13 The high rate of emergence of the protease resistant variant, R155K, in genotype 1a–infected, but not in genotype 1b–infected, patients DMXAA has also been described previously with this class of agent and is reflective of single-nucleotide change required for the development of resistance in genotype 1a patients, but two-nucleotide changes in the majority of genotype 1b patients. 27 It is of note that single-nucleotide change is required for both mutations at NS3 R155 and D168 in genotype

1a patients; however, a mutation at only R155, and not D168, was identified in genotype 1a patients by population sequencing. The R155 nucleotide sequence may be more susceptible to change than D168, or the R155K may be more fit than mutations at D168 in this genotype. Mutations at D168 were commonly selected in genotype

1b–infected patients, consistent with genotype 1b replicon data. The Y448H mutation observed with www.selleckchem.com/products/AZD6244.html tegobuvir has been observed frequently in monotherapy studies and is consistent with in vitro mutational data, indicating the tegobuvir interaction likely involves the β-hairpin in the thumb subdomain of the NS5B polymerase. 20 In the present study, 7 of 8 genotype 1a patients developed dual-class resistance: R155K against the NS3 protease inhibitor and Y448H for the NS5B polymerase inhibitor. However, with the addition of RBV, the incidence of resistance was significantly reduced, with none of genotype 1a patients (n = 3) exhibiting drug-resistant variants. Though RBV has been shown to have modest antiviral activity, 28 its ability to significantly reduce the development of resistance highlights a distinct mechanism of action. This may indicate

a broader mutational effect of RBV on viral fitness, which renders a proportion of virus noninfectious, regardless of oral antiviral-resistance mutations. Although similar trials have been reported on, 29 the present study is the first report of an IFN-free NS5B polymerase/NS3 protease combination both with and without RBV, thus allowing for a prospective evaluation 上海皓元医药股份有限公司 of the contribution of RBV to the antiviral effect of the regimen. The emergence of various classes of DAAs for treating chronic HCV infection has enabled an evaluation of multiple combination approaches either with or without Peg-IFN and RBV. 19, 30, 31 Specifically, the strategy of quadruple therapy with a non-nucleoside analog, a protease inhibitor, and Peg-IFN and RBV has been supported by results from a recently reported study, in which the non-nucleoside NS5B polymerase inhibitor, VX-222, telaprevir, and peg-IFN/RBV resulted in RVR in 51 of 59 (86%) of treatment-naïve patients, 19 which is higher than those reported with telaprevir and Peg-IFN/RBV. 6, 9 In this study, 100% of patients receiving quadruple therapy achieved RVR at week 4, and a high proportion of patients (71%) had HCV RNA below 25 IU/mL at week 2.

No HBsAg decline by week 12 of therapy was associated with a low chance of a sustained response (97% probability of nonresponse) and was proposed as an early stopping rule for peginterferon therapy. Because this rule needs to be validated in other studies, we investigated how the rule would have performed in HBeAg-positive patients treated with peginterferon alfa-2a during two independent, large-scale studies.2, 3 HBeAg-positive patients received peginterferon alfa-2a (180 μg/week) with or without lamivudine (100 mg/day) for 48 weeks

as part of a phase 3 study2 (n = 542) or peginterferon alfa-2a (180 μg/week) for 48 weeks as part of the Nephrotic Syndrome Study Network (NEPTUNE) study (n = 136).3 Overall, the rates of HBeAg loss and hepatitis B virus (HBV) DNA levels < 10,000 copies/mL in the phase 3 and NEPTUNE peginterferon alfa-2a studies were similar (25% and 24%, respectively), Selleckchem Palbociclib http://www.selleckchem.com/products/ly2157299.html and they were higher than those in Sonneveld et al.’s analysis (19%).1 In accordance with Sonneveld et al.’s data, the HBsAg decline was more pronounced in patients with a response 6 months post-treatment versus nonresponders. Patients with no HBsAg decline from the baseline to week 12 had 82% (80/97) and 71% (22/31) probabilities of nonresponse in the phase 3 and NEPTUNE studies, respectively; these were considerably lower than the probability of 97% in

Sonneveld et al.’s study (Fig. 1). The probabilities of response in patients with no HBsAg decline were 18% (17/97) and 29% (9/31), respectively. Applying the stopping rule would have resulted in premature treatment discontinuation in some patients (17 and 9, respectively) who would have responded. HBeAg seroconversion 6 months post-treatment, rather than HBeAg loss and HBV DNA levels <10,000 copies/mL, was the primary endpoint in the peginterferon alfa-2a studies. Using this more robust indicator of sustained immune control would have resulted in some patients in the phase 3 and NEPTUNE studies (30 and 12, respectively) discontinuing their treatment prematurely if the stopping rule had been applied. Differences in the study populations could explain the varying

response rates and the fact that the proposed stopping rule could not be validated by the peginterferon alfa-2a analyses. Sonneveld et al.’s analysis1 was a European medchemexpress study in which only 20% of the patients were Asian, whereas the populations of the phase 3 and NEPTUNE peginterferon alfa-2a studies were predominantly Asian (>80%). This influenced the genotype distribution; Sonneveld et al.’s study had a high proportion of genotype A or D patients, whereas the peginterferon alfa-2a studies included predominantly genotype B and C patients. In combination with the differences in the treatment regimens (peginterferon alfa-2a versus peginterferon alfa-2b and 48 weeks of therapy versus 52 weeks) and in the numbers of patients included in the analyses, this may account for the differences in the results.

Methods. We provided 100 consecutive CHB patients in 2 academic hospitals with a medication dispenser that monitors ETV intake in real time (Sensemedic, Evalan, Amsterdam, the Netherlands). During 16 weeks of treatment, adherence data were directly transferred to a central server. Poor adherence was BGB324 manufacturer defined as <80% pill intake during the study period. At both baseline and 16-week follow-up visits, quantitative serum HBV DNA (Cobas Taqman, Roche, Almere, the Netherlands: lower limit of detection 20 IU/mL) was performed. Results. At start of the study, 64% of patients were HBe-negative, 67% were treated > 1 year with ETV and 76% were HBV DNA unde-tectable.

29% was (PEG-)interferon-experienced, and 27% NUC-experienced. Adherence over 16 weeks averaged 85±17%. Percentages of patients with ≧70%, ≧80%, ≧90% and ≧95% adherence were 81 %, 70%, 52% and 43%, respectively. The longest interruption between two consecutive ETV doses was a median of 3 days (range 1-53). Patients with poor adherence were significantly younger (40 vs. 47 years, p=0.01), Erlotinib clinical trial while no other predictors of poor adherence were identified. 82 patients had HBV DNA <20 IU/mL after 16 weeks, whereas in 18 patients HBV DNA levels >20 IU/mL were measured. No virological breakthrough

occurred. Patients with HBV DNA >20 IU/mL were younger (37 vs. 47 years, p=0.001), more frequently treated <1 year (75% vs. 28%, p<0.001), more frequently HBeAg positive (72% vs. 28%, p=0.002), NUC-naive (89 vs. 69%, p=0.11), and had lower mean adherence (83% vs. 91% (p=0.19). In multivariate analysis, duration of ETV treatment (adjusted OR 18.8 (4.1-87.0, p<0.001) and negative HBe-status (adjusted OR 11.9 (2.6-53.6), p=0.001) predicted HBV DNA negativity, whereas adherence was not a significant predictor (adjusted OR 1.02 (0.98-1.07), p=0.34). Adherence tended to be lower in the 7 patients with HBV DNA >200 IU/mL compared to the 1 1 patients with HBV DNA 20-200 IU/mL (71 vs. 95%, p=0.1 0). Conclusions: Overall 70% of our CHB patients exhibited MCE good adherence to ETV therapy,

with younger patients being more prone to poor adherence. Even in case of poor adherence, virological responses seem to be generally excellent and poor adherence was not an independent predictor of virological response. Disclosures: Joop Arends – Advisory Committees or Review Panels: MSD, BMS Harry L. Janssen – Consulting: Abbott, Bristol Myers Squibb, Debio, Gilead Sciences, Merck, Medtronic, Novartis, Roche, Santaris; Grant/Research Support: Anadys, Bristol Myers Squibb, Gilead Sciences, Innogenetics, Kirin, Merck, Medtronic, Novartis, Roche, Santaris Karel J. van Erpecum – Grant/Research Support: Bristol Meyers Squibb, MSD The following people have nothing to disclose: Lotte G. van Vlerken, Pauline Arends, Faydra I. Lieveld, Willem Pieter Brouwer, Peter D.

Due to the longer treatment duration of the triple combination, there are no sufficient data yet for patients reaching the end of treatment for BOC. In the cohort creatinine results were recorded at baseline, week 12, week 24, and every 12 weeks thereafter until 24 weeks after end of treatment. No documentation of urine analysis was recorded. The eGFR was calculated with the recently presented Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula, which may be best suited to reflect changes of eGFR in patients with normal or mildly impaired renal function.[6] For statistical analysis in a first step, univariate ALK inhibitor regression analysis

was used. All variables reaching P < 0.05 in the univariate analysis were entered in a multiple logistic regression analysis. Software used was IBM SPSS Statistics v. 21.0.0.0. Overall, 895 patients were find more included, 575 on TLV, 211 on BOC, and 109 on dual therapy. Baseline demographics are shown in Table 1. As expected, HCV genotype 1 patients treated with dual

therapy were younger, had more frequently low level HCV-RNA, and had a lower proportion of patients with diabetes mellitus or arterial hypertension, reflecting a selection for variables associated with better treatment outcome or being naïve to HCV therapy. At week 12 a decrease of eGFR to <60 mL/min in patients with >60 mL/min at baseline was observed in 49/895 (5.5%) patients overall. Patients on TLV 38/575 (6.6%) and BOC 10/211 (4.7%) experienced more frequently a decrease in eGFR to <60 mL/min compared to patients on PEG/RBV 1/109 (0.9%) (P < 0.05). Risk factors associated with eGFR <60 mL/min corresponding to renal insufficiency stage 3 were age (P < 0.001), arterial hypertension (P < 0.001), diabetes mellitus (P < 0.05), a higher

serum creatinine at baseline (P < 0.001), MCE and being on triple therapy with TLV or BOC (P < 0.05). There was no association with baseline hemoglobin, smoking, uric acid, alanine aminotransferase (ALT), aspartate aminotransferase (AST), HCV-RNA, HCV treatment history, sex, APRI score, or comedications including nonsteroidal antiinflammatory drugs. In the multiple regression analysis age (P < 0.001), a higher creatinine at baseline (P < 0.001), being on triple therapy with TLV or BOC (P < 0.01), and arterial hypertension (P < 0.05) remained significantly associated with a decrease in eGFR to <60 mL/min. Patients with a drop of eGFR to <60 mL/min had a lower absolute mean hemoglobin at week 12 with 9.7 g/dL ± 1.4 g/dL compared to 11.0 g/dL ± 1.7 g/dL in patients with an eGFR >60 mL/min (P < 0.001). The absolute decrease in hemoglobin was also different, with 5.3 g/dL ± 1.3 g/dL compared to 3.8 g/dL ± 1.6 g/dL, respectively (P < 0.001). In the second analysis a smaller patient subset which had already reached week 24 of therapy was assessed.

Various investigations for viral hepatitis, autoimmune disease and Wilson’s disease were unhelpful. An abdominal ultrasound study and computed tomography (CT) scan showed dilatation of intrahepatic ducts and splenomegaly. Magnetic resonance cholangiopancreatography (MRCP) showed cystic dilatation of the hilar bile duct Kinase Inhibitor Library research buy and moderate dilatation of intrahepatic ducts. The gallbladder (GB) and common bile duct (BD) were clearly shown and the gallbladder appeared to be linked to intrahepatic ducts (Figure 1). Endoscopic retrograde cholangiopancreatography

(ERCP) was also performed and showed contrast passing from the common bile duct into the cystic duct and gallbladder (Figure 2). The common hepatic duct was not outlined. Endoscopy revealed esophageal and gastric

varices while CT angiography showed a normal hepatic artery, portal vein and inferior vena cava. At laparotomy, the patient had features of cirrhosis. An operative cholangiogram was performed by injection of contrast into the gallbladder and only showed contrast in the common bile duct, similar to findings at ERCP. In the process of mobilizing the gallbladder, bile ducts in the gallbladder bed were shown to communicate with the gallbladder. The common hepatic duct could not be identified but dissection revealed a hilar pouch containing bile. Two hepaticojejunostomies were performed to drain bile from the gallbladder CP-690550 price bed and from the hilar pouch. Splenectomy was also performed. The anastomoses in the gallbladder bed were shown to be patent by passage of contrast through a stent. Liver function tests returned to normal after MCE公司 8 months. This may be the first report of biliary atresia diagnosed in an adult. In this case, he had an unusual variant characterized by absence of the common hepatic duct (type II). The diagnosis was delayed because of the development of anastomoses between branches of the right hepatic duct and the gallbladder. Despite this,

there was persistent cholestasis with the development of biliary cirrhosis and portal hypertension. The surgical procedure appears to have been helpful in the short-term but the longer-term outcome remains unclear. Contributed by “
“We read with great interest the excellent article by Ghouri and coworkers,1 who reviewed the current literature on the levels of gamma-glutamyltransferase (GGT) and alanine aminotransferase (ALT) as potential predictors of incident cardiovascular disease. The authors elegantly demonstrate that there may be a statistically significant association between higher GGT levels and incident cardiovascular disease events, although this association may be clinically questionable because it is confounded by age. In contrast, ALT levels are not significantly associated with cardiovascular risk.

1997), and morphological comparisons have confirmed interocean population differences (Kitchener et al. 1990). Baird et al. (2008) have pointed out that dedicated studies of false killer whales are frequently hindered by the rarity with which the species is encountered at sea, resulting in a very low rate of data accumulation. This situation makes specimen materials from mass strandings and dedicated fisheries important sources of information, not

only for investigating population distinction but also for elucidating the basic biology of the species. In this paper we analyze data from a stranded school in South Africa and from several shore-driven schools in Japan to describe the patterns of growth buy GSI-IX and reproduction in false killer whales and investigate what differences, if any, exist between these and other populations. The South

African material was collected from 65 false killer whales that stranded en masse on the west coast of the Western Cape Province on 19 August 1981, of which 56 were found over a 1.5 km stretch of beach in St. Helena Bay (32.781ºS, 18.1ºE). No known attempts to refloat animals were made. As scientists reached the site only two days later, the fixation of the material was suboptimal to poor. Regorafenib Data are available from 63 individuals (41 females and 22 males). Additional information from several other South African strandings was considered when relevant (e.g., length at birth). The Japanese material originated from 156 specimens (96 females and 60 males) from the following six schools taken in drive fisheries at Iki Island (33.8ºN, 129.718ºE), designed as culling operations to reduce fishery interactions (Kasuya 1985): 20 animals on 8 March (4 females, 上海皓元医药股份有限公司 1 male examined), 138 on 15 March (20 females, 15 males), 160 on 19 March 1979 (16 females, 12 males), 10 on 22 February (2 females, 4 males), 80 on 27 February (38 females, 18 males), and 155 on 6 March 1980 (16 females and 10 males). The date of capture does not necessarily correspond to the date of death, as groups were kept alive in a netted bay until

sampled. As many false killer whales as possible in each school were randomly selected and systematically examined while fishermen independently slaughtered and processed their catch. After recording sex and total length (cm), one to three adjacent teeth were removed from the center of the lower jaw of each specimen and fixed in 10% buffered formalin (Japan) or 70% ethanol (South Africa). The presence and color of milk was checked by pressing and then cutting the mammary gland. The maximum thickness (cm) of one gland was recorded at its widest point, and a sample fixed in 10% buffered formalin (South Africa). Both ovaries were collected and the presence of corpora lutea, corpora albicantia, or large follicles recorded before the ovaries were fixed in 10% buffered formalin.

2002, Rayment et al. 2009). The deep water of Cook Strait was thought

to deter these dolphins from moving between the North and South Islands, consistent with most observations of Hector’s dolphins occurring in depths less than 39 m (Bräger et al. 2003, Rayment et al. 2011) and the rarity of sightings in the Fiordland area where depths can exceed 300 m (Cawthorn 1988). However, our identification of two Hector’s dolphins from the West Coast South Island confirm that movements between click here the islands do occasionally occur, even if it is not known whether the dolphins are crossing the deeper waters at the narrowest point of Cook Strait or perhaps following an offshore corridor of shallower water to the northwest. The ambiguous assignment of four dolphins to the Hector’s dolphin populations, suggests the potential for a previously unsampled population

of Hector’s dolphins that is not included in our baseline reference data, or perhaps an area of interbreeding between the East and West Coast Hector’s dolphin populations. Therefore, the potential for a small and elusive resident population of Hector’s PLX4032 solubility dmso dolphins along the southern part of the North Island, outside the current range of the Maui’s dolphin, or along the northern part of the South Island between the East and West Coast populations of Hector’s dolphins should be investigated. The protection of habitat and removal of anthropogenic threats are crucial if the Maui’s dolphin is to survive (Currey et al. 2012). The New Zealand government MCE公司 has recognized this by establishing the West Coast North Island Marine Mammal

Sanctuary and placing restrictions on seabed mining, acoustic seismic surveys, and fishing activities (New Zealand Department of Conservation 2008, New Zealand Ministry of Fisheries 2012). However, with the known distance of individual movement greatly increased to at least 400 km and the confirmation that these dolphins will at least occasionally disperse from the South Island to North Island, there is the possibility that genetic exchange between the subspecies will also benefit the Maui’s dolphin and promote the survival of the species on the west coast of the North Island. If protected corridors connecting the Maui’s dolphin on the North Island and Hector’s dolphin populations on the South Island are not maintained, then such natural dispersal events are less likely to occur. Rare natural dispersal events similar to the one described here for Hector’s dolphins have been beneficial for improving the genetic diversity and fitness of wolves in Scandinavia (Vila et al. 2003) and Isle Royal National Park (Adams et al. 2011), and perhaps other cases overlooked by a narrow definition of genetic rescue (Hedrick et al. 2011).

This was followed by a provider-administered survey regarding pain directionality. Survey questions were designed to allow the patient to express pain directionality utilizing simple written and pictorial representations of pain (Fig. 1). The design of the questions and diagrams were similar to those utilized by Jakubowski et al.[3] The survey classified migraine pain directionality as “exploding alone, imploding alone, ocular alone, or mixed (ie, combination of any 2 types or all 3 types).” Patients were given a paper survey with

the pictorial representations listed first followed by the written question, “Is your headache pain pushing in or pushing out of your head or is it located within your eye socket (ocular).” After the patient completed the written survey, the clinician conducted a scripted interview from which headache directionality, interattack variability in headache directionality and intra-attack variability in headache check details directionality were determined (Fig. 2). The clinician was blinded to the patient self-assignments of headache directionality. Summary statistics were used to describe BMN-673 the study sample. Mean ± standard deviation was reported for continuous variables, and percentage/frequency count was computed for nominal variables. For comparison between groups, Kruskal–Wallis test and Pearson’s chi-square

test (or Fisher’s exact test, if applicable) were applied. If the overall test was significant, pairwise comparison was performed using Bonferroni adjustment. Using a 2-sided test, a P value < .05 for overall test was considered statistically significant. Kappa coefficients were calculated to determine concordance between the different methods of assigning headaches to 1 of 4 pain directionalities: imploding ± ocular, exploding ± ocular, ocular, or imploding and exploding. Kappa coefficients were considered

MCE weak if less than 0.41, moderate if between 0.41 and 0.60, and strong if 0.61 or greater.[9] Analyses were conducted using SAS 9.2 (SAS Institute, Inc., Cary, NC, USA). One hundred ninety-eight female patients between the ages of 18 years and 77 years were included in the study. Mean age was 48 ± 12.4 years, and median age was 50 years. Race was self-reported as white by 88%, Asian/Pacific Islander by 4%, African American by 3%, and Other by 5%. Highest level of education was graduated college or higher by 65.5%, some college or technical school by 31%, graduated high school by 4%, and grade 11 or less by 1%. There were no differences in age, race, or highest level of education when comparing subjects with different headache directionality. Ninety-five percent (n = 188) of patients in the study reported episodic migraine (<45 headache days in 90), while 5% (n = 10) reported chronic migraine (>45 headache days in 90 days). According to patient selection of pictures that best represented their pain directionality, 14.

4 Multistage hepatocarcinogenesis is influenced by genetic and epigenetic changes as well as microenvironmental factors. Included among the former are mutation and/or inactivation of tumor suppressor genes such as TP53 and Rb and the activation of oncogenes such as Ras and c-Myc (hereafter Myc).1-7 Myc, a helix-loop-helix leucine zipper (HLH-ZIP) transcription factor, dimerizes with Max, another HLH-ZIP protein, and binds to E-box sequences to activate transcription of target genes or microRNAs (miRNAs).8 Myc also acts as a transcriptional repressor 26s Proteasome structure by interacting with and

suppressing other transcription factors and by modulating chromatin status.8 Myc is a downstream effector of many signaling pathways, and its expression is tightly regulated by many factors, including miRNAs.8-10 Through a myriad of such downstream targets, Myc plays important roles in cell growth,

survival, metabolism, and tumorigenesis.5-12 Myc is frequently amplified and selleck products overexpressed in many different human malignancies, including HCC.2, 3, 13, 14 Up-regulation of Myc and the reprogramming of transcription signature are critical steps in HCC progression in mice,15 and Myc is one of the critical genes activated in cancers believed to be caused by infection with HBX virus.16 Transforming growth factor-β1 and E2F1 may contribute to the promotion and progression of liver carcinogenesis in Myc transgenic mice.17, 18 However, precisely how Myc contributes to hepatocarcinogenesis at the molecular level has not been well characterized. Here we report that Myc is pathologically activated in and essential for several of the phenotypes associated with human HCC. Contributing to hepatocellular tumorigenicity is Myc’s repression of two miRNAs, miR-148a-5p and miR-363-3p, that comprise a negative feedback

loop involving Myc itself and ubiquitin-specific protease 28 (USP28)19; Myc 上海皓元医药股份有限公司 directly binds the conserved regions in the promoters of miR-148a-5p and miR-363-3p and represses their expression. These miRNAs function as tumor suppressors that promote cell cycle arrest and inhibit tumor growth. We also report that miR-148a-5p directly targets and inhibits Myc, whereas miR-363-3p destabilizes Myc indirectly by directly targeting and inhibiting USP28, which promotes the proteasome-mediated degradation of Myc protein. Finally, we show that this Myc-miRNA feedback loop is dysregulated in human HCC. These results help to clarify the regulatory mechanism by which Myc is overexpressed in this disease. DMEM, Dulbecco’s modified Eagle’s medium; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; GFP, green fluorescent protein; HCC, hepatocellular carcinoma; HLH-ZIP, helix-loop-helix leucine zipper; IgG, immunoglobulin G; IP, immunoprecipitation; miRNA, microRNA; mRNA, messenger RNA; RPE, retinal pigmented epithelium; RT-PCR, reverse-transcription polymerase chain reaction; siRNA, small interfering RNA; USP28, ubiquitin-specific peptidase 28; UTR, untranslated region.

Resistance mutations to lamivudine and/or ETV was detected only in 3 and 2 patients selleck chemicals llc in the TDF and TDF+ETV groups, respectively, at 48 weeks. None developed additional resistance mutations. None in the TDF group required protocol-defined switch over of treatment. Both treatments were

well tolerated, and safety and adverse event profiles were similar in the two groups. Conclusions: TDF monotherapy showed similarly high antiviral efficacy and safety as TDF and ETV combination therapy during 48 weeks of treatment in patients with ETV-resistant HBV. None developed additional resistance mutations. KEY WORDS: Lami-vudine, Monotherapy, Resistance, Virologic response Disclosures: Young-Suk Lim – Advisory Committees or Review

Panels: Gilead Science, Bayer; Grant/Research Support: Gilead Science, Novartis, Bayer; Speaking and Teaching: BMS Kwan Soo Byun – Advisory Committees or Review Panels: Gilead; Grant/ Research Support: Gilead, BMS, Taiho, Jassen; Speaking and Teaching: BMS Han Chu Lee – Grant/Research Support: Medigen Biotechnology Co., Novartis, Roche, Bayer HealthCare, Bristol-Myers Squibb, INC research, Boehringer Ingel-heim, Taiho Pharmaceutical CT99021 clinical trial Co., Yuhan Co. The following people have nothing to disclose: Geum-Youn Gwak, Byung Chul Yoo, So Young Kwon, Yoon Jun Kim, Jihyun An, Yung Sang Lee Background: Antiviral therapy may reduce HCC risk but it is unclear what the residual risk would be in treated patients. Our aim is to characterize MCE HCC incidence in treated and untreated patients by cirrhosis status, age (< 45 or ≥45), and gender. Methods: In this retrospective cohort study, 3933 consecutive CHB patients were identified at 3 US centers from 1991-2014. Patients were included if they had at least one year of follow-up and treatment-naïve. Exclusion criteria included HCC at initial presentation and the development of HCC within the first year of follow-up. Diagnosis was based on AASLD criteria for HCC and histology or clinical or imaging data for cirrhosis. Annual

incidence was calculated in cases per 1000 person years. Results: We included a total of 3220 patients with 102 incident HCC cases over a median time of follow-up of 4.1 (1-17) years. In multivariate analysis, antiviral therapy was an independent predictor for reduced HCC risk (HR 0.43, 95% CI 0.23-0.79) following adjustment for age, gender, cirrhosis, HBeAg, ALT, and HBV DNA. In cirrhotic men, regardless of age, the treated group had a lower incidence of HCC (Figure 1). For the non-cirrhotic cohort, the effects of antivirals, while beneficial were modest with the exception of men ≥45 years of age. HCC incidence in treated non-cirrhotic patients ranged from 0 to 1.2 cases per 1000 person years among the various age and gender groups compared to 0 to 6.4 per 1000 person years if untreated. HCC incidence in cirrhotic patients still ranged 16.