- Email: [email protected]
Sa1043 Outcomes of Oral Antiviral Treatment for Chronic Hepatitis B (CHB) in Routine Clinical Practice
mellitus, arterial hypertension, older age and systemic inflammation in non-cirrhotic patients, it is unclear whether these factors are important for DD in cirrhosis. We aimed to investigate the prevalence and predictors of DD in a cohort of cirrhotic liver transplant candidates. Methods: All adult patients with cirrhosis undergoing pretransplant evaluation between 2004-2007 in a single European center were prospectively enrolled in a study on the pathogenesis of fatigue and the effect of liver transplantation (Kalaitzakis et al, Clin Gastroenterol Hepatol 2011). All available echocardiographies (Echo), routinely performed in all patients at pretransplant evaluation, were reviewed. DD was defined as E/A ratio ≤ 1. Body mass index (BMI) and fat mass was measured by means of dual x-ray absorptiometry. Clinical and routine laboratory values were collected from medical records. All patients underwent fasting plasma glucose and insulin measurements. Insulin resistance was defined as a homeostasis model assessment index >2.29 (Exp Clin Endocrinol Diabetes 2006). Serum TNFalfa and IL-1 were also determined. Patients were followed until end of 2009 or death. Results: A total of 75 transplant candidates with an available echocardiogram were included. Eighteen out of 75 (24%) had DD. Mean age was 54 (SD 9), 69% were male, 24% had HCC, 37% ALD, 35% HCV and 16% cholestatic disease. Mean MELD was 15.1 (6). In all, 9% had arterial hypertension 59% were smokers, and 61% had anemia. Twenty-nine percent had diabetes but insulin resistance was detected in 68%. Mean BMI was 26.5 while 51% were overweight and 23% obese. Mean fat (kg) mass was 22.4 (10.1). During follow-up (mean 50 months), 21 (28 %) died or received a transplant. In logistic regression analysis, DD was independently related only to older age (Odds ratio (OR) (per yr) 1.146 95 % Confidence interval (CI) 1.048-1.254) and lower hemoglobin (OR (per mg/l) 1.041 95 % CI 1.0031.082), but not to etiology or severity of cirrhosis, nor to obesity or fat mass, insulin resistance, or levels of proinflammatory cytokines. Conclusions: Diastolic dysfunction is common in liver transplant candidates with cirrhosis. Older age and anemia were the only independent predictors of diastolic dysfunction in these patients. Neither liver disease etiology or severity nor obesity, insulin resistance or systemic inflammation were related to diastolic dysfunction.
without SBP. SBP with cirrhosis also leads to increased hospital costs (mean cost $76000 versus $43000). Conclusions: Spontaneous bacterial peritonitis in cirrhosis is associated with increased morbidity and mortality in hospitalized patients. Sa1043
Purpose: Four approved antiviral oral agents are commonly used to treat chronic hepatitis B (CHB) in the United States: lamivudine (LAM), adeofovir (ADV), entecavir (ETV) and tenofovir (TDF). Current data from clinical registration trials indicated that CHB treatment by these nucleos(t)ide analogues differ in potency and resistance profile. The goals of this study were to examine the treatment outcomes of these agents in a routine clinical care setting. Methods: Using ICD-9 diagnosis query, 1239 patients who received LAM, ADV, ETV or TDF in two clinics in California between January 2001 and January 2011 were identified. Of these, a total of 957 consecutive patients who received treatment for at least 6 months were included in study analysis. The median on-treatment follow-up was 42 (6 - 120) months. Study endpoints were complete viral suppression (CVS) rate (defined as having undetectable HBV DNA of < 40-60 IU/mL) and ALT normalization (defined as ALT ≤ 40 U/L) at 6 and 12 months of therapy. Results: All patients were Asians and predominantly male (65%) with a mean age of 47±13 years. As shown in Figure 1, CVS in treatment naïve patients was similarly low at 6 and 12 months for LAM and ADV (38-44% and 37-50%, respectively), while CVS was similarly high with at the same time points for ETV and TDF (63-63% and 73-79%, respectively). In the subsets of treatment-naïve patients treated with ETV (n=373) or TDF (n=107), these patients were similar in terms of age (45-47 years), sex (61-64% males), hepatitis B e antigen positivity (36-37%), baseline mean HBV DNA levels (6.23±1.51 vs. 6.14±1.56 log10 IU/mL, p=0.55), and baseline median ALT levels (61 [13-839] vs. 51 [8-631] U/L, p=0.52). CVS and Alt normalization rates at 6 and 12 months were also similar in these two groups (Figure 2). Among treatment-experienced patients treated with ETV (n=165) or TDF (n=67), patients treated with ETV had significantly higher mean baseline HBV DNA levels (3.82±2.96 vs. 2.33±2.97 log10 IU/mL, p<0.001) and also higher median baseline ALT (35 [12-880] vs. 29 [9-417] U/L, p=0.07). However, both treatment-experienced groups achieved comparable rates of CVS and ALT normalization (Figure 2). Antiviral resistance was not detected in any of the ETV and TDF treatment cohorts. Conclusion: In this large cohort of patients treated with various oral antiviral agents for CHB, treatment outcomes were clearly favorable in new agents (ETV and TDF) compared to older agents (LAM and ADV). Among those treated with ETV and TDF, CVS and ALT normalization rates were similar for both treatment-naïve and treatment-experienced. Baseline characteristics of ETV and TDF were similar except for higher HBV DNA and ALT levels among ETV treatment-experienced compared to TDF treatment-experienced patient.
Sa1041 Left Ventricular Diastolic Dysfunction is Related to Post Transplant Mortality but Not to Quality of Life or Fatigue in Liver Transplant Candidates With Cirrhosis Axel Josefsson, Michael Fu, Einar Bjornsson, Maria Castedal, Evangelos Kalaitzakis Background Left ventricular diastolic dysfunction (DD) is a common finding in patients with liver cirrhosis and has been shown to be related to survival post-TIPS. Although DD is known to be related to quality of life (QoL) in non-cirrhotic patients, this is unexplored in patients with cirrhosis. We aimed to evaluate the prognostic significance of DD in liver transplant candidates with cirrhosis and its potential relation to pre- and post-transplant quality of life (QoL) and fatigue. Methods All adult patients with cirrhosis undergoing pretransplant evaluation between 2004-2007 in a single European center were prospectively enrolled in a study on the pathogenesis of fatigue and the potential effect of liver transplantation (Kalaitzakis et al, Clin Gastroenterol Hepatol 2011). Two validated questionnaires were used to assess QoL (Short Form-36, SF-36) and fatigue (Fatigue impact scale, FIS) at both baseline and 1 year post-transplant. All available echocardiographies (Echo), routinely performed in all patients at pretransplant evaluation, were reviewed. DD was defined as E/ A ratio ≤ 1. Patients were followed until end of 2009 or death. Results A total of 73 out of 110 transplant candidates with an available echo at baseline were included. Eighteen out of 73 (25%) had DD. Mean age was 53.5 (SD 9.5), 68% were male, 37% had ALD, 36% HCV, and 16% cholestatic disease. Mean MELD was 14.9 (SD 5.6). In all, 8.5% of patients had arterial hypertension and 57% were smokers. Of the 73 patients with an echo, 49 underwent transplantation. Patients with vs. without DD did not show any differences in QoL (mean SF-36 physical component summary score 35.2 (SD 13.6) vs. 37.4 (SD 11.5) respectively, p=0.52; mean SF-36 mental component summary score 42.9 (SD 13.3) vs. 41.4 (SD 12.8) respectively, p=0.66) or fatigue indices (total FIS score 61.2 (SD 44) vs 63.5 (SD 43.8) respectively, p=0.85). No other standard echo parameters (ejection fraction, atrial and ventricular dimensions or wall thickness) had any impact on either QoL or fatigue (p>0.05 for all). DD was significantly related to decreased overall and post-transplant survival (Kaplan meier, Log rank test p=0.001, see figure for post-transplant survival). However, DD had no impact on either total hospital inpatient time (DD 26.1 vs rest of cohort25.8 days p=0.96) or time in the intensive care unit (DD 3.1 vs rest of cohort 5.7 days p=0.087) following transplantation. Conclusions Diastolic dysfunction in liver transplant candidates with cirrhosis seems to have a negative impact on overall and post-transplant survival. However it was not associated with pre- or post- transplant quality of life or fatigue and the same was true for all other baseline echocardiographic variables.
Figure 1. Complete viral suppression rates of treatment-naïve patients at 6 and 12 months with lamivudine (LAM), adefovir (ADV), entecavir (ETV), and tenofovir (TDF).
Sa1042 Spontaneous Bacterial Peritonitis Predicts Mortality in Hospitalized Patients With Cirrhosis Shahryar Ahmad, Muhammad Ali, Gagan Kumar, Nilay Kumar Background: Spontaneous bacterial peritonitis, a complication of hospitalized patients with cirrhosis has been associated with worse outcomes. We wanted to determine the effects of spontaneous bacterial peritonitis in hospitalized patients with cirrhosis. Methods: We queried the Nationwide Inpatient Sample (NIS) from year 2008. NIS is the largest inpatient discharge database in the US. Appropriate international Classification of Diseases (ICD-9CM) codes were used to identify patients with primary diagnosis of spontaneous bacterial peritonitis and any diagnosis of cirrhosis. Chi Square test and logistic regression were used for analysis. STATA 10 was used for analysis. Outcomes measured were length of stay, hospital cost and mortality. Results: There were 16,335 patients with any diagnosis of cirrhosis admitted with a primary diagnosis of SBP. Prevalence spontaneous bacterial peritonitis in hospitalized patients with cirrhosis was 2.29%. Mortality among cirrhotics with SBP was significantly higher as compared to cirrhotics without SBP(6.18% vs. 18.84%, p value <0.00). After adjusting for various demographic variables, patients with cirrhosis who also had spontaneous bacterial peritonitis had 3.5 times the odds of dying (OR 3.50 95%CI 3.19-3.89). SBP in patients with cirrhosis lead to a higher length of stay 9.9 days versus 6 days in cirrhotic
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Outcomes of Oral Antiviral Treatment for Chronic Hepatitis B (CHB) in Routine Clinical Practice Mindie H. Nguyen, Huy N. Trinh, Huy A. Nguyen, Khanh K. Nguyen, Ruel T. Garcia, Hong Tang, Brian S. Levitt, Timothy Juday
interval, were retrospectively enrolled. Forty four patients were excluded due to have hepatocellular carcinoma, hepatitis C coinfection, alanine aminotransferase (ALT) >80 U/L at the time of the first TE exam, and start ONA after the first TE exam. Final 112 patients were investigated for the change of LS. Because there is some difference of interval between the two TEs, the annual change of LS was estimated [(the first LS-the second LS)Í12/interval (months)]. All the patients were grouped according to the estimated annual change of the LS >0 kPa (improved) or ≤0 kPa (aggravated). Results: Seventy nine patients have been taking ONA before the first TE. The other 33 patients did not take ONA, because they had not indication of antiviral therapy such as low HBV DNA or low ALT levels. Seventy one patients had improvement of LS [improved group, 2.83(0.04 to 23.8) kPa], and 41 patients had aggravation of LS [aggravated group, -2.47(-29 to 0) kPa]. There were no differences in age, gender, liver functions, HBV DNA level, and proportion of liver cirrhosis at the first TE between the two groups. In addition, the proportion of low viral load (HBV DNA <2000 copies/mL) throughout the study period was not different between the two groups. However, the mean LS at the first TE was higher in improved than in aggravated group (13.4±13.2 vs. 7.6±4.7 kPa, p=0.001). The proportion of patients taking ONA was higher in improved than in aggravated group (77.5% vs. 58.5%, p=0.034). The proportion of patients having normal ALT level (<40 U/L) throughout the study period was higher in improved than in aggravated group (54.9% vs. 26.8%, p=0.004). In multivariate analysis, higher LS at the first TE (OR: 1.2, 95% CI: 1.02-1.21, p=0.011), ONA therapy (OR: 2.8, 95% CI: 1.1-7.1, p=0.031), and normal ALT throughout the study period (OR: 3.4, 95% CI: 1.4-8.2, p= 0.007) were the independent factors that affect the improvement of LS. Conclusions: Antiviral therapy or maintained normal ALT level improve LS in patients with CHB. However, further study is needed to investigate whether these results match the liver histologic study.
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Sa1046 Efficacy of 5 Years of Tenofovir Disoproxil Fumarate (TDF) in Chronic Hepatitis B Patients With High Viral Load (HBV DNA ≥9 Log10 Copies/Ml) Stuart C. Gordon, Patrick Marcellin, Zahary Krastev, Andrzej Horban, Jörg Petersen, Jan Sperl, Phillip Dinh, Eduardo B. Martins, Leland J. Yee, John F. Flaherty, Kathryn M. Kitrinos, Nika Berger, Vinod K. Rustgi, E. Jenny Heathcote Background: TDF is a potent antiviral with activity against hepatitis B virus. Year 4 data demonstrated 97-99% of HBeAg+ and HBeAg− patients on treatment at week(W)192 achieved HBV DNA <400 copies (c)/mL (69 IU/mL). Whether patients with extremely high baseline levels of viremia respond less well than those with lower viral levels remains unclear. Goal: To evaluate the antiviral response over 5 years in both HBeAg− and HBeAg+ patients with markedly high baseline viral load, as defined by HBV DNA ≥9 log10 c/mL (8.24 log10 IU/ mL). Methods: 129 chronic hepatitis B (CHB) patients (11 HBeAg− and 118 HBeAg+) with high viral load were enrolled across the pivotal studies GS-US-174-0102 and GS-US-1740103 and were randomized to TDF 300 mg (n=82) or adefovir dipivoxil (ADV) 10 mg (n= 47). After W48, eligible patients (with a W48 liver biopsy) initiated open-label TDF for 7 additional years. On or after W72, patients with a confirmed HBV DNA ≥400 c/mL had the option to add emtricitabine (FTC) at the discretion of the investigator. Results: Overall, approximately 20% (129/641) of patients enrolled in studies 102 and 103 had an HBV viral load ≥9 log10 c/mL. Baseline disease and demographic characteristics were: median age 32 years, 74% male, 67% Caucasian, 22% Asian, median baseline HBV DNA 9.52 log10 c/mL (9.01-10.92), and median ALT 111 U/L (30-670). Ninety-six percent of patients on treatment at W240 achieved HBV DNA <400 c/mL (66% by intent-to-treat analysis). Twenty-nine patients (out of 36 who were eligible) opted to add FTC between W72 and W240: 15 successfully achieved HBV DNA <400 c/mL at W240, 2 had HBV DNA ≥400 c/mL at W240, and 12 did not complete W240 (4 of whom had HBV DNA <400 c/mL at the last time point). Additionally, of the 7 patients who were eligible but did not add FTC, 6 achieved HBV DNA <400 c/mL by W240. For patients on study at W240, median (range) HBV DNA was 2.23 log10 c/mL (2.23, 3.82) and median decline from baseline was 7.26 log10 c/mL. Median (range) ALT was 30 U/L (13, 329) and 70% of patients normalized ALT. At W240, 38% of HBeAg+ patients achieved HBeAg loss with 30% seroconversion to anti-HBe. Cumulatively, 17 (15.2%) HBeAg+ patients lost HBsAg (Kaplan-Meier estimate). There were no patients with persistent viremia in the entire cohort. Resistance analyses showed no amino acid substitutions that could be associated with TDF resistance in patients with detectable HBV DNA at W240, discontinuation, or when FTC was added. Conclusion: TDF is highly efficacious in patients with high baseline HBV viral load ≥9 log10 c/mL. Greater than 95% of patients achieved HBV DNA <400 c/mL, high rates of HBeAg and HBsAg loss were achieved, and no TDF resistance was observed.
Figure 2.Treatment outcomes of entecavir (ETV) and tenofovir (TDF) treatment groups, by prior treatment status. Sa1044 Hepatitis B E-Antigen Seroconversion is Associated With Older Age and Advanced Cirrhosis Stephen Oh, Ross Hansen, Venessa Pattullo, Brett Jones Background and aims Long term suppression of Hepatitis B virus (HBV) replication with nucleos(t)ide analogues (NA) is associated with biochemical improvement and viral suppression. However the factors affecting this response remain unclear. Method A cohort of 107 HBV infected patients undergoing treatment with NA at Royal North Shore Hospital (20002011) was studied. Demographic, viral, biochemical and histological data were collected prospectively during treatment and subjected to univariate and multivariate analysis. Result Seventy-eight percent of the total cohort were Asian, 70% were males and 47% had advanced fibrosis (F≥3) at baseline. Mean HBV DNA PCR was 5.62 log IU/mL and mean ALT was 129 IU/L at baseline. Mean duration of treatment was 66 months. There were 42 eAg positive and 65 eAg negative patients. In the combined cohort, 64% had undetectable DNA at week 48. Negative eAg at baseline, lower DNA at baseline, no interferon use (before or during the therapy), normalised ALT at week 48 and older age were associated with undetectable DNA at week 48. (p<0.05) However, logistic regression analysis identified baseline eAg negativity as the only significant predictor of undetectable DNA at week 48. (p=0.02) Sixtytwo percent had normalised ALT at week 48, and associated factors were undetectable DNA at week 48, shorter time to undetectable DNA and higher ALT at baseline. (p<0.05) Logistic regression identified shorter time to lowest DNA as the only predictor of normalised ALT at week 48. (p=0.02) In patients with positive eAg at baseline, 55% and 7% achieved eAg seroconversion (or loss) and sAg seroconversion (or loss) respectively. Older age and advanced fibrosis were significantly associated with eAg seroconversion and/or eAg loss. (p≤0.05) No patients developed progressive liver failure while on treatment in the absence of hepatocellular cancer. Conclusion NA therapy in the clinic setting is associated with effective long term viral suppression with improved eAg seroconversion in older patients and those with advanced fibrosis. Higher rates of sAg seroconversion or loss were observed in patients with positive eAg at baseline.
Sa1047 Combination of HBsAg Level and Hepatitis B Viral Load at Week 12 is the Best Stopping Rule for Chronic Hepatitis B, HBeAg Positive Patients Treated With Peginterferon ALPHA-2A Pochamana Phisalprapa, Tawesak Tanwandee Background/Aims: Treatment with peginterferon alpha-2a (PEG-IFN) can achieve sustained virological response (SVR) and had high rate of HBsAg loss than nucleos(t)ide analogues. Many predictors of SVR didnot strong enough to change treatment decision. This study aimed to evaluate the usefulness of HBsAg level and HBV DNA reduction during treatment as early predictors of SVR. Methods: HBeAg positive patients were enrolled to receive PEGIFN 180 mcg/week for 48 weeks prospectively. Serum HBV DNA, HBsAg quantitation and HBeAg index were serially assessed at baseline and every 12 weeks to week 72. Treatment endpoints were HBeAg seroconversion and HBV DNA less than 2,000 IU/mL at week 72 (SVR). Results: There were 44 patients, mean age of 41 years and 57% were male. Mean baseline of log10 HBV DNA (IU/mL) and HBsAg (IU/mL) were 7.2, 4.1 and 2.5, respectively. HBsAg level were strong correlated with serum HBV DNA (Spearman's correlation coefficient= 0.75, P <0.001) and HBeAg index (Spearman's correlation coefficient=0.71, P <0.001). Six patients (13.6%) were genotype B and 38 patients (86.4%) were genotype C. At week 48, there were 11 (25%) HBeAg seroconversion and 4 (9%) HBsAg loss. At week 72, there were 12 (27.3%) HBeAg seroconversion and 5 (11.4%) HBsAg loss (1 genotype B and 4 genotype C). There was no different in baseline characteristic between responders and nonresponders.
Sa1045 Factors That Affect the Improvement of Liver Stiffness in Patients With Chronic Hepatitis B Oh Sang Kwon, Sunyoung Na, Young Kul Jung, Yun Soo Kim, Joo Hyun Kim Backgrounds and Aims: Oral nucleot(s)ide analogues (ONA) improve liver fibrosis in patients with chronic hepatitis B (CHB). Although liver biopsy is a standard tool for evaluation of this improvement, it is an invasive method. In addition, it is difficult to repeat liver biopsy. Transient elastography(TE), a novel noninvasive and repeatable method, is a tool for assessing liver fibrosis quantitatively by measuring liver stiffness (LS) which is well correlated with the histologic stage of fibrosis. This study investigated the factors that affect the improvement of LS in patients with CHB for about 2 years interval. Patients and Methods: Between April 2007 and August 2011, 156 patients with CHB who underwent TE for mean 25 months
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without SBP. SBP with cirrhosis also leads to increased hospital costs (mean cost $76000 versus $43000). Conclusions: Spontaneous bacterial peritonitis in cirrhosis is associated with increased morbidity and mortality in hospitalized patients. Sa1043
Purpose: Four approved antiviral oral agents are commonly used to treat chronic hepatitis B (CHB) in the United States: lamivudine (LAM), adeofovir (ADV), entecavir (ETV) and tenofovir (TDF). Current data from clinical registration trials indicated that CHB treatment by these nucleos(t)ide analogues differ in potency and resistance profile. The goals of this study were to examine the treatment outcomes of these agents in a routine clinical care setting. Methods: Using ICD-9 diagnosis query, 1239 patients who received LAM, ADV, ETV or TDF in two clinics in California between January 2001 and January 2011 were identified. Of these, a total of 957 consecutive patients who received treatment for at least 6 months were included in study analysis. The median on-treatment follow-up was 42 (6 - 120) months. Study endpoints were complete viral suppression (CVS) rate (defined as having undetectable HBV DNA of < 40-60 IU/mL) and ALT normalization (defined as ALT ≤ 40 U/L) at 6 and 12 months of therapy. Results: All patients were Asians and predominantly male (65%) with a mean age of 47±13 years. As shown in Figure 1, CVS in treatment naïve patients was similarly low at 6 and 12 months for LAM and ADV (38-44% and 37-50%, respectively), while CVS was similarly high with at the same time points for ETV and TDF (63-63% and 73-79%, respectively). In the subsets of treatment-naïve patients treated with ETV (n=373) or TDF (n=107), these patients were similar in terms of age (45-47 years), sex (61-64% males), hepatitis B e antigen positivity (36-37%), baseline mean HBV DNA levels (6.23±1.51 vs. 6.14±1.56 log10 IU/mL, p=0.55), and baseline median ALT levels (61 [13-839] vs. 51 [8-631] U/L, p=0.52). CVS and Alt normalization rates at 6 and 12 months were also similar in these two groups (Figure 2). Among treatment-experienced patients treated with ETV (n=165) or TDF (n=67), patients treated with ETV had significantly higher mean baseline HBV DNA levels (3.82±2.96 vs. 2.33±2.97 log10 IU/mL, p<0.001) and also higher median baseline ALT (35 [12-880] vs. 29 [9-417] U/L, p=0.07). However, both treatment-experienced groups achieved comparable rates of CVS and ALT normalization (Figure 2). Antiviral resistance was not detected in any of the ETV and TDF treatment cohorts. Conclusion: In this large cohort of patients treated with various oral antiviral agents for CHB, treatment outcomes were clearly favorable in new agents (ETV and TDF) compared to older agents (LAM and ADV). Among those treated with ETV and TDF, CVS and ALT normalization rates were similar for both treatment-naïve and treatment-experienced. Baseline characteristics of ETV and TDF were similar except for higher HBV DNA and ALT levels among ETV treatment-experienced compared to TDF treatment-experienced patient.
Sa1041 Left Ventricular Diastolic Dysfunction is Related to Post Transplant Mortality but Not to Quality of Life or Fatigue in Liver Transplant Candidates With Cirrhosis Axel Josefsson, Michael Fu, Einar Bjornsson, Maria Castedal, Evangelos Kalaitzakis Background Left ventricular diastolic dysfunction (DD) is a common finding in patients with liver cirrhosis and has been shown to be related to survival post-TIPS. Although DD is known to be related to quality of life (QoL) in non-cirrhotic patients, this is unexplored in patients with cirrhosis. We aimed to evaluate the prognostic significance of DD in liver transplant candidates with cirrhosis and its potential relation to pre- and post-transplant quality of life (QoL) and fatigue. Methods All adult patients with cirrhosis undergoing pretransplant evaluation between 2004-2007 in a single European center were prospectively enrolled in a study on the pathogenesis of fatigue and the potential effect of liver transplantation (Kalaitzakis et al, Clin Gastroenterol Hepatol 2011). Two validated questionnaires were used to assess QoL (Short Form-36, SF-36) and fatigue (Fatigue impact scale, FIS) at both baseline and 1 year post-transplant. All available echocardiographies (Echo), routinely performed in all patients at pretransplant evaluation, were reviewed. DD was defined as E/ A ratio ≤ 1. Patients were followed until end of 2009 or death. Results A total of 73 out of 110 transplant candidates with an available echo at baseline were included. Eighteen out of 73 (25%) had DD. Mean age was 53.5 (SD 9.5), 68% were male, 37% had ALD, 36% HCV, and 16% cholestatic disease. Mean MELD was 14.9 (SD 5.6). In all, 8.5% of patients had arterial hypertension and 57% were smokers. Of the 73 patients with an echo, 49 underwent transplantation. Patients with vs. without DD did not show any differences in QoL (mean SF-36 physical component summary score 35.2 (SD 13.6) vs. 37.4 (SD 11.5) respectively, p=0.52; mean SF-36 mental component summary score 42.9 (SD 13.3) vs. 41.4 (SD 12.8) respectively, p=0.66) or fatigue indices (total FIS score 61.2 (SD 44) vs 63.5 (SD 43.8) respectively, p=0.85). No other standard echo parameters (ejection fraction, atrial and ventricular dimensions or wall thickness) had any impact on either QoL or fatigue (p>0.05 for all). DD was significantly related to decreased overall and post-transplant survival (Kaplan meier, Log rank test p=0.001, see figure for post-transplant survival). However, DD had no impact on either total hospital inpatient time (DD 26.1 vs rest of cohort25.8 days p=0.96) or time in the intensive care unit (DD 3.1 vs rest of cohort 5.7 days p=0.087) following transplantation. Conclusions Diastolic dysfunction in liver transplant candidates with cirrhosis seems to have a negative impact on overall and post-transplant survival. However it was not associated with pre- or post- transplant quality of life or fatigue and the same was true for all other baseline echocardiographic variables.
Figure 1. Complete viral suppression rates of treatment-naïve patients at 6 and 12 months with lamivudine (LAM), adefovir (ADV), entecavir (ETV), and tenofovir (TDF).
Sa1042 Spontaneous Bacterial Peritonitis Predicts Mortality in Hospitalized Patients With Cirrhosis Shahryar Ahmad, Muhammad Ali, Gagan Kumar, Nilay Kumar Background: Spontaneous bacterial peritonitis, a complication of hospitalized patients with cirrhosis has been associated with worse outcomes. We wanted to determine the effects of spontaneous bacterial peritonitis in hospitalized patients with cirrhosis. Methods: We queried the Nationwide Inpatient Sample (NIS) from year 2008. NIS is the largest inpatient discharge database in the US. Appropriate international Classification of Diseases (ICD-9CM) codes were used to identify patients with primary diagnosis of spontaneous bacterial peritonitis and any diagnosis of cirrhosis. Chi Square test and logistic regression were used for analysis. STATA 10 was used for analysis. Outcomes measured were length of stay, hospital cost and mortality. Results: There were 16,335 patients with any diagnosis of cirrhosis admitted with a primary diagnosis of SBP. Prevalence spontaneous bacterial peritonitis in hospitalized patients with cirrhosis was 2.29%. Mortality among cirrhotics with SBP was significantly higher as compared to cirrhotics without SBP(6.18% vs. 18.84%, p value <0.00). After adjusting for various demographic variables, patients with cirrhosis who also had spontaneous bacterial peritonitis had 3.5 times the odds of dying (OR 3.50 95%CI 3.19-3.89). SBP in patients with cirrhosis lead to a higher length of stay 9.9 days versus 6 days in cirrhotic
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Outcomes of Oral Antiviral Treatment for Chronic Hepatitis B (CHB) in Routine Clinical Practice Mindie H. Nguyen, Huy N. Trinh, Huy A. Nguyen, Khanh K. Nguyen, Ruel T. Garcia, Hong Tang, Brian S. Levitt, Timothy Juday
interval, were retrospectively enrolled. Forty four patients were excluded due to have hepatocellular carcinoma, hepatitis C coinfection, alanine aminotransferase (ALT) >80 U/L at the time of the first TE exam, and start ONA after the first TE exam. Final 112 patients were investigated for the change of LS. Because there is some difference of interval between the two TEs, the annual change of LS was estimated [(the first LS-the second LS)Í12/interval (months)]. All the patients were grouped according to the estimated annual change of the LS >0 kPa (improved) or ≤0 kPa (aggravated). Results: Seventy nine patients have been taking ONA before the first TE. The other 33 patients did not take ONA, because they had not indication of antiviral therapy such as low HBV DNA or low ALT levels. Seventy one patients had improvement of LS [improved group, 2.83(0.04 to 23.8) kPa], and 41 patients had aggravation of LS [aggravated group, -2.47(-29 to 0) kPa]. There were no differences in age, gender, liver functions, HBV DNA level, and proportion of liver cirrhosis at the first TE between the two groups. In addition, the proportion of low viral load (HBV DNA <2000 copies/mL) throughout the study period was not different between the two groups. However, the mean LS at the first TE was higher in improved than in aggravated group (13.4±13.2 vs. 7.6±4.7 kPa, p=0.001). The proportion of patients taking ONA was higher in improved than in aggravated group (77.5% vs. 58.5%, p=0.034). The proportion of patients having normal ALT level (<40 U/L) throughout the study period was higher in improved than in aggravated group (54.9% vs. 26.8%, p=0.004). In multivariate analysis, higher LS at the first TE (OR: 1.2, 95% CI: 1.02-1.21, p=0.011), ONA therapy (OR: 2.8, 95% CI: 1.1-7.1, p=0.031), and normal ALT throughout the study period (OR: 3.4, 95% CI: 1.4-8.2, p= 0.007) were the independent factors that affect the improvement of LS. Conclusions: Antiviral therapy or maintained normal ALT level improve LS in patients with CHB. However, further study is needed to investigate whether these results match the liver histologic study.
AASLD Abstracts
Sa1046 Efficacy of 5 Years of Tenofovir Disoproxil Fumarate (TDF) in Chronic Hepatitis B Patients With High Viral Load (HBV DNA ≥9 Log10 Copies/Ml) Stuart C. Gordon, Patrick Marcellin, Zahary Krastev, Andrzej Horban, Jörg Petersen, Jan Sperl, Phillip Dinh, Eduardo B. Martins, Leland J. Yee, John F. Flaherty, Kathryn M. Kitrinos, Nika Berger, Vinod K. Rustgi, E. Jenny Heathcote Background: TDF is a potent antiviral with activity against hepatitis B virus. Year 4 data demonstrated 97-99% of HBeAg+ and HBeAg− patients on treatment at week(W)192 achieved HBV DNA <400 copies (c)/mL (69 IU/mL). Whether patients with extremely high baseline levels of viremia respond less well than those with lower viral levels remains unclear. Goal: To evaluate the antiviral response over 5 years in both HBeAg− and HBeAg+ patients with markedly high baseline viral load, as defined by HBV DNA ≥9 log10 c/mL (8.24 log10 IU/ mL). Methods: 129 chronic hepatitis B (CHB) patients (11 HBeAg− and 118 HBeAg+) with high viral load were enrolled across the pivotal studies GS-US-174-0102 and GS-US-1740103 and were randomized to TDF 300 mg (n=82) or adefovir dipivoxil (ADV) 10 mg (n= 47). After W48, eligible patients (with a W48 liver biopsy) initiated open-label TDF for 7 additional years. On or after W72, patients with a confirmed HBV DNA ≥400 c/mL had the option to add emtricitabine (FTC) at the discretion of the investigator. Results: Overall, approximately 20% (129/641) of patients enrolled in studies 102 and 103 had an HBV viral load ≥9 log10 c/mL. Baseline disease and demographic characteristics were: median age 32 years, 74% male, 67% Caucasian, 22% Asian, median baseline HBV DNA 9.52 log10 c/mL (9.01-10.92), and median ALT 111 U/L (30-670). Ninety-six percent of patients on treatment at W240 achieved HBV DNA <400 c/mL (66% by intent-to-treat analysis). Twenty-nine patients (out of 36 who were eligible) opted to add FTC between W72 and W240: 15 successfully achieved HBV DNA <400 c/mL at W240, 2 had HBV DNA ≥400 c/mL at W240, and 12 did not complete W240 (4 of whom had HBV DNA <400 c/mL at the last time point). Additionally, of the 7 patients who were eligible but did not add FTC, 6 achieved HBV DNA <400 c/mL by W240. For patients on study at W240, median (range) HBV DNA was 2.23 log10 c/mL (2.23, 3.82) and median decline from baseline was 7.26 log10 c/mL. Median (range) ALT was 30 U/L (13, 329) and 70% of patients normalized ALT. At W240, 38% of HBeAg+ patients achieved HBeAg loss with 30% seroconversion to anti-HBe. Cumulatively, 17 (15.2%) HBeAg+ patients lost HBsAg (Kaplan-Meier estimate). There were no patients with persistent viremia in the entire cohort. Resistance analyses showed no amino acid substitutions that could be associated with TDF resistance in patients with detectable HBV DNA at W240, discontinuation, or when FTC was added. Conclusion: TDF is highly efficacious in patients with high baseline HBV viral load ≥9 log10 c/mL. Greater than 95% of patients achieved HBV DNA <400 c/mL, high rates of HBeAg and HBsAg loss were achieved, and no TDF resistance was observed.
Figure 2.Treatment outcomes of entecavir (ETV) and tenofovir (TDF) treatment groups, by prior treatment status. Sa1044 Hepatitis B E-Antigen Seroconversion is Associated With Older Age and Advanced Cirrhosis Stephen Oh, Ross Hansen, Venessa Pattullo, Brett Jones Background and aims Long term suppression of Hepatitis B virus (HBV) replication with nucleos(t)ide analogues (NA) is associated with biochemical improvement and viral suppression. However the factors affecting this response remain unclear. Method A cohort of 107 HBV infected patients undergoing treatment with NA at Royal North Shore Hospital (20002011) was studied. Demographic, viral, biochemical and histological data were collected prospectively during treatment and subjected to univariate and multivariate analysis. Result Seventy-eight percent of the total cohort were Asian, 70% were males and 47% had advanced fibrosis (F≥3) at baseline. Mean HBV DNA PCR was 5.62 log IU/mL and mean ALT was 129 IU/L at baseline. Mean duration of treatment was 66 months. There were 42 eAg positive and 65 eAg negative patients. In the combined cohort, 64% had undetectable DNA at week 48. Negative eAg at baseline, lower DNA at baseline, no interferon use (before or during the therapy), normalised ALT at week 48 and older age were associated with undetectable DNA at week 48. (p<0.05) However, logistic regression analysis identified baseline eAg negativity as the only significant predictor of undetectable DNA at week 48. (p=0.02) Sixtytwo percent had normalised ALT at week 48, and associated factors were undetectable DNA at week 48, shorter time to undetectable DNA and higher ALT at baseline. (p<0.05) Logistic regression identified shorter time to lowest DNA as the only predictor of normalised ALT at week 48. (p=0.02) In patients with positive eAg at baseline, 55% and 7% achieved eAg seroconversion (or loss) and sAg seroconversion (or loss) respectively. Older age and advanced fibrosis were significantly associated with eAg seroconversion and/or eAg loss. (p≤0.05) No patients developed progressive liver failure while on treatment in the absence of hepatocellular cancer. Conclusion NA therapy in the clinic setting is associated with effective long term viral suppression with improved eAg seroconversion in older patients and those with advanced fibrosis. Higher rates of sAg seroconversion or loss were observed in patients with positive eAg at baseline.
Sa1047 Combination of HBsAg Level and Hepatitis B Viral Load at Week 12 is the Best Stopping Rule for Chronic Hepatitis B, HBeAg Positive Patients Treated With Peginterferon ALPHA-2A Pochamana Phisalprapa, Tawesak Tanwandee Background/Aims: Treatment with peginterferon alpha-2a (PEG-IFN) can achieve sustained virological response (SVR) and had high rate of HBsAg loss than nucleos(t)ide analogues. Many predictors of SVR didnot strong enough to change treatment decision. This study aimed to evaluate the usefulness of HBsAg level and HBV DNA reduction during treatment as early predictors of SVR. Methods: HBeAg positive patients were enrolled to receive PEGIFN 180 mcg/week for 48 weeks prospectively. Serum HBV DNA, HBsAg quantitation and HBeAg index were serially assessed at baseline and every 12 weeks to week 72. Treatment endpoints were HBeAg seroconversion and HBV DNA less than 2,000 IU/mL at week 72 (SVR). Results: There were 44 patients, mean age of 41 years and 57% were male. Mean baseline of log10 HBV DNA (IU/mL) and HBsAg (IU/mL) were 7.2, 4.1 and 2.5, respectively. HBsAg level were strong correlated with serum HBV DNA (Spearman's correlation coefficient= 0.75, P <0.001) and HBeAg index (Spearman's correlation coefficient=0.71, P <0.001). Six patients (13.6%) were genotype B and 38 patients (86.4%) were genotype C. At week 48, there were 11 (25%) HBeAg seroconversion and 4 (9%) HBsAg loss. At week 72, there were 12 (27.3%) HBeAg seroconversion and 5 (11.4%) HBsAg loss (1 genotype B and 4 genotype C). There was no different in baseline characteristic between responders and nonresponders.
Sa1045 Factors That Affect the Improvement of Liver Stiffness in Patients With Chronic Hepatitis B Oh Sang Kwon, Sunyoung Na, Young Kul Jung, Yun Soo Kim, Joo Hyun Kim Backgrounds and Aims: Oral nucleot(s)ide analogues (ONA) improve liver fibrosis in patients with chronic hepatitis B (CHB). Although liver biopsy is a standard tool for evaluation of this improvement, it is an invasive method. In addition, it is difficult to repeat liver biopsy. Transient elastography(TE), a novel noninvasive and repeatable method, is a tool for assessing liver fibrosis quantitatively by measuring liver stiffness (LS) which is well correlated with the histologic stage of fibrosis. This study investigated the factors that affect the improvement of LS in patients with CHB for about 2 years interval. Patients and Methods: Between April 2007 and August 2011, 156 patients with CHB who underwent TE for mean 25 months
AASLD Abstracts
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