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MRI Scan
correlated with risk of HCC recurrence (P= 0.039). Conversely, multiple binary regression analysis showed no correlation of the other markers with outcome. Conclusions. The biomolecular markers, used in this study were of no value in the prognostic evaluation of HCC. Positivity of CD34 was correlated with risk of HCC recurrence.
classified as inappropriate based on a) without diagnosis codes for HCC or other symptoms on CT/MRI claim, or CT guided liver biopsy on same date and b) without symptoms/liver biopsies in 3 months prior to CT/MRI. Subjects with cirrhosis and other cancer or without cancer were randomly assigned an index month/year mimicking month/year in HCC cohort and were analyzed using same selection criteria as for HCC cohort. To estimate proportion of receiving screening USG and inappropriately using CT/MRI in cirrhosis patients, we combined the three cohorts with a weight of 20 assigned to each subject in the other cancer and non-cancer cohorts. Results: Among patients with cirrhosis with HCC (N=3057), 400 (13%) received HCC screening USG within 6-12 months before HCC diagnosis. A total of 636 patients in this group received CT/MRI scan within 6-12 mo. before HCC diagnosis, about 44.8% of which were inappropriate scans. Among other cancer (N=927) and noncancer group (3075), about 3.1% and 3.6% respectively received screening USG within 612 months from the index date. In these two groups, 111 and 164 patients underwent CT/ MRI scans, of which 41.1 and 30.8% respectively were inappropriate scans. Of 83,097 cirrhotics in this Medicare population (after assigning weight of 20 to non-cancer and other cancer groups), only about 4% received screening USG. Of 16,696 CT/MRI scans in the weighted cohort, about 35% were inappropriately performed. Discussion: In this Medicare population, proportion of patients receiving HCC screening USG was low. Further, a large proportion of CT / MRI scans were used inappropriately. Apart from increasing health care cost, inappropriate CT/MRI scan puts patients at risk for radiation exposure. Studies are needed for strategies to improve rigorous adherence to HCC screening and also identify high risk patients which may benefit from use of CT/MRI.
Sa1873 In Hepatitis B Virus (HBV)-Associated Hepatocellular Carcinoma (HCC), Patients With Cirrhosis Have Similar Short-Term but Decreased Long-Term Survival Compared to Those Without Cirrhosis Vincent L. Chen, Lily H. Kim, Pauline Nguyen, Changqing Zhao, Mindie H. Nguyen Background: Chronic hepatitis B (CHB) can lead to HCC in either the presence or absence of cirrhosis. In this study, we characterized the baseline characteristics, treatments, and outcomes of HBV-associated HCC patients by cirrhosis status. Methods: This was a retrospective single-center cohort study of 493 consecutive patients diagnosed with HBV-related HCC at a U.S. university medical center between 2005 and 2014. Patients were identified via ICD-9 diagnosis query for HCC, and were included in the cohort if they had serologic evidence of CHB and HCC diagnosed by pathology or imaging based on AASLD criteria. Patients were designated as having cirrhosis if there was clinical, laboratory, imaging, or biopsy evidence of portal hypertension or fibrosis stage 4. Survival was obtained via chart review and/or National Death Index search. Results: Mean age was 60; 80% were male; 89% were Asian; and 62% had cirrhosis. Compared to patients without cirrhosis, those with cirrhosis were older (mean age 61.2 vs. 57.5 years, p = 0.002) and more likely to have hypertension (46.4% vs. 35.4%, p = 0.02) and diabetes (29.2% vs. 13.6%, p < 0.001). Patients with and without cirrhosis had similar baseline BCLC stage (70.7% vs. 77.0% stage A or B, p = 0.14) and proportion of patients within UCSF- (57.4% vs. 52.8%, p = 0.36) or Milan (37.1% vs. 40.8%, p = 0.45) criteria for liver transplantation (LT). Patients with cirrhosis were much less likely than those without cirrhosis to undergo partial hepatic resection (19.6% vs. 34.6%, p < 0.001), more likely to undergo LT (9.1% vs. 1.4%, p < 0.001), and equally likely to undergo any surgical treatment (28.7% vs. 35.9%, p = 0.10). Interestingly, survival did not depend on cirrhosis status for the first two years after diagnosis, but diverged significantly thereafter (Fig. 1A). Surgical treatment was associated with improved survival relative to nonsurgical treatment, particularly among patients without cirrhosis, who had 5-year survival of 77.1% with surgical treatment vs. 20.5% for nonsurgical treatment, compared to 70.5% and 26.3% for patients with cirrhosis (Fig. 1B). Conclusions: Compared to patients without cirrhosis, patients with cirrhosis and CHB-related HCC presented with similar tumor stage and had similar 2-year survival but markedly decreased 5year survival. Surgical treatments were associated with greater 5-year survival than were nonsurgical options, and the benefit appeared even greater in patients without cirrhosis
Therapeutic Inhibition of miRNA-132 Attenuates CCL4-Induced Liver Fibrosis Shashi Bala, Fatemeh Momen-heravi, Timea Csak, Donna Catalano, Gyongyi Szabo, Kaimin Li Background: Liver homeostasis is crucial for its normal function. Liver fibrosis is characterized by excessive scarring, caused by chronic inflammatory processes during liver diseases of various origin. microRNAs (miRNAs, small non-coding RNAs) have emerged as new crucial regulatory players in all cellular processes. Recently, we showed induction of miRNA132 in a mouse model of alcoholic liver disease. However, the functional role of miR-132 in liver disease is largely unknown. In this study, we evaluated the therapeutic effect of miR-132 inhibition in liver fibrosis. Methods: Liver tissues of control individuals and patients with alcoholic fibrosis/cirrhosis (n=8) were analyzed for miR-132 levels using TaqMan miRNA assay. For in vivo study, C57BL/6 male mice (n=8) were injected either with control or miR-132- lock nucleic acid (LNA)-inhibitor (@15mg/kg) intraperitoneal. Mice received either corn oil (vehicle) or CCl4 (0.6ml/kg; i.p. diluted in corn oil @1:3) twice a week for two weeks. Mice were sacrificed 72h after the last CCl4 injection. Some mice were perfused to isolate hepatocytes and Kupffer cells (KCs). Extracellular vesicles (EVs) were characterized from plasma by Nanosight and electron microscopy. Results: Our data indicate a 4-fold induction of miR-132 in the fibrotic livers of alcoholic patients. A significant and sustained induction of miR-132 was found in the livers of mice administrated with CCl4 for 2 and 6 weeks. Inhibition of miR-132 function in mice with anti-miR-132 caused a decrease in collagen deposition evidenced by Sirius Red staining and attenuation in CCl4-induced α smooth muscle actin. CCl4 treatment induced an increase in CD68 levels in LNA-anticontrol but not in anti-miR-132 treated mice. An induction of macrophage metalloelastase (MMP12) was found in anti-control treated mice after CCl4 treatment, which was further augmented in LNAanti- miR-132 treated mice. CCl4 treatment increased caspase-3 activity only in anti-control treated mice and not in anti-miR-132 treated mice. At the cellular level, miR-132 was increased in both hepatocytes and KCs isolated after 2 weeks of CCl4 treatment. Functionally, inhibition of miR- 132 in KCs and not in hepatocytes was associated with further increase in MMP12, suggesting a functional role of miR-132 in KCs. The number of EVs is shown to increase in liver disease and consistent with this we found an increase of EVs in the plasma after CCl4 treatment in anti-control but not in anti-miR-132 treated mice. These data suggest that anti-miR-132 treated mice are protected from CCl4-induced liver injury. Conclusion: Our results from mouse studies suggest a functional role of miR132 in liver fibrosis and therapeutic inhibition of miR-132 might be an attractive strategy to ameliorate liver fibrosis. Sa1876 Evaluation of Acoustic Radiation Force Elastography (ARFI) in the Diagnosis of Hepatic Fibrosis and Portal Hypertension Deepak Amarapurkar, Rupesh K. Kashikar, Somesh Lala, Sonali Gautam, Anjali D. Amarapurkar Transient elastography by fibroscan is widely used as non-invasive marker for diagnosis of liver fibrosis. Fibroscan is limited in accuracy in patients with acute hepatitis, ascites and patients with BMI >30 and it requires separate equipment. ARFI is a new way of assessing liver fibrosis and is incorporated in ultrasound machine. In a prospective study we evaluated utility of ARFI in 181 consecutive patients undergoing liver biopsy and assessed misclassification rate of fibrosis in patients with acute hepatitis ascites, ascites and patients with BMI >25. Material & method: 181 consecutive patients (males 60%, age mean ±SD 46.04±13.34 years) undergoing liver biopsy were evaluated for ARFI by Acuson S2000, Siemens ultrasonography machine. In addition to abdominal ultrasound with doppler examination, patients were subjected to 10 acquisitions of ARFI were obtained between ribs of liver from right lobe in dorsal decubitus position and momentary breath holding. All the patients were evaluated with appropriate clinical history, physical examination, laboratory evaluation, endoscopy and other ancillary tests as required. Major indications for liver biopsy were autoimmune liver disease (38), non-alcoholic fatty liver disease (24), cryptogenic liver disease (10), noncirrhotic portal hypertension (27) and viral hepatitis (17). Liver biopsy was graded by single pathologist blind folded by Metavir classification. Aspartate aminotransferase to platelet ratio index (APRI) was calculated in each patient. ARFI values for liver and spleen were correlated with presence and size of esophageal varices (no varices, small and large varices). Results: Median ARFI score with interquartile range were 1.59 (1.33-1.99), 1.91 (1.45-2.16), 2.45 (2.07-2.98) in fibrosis stage 0 (n=54), fibrosis stage 1&2 (n=28), fibrosis
Sa1874 Hepatocellular Carcinoma Screening in Cirrhosis: Inappropriate Use of CT/ MRI Scan Siddharth Bansal, Yu-li Lin, Yong Fang Kuo, Ashwani K. Singal Background: Ultrasound (USG) is recommended for hepatocellular (HCC) screening in cirrhosis. CT/MRI is used to confirm HCC. However, CT / MRI scan is often inappropriately used for screening. Aim: Data on inappropriate CT/MRI use for screening HCC is scanty. Methods: Using the SEER-Medicare Linked Database (1993-2009) with files containing 100% HCC cases, 5% cases of other cancers and 5% non-cancer Medicare beneficiaries to determine use of USG for HCC screening and inappropriate use of CT/MRI. Our study cohort included cirrhotics with HCC, 67 yrs. or older at diagnosis, with complete Medicare enrollment, without enrollment in any managed care and without liver transplant in preceding 2 years. Analysis was done for receipt of HCC screening with USG between 6 and 12 months before HCC diagnosis. CT/MRI done between 6 and 12 months before HCC diagnosis was
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AASLD Abstracts
AASLD Abstracts
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classified as inappropriate based on a) without diagnosis codes for HCC or other symptoms on CT/MRI claim, or CT guided liver biopsy on same date and b) without symptoms/liver biopsies in 3 months prior to CT/MRI. Subjects with cirrhosis and other cancer or without cancer were randomly assigned an index month/year mimicking month/year in HCC cohort and were analyzed using same selection criteria as for HCC cohort. To estimate proportion of receiving screening USG and inappropriately using CT/MRI in cirrhosis patients, we combined the three cohorts with a weight of 20 assigned to each subject in the other cancer and non-cancer cohorts. Results: Among patients with cirrhosis with HCC (N=3057), 400 (13%) received HCC screening USG within 6-12 months before HCC diagnosis. A total of 636 patients in this group received CT/MRI scan within 6-12 mo. before HCC diagnosis, about 44.8% of which were inappropriate scans. Among other cancer (N=927) and noncancer group (3075), about 3.1% and 3.6% respectively received screening USG within 612 months from the index date. In these two groups, 111 and 164 patients underwent CT/ MRI scans, of which 41.1 and 30.8% respectively were inappropriate scans. Of 83,097 cirrhotics in this Medicare population (after assigning weight of 20 to non-cancer and other cancer groups), only about 4% received screening USG. Of 16,696 CT/MRI scans in the weighted cohort, about 35% were inappropriately performed. Discussion: In this Medicare population, proportion of patients receiving HCC screening USG was low. Further, a large proportion of CT / MRI scans were used inappropriately. Apart from increasing health care cost, inappropriate CT/MRI scan puts patients at risk for radiation exposure. Studies are needed for strategies to improve rigorous adherence to HCC screening and also identify high risk patients which may benefit from use of CT/MRI.
Sa1873 In Hepatitis B Virus (HBV)-Associated Hepatocellular Carcinoma (HCC), Patients With Cirrhosis Have Similar Short-Term but Decreased Long-Term Survival Compared to Those Without Cirrhosis Vincent L. Chen, Lily H. Kim, Pauline Nguyen, Changqing Zhao, Mindie H. Nguyen Background: Chronic hepatitis B (CHB) can lead to HCC in either the presence or absence of cirrhosis. In this study, we characterized the baseline characteristics, treatments, and outcomes of HBV-associated HCC patients by cirrhosis status. Methods: This was a retrospective single-center cohort study of 493 consecutive patients diagnosed with HBV-related HCC at a U.S. university medical center between 2005 and 2014. Patients were identified via ICD-9 diagnosis query for HCC, and were included in the cohort if they had serologic evidence of CHB and HCC diagnosed by pathology or imaging based on AASLD criteria. Patients were designated as having cirrhosis if there was clinical, laboratory, imaging, or biopsy evidence of portal hypertension or fibrosis stage 4. Survival was obtained via chart review and/or National Death Index search. Results: Mean age was 60; 80% were male; 89% were Asian; and 62% had cirrhosis. Compared to patients without cirrhosis, those with cirrhosis were older (mean age 61.2 vs. 57.5 years, p = 0.002) and more likely to have hypertension (46.4% vs. 35.4%, p = 0.02) and diabetes (29.2% vs. 13.6%, p < 0.001). Patients with and without cirrhosis had similar baseline BCLC stage (70.7% vs. 77.0% stage A or B, p = 0.14) and proportion of patients within UCSF- (57.4% vs. 52.8%, p = 0.36) or Milan (37.1% vs. 40.8%, p = 0.45) criteria for liver transplantation (LT). Patients with cirrhosis were much less likely than those without cirrhosis to undergo partial hepatic resection (19.6% vs. 34.6%, p < 0.001), more likely to undergo LT (9.1% vs. 1.4%, p < 0.001), and equally likely to undergo any surgical treatment (28.7% vs. 35.9%, p = 0.10). Interestingly, survival did not depend on cirrhosis status for the first two years after diagnosis, but diverged significantly thereafter (Fig. 1A). Surgical treatment was associated with improved survival relative to nonsurgical treatment, particularly among patients without cirrhosis, who had 5-year survival of 77.1% with surgical treatment vs. 20.5% for nonsurgical treatment, compared to 70.5% and 26.3% for patients with cirrhosis (Fig. 1B). Conclusions: Compared to patients without cirrhosis, patients with cirrhosis and CHB-related HCC presented with similar tumor stage and had similar 2-year survival but markedly decreased 5year survival. Surgical treatments were associated with greater 5-year survival than were nonsurgical options, and the benefit appeared even greater in patients without cirrhosis
Therapeutic Inhibition of miRNA-132 Attenuates CCL4-Induced Liver Fibrosis Shashi Bala, Fatemeh Momen-heravi, Timea Csak, Donna Catalano, Gyongyi Szabo, Kaimin Li Background: Liver homeostasis is crucial for its normal function. Liver fibrosis is characterized by excessive scarring, caused by chronic inflammatory processes during liver diseases of various origin. microRNAs (miRNAs, small non-coding RNAs) have emerged as new crucial regulatory players in all cellular processes. Recently, we showed induction of miRNA132 in a mouse model of alcoholic liver disease. However, the functional role of miR-132 in liver disease is largely unknown. In this study, we evaluated the therapeutic effect of miR-132 inhibition in liver fibrosis. Methods: Liver tissues of control individuals and patients with alcoholic fibrosis/cirrhosis (n=8) were analyzed for miR-132 levels using TaqMan miRNA assay. For in vivo study, C57BL/6 male mice (n=8) were injected either with control or miR-132- lock nucleic acid (LNA)-inhibitor (@15mg/kg) intraperitoneal. Mice received either corn oil (vehicle) or CCl4 (0.6ml/kg; i.p. diluted in corn oil @1:3) twice a week for two weeks. Mice were sacrificed 72h after the last CCl4 injection. Some mice were perfused to isolate hepatocytes and Kupffer cells (KCs). Extracellular vesicles (EVs) were characterized from plasma by Nanosight and electron microscopy. Results: Our data indicate a 4-fold induction of miR-132 in the fibrotic livers of alcoholic patients. A significant and sustained induction of miR-132 was found in the livers of mice administrated with CCl4 for 2 and 6 weeks. Inhibition of miR-132 function in mice with anti-miR-132 caused a decrease in collagen deposition evidenced by Sirius Red staining and attenuation in CCl4-induced α smooth muscle actin. CCl4 treatment induced an increase in CD68 levels in LNA-anticontrol but not in anti-miR-132 treated mice. An induction of macrophage metalloelastase (MMP12) was found in anti-control treated mice after CCl4 treatment, which was further augmented in LNAanti- miR-132 treated mice. CCl4 treatment increased caspase-3 activity only in anti-control treated mice and not in anti-miR-132 treated mice. At the cellular level, miR-132 was increased in both hepatocytes and KCs isolated after 2 weeks of CCl4 treatment. Functionally, inhibition of miR- 132 in KCs and not in hepatocytes was associated with further increase in MMP12, suggesting a functional role of miR-132 in KCs. The number of EVs is shown to increase in liver disease and consistent with this we found an increase of EVs in the plasma after CCl4 treatment in anti-control but not in anti-miR-132 treated mice. These data suggest that anti-miR-132 treated mice are protected from CCl4-induced liver injury. Conclusion: Our results from mouse studies suggest a functional role of miR132 in liver fibrosis and therapeutic inhibition of miR-132 might be an attractive strategy to ameliorate liver fibrosis. Sa1876 Evaluation of Acoustic Radiation Force Elastography (ARFI) in the Diagnosis of Hepatic Fibrosis and Portal Hypertension Deepak Amarapurkar, Rupesh K. Kashikar, Somesh Lala, Sonali Gautam, Anjali D. Amarapurkar Transient elastography by fibroscan is widely used as non-invasive marker for diagnosis of liver fibrosis. Fibroscan is limited in accuracy in patients with acute hepatitis, ascites and patients with BMI >30 and it requires separate equipment. ARFI is a new way of assessing liver fibrosis and is incorporated in ultrasound machine. In a prospective study we evaluated utility of ARFI in 181 consecutive patients undergoing liver biopsy and assessed misclassification rate of fibrosis in patients with acute hepatitis ascites, ascites and patients with BMI >25. Material & method: 181 consecutive patients (males 60%, age mean ±SD 46.04±13.34 years) undergoing liver biopsy were evaluated for ARFI by Acuson S2000, Siemens ultrasonography machine. In addition to abdominal ultrasound with doppler examination, patients were subjected to 10 acquisitions of ARFI were obtained between ribs of liver from right lobe in dorsal decubitus position and momentary breath holding. All the patients were evaluated with appropriate clinical history, physical examination, laboratory evaluation, endoscopy and other ancillary tests as required. Major indications for liver biopsy were autoimmune liver disease (38), non-alcoholic fatty liver disease (24), cryptogenic liver disease (10), noncirrhotic portal hypertension (27) and viral hepatitis (17). Liver biopsy was graded by single pathologist blind folded by Metavir classification. Aspartate aminotransferase to platelet ratio index (APRI) was calculated in each patient. ARFI values for liver and spleen were correlated with presence and size of esophageal varices (no varices, small and large varices). Results: Median ARFI score with interquartile range were 1.59 (1.33-1.99), 1.91 (1.45-2.16), 2.45 (2.07-2.98) in fibrosis stage 0 (n=54), fibrosis stage 1&2 (n=28), fibrosis
Sa1874 Hepatocellular Carcinoma Screening in Cirrhosis: Inappropriate Use of CT/ MRI Scan Siddharth Bansal, Yu-li Lin, Yong Fang Kuo, Ashwani K. Singal Background: Ultrasound (USG) is recommended for hepatocellular (HCC) screening in cirrhosis. CT/MRI is used to confirm HCC. However, CT / MRI scan is often inappropriately used for screening. Aim: Data on inappropriate CT/MRI use for screening HCC is scanty. Methods: Using the SEER-Medicare Linked Database (1993-2009) with files containing 100% HCC cases, 5% cases of other cancers and 5% non-cancer Medicare beneficiaries to determine use of USG for HCC screening and inappropriate use of CT/MRI. Our study cohort included cirrhotics with HCC, 67 yrs. or older at diagnosis, with complete Medicare enrollment, without enrollment in any managed care and without liver transplant in preceding 2 years. Analysis was done for receipt of HCC screening with USG between 6 and 12 months before HCC diagnosis. CT/MRI done between 6 and 12 months before HCC diagnosis was
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AASLD Abstracts
AASLD Abstracts
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