate, re-bleed rate and body weight were performed to assess model robustness. In the base-case, the total medical cost to treat a bleed with APCC or rFVIIa as first-line medication was US$25 969 and US$35 838,

respectively. One-way sensitivity analyses showed that results were insensitive to the efficacy of rFVIIa, unit price of APCC or rFVIIa, switch rate, re-bleed rate or body weight. The rFVIIa will reach cost neutrality when the efficacy of APCC is as low as 60%, or rFVIIa is infused only twice for each line, or APCC is infused three times for each line. Two-way sensitivity analyses showed that results were quite sensitive to the assumed infusion frequency for both products. First-line APCC compared with rFVIIa can be a cost-saving alternative for home treatment of mild-to-moderate bleeds in haemophilia patients with inhibitors. “
“An elevated body mass index (BMI) may make venipuncture more difficult, potentially impacting the use of home infusion (HI) and self-infusion (SI).

For these 604 patients, the estimated vCJD risk http://www.selleckchem.com/products/gsk2126458.html is ≥1% for 595, ≥50% for 164 and 100% for 51. This is additional to background UK population risk due to dietary exposure. Of 604 patients, 94 (16%) received implicated batches linked to donors who developed clinical

vCJD within 6 months of their donations. One hundred and fifty-one (25%) had received their first dose when under 10 years of age. By 1st January 2009, none of these patients had developed clinical vCJD. The absence of clinical vCJD cases in this cohort to date suggests that either plasma fraction infectivity estimates are overly precautionary, or the incubation period is longer for this cohort than for implicated cellular blood product recipients. Further follow-up of this cohort is needed. “
“This chapter contains sections titled: Introduction Products of local and blood bank production Products of large-scale plasma fractionation Issues related to hemophilia concentrates from recombinant technology Conclusion References

“
“Summary.  To construct a cost-minimization model comparing activated prothrombin complex concentrates (APCC) vs. recombinant factor VIIa (rFVIIa) in haemophilia patients with inhibitors from a US third party payer Ibrutinib supplier perspective. A literature-based decision model was used to model inhibitor treatment costs and outcomes. As existing clinical trials fail to demonstrate differences in the relative efficacy or safety of APCC vs. rFVIIa, we assumed the same efficacy for both products in the base-case. Regimens of APCC (75 IU kg−1 × 2 doses) and rFVIIa (90 μg kg−1 × 3 doses) were assumed according to manufacturer recommendations. If the first-line treatment failed, patients chose to continue the current treatment or switch MCE公司 to another drug. All costs were adjusted to 2009 US dollars. Sensitivity analyses on the infusion frequency, efficacy, unit price, switch rate, re-bleed rate and body weight were performed to assess model robustness. In the base-case, the total medical cost to treat a bleed with APCC or rFVIIa as first-line medication was US$25 969 and US$35 838,

respectively. One-way sensitivity analyses showed that results were insensitive to the efficacy of rFVIIa, unit price of APCC or rFVIIa, switch rate, re-bleed rate or body weight. The rFVIIa will reach cost neutrality when the efficacy of APCC is as low as 60%, or rFVIIa is infused only twice for each line, or APCC is infused three times for each line. Two-way sensitivity analyses showed that results were quite sensitive to the assumed infusion frequency for both products. First-line APCC compared with rFVIIa can be a cost-saving alternative for home treatment of mild-to-moderate bleeds in haemophilia patients with inhibitors. “
“An elevated body mass index (BMI) may make venipuncture more difficult, potentially impacting the use of home infusion (HI) and self-infusion (SI).

004; OR = 2.98). Of note, carriers of NOD2 risk alleles showed a significantly (P = 0.007) reduced mean survival time RAD001 (274 days) in comparison to patients with wildtype genotypes (395 days). Conclusion: Common NOD2 variants linked previously to impaired mucosal barrier function may be genetic risk factors for death and SBP. These findings might serve to identify patients with cirrhotic ascites eligible for preemptive antibiotic treatment. (HEPATOLOGY 2010.) Spontaneous bacterial peritonitis (SBP) is a frequent

and severe complication of cirrhosis. As a marker of severe hepatic dysfunction, SBP occurs in up to 30% of patients with cirrhosis and ascites.1 The survival of patients with liver cirrhosis who recover from a first episode of SBP is significantly reduced and despite antibiotic treatment, SBP is still associated with in-hospital mortality rates between 15% and

30%.2–4 The term SBP was coined more than 40 years ago by Conn,5, 6 who speculated that the translocation of intestinal bacteria represents a critical event in the development of SBP. However, genetic Saracatinib clinical trial factors predisposing to bacterial translocation and SBP have not been identified to date. It has long been anticipated that in addition to intestinal bacterial overgrowth and immune dysfunction, patients at risk for SBP demonstrate increased intestinal permeability, a prerequisite for bacterial translocation from the gut,7–9 which is defined as the migration of bacteria from the intestinal lumen to mesenteric lymph nodes or other extraintestinal sites.4 In 2001, variants of the NOD2 (nucleotide-binding oligomerization domain containing 2) gene (Supporting Fig.) were associated with impaired mucosal barrier function in Crohn disease.10–12 Because NOD2 is involved in the intestinal recognition of bacteria and bacterial products, insufficient activation

of NF-κB in carriers of NOD2 risk variants may result in deficient elimination of bacteria and enhancement of their translocation from the intestine.13 It has also been shown that NOD2 variants influence survival in sepsis14 and graft-versus-host disease (GvHD),15 but there is no evidence for a correlation with any liver disease. We hypothesized that the development of SBP in patients with liver cirrhosis 上海皓元医药股份有限公司 is also associated with NOD2 risk variants. The aim of the present study was to assess the potential role of NOD2 as a gene conferring susceptibility to SBP or even death in a large series of patients with cirrhosis and advanced liver cirrhosis and ascites. For the study, we selected those three NOD2 variants (p.R702W, pG908R, and c.3020insC; Supporting Fig.) that are known to confer a deficit in NF-κB activation in response to lipopolysaccharide and peptidoglycan,16 providing evidence for a unifying pathomechanism whereby NOD2 variants confer an increased risk for complications of liver cirrhosis.

004; OR = 2.98). Of note, carriers of NOD2 risk alleles showed a significantly (P = 0.007) reduced mean survival time selleck chemical (274 days) in comparison to patients with wildtype genotypes (395 days). Conclusion: Common NOD2 variants linked previously to impaired mucosal barrier function may be genetic risk factors for death and SBP. These findings might serve to identify patients with cirrhotic ascites eligible for preemptive antibiotic treatment. (HEPATOLOGY 2010.) Spontaneous bacterial peritonitis (SBP) is a frequent

and severe complication of cirrhosis. As a marker of severe hepatic dysfunction, SBP occurs in up to 30% of patients with cirrhosis and ascites.1 The survival of patients with liver cirrhosis who recover from a first episode of SBP is significantly reduced and despite antibiotic treatment, SBP is still associated with in-hospital mortality rates between 15% and

30%.2–4 The term SBP was coined more than 40 years ago by Conn,5, 6 who speculated that the translocation of intestinal bacteria represents a critical event in the development of SBP. However, genetic Depsipeptide supplier factors predisposing to bacterial translocation and SBP have not been identified to date. It has long been anticipated that in addition to intestinal bacterial overgrowth and immune dysfunction, patients at risk for SBP demonstrate increased intestinal permeability, a prerequisite for bacterial translocation from the gut,7–9 which is defined as the migration of bacteria from the intestinal lumen to mesenteric lymph nodes or other extraintestinal sites.4 In 2001, variants of the NOD2 (nucleotide-binding oligomerization domain containing 2) gene (Supporting Fig.) were associated with impaired mucosal barrier function in Crohn disease.10–12 Because NOD2 is involved in the intestinal recognition of bacteria and bacterial products, insufficient activation

of NF-κB in carriers of NOD2 risk variants may result in deficient elimination of bacteria and enhancement of their translocation from the intestine.13 It has also been shown that NOD2 variants influence survival in sepsis14 and graft-versus-host disease (GvHD),15 but there is no evidence for a correlation with any liver disease. We hypothesized that the development of SBP in patients with liver cirrhosis 上海皓元医药股份有限公司 is also associated with NOD2 risk variants. The aim of the present study was to assess the potential role of NOD2 as a gene conferring susceptibility to SBP or even death in a large series of patients with cirrhosis and advanced liver cirrhosis and ascites. For the study, we selected those three NOD2 variants (p.R702W, pG908R, and c.3020insC; Supporting Fig.) that are known to confer a deficit in NF-κB activation in response to lipopolysaccharide and peptidoglycan,16 providing evidence for a unifying pathomechanism whereby NOD2 variants confer an increased risk for complications of liver cirrhosis.

1E). Genes associated with messenger RNA processing were enriched in clusters A (red bar) and B (orange bar). Surprisingly, genes in cluster C were significantly associated with pathways involved in blood-vessel Selleck PLX4720 morphogenesis, angiogenesis, neurogenesis, and epithelial mesenchymal transition (EMT) (light blue bar). Close examination of genes in each cluster suggested that known hepatic

transcription factors (FOXA1), Wnt regulators (TCF7L2 and DKK1), and a hepatic stem cell marker (CD24) were dominantly up-regulated in EpCAM+ and CD133+ HCCs (Fig. 1F). By contrast, genes associated with blood-vessel morphogenesis (TIE1 and FLT1), EMT (TGFB1), and neurogenesis (NES) were activated dominantly in CD90+ HCCs and CD133+ HCCs. Because CD133+ HCCs were relatively rare and constituted

only 13% (microarray cohort) to 20% (FACS cohort) of all HCC samples analyzed, we focused on the characterization learn more of EpCAM and CD90. To clarify the cell identity of EpCAM+ or CD90+ cells in primary HCCs, we performed IHC analysis of 18 needle-biopsy specimens of premalignant dysplastic nodules (DNs), 102 surgically resected HCCs, and corresponding NT liver tissues. When examining the expression of EpCAM and CD90 in cirrhotic liver tissue by double-color IHC analysis, we found that EpCAM+ cells and CD90+ cells were distinctively located and not colocalized (Supporting Fig. 1A). Immunoreactivity (IR) to anti-CD90 antibodies (Abs) was detected in vascular endothelial cells (VECs), inflammatory cells, fibroblasts, and neurons, but not in hepatocytes or cholangiocytes, in the cirrhotic

liver (Supporting Fig. 1B, panels a,b). IR to anti-EpCAM Abs was detected in hepatic progenitors adjacent to the periportal area and bile duct epithelial cells in liver cirrhosis (Supporting Fig. 1B, panels c,d). IR to anti-EpCAM Abs was detected in 37 medchemexpress of 102 surgically resected HCCs (Fig. 2A, panel b), but not in 18 DNs (Fig. 2A, panel a). By contrast, no tumor epithelial cells (TECs) showing IR to anti-CD90 Abs were found in any of the 18 DNs or 102 HCCs examined (Fig. 2A, panels c,d). However, we identified CD90+ cells that were morphologically similar to VECs or fibroblasts within the tumor nodule in 37 of the 102 surgically resected HCC tissues (≥5% positive staining in a given area). IR to anti-CD90 Abs was also detected in hepatic mesenchymal tumors (Supporting Fig. 1C, panels a-c), indicating that CD90 is also a marker of liver stromal tumors. Double-color IHC and immunofluorescence (IF) analysis confirmed the distinct expression of EpCAM and CD90 in HCC (Fig. 2B), consistent with the FACS data (Fig. 1A).

1E). Genes associated with messenger RNA processing were enriched in clusters A (red bar) and B (orange bar). Surprisingly, genes in cluster C were significantly associated with pathways involved in blood-vessel mTOR inhibitor morphogenesis, angiogenesis, neurogenesis, and epithelial mesenchymal transition (EMT) (light blue bar). Close examination of genes in each cluster suggested that known hepatic

transcription factors (FOXA1), Wnt regulators (TCF7L2 and DKK1), and a hepatic stem cell marker (CD24) were dominantly up-regulated in EpCAM+ and CD133+ HCCs (Fig. 1F). By contrast, genes associated with blood-vessel morphogenesis (TIE1 and FLT1), EMT (TGFB1), and neurogenesis (NES) were activated dominantly in CD90+ HCCs and CD133+ HCCs. Because CD133+ HCCs were relatively rare and constituted

only 13% (microarray cohort) to 20% (FACS cohort) of all HCC samples analyzed, we focused on the characterization PD98059 nmr of EpCAM and CD90. To clarify the cell identity of EpCAM+ or CD90+ cells in primary HCCs, we performed IHC analysis of 18 needle-biopsy specimens of premalignant dysplastic nodules (DNs), 102 surgically resected HCCs, and corresponding NT liver tissues. When examining the expression of EpCAM and CD90 in cirrhotic liver tissue by double-color IHC analysis, we found that EpCAM+ cells and CD90+ cells were distinctively located and not colocalized (Supporting Fig. 1A). Immunoreactivity (IR) to anti-CD90 antibodies (Abs) was detected in vascular endothelial cells (VECs), inflammatory cells, fibroblasts, and neurons, but not in hepatocytes or cholangiocytes, in the cirrhotic

liver (Supporting Fig. 1B, panels a,b). IR to anti-EpCAM Abs was detected in hepatic progenitors adjacent to the periportal area and bile duct epithelial cells in liver cirrhosis (Supporting Fig. 1B, panels c,d). IR to anti-EpCAM Abs was detected in 37 medchemexpress of 102 surgically resected HCCs (Fig. 2A, panel b), but not in 18 DNs (Fig. 2A, panel a). By contrast, no tumor epithelial cells (TECs) showing IR to anti-CD90 Abs were found in any of the 18 DNs or 102 HCCs examined (Fig. 2A, panels c,d). However, we identified CD90+ cells that were morphologically similar to VECs or fibroblasts within the tumor nodule in 37 of the 102 surgically resected HCC tissues (≥5% positive staining in a given area). IR to anti-CD90 Abs was also detected in hepatic mesenchymal tumors (Supporting Fig. 1C, panels a-c), indicating that CD90 is also a marker of liver stromal tumors. Double-color IHC and immunofluorescence (IF) analysis confirmed the distinct expression of EpCAM and CD90 in HCC (Fig. 2B), consistent with the FACS data (Fig. 1A).

Abs, antibodies; CLEVER-1, common lymphatic endothelial and vascular endothelial receptor-1; CLL, chronic lymphocytic leukemia; ECs, endothelial

cells; FACS, fluorescence-activated cell sorting; FCS, fetal calf serum; GPC, G protein coupled; HGF, hepatocyte growth factor; HSEC, hepatic sinusoidal endothelial cell; ICAM-1, intercellular adhesion molecule-1; IFN-γ, interferon-gamma; IgG, immunoglobulin G; MZL, marginal zone lymphoma; NHL, non-Hodgkin’s lymphoma; PBC, primary biliary cirrhosis; PBS, phosphate-buffered saline; TNF-α, BMS-354825 price tumor necrosis factor alpha; VAP-1, vascular adhesion protein-1; VCAM-1, vascular cell adhesion molecule-1; VEGF, vascular endothelial growth factor. Liver endothelial cells (ECs) were isolated from human liver tissue obtained from explanted livers or donor tissue surplus to surgical requirements, as described previously.4 All tissue was collected from patients in the Liver Unit at the Queen Elizabeth Hospital in Birmingham (Birmingham, UK) with informed consent and under local ethics committee approval. In brief, approximately 30 g of tissue underwent collagenase digestion Silmitasertib manufacturer (0.2% collagenase

type Ia; Sigma-Aldrich, St. Louis, MO). The digested tissue was placed over a 33%/77% Percoll (Amersham Biosciences, GE Healthcare, Little Chalfont, UK) density gradient. ECs were isolated MCE by immunomagnetic selection using antibodies (Abs) against CD31 conjugated to Dynabeads (Invitrogen, Paisley, UK). ECs were then cultured

in medium composed of human endothelial basal growth medium (Invitrogen), 10% AB human serum (HD Supplies, Glasgow, UK), 10 ng/mL of vascular endothelial growth factor (VEGF), and 10 ng/mL of hepatocyte growth factor (HGF) (PeproTech, Peterborough, UK). Cells were grown in collagen-coated culture flasks and were maintained at 37°C in a humidified incubator with 5% CO2 until confluence. Using this protocol, a sufficient number of cells were isolated from either diseased or healthy tissue for use in functional assays. Peripheral blood lymphocytes were isolated as previously described by density-gradient centrifugation over Lympholyte (VH Bio, Gateshead, UK) for 25 minutes at 800×g.13 Harvested lymphocytes were washed in phosphate-buffered saline (PBS) and resuspended in RPMI 1640 with 10% fetal calf serum (FCS). CD4, CD8, and B-cell populations were isolated by using negative immunomagnetic selection kits (Invitrogen). Kits were used as per the manufacturer’s instructions. Highly pure populations of untouched peripheral blood B cells were obtained. Flow cytometry demonstrated greater than 98% expression of CD19 on isolated populations.

We measured serum ferritin for 241 persons; 121/241 were H. pylori positive. The geometric mean ferritin (GMF) for persons with and without H. pylori infection was 37 μg/L and 50 μg/L, respectively (p = .04). At enrollment, 19/121 H. pylori-positive persons had iron deficiency compared with 8/120 H. pylori negative (p = .02). Among 66 persons tested at 24 months, the GMF was higher at 24 months (49.6 μg/L) versus enrollment (36.5 μg/L;

p = .02). Six of 11 persons with iron deficiency at enrollment no longer had iron deficiency and had a higher GMF (p = .02) 24 months after treatment. H. pylori infection was correlated with lower serum ferritin and iron deficiency. After H. pylori eradication, serum ferritin increased and approximately half of persons resolved their iron deficiency. Testing for H. pylori infection and subsequent treatment of those positive Target Selective Inhibitor Library could be considered in persons with unexplained iron deficiency. “
“Helicobacter pylori infection and disease outcome are mediated by a complex interplay between

bacterial, host, and environmental factors. Over the past year, our understanding of this complex interplay has been improved by a variety of studies focusing on both host and bacterial factors. These include studies assessing novel virulence factors as well as those most frequently associated with severity of disease outcome including cagA and the cag Selumetinib nmr pathogenicity island, and the vacuolating cytotoxin. Several studies have focused on regulation of virulence factors by environmental factors. In addition, mechanisms by which bacterial virulence factors influence the host response and disease, by inducing epigenetic changes, autophagy and altered MCE公司 oxidative stress have also been elucidated. This review highlights key findings in the pathogenesis of H. pylori infection reported over the past year. Helicobacter pylori remains an outstanding

pathogen and serves as a key model system for understanding the fascinating intricacies of host–pathogen interactions in the gastrointestinal tract, as well as in infection- and inflammation-mediated cancers. This review highlights recent advances in H. pylori pathogenesis over the past year. To promote chronic infection, H. pylori has developed a variety of mechanisms to survive in the harsh acidic environment of the gastric mucosa. One of these is an “acid acclimation mechanism” that promotes adjustment of periplasmic pH in the acidic environment of the stomach by regulating activity of urease, UreI, and α-carbonic anhydrase. Two-component systems, which generally are composed of histidine kinases and a response regulator, are important mechanisms that allow bacteria to respond to environmental signals. Previous studies indicated that the ArsS two-component system regulated transcription of urease [1].

5 years. Patients in whom HCV RNA was undetectable at week 20 were categorized as responders and continued full-dose combination therapy for up to 48 weeks. Initial responders

were eligible for randomization into the trial if virologic breakthrough occurred during extended therapy or relapse followed 48 weeks of therapy. In addition, patients who were treated with peginterferon and ribavirin outside the lead-in phase of the HALT-C Trial were also eligible for randomization (“express” group) if they met criteria for nonresponse, breakthrough, or relapse. This approach to enrollment ensured that all patients had received optimal therapy with peginterferon and ribavirin8, 9 before they were enrolled into this long-term selleck chemicals llc trial, during which they might not be treated.5 After randomization, patients in both groups were seen at 3-month intervals for 3.5 years, at which point peginterferon was discontinued in the treatment group.

Nine patients assigned to the control group were treated “off-protocol” by nonstudy physicians, but they were included as controls in see more our intention-to-treat analysis. Thereafter, all patients remained untreated and were seen at 6-month intervals. At each visit the occurrence of clinical outcomes (which had been established prospectively) was noted, including clinical events and laboratory markers of hepatic decompensation, HCC, or death. Although not a primary clinical outcome in the

HALT-C Trial, liver transplantation was included in this mortality analysis because these patients were likely to have died in the absence of liver transplantation. Most deaths were identified by study coordinators interacting with family members by way of telephone. In addition, periodic on-line searches were performed of the U.S. Social Security Death Index (SSDI) (http://ssdi.rootsweb.com/), which is generated from the U.S. Social Security Administration’s Death Master File. The SSDI was queried for any participant with whom the study site had no contact for at least 6 months. The last search of the SSDI was conducted in October, 2009. To account for the potential lag between date of death and 上海皓元 report to the SSDI, we included in our analysis deaths occurring on or before December 31, 2008. All deaths were reviewed by a seven-person, central review committee consisting of HALT-C Trial investigators blinded to the identity of the subject, study site, fibrosis versus cirrhosis stratum, but not randomization allocation (treatment or control), this information being required to assess treatment relatedness. The committee classified the primary cause of death into one of 15 categories (Supporting Table 1).