s1265 risk of non-melanoma skin cancer in autoimmune hepatitis

1
AGA Abstracts to 4. Prior constitutional symptoms were present in 14%, and 38% were asymptomatic. Acute icteric feature was seen in 47%. Twelve patients had cirrhosis and were transplanted (57%). One had spontaneous remission and 1 died of liver failure. Remaining 7 patients achieved remission (43%) following treatment with steroid and azathioprine. Relapse on maintenance treatment was 28%. In group 2, the mean age was 38+14 years, female to male ratio was 30 to 7. Prior constitutional symptoms were present in 70% and 11% were asymptomatic. These parameters were significantly different between the groups (p<0.05). Acute icteric feature was seen in 19%. Twelve patients (32%) were transplanted. Eight had spontaneous remission. Remaining 17 patients achieved remission (41%) following treatment. Relapse on maintenance treatment was 59%. Conclusions: Elderly patients with AIH are more often asymptomatic or have less constitutional symptoms. AIH in elderly is usually an advanced disease at presentation than in younger patients. Relapse of AIH after remission is less common in the elderly. 1. Distinctive phenotype and treatment outcome of AIH in elderly. Hepatology 43:532, 2006 Table 1 S1263 Predictors of Sustained Virological Response Among Patients With Hepatitis C Post OLT and the Impact of Sustained Virological Response on Mortality Matthew J. Moeller, George Divine, Kimberly Ann Brown Background: Graft and patient survival following liver transplantation for HCV is reduced when compared to other groups. SVR rates from 25-47% have been reported in patients receiving anti-viral therapy for HCV following OLT. However, these studies are limited by small sample sizes, short duration of follow up, and lack of survival analyses. Aim: To evaluate predictors of SVR following antiviral treatment of patients with HCV post OLT. To evaluate the impact of SVR on mortality in treated patients. Methods: 241 consecutive patients undergoing OLT from 1999-2006 for HCV were included. Patients were offered treatment if they had a positive HCV RNA, elevated ALT, histologic evidence of recurrent HCV with at least Stage I fibrosis, and stable immunosuppression for a minimum of 3 months. Patients were excluded if they had evidence of graft failure, creatinine > 2, ongoing psychiatric issues, refusal, or history of non-compliance. Patients received either non-pegyl- ated interferon tiw or pegylated interferon weekly in combination with ribavirin. Dose escalation with a goal of IFN 3 mu tiw or peg-interferon 180 ug/wk plus ribavirin 100- 1200 mg/day was used. Univariate analysis and multivariable models with Cox regression and log-rank analysis were constructed to compare baseline and treatment characteristics with response and survival. Results: 66/241 patients received at least one dose of interferon and ribavirin. Donor and recipient baseline characteristics were similar in treated and untreated patients. 26/66 (39%) treated patients achieved EOT response. 22/66 (33%) achieved SVR and 2/24 (8 %) relapsed. Genotype 1 patients failed more than genotype 3 patients in achieving SVR (32% vs 68%; p<0.018). Patients achieving SVR had a statistically significant longer length of treatment (in weeks) than those who did not achieve SVR (86.6 vs. 59.9; P=0.011). In our cohort of patients, among those who did achieve SVR, there were no deaths observed. Among 45 patients observed long enough for SVR status to be deter- mined, SVR was associated with 100% five-year survival vs. 86% for those without SVR (log-rank p=0.11). Older donor age at transplant was associated with an increase in mortality (HR 1.37) for each 10 year increase in donor age (p<0.0004). Conclusion: We found that genotype 2/3 status and length of treatment were predictors of SVR. There was a trend towards improved survival among those who achieved SVR, although this was statistically insignificant. It is likely that longer follow up will be required to detect significant differences in mortality in patients with and without SVR undergoing antiviral therapy following liver transplantation. S1264 The Adequacy of Liver Biopsies Can Be Predicted From the Length of Fresh Tissue Obtained at the Time of Biopsy Victoria J. Appleby, Mark Kon, Izabela B. Georgiades, Sulleman Moreea Introduction: An adequate liver biopsy should contain 10 portal tracts. Aim: what length of fresh tissue would guarantee enough microscopic tissue for an adequate liver biopsy after allowing for tissue shrinkage during fixation and processing? Methods: Data for liver biopsies taken between 2004-8 was analysed for the following: macroscopic length-length of tissue before processing, microscopic length on pathology slides, number of portal tracts in each biopsy and diagnosis. We conducted a prospective pilot study to correlate length of fresh tissue at the time of biopsy with the length of formalin-preserved tissue at the time of arrival in the lab. Results: There were 412 ultrasound-guided liver biopsies taken with 18 Fr needles in 195 females(F) and 217 males(M). Portal tracts could not be counted in the following: 98 cases of malignancy, 42 cases of cirrhosis and 14 insufficient biopsies. Of the remaining 258 biopsies, statistical analysis was performed on 192(75%) samples where all of macro- scopic length, microscopic length and number of portal tracts were recorded. The diagnoses were: 119 viral hepatitis (F=45,M=74 mean 37yrs) 35 fatty liver disease (F= 14,M= 21 mean 49yrs) 10 haemochromatosis (F=2,M=8 mean 59yrs) 7 autoimmune hepatitis (F=6,M=1 mean 50 yrs) 6 normal liver ( F=3,M=3 , mean 43 y) 4 cholestatic liver disease (F=2,M=2 mean 54yrs) 4 drug induced liver injury (F=3,M=1 mean 39yrs) 7 others (F=5,M=2 mean 51yrs). Tissue shrank consistently (r=0.837, p<0.01) from a mean length of 23.8 mm to 21.0 mm after processing. Macroscopic length was found to be highly predictive of micro- scopic length (variance 95.1%) and the number of portal tracts (variance 85.2%). Age and sex were non-significant parameters for an adequate liver biopsy. We calculated that 17.55 mm of macroscopic tissue equating to 15.89 mm of microscopic tissue (p<0.01) would S-216 AGA Abstracts guarantee an adequate liver biopsy with 10 portal tracts in any diagnosis excluding cirrhosis and malignancy. Similarly, 30 mm of fresh tissue would guarantee 15 portal tracts in >99% of cases. Our pilot study of 10 consecutive biopsies showed no tissue shrinkage during transport in formalin to the lab. Conclusion: The length of fresh tissue from a liver biopsy directly correlates to the number of portal tracts in all diagnoses excluding cirrhosis and malignancy. To ensure that patients have an adequate diagnosis and avoid a repeat biopsy we suggest that operators measure and ensure at least 18 mm of fresh liver tissue at a cut- off of 10 portal tracts and 30 mm of tissue at a cut-off of 15 portal tracts. S1265 Risk of Non-Melanoma Skin Cancer in Autoimmune Hepatitis John Leung, Lauren N. Dowling, Isi Obadan, James S. Davis, Peter Bonis, Marshall Kaplan, Darlene Casey, Kathleen Viveiros BACKGROUND: Most patients with autoimmune hepatitis (AIH) require long-term immuno- suppressive therapy (IS). While it is well established that solid organ transplant recipients have a high risk of developing non-melanoma skin cancer (NMSC) as a result of immunos- uppression, little is known about the risk of NMSC associated with IS in patients with AIH. OBJECTIVES: The aim of this study is to determine the incidence and risk factors for NMSC in patients on IS for AIH. METHODS: We reviewed medical records of all patients with AIH seen at a tertiary care medical center between1998-2008. We compared the incidence of NMSC to an age and sex-matched control population and analyzed risk factors for NMSC. RESULTS: A total of forty-five patients with AIH were identified. Twenty NMSC lesions were found in eight patients. Compared with the age and sex-matched general population, the risk of SCC and BCC were increased as quantified by elevated standardized incidence ratios (28.48 and 4.97 respectively). Patients who developed NMSC were on average 24 years older (78.4 vs. 54.2 year old, p<0.0001) and had AIH diagnosed at a more advanced age (66.0 vs. 45.4 year old, p = 0.0003). CONCLUSION: The risk of NMSC is significantly increased in patients with AIH on immunosuppression. Independent risk factors include current age and age at diagnosis of AIH. S1266 Mean or Median Values of Acoustic Radiation Force Impulse Elastography: Which One to use in Clinical Practice? Roxana Sirli, Ioan Sporea, Simona I. Bota, Alina Popescu, Mirela Danila Background: Acoustic radiation force impulse elastography (ARFI) is a new ultrasound based method for the non-invasive evaluation of liver fibrosis. The aim of our paper was to find out which one, the mean or then median values of ARFI measurements, is the most accurate for liver stiffness (LS) evaluation. Patients and methods: Our study included 179 subjects (92 females and 87 males, mean age 46.9+/-15.9): 69 subjects without fibrosis (healthy volunteers - considered F0 Metavir), 8 subjects with F1, 25 subjects with F2, 24 patients with F3 (all patients underwent liver biopsy) and 53 patients with liver cirrhosis (16 with liver biopsy and 37 with clinically, ultrasonographic and/or endoscopic signs of cirrhosis). In each patient we performed ARFI (by using a Siemens Acuson S2000TM ultrasound system) and: 10 measurements (mean and median values were calculated, measured in meters/second). We compared the diagnostic performance of ARFI mean and median values. Results: A direct, strong, linear correlation (Spearman rho=0.663) was found between median ARFI measurements and fibrosis (p<0.0001), as well as between mean ARFI measurements and fibrosis (rho=0.655) (p<0.0001). There were not statistically significant differences between the predictive values of mean and median values of ARFI measurements for signific- ant fibrosis (F2 Metavir), severe fibrosis (F3 Metavir) and cirrhosis, as seen in the following table: Conclusion: For ARFI evaluation of liver fibrosis, mean or median values can probably be used with the same diagnostic performances. S1267 Role of 13C-Methacetin Breath Test for Noninvasive Staging of Liver Fibrosis in Patients With Chronic Hepatitis C Virus Infection Carmen Fierbinteanu, Laura Tribus, Ana Petrisor, Radu Usvat, Cristian Busegeanu, Catalina Diaconu, Ileana Stan Background: Liver biopsy is an invasive procedure with certain unavoidable risks and complications. Therefore, the development of noninvasive tests to assess hepatic inflammation and fibrosis has been an active area of research. The 13C-methacetin breath test (MBT) has been proposed for the noninvasive evaluation of hepatic microsomal activity. Aim: to evaluate the role of 13C-methacetin breath test (MBT) for the diagnosis of liver fibrosis and to establish the accuracy of MBT for liver fibrosis staging. Methods: 13C-methacetin breath test (MBT) was performed on 100 patients with chronic hepatitis C virus infection (CHC) who underwent liver biopsy for treatment decision and on 44 healthy controls. The correlation between the 13C-methacetin breath test and liver biopsy was tested using Spearman's coefficient. The overall validity was measured using the area under receiver operating charac- teristic curve (AUROC) with 95%CI. Results: Delta over baseline values (DOB) of CHC patients at 20 min were significantly reduced from control (15.20 vs. 21.35, P<0,001). There were also significant differences between CHC patients and control as regards the metabolisation speed (dose/h: 9.80 vs 16.20, P<0,001) and metabolisation capacity (cumulat- ive recovery after 40 minutes: 12.35 vs 17.95, P<0,001 ). However, there was only a moderate correlation between the MBT values and the histological fibrosis (r=0.602 for DOB and 0.398 for cumulative recovery, P < 0.01). The diagnostic accuracy of MBT expressed as area

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sto 4. Prior constitutional symptoms were present in 14%, and 38% were asymptomatic.Acute icteric feature was seen in 47%. Twelve patients had cirrhosis and were transplanted(57%). One had spontaneous remission and 1 died of liver failure. Remaining 7 patientsachieved remission (43%) following treatment with steroid and azathioprine. Relapse onmaintenance treatment was 28%. In group 2, the mean age was 38+14 years, female tomale ratio was 30 to 7. Prior constitutional symptoms were present in 70% and 11% wereasymptomatic. These parameters were significantly different between the groups (p<0.05).Acute icteric feature was seen in 19%. Twelve patients (32%) were transplanted. Eight hadspontaneous remission. Remaining 17 patients achieved remission (41%) following treatment.Relapse on maintenance treatment was 59%. Conclusions: Elderly patients with AIH aremore often asymptomatic or have less constitutional symptoms. AIH in elderly is usuallyan advanced disease at presentation than in younger patients. Relapse of AIH after remissionis less common in the elderly. 1. Distinctive phenotype and treatment outcome of AIH in elderly. Hepatology

43:532, 2006

Table 1

S1263

Predictors of Sustained Virological Response Among Patients With Hepatitis CPost OLT and the Impact of Sustained Virological Response on MortalityMatthew J. Moeller, George Divine, Kimberly Ann Brown

Background: Graft and patient survival following liver transplantation for HCV is reducedwhen compared to other groups. SVR rates from 25-47% have been reported in patientsreceiving anti-viral therapy for HCV following OLT. However, these studies are limited bysmall sample sizes, short duration of follow up, and lack of survival analyses. Aim: Toevaluate predictors of SVR following antiviral treatment of patients with HCV post OLT. Toevaluate the impact of SVR on mortality in treated patients. Methods: 241 consecutivepatients undergoing OLT from 1999-2006 for HCV were included. Patients were offeredtreatment if they had a positive HCV RNA, elevated ALT, histologic evidence of recurrentHCV with at least Stage I fibrosis, and stable immunosuppression for a minimum of 3months. Patients were excluded if they had evidence of graft failure, creatinine > 2, ongoingpsychiatric issues, refusal, or history of non-compliance. Patients received either non-pegyl-ated interferon tiw or pegylated interferon weekly in combination with ribavirin. Doseescalation with a goal of IFN 3 mu tiw or peg-interferon 180 ug/wk plus ribavirin 100-1200 mg/day was used. Univariate analysis and multivariable models with Cox regressionand log-rank analysis were constructed to compare baseline and treatment characteristicswith response and survival. Results: 66/241 patients received at least one dose of interferonand ribavirin. Donor and recipient baseline characteristics were similar in treated anduntreated patients. 26/66 (39%) treated patients achieved EOT response. 22/66 (33%)achieved SVR and 2/24 (8 %) relapsed. Genotype 1 patients failed more than genotype 3patients in achieving SVR (32% vs 68%; p<0.018). Patients achieving SVR had a statisticallysignificant longer length of treatment (in weeks) than those who did not achieve SVR (86.6vs. 59.9; P=0.011). In our cohort of patients, among those who did achieve SVR, there wereno deaths observed. Among 45 patients observed long enough for SVR status to be deter-mined, SVR was associated with 100% five-year survival vs. 86% for those without SVR(log-rank p=0.11). Older donor age at transplant was associated with an increase in mortality(HR 1.37) for each 10 year increase in donor age (p<0.0004). Conclusion: We found thatgenotype 2/3 status and length of treatment were predictors of SVR. There was a trendtowards improved survival among those who achieved SVR, although this was statisticallyinsignificant. It is likely that longer follow up will be required to detect significant differencesin mortality in patients with and without SVR undergoing antiviral therapy followingliver transplantation.

S1264

The Adequacy of Liver Biopsies Can Be Predicted From the Length of FreshTissue Obtained at the Time of BiopsyVictoria J. Appleby, Mark Kon, Izabela B. Georgiades, Sulleman Moreea

Introduction: An adequate liver biopsy should contain ≥10 portal tracts. Aim: what lengthof fresh tissue would guarantee enough microscopic tissue for an adequate liver biopsy afterallowing for tissue shrinkage during fixation and processing? Methods: Data for liver biopsiestaken between 2004-8 was analysed for the following: macroscopic length-length of tissuebefore processing, microscopic length on pathology slides, number of portal tracts in eachbiopsy and diagnosis. We conducted a prospective pilot study to correlate length of freshtissue at the time of biopsy with the length of formalin-preserved tissue at the time of arrivalin the lab. Results: There were 412 ultrasound-guided liver biopsies taken with 18 Fr needlesin 195 females(F) and 217 males(M). Portal tracts could not be counted in the following:98 cases of malignancy, 42 cases of cirrhosis and 14 insufficient biopsies. Of the remaining258 biopsies, statistical analysis was performed on 192(75%) samples where all of macro-scopic length, microscopic length and number of portal tracts were recorded. The diagnoseswere: 119 viral hepatitis (F=45,M=74 mean 37yrs) 35 fatty liver disease (F= 14,M= 21 mean49yrs) 10 haemochromatosis (F=2,M=8 mean 59yrs) 7 autoimmune hepatitis (F=6,M=1mean 50 yrs) 6 normal liver ( F=3,M=3 , mean 43 y) 4 cholestatic liver disease (F=2,M=2mean 54yrs) 4 drug induced liver injury (F=3,M=1 mean 39yrs) 7 others (F=5,M=2 mean51yrs). Tissue shrank consistently (r=0.837, p<0.01) from a mean length of 23.8 mm to21.0 mm after processing. Macroscopic length was found to be highly predictive of micro-scopic length (variance 95.1%) and the number of portal tracts (variance 85.2%). Age andsex were non-significant parameters for an adequate liver biopsy. We calculated that 17.55mm of macroscopic tissue equating to 15.89 mm of microscopic tissue (p<0.01) would

S-216AGA Abstracts

guarantee an adequate liver biopsy with 10 portal tracts in any diagnosis excluding cirrhosisand malignancy. Similarly, 30 mm of fresh tissue would guarantee ≥15 portal tracts in>99% of cases. Our pilot study of 10 consecutive biopsies showed no tissue shrinkage duringtransport in formalin to the lab. Conclusion: The length of fresh tissue from a liver biopsydirectly correlates to the number of portal tracts in all diagnoses excluding cirrhosis andmalignancy. To ensure that patients have an adequate diagnosis and avoid a repeat biopsywe suggest that operators measure and ensure at least 18 mm of fresh liver tissue at a cut-off of 10 portal tracts and 30 mm of tissue at a cut-off of ≥15 portal tracts.

S1265

Risk of Non-Melanoma Skin Cancer in Autoimmune HepatitisJohn Leung, Lauren N. Dowling, Isi Obadan, James S. Davis, Peter Bonis, MarshallKaplan, Darlene Casey, Kathleen Viveiros

BACKGROUND: Most patients with autoimmune hepatitis (AIH) require long-term immuno-suppressive therapy (IS). While it is well established that solid organ transplant recipientshave a high risk of developing non-melanoma skin cancer (NMSC) as a result of immunos-uppression, little is known about the risk of NMSC associated with IS in patients with AIH.OBJECTIVES: The aim of this study is to determine the incidence and risk factors for NMSCin patients on IS for AIH. METHODS: We reviewed medical records of all patients withAIH seen at a tertiary care medical center between1998-2008. We compared the incidenceof NMSC to an age and sex-matched control population and analyzed risk factors for NMSC.RESULTS: A total of forty-five patients with AIH were identified. Twenty NMSC lesionswere found in eight patients. Compared with the age and sex-matched general population,the risk of SCC and BCC were increased as quantified by elevated standardized incidenceratios (28.48 and 4.97 respectively). Patients who developed NMSC were on average 24years older (78.4 vs. 54.2 year old, p<0.0001) and had AIH diagnosed at a more advancedage (66.0 vs. 45.4 year old, p = 0.0003). CONCLUSION: The risk of NMSC is significantlyincreased in patients with AIH on immunosuppression. Independent risk factors includecurrent age and age at diagnosis of AIH.

S1266

Mean or Median Values of Acoustic Radiation Force Impulse Elastography:Which One to use in Clinical Practice?Roxana Sirli, Ioan Sporea, Simona I. Bota, Alina Popescu, Mirela Danila

Background: Acoustic radiation force impulse elastography (ARFI) is a new ultrasound basedmethod for the non-invasive evaluation of liver fibrosis. The aim of our paper was to findout which one, the mean or then median values of ARFI measurements, is the most accuratefor liver stiffness (LS) evaluation. Patients and methods: Our study included 179 subjects(92 females and 87 males, mean age 46.9+/-15.9): 69 subjects without fibrosis (healthyvolunteers - considered F0 Metavir), 8 subjects with F1, 25 subjects with F2, 24 patientswith F3 (all patients underwent liver biopsy) and 53 patients with liver cirrhosis (16 withliver biopsy and 37 with clinically, ultrasonographic and/or endoscopic signs of cirrhosis).In each patient we performed ARFI (by using a Siemens Acuson S2000TM ultrasoundsystem) and: 10 measurements (mean and median values were calculated, measured inmeters/second). We compared the diagnostic performance of ARFI mean and median values.Results: A direct, strong, linear correlation (Spearman rho=0.663) was found between medianARFI measurements and fibrosis (p<0.0001), as well as between mean ARFI measurementsand fibrosis (rho=0.655) (p<0.0001). There were not statistically significant differencesbetween the predictive values of mean and median values of ARFI measurements for signific-ant fibrosis (F≥2 Metavir), severe fibrosis (F≥3 Metavir) and cirrhosis, as seen in thefollowing table: Conclusion: For ARFI evaluation of liver fibrosis, mean or median valuescan probably be used with the same diagnostic performances.

S1267

Role of 13C-Methacetin Breath Test for Noninvasive Staging of Liver Fibrosisin Patients With Chronic Hepatitis C Virus InfectionCarmen Fierbinteanu, Laura Tribus, Ana Petrisor, Radu Usvat, Cristian Busegeanu,Catalina Diaconu, Ileana Stan

Background: Liver biopsy is an invasive procedure with certain unavoidable risks andcomplications. Therefore, the development of noninvasive tests to assess hepatic inflammationand fibrosis has been an active area of research. The 13C-methacetin breath test (MBT) hasbeen proposed for the noninvasive evaluation of hepatic microsomal activity. Aim: to evaluatethe role of 13C-methacetin breath test (MBT) for the diagnosis of liver fibrosis and toestablish the accuracy of MBT for liver fibrosis staging. Methods: 13C-methacetin breathtest (MBT) was performed on 100 patients with chronic hepatitis C virus infection (CHC)who underwent liver biopsy for treatment decision and on 44 healthy controls. The correlationbetween the 13C-methacetin breath test and liver biopsy was tested using Spearman'scoefficient. The overall validity was measured using the area under receiver operating charac-teristic curve (AUROC) with 95%CI. Results: Delta over baseline values (DOB) of CHCpatients at 20 min were significantly reduced from control (15.20 vs. 21.35, P<0,001).There were also significant differences between CHC patients and control as regards themetabolisation speed (dose/h: 9.80 vs 16.20, P<0,001) and metabolisation capacity (cumulat-ive recovery after 40 minutes: 12.35 vs 17.95, P<0,001 ). However, there was only a moderatecorrelation between the MBT values and the histological fibrosis (r=0.602 for DOB and0.398 for cumulative recovery, P < 0.01). The diagnostic accuracy of MBT expressed as area