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Trattamento antivirale e controllo della malattia: benefici a lungo termine
- 1. Infezione cronica da virus B Trattamento antivirale e controllo della malattia: benefici a lungo termine Nuovi target di terapia antivirale: la lunga strada verso la cura Pietro Andreone Dipartimento di Scienze Mediche e Chirurgiche Università di Bologna Ospedaletto di Pescantina, 25 Giugno 2014
- 2. − Long term benefit − News from EASL − The long way to cure Outline
- 3. • Clinical – Control of symptoms • Biochemical – AST/ALT normalization • Serological – HBeAg loss – HBsAg loss • Virological – HBV-DNA suppression Long-term benefits • Histological – Inflammation/Fibrosis reduction • Portal pressure measurement – HVPG decrease • Liver Function – CTP/MELD scores
- 4. • Advantages – Relevant to patients • Disadvantages – Often asymptomatic even with advanced disease – Non specific Long-term benefits Clinical: control of symptoms
- 5. • Advantages – Inexpensive – Correlation with disease activity • Disadvantages – Significant fluctuation – Not specific to HBV – Imprecise correlation with histology Long-term benefits Biochemical: normalization of AST/ALT
- 6. • Advantages – Predicts favorable outcome if maintained off therapy • Disadvantages – Durability limited when treatment-induced – HBeAg-negative disease may develop Long-term benefits Serological: HBeAg loss ± HBeAb development
- 7. • Advantages – Associated with excellent prognosis (particularly if before 50 yrs) • Disadvantages – Rare event with current therapy – Difficult to predict (?) Long-term benefits Serological: HBsAg loss ± HBsAb development
- 8. • Advantages – On-treatment suppression associated with favorable short to medium- term outcome – Useful to identify viral resistance • Disadvantages – Poor durability off treatment (especially in HBeAg-negative) Surrogate Endpoints in CHB Virological: HBV-DNA suppression
- 9. Long term benefits Serological: HBsAg loss ± HBsAb development Aghemo A et al, J Hepatol 2012 Virological and serological responses after 12 mo (Peg-IFN after 6 mo of FU)
- 10. • Advantages – Accurate assessment of liver injury – Clinically relevant • Disadvantages – Invasive – Costly – Subject to sampling error – Slow to change (especially fibrosis) Long-term benefits Histological: inflammation/fibrosis improvement
- 11. Chang TT et al, Hepatology 2010 Long-term benefits Histological: inflammation/fibrosis improvement Fibrosis regression during long-term ETV treatment in 57 pts (10 with ≥F5) HBeAg+ and HBeAb+
- 12. Long-term benefits Histological: inflammation/fibrosis improvement Marcellin P et al, Lancet 2013 Fibrosis regression during long-term TDF treatment in 396 pts (96 with ≥F5) HBeAg+ and HBeAb+
- 13. • Advantages – Non invasive – Relatively good correlation with histology • Disadvantages – Limited validation in HBV – Longitudinal data lacking Long-term benefits Fibrosis serum markers/Fibroscan improvement
- 14. • Advantages – Accurate assessment of portal hypertension – Clinically relevant • Disadvantages – Invasive – Costly – Subject to sampling error – Slow to change (linked to fibrosis regression) Long-term benefits Portal pressure reduction
- 15. HVPG decrease in cirrhotic patients with significant (>10 mm Hg) portal hypertension treated with LMV Manolakopoulos S et al, J Hepatol 2009 Long-term benefits Portal pressure reduction
- 16. − Long term benefit − News from EASL − The long way to cure Outline
- 17. Jacobson I, EASL, 2014, Poster #1084 Coexisting steatosis and HBeAg+ status were independent predictors of pALT in HBV patients receiving long-term TDF treatment News from EASL 2014 Combined Impact of Baseline Steatosis and HBeAg Status on pALT after 5 yrs of TDF *Fisher exact test
- 18. Presence of steatosis was associated with a lower likelihood of regression of cirrhosis Buti MM, EASL, 2014, Poster #677 Regression of Cirrhosis in Obese and Non-Obese Patients With and Without Steatosis News from EASL 2014 Prediction of Liver Cirrhosis Regression in TDF-treated CHB Patients with Hepatic Steatosis P=0.05
- 19. Pageaux G-P, EASL, 2014, Poster #1061 News from EASL 2014 TDF in Treatment-Naïve or –Experienced CHB Patients (n=440) in a 3 yrs Real Life Practice 94–97% HBV DNA undetectable, with no difference between TN and TE Overall HBsAg-loss: 12 (2.7%) 3 cases of HCC reported over 3 years Virologic Response Rates 97% n=110 n=119 94% n=101 n=189 n=171 n=158 Patients with HBV-DNA <69IU/mL (%) Overall Population (N=440) eGFR ≥ 60 and < 90 (n=98) eGFR ≥ 90 (n=238) eGFR ≥ 30 and < 60 (n=24)
- 20. Causse X, EASL, 2014, Poster #1062 News from EASL 2014 TDF in CHB Patients with Older Age and Comorbidities Patients with HBV-DNA <69IU/mL (%) n=268 n=252 n=40 n=29 n=26 n=233 100% 95% Incidence of comorbidities in elderly patients: 35% HTN, 17% diabetes 58% were F3-F4 (METAVIR) at baseline
- 21. Lim Y-S, EASL, 2014, Poster #1064 Mean Change in Serum Creatinine Proportion of Patients with Virologic Response News from EASL 2014 TDF Monotherapy vs. TDF+ETV in ADV*-Resistant HBV * 30/102 had rtA181T/V and rtN236T mutations n=50 n=52 n=50 n=52 Intention-to-treat analysis
- 22. Abu-Amara M, EASL, 2014, Poster #194 778 patients treated; 70 patients developed HCC (median f/u of 47 months) Cumulative incidence of HCC – 5-year, 2.53% – 10-year, 3.32% News from EASL 2014 Risk of Hepatitis B-Related HCC with Antiviral Therapy External validation of three HCC risk models (NGM1-HCC, CU-HCC, REACH-B) in a North American mixed genotype population (n=2,105) Treatment modified the predicted risk of HCC, with lower than predicted incidence observed to a greater extent in high risk groups REACH-B Full Patient Cohort 0.1 0.3 0.4 0.5 Observed HCC Risk Predicted HCC Risk 0 0.2 0.0 0.1 0.2 0.3 0.4 0.5 HR HR HR LR MR MR 5 Years 3 Years High Risk
- 23. Ahn SJ, EASL, 2014, Poster #1069 News from EASL 2014 Efficacy of ETV in Naïve and LAM-Experienced CHB Patients Retrospective analysis of 342 consecutive NUC-naïve and LAM-experienced patients without LAM resistance treated with ETV for ≥ 30 months from 2006–2012 NA-Naïve n=270 LAM- Experience d n=72 P- value Median duration of ETV, months (SD) 44.1 (10.0) 44.8 (9.9) 0.584 Virologic response, % 97 94.4 0.295 Virologic breakthrough*, % 3.5 17 0.000 ETV resistance*, % 2.6 12.2 0.013 Independent predictive factors for developing ETV resistance: – Lack of virologic response at Month 12, HR 20.71, P=0.005 – LAM exposure, HR 5.01, P=0.035 *At Month 60
- 24. Chi H, EASL, 2014, Poster #1077 News from EASL 2014 Virologic Relapse Rate After NUC Discontinuation in CHB International study investigating off-treatment response after NUC therapy discontinuation in 94 CHB patients Mean f/u: 19.4 months Cirrhosis: 27 (28.7%) Median therapy duration: 4.1 years Patients with cirrhosis had lower risk of relapse (HR: 0.39; 95% CI 0.21-0.74) 20 60 80 100 Cumulative Rate, % Months After Discontinuation 0 40 0 12 24 36 48 Cumulative Rate of Virologic Relapse in Patients With and Without Cirrhosis 66.2% Cirrhosis No Cirrhosis 44.7% P=0.037 82.9% 70.1% Cirrhosis No Cirrhosis 17 12 67 27 No Cirrhosis Cirrhosis 10 4 5 2 4 1 Number at Risk
- 25. Patwardhan V, EASL, 2014, Poster #1080 News from EASL 2014 Treatment Cessation After Prolonged Suppression with NUCs in HBeAg-Negative Non-Cirrhotic Patients Single-center, retrospective chart review of HBeAg-negative patients on treatment with suppression for 4–5 years who stopped treatment Median f/u: 3 years 33 patients met eligibility criteria (LAM, 3; ADV, 14; ETV, 4; TDF, 12) 37% of patients stayed off treatment safely and without viral relapse after 5 years on suppressive NUC therapy 20 60 80 100 Cumulative Proportional Rate of Relapse Duration of Follow Up (Months) 0 40 0 10 20 30 40 50 60 63%
- 26. − Long term benefit − News from EASL − The long way to cure Outline
- 27. The long way to cure HBV Next-Generation Delivery System of Tenofovir N N N N NH2 O P O O O O O O O O O N N N N NH2 O P O HO OH N N N N NH2 O P O N H O O O Tenofovir Disoproxil Fumarate Tenofovir Tenofovir Alafenamide LYMPHOID CELLS/ HEPATOCYTES PLASMA GUT TFV TFV TFV-MP TFV-DP TDF/TFV TDF TFV TDF TAF TAF Cathepsin A CES1 TAF TAF ♦ Improved stability in plasma: – Enhanced delivery of active form (TFV-DP) to hepatocytes – Lower doses are used; systemic exposures of TFV reduced CES1 = carboxylesterase 1; DP= di-phosphate; MP= mono-phosphate.
- 28. The long way to cure HBV TAF Phase 3 Program • 2 phase 3, randomized, double-blind studies • Primary endpoint (non inferiority margin of 10%) – HBV DNA <29 IU/mL at Week 48 • Secondary endpoints – Bone mineral density – Renal parameters TAF 25 mg TDF 300 mg 2:1 randomization Open-label TAF Week 96 Week 144 (Year 3) Study 1 HBeAg+ N=864 Study 2 HBeAg- N=390 GS-US-320-0108 – Clinicaltrials.gov NCT01940341 GS-US-320-0110– Clinical trials.gov NCT01940471
- 29. The long way to cure HBV Combination therapy of TDF and PEG-IFN on HBsAg loss in noncirrhotic HBeAg(+) and HBeAg(-) CHB Primary endpoint: loss of HBsAg at Week 72 Arm A N=186 TDF PEG TDF PEG TDF PEG 48 72 120 Weeks 16 wks Arm B N=184 Arm C N=185 Arm D N=185 GS-US-174-0149 - Clinicaltrials.gov NCT01940341
- 30. HBsAg loss 8.5% HBsAb seroconversion 4.3% HBsAg loss 0% HBsAb seroconversion 0% Ning Q et al, J Hepatol 2014 in press The long way to cure HBV Combination therapy of ETV and PEG-IFN on HBsAg and HBeAg loss in CHB
- 31. The long way to cure HBV Oral Toll-Like Receptor 7 (TLR7) Agonist Pro-inflammatory cytokines NF-B IFN-α and other IFNs IRF7 MyD88 TLR7 TLR7: part of the innate immune system • Expressed in pDCs and B cells • Activated by ssRNA or small molecules GS-9620 Roethle et al. J Med Chem 2013
- 32. The long way to cure HBV HBV-Specific Therapeutic Vaccine • Recombinant yeast is efficiently taken up by professional antigen-presenting cells (APCs) • Processed viral antigens are then presented to T cells via MHC I and II. Haller AA, et al. Vaccine 2007;25:1452-63; Lu Y, et al. Cancer Res 2004;64:5084-8; Franzusoff A, et al. Expert Opin Biol Ther 2005;5:565-75
- 33. The long way to cure HBV Tarmogen Phase 2 in Chronic Hepatitis B • On treatment with nucleos(t)ide polymerase inhibitor (HBV DNA undetectable), excludes cirrhotics • Endpoints – HBsAg decline at Week 24 (primary) – HBsAg loss/seroconversion (secondary) – Immunology evaluation* Antiviral Antiviral n=25 Antiviral + 2 YU GS-4774 (q4wk) Antiviral n=50 Antiviral + 10 YU GS-4774 (q4wk) Antiviral n=50 Antiviral + 40 YU GS-4774 (q4wk) Antiviral n=50 0 24 48 Wk * Flow cytometry, ELISpot response to HBV antigens, pentamer evaluation for HBV-specific T-cells (number and phenotype), serum cytokine profile, PBMC mRNA expression changes, HLA typing. GS-US-330-0101 - Clinicaltrials.gov NCT01943799
- 34. The long way to cure HBV cccDNA inhibitor NUC Agent to prevent viral spread, cccDNA re-amplification Agents to activate antiviral immunity or relieve repression of the system Selective agent to deplete or perturb cccDNA Immune activator + + HBV antigen inhibition Agents to inhibit other components in the HBV life cycle [entry or cell-spread, capsid, HBX, HBsAg] +
Editor's Notes
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- Transition This slide shows the results of the exploration of baseline and on-treatment factors in HBeAg-positive (HBeAg+) and -negative (HBeAg−) patients with chronic HBV after 5 years of TDF treatment that are associated with persistently elevated ALT levels (pALT) Main Messages Nearly all patients (98%; 463/471) achieved complete suppression (HBV DNA < 69 IU/mL) at year 5 ~20% of suppressed patients on TDF at 5 years have pALT levels (Marcellin P, et al. Lancet 2013;381:468-75; Jacobson IM, et al. AASLD 2012, Poster 411) In univariate analyses, pALT at year 5 was associated with higher baseline BMI (p < 0.001) In multivariate analysis, pALT at year 5 was associated with baseline HBeAg+ status (p < 0.001); presence of baseline steatosis [<5% vs >=5%], (odds ratio=0.455, p=0.047); and year 5 steatosis [<5% vs >=5%], (odds ratio=0.202, p<0.001) Coexisting steatosis and HBeAg+ status were independent predictors of pALT Etiologies other than HBV infection may have contributed to pALT on long-term TDF treatment Background Methods All patients on TDF through Year 5 were included (N=471/641 [73%]) In a pooled analysis (N=471) from Studies 102 (HBeAg-) and 103 (HBeAg+), relationships were assessed between baseline demographic and disease characteristics, and on treatment response parameters with pALT at year 5. pALT (n=87) and normal ALT (n=384) patients were compared pALT was defined as serum ALT >upper limit of normal (ULN) at Year 5. Upper limit of ALT normal range: males 43 U/L (18–69 y) and 35 U/L (≥69 y); females 34 U/L (18–69 y) and 32 U/L (≥69 y) Hepatic steatosis scores were determined by independent pathologist based on biopsy slides at baseline (n=467/471 [99%]) and Year 5 (n=339/471 [72%]) Steatosis scoring: <5% (grade 0), ≥5% to < 34% (grade 1), ≥34% to <66% (grade 2), ≥66% (grade 3) If patients have steatosis, they are significantly less likely to have viral suppression <69 IU/ml. Assessment of steatosis and associated metabolic risk factors should be considered in CHB patients who have pALT while on effective antiviral therapy.
- Transition This slide shows the results of a subanalysis of the TDF Studies 102/103 done to assess the impact of hepatic steatosis on the persistance of cirrhosis in patients with long-term HBV DNA suppression at Year 5 which has never been studied. Main Messages Hepatic steatosis at baseline correlated with baseline BMI. Among obese patients with cirrhosis, the presence of hepatic steatosis was associated with a lower likelihood of cirrhosis regression. BMI was the strongest predictor of cirrhosis regression with obese patients having the lowest likelihood of regression despite having complete viral suppression. The mechanism by which obesity reduces the likelihood of regression of cirrhosis is unclear but obesity, metabolic syndrome and steatohepatitis may play a role in histological response. Background Methods: Out of the 351 patients that had biopsies after 240 weeks of treatment, 96 patients had cirrhosis. Steatosis grading was based on system used to assess nonalcoholic steatohepatitis: Grade 0: < 5% steatosis, Grade 1: > 5% to < 34% steatosis, Grade 2: > 34% to < 66% steatosis Grade 3: > 66% steatosis Of the 96 TDF treated patients with cirrhosis (Ishak score 5 or 6) at baseline, 71 (74%) no longer had cirrhosis versus 3 of 252 patients without cirrhosis at baseline progressed to cirrhosis at year 5 (p < 0.0001). (Marcellin P, et al. Lancet 2013;381:468-75.) Results: Overall, in the 96 patients with cirrhosis, Steatosis Grade > 1 at baseline correlated with a lower likelihood of cirrhosis regression at Week 240 in univariate analysis (OR [95% CI] 2.76 [1.08-7.07]) but was not a significant negative predictor of cirrhosis regression in a multivariate model (NS). Of the 96 patients, 18% were obese. Among non-obese patients(78/95), cirrhosis regression occurred at a similar rate in those with and without steatosis. Among obese patients (17/95) with and without steatosis, those without steatosis were more likely to have regression of cirrhosis (p=0.05). BMI correlated with cirrhosis regression in normal weight patients (compared to obese) in a multivariate model (p< 0.001). BMI definition (CDC, http://www.cdc.gov/healthyweight/assessing/bmi/adult_bmi/): Underweight: <18.5; Normal: 18.5 – 24.9; Overweight: 25 – 29.9; Obese: > 30
- Transition The real-life VIREAL multicenter prospective study follows 440 patients in France recruited during June 2009–April 2010. The 2-year treatment data on TDF efficacy and tolerability was previously reported at EASL 2013 (Hézode et al. J Hepatol 2013 Supp1:58(748);S303 Poster#748). The objective of this analysis was to assess the 3-year treatment data on TDF efficacy and tolerability. Main Messages This slide reviews the virologic response both in treatment-naïve or –experienced. 94-97% HBV DNA undetectable, with no difference between TN and TE Overall HBsAg-loss: 12 (2.7%) Mean eGFR (CKD-EPI) remains stable for 3 years, including patients previously treated with ADV and those with low baseline CrCl. In real life practice, 3 years of TDF therapy was associated with high virologic response, very low number of HCC cases and a favorable safety profile Background AE rate: 14% Most common AEs: Asthenia (n=14), abdominal pain (n=14), nausea (n=7), vomiting (n=7), diarrhea (n=6) 7 patients stopped trial due to renal insufficiency (from raw data) HBsAg loss observed in 3 HBeAg+ (2.8%) and 9 HBeAg- (3.0%) Among the 12 patients, 3 stopped TDF and 9 continued S seroconversion observed in 4 patients (HBeAg-). None observed in HBeAg+ (from raw database) 3 cases of HCC (all F4 at Baseline; reported at 3, 12 and 36-month) 10 deaths (none related to TDF): 1 HCC, 2 leukemia, 1 breast cancer, 1 suicide (post-liver transplantation), 1 stroke, 1 post surgery (liver transplantation), 1 cholangiocarcinoma, 2 end-stage liver disease (1 hepatic encephalopathy, 1 spontaneous bacterial peritonitis) Inclusion criteria: HBsAg-positive for > 6 months, first prescription of TDF, Patients informed about collection of their medical data, and having signed an informed consent form Exclusion criteria: Patients with HIV, hepatitis C or D virus co-infection, HCC (suspected or diagnosed), or participating in an ongoing interventional clinical trial
- Transition This slide shows the 3-year final analysis in the subgroup of 48 elderly patients from Vireal study, a French real-life cohort evaluating TDF treatment in chronic hepatitis B patients. Main Messages Elderly patients (age ≥ 65 years) had similar rates of undetectable HBV-DNA at 3 years when compared to younger patients (100% vs 95%). TDF treatment was well tolerated in all subgroups, including elderly patients. Renal function, described in terms of mean estimated glomerular filtration rate by CKD-EPI formula, was stable over 3 years in young and elderly patients. Background 1 patient had HCC at baseline and was removed from the elderly cohort analysis TDF treatment in elderly patient was not well described. Only 5 patients ≥ 65 years were included in studies 102/103. Baseline characteristics of elderly patients (n=48): age 71±6 yrs, male 73%, HBeAg(-) 85%, F3-F4 58%, treatment naïve 23% Results for full cohort: Overall HBsAg-loss: 12 (2.7%) patients at 3 years HBsAg-loss according to age: 10 (2.6%) and 2 (4.2%) in < 65 and ≥ 65 years, respectively Decrease in n’s is due to the availability of data at collection Safety for full cohort: Rate of AE in overall population: 14%. Similar rates of AE in elderly patients (14%). Liver-related complications in 5 patients: 3 HCC (all F4 at baseline, reported at 3-month, 12-month and 36-month), 1 hepatic encephalopathy and 1 spontaneous bacterial peritonitis 10 deaths (none related to TDF) Renal safety in elderly patients with comorbidities was presented at AASLD 2013 (Zoulim F, et al. AASLD 2013, poster#969): eGFR estimated by CKD-EPI was stable after 2 years of TDF therapy in elderly patients with hypertension (n=16) or diabetes (n=8). Among 48 elderly patients, 10 had eGFR < 50 mL/min (esti2mated by C-G formula). Among these 10 patients who should have a TDF dose adjustment (according to SmPC), 4 patients started treatment with full dose of TDF 300mg QD (non published data).
- Transition This is a study from South Korea comparing the efficacy and safety of combination therapy with tenofovir disoproxil fumarate (TDF, 300mg/day) and entecavir (ETV, 1mg/day) versus TDF monotherapy in patients with documented adefovir (ADV) resistance and persistent viremia (suboptimal virologic response to prior treatment). Main Messages Virologic response was similar between TDF+ETV and TDF-alone after 48 weeks (“about 63%”). Reduction in HBV DNA was similar between the two groups as well. There was a marked reduction in detectable resistance mutations with no additional resistance mutations in either group. Treatment was well tolerated with no significant increase in creatinine and no significant decrease in bone mineral density seen. Background Patients randomized to TDF+ETV combination therapy (n=52) or TDF monotherapy (n=50). 2 patients in the group assigned TDF+ETV withdrew consent and did not complete treatment. 1 patient in each group had virologic breakthrough, however both had documented non-adherence. Baseline characteristics: Average age: 46.9 yrs, 86.3% were Male, 18.6% had cirrhosis, 88.2% were HBeAg+. HBV DNA: 3.38 log. (HBV DNA for two treatment arms were similar at baseline) 74.5% had been previously treated with ADV, LAM and ETV 71% had either rtA181V/T or rtN236T 29% had both rtA181V/T and rtN236T 86 patients had resistant mutations to LAM and ADV; and 35 of these patients had resistant mutations to LAM, ADV and ETV. (calculated from the table in back-up) Results: No statistically significant difference in HBV DNA reduction between the two groups overall and including: patients with rtA181V/T or rtN236T, patients with rtA181V/T and rtN236T, patients with high viral load (>5 log10). There was a trend in favor of TDF+ETV in patients with rtA181V/T and rtN236T to reduce HBV DNA Error bars indicates 95% confidence interval No T or Z-score data provided on the poster, the BMD changes were not statistically significant Note: EASL 2012 (corrigendum 2013) cross resistance data lists TDF as having intermediate (I) sensitivity to the individual mutations rtA181V/T, rtN236T and being intermediate/resistant (I/R) to the combination of these two mutations based upon in-vitro data.
- Transition HCC Risk Score Calculators are being increasingly used to evaluate cohorts of HBV patients to determine if HCC incidence decreases with treatment. This analysis was conducted in North America (Toronto) and included 2105 treated and untreated patients, and utilized 3 HCC risk scores, including REACH-B, which is derived from the REVEAL cohort. Main Messages Authors concluded that treatment of HBV demonstrably reduced the predicted risk of HCC as predicted by three HCC calculators (CU-HCC, REACH-B, and NGM1-HCC) in the mixed population (14% Caucasian) of HBV patients. The trend was seen at 5 years and was even more pronounced at 10 years, particularly in cirrhotic patients. Results also indicate the models predicted the risk of HCC more accurately in cirrhotics compared to non-cirrhotics. Background All 3 risk-prediction models accurately identify CHB patients at low risk of HCC in a North American mixed genotype population. For medium- and high-risk patients, the models performed better in cirrhotics compared to non-cirrhotics and in treated compared to untreated patients. Patient Characteristics (N = 2105): Asian – Chinese: 1016 (48%), Asian – Southeast: 552 (26%), Asian – Other: 95 (4.5%) Black: 107 (5%), Caucasian: 291 (14%), Other: 17 (0.8%) Treated patients: 778 (37%), treated with NUCs only: 754 (36%), treated with IFN only: 15 (0.7%), treated with NUCs and IFN: 9 (0.4%) A significant factor of this study is that it compares treated to untreated patients. This allows the calculators to be analyzed for the HCC prediction accuracy for both treated and untreated patients. All three models tended to overestimate the predicted risk of HCC compared to the actual risk in high-risk groups. References for the three risk models: NGM1-HCC: Wong VW, et al. J Clin Oncol. 2010;28:1660-5 REACH-B: Yang HI, et al. Lancet Oncol. 2011;12:568-74 CU-HCC: Yang HI, et al. J Clin Oncol. 2010;28:2437-44
- Transition This study evaluated ETV efficacy in NA-naïve versus LAM-experienced patients. Main Messages Both NA-naïve and LAM-experienced patients achieve high levels of virologic response with ETV treatment (97 vs 94.4%) after a median duration of 44.1 (NA-naïve) or 44.8 months (LAM-experienced). However, more virologic breakthrough is observed in the LAM-experienced group (3.5% NA-naïve vs 17% LAM-experienced). The authors also observe more frequent development of ETV resistance in LAM-experienced patients versus NA naïve patients (12.2% vs 2.6% (P=0.013)). Background All patients were treated with 0.5 mg ETV. Baseline characteristics were similar between the groups, except for gender (74.2% male in NA naïve vs 91.6% in LAM-experienced; P=0.001). Approximately one third of this cohort had cirrhosis at baseline (32.5% in NA naïve vs 26.3% in LAM-experienced; P=0.313). Virologic response in this study was defined as HBV DNA<20 IU/ml during the treatment period. Please note that the poster does not state how absence of LAM resistance in these patients was evaluated.
- . Data to be presented at EASL 2015