- Email: [email protected]
947 FEASIBILITY AND PERFORMANCE OF THE LIVER STIFFNESS (LSM) MEASUREMENT FOR THE DIAGNOSIS OF FIBROSIS IN NAFLD
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945 HISTOLOGICAL DEFINITIONS OF NON-ALCOHOLIC STEATOHEPATITIS IN A COHORT OF MORBIDLY OBESE PATIENTS SUBMITTED TO BARIATRIC SURGERY: COMPARISON OF TWO CLASSIFICATIONS AND METABOLIC CORRELATES M.V. Machado1 , A. Costa2 , J. Coutinho3 , F. Carepa3 , N. Alves3 , H. Cortez-Pinto1,4 . 1 Departamento de Gastrenterologia e Hepatologia, 2 Departamento de Anatomia Patol´ ogica, 3 Departamento de Cirurgia, Hospital de Santa Maria, Lisboa, Portugal, 4 Unidade de Nutri¸ca˜ o e Metabolismo, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal E-mail: [email protected] Background and Aims: Histological definition of non-alcoholic steatohepatitis (NASH), in morbidly obese patients, is controversial, being the most accepted classifications the one proposed by Matteoni et al. (MC) and the NAFLD Activity Score (NAS). We aimed to compare both classifications, analyzing factors related to NASH. Methods: Morbidly obese patients submitted to bariatric surgery were consecutively and prospectively recruited. Other causes of liver disease and alcohol intake >20 g/day were excluded. Surgical liver biopsies were evaluated using Matteoni et al. (MC) and the NAFLD Activity Score (NAS). Results: 40 patients, 3 men; age: 42±12 years; body mass index (BMI): 47±9 kg/m2 . Steatosis (>5%), was present in 95%; fibrosis in 97.5%, severe in 10%, one patient presenting with unexpected hepatic cirrhosis. With MC, NASH was diagnosed in 4 patients, simple steatosis in 18 patients, and 16 patients were classified in the controversial group 2 (steatosis plus inflammation without criteria of NASH). With NAS, definitive diagnosis of NASH was made in 8 patients, exclusion of NASH in 21 patients, 11 remaining unclassified. Inter-rater agreement between both classifications, when categorized in 3 subgroups, definitive NASH (NAS 5/MC 3 and 4), unclassified (NAS 3−4/MC 2) and exclusion of NASH (NAS < 3/MC 1), was 0.77 (p = 0.123). Group 2 of MC occurred in all subgroups of NAS. NASH diagnosed by either MC or NAS associated to increases in aminotransferases levels, hypertriglyceridaemia, a higher HOMA and a greater number of metabolic syndrome features (p < 0.05). All patients with NASH (MC or NAS) had evidence of insulin resistance (HOMA 3) and criteria for metabolic syndrome (3 features) (p < 0.05). Both classifications associated to steatosis severity, but only MC NASH with fibrosis severity. Conclusion: MC and NAS classifications presented only a moderate agreement in respect to the diagnosis of NASH. Using NAS score, NASH was two fold more frequent than if MC was applied. MC correlated better to the severity of hepatic fibrosis, the main factor associated to more advanced disease, however a more significant percentage of patients are left on a rather undefined group of NAFLD. Applying either classification, NASH associated strongly with metabolic disturbances, in morbidly obese. 946 PREDICTION OF MORTALITY IN PATIENTS WITH ALCOHOLIC HEPATITIS: COMPARISON OF PROGNOSTIC SCORES M.V. Machado, J. Nunes, H. Cortez-Pinto, F. Ramalho, E. Monteiro. Departamento de Gastroenterologia E Hepatologia, Hospital de Santa Maria, Lisbon, Poland E-mail: [email protected] Background: Severity stratification in patients with alcoholic hepatitis (AH), allow us to predict mortality risk and to guide our clinical management. Although there are several prognostic models, information is lacking concerning the comparison of their prognostic value. Aims: 1) To evaluate mortality, its causes, and related risk factors in patients with AH. 2) To compare Child-Pugh-Turcotte (CPT), modified
Maddrey Index (MI), MELD and Glasgow Alcoholic Hepatitis Score (GASH), as mortality predictors. Methods: From 2002 to 2006 all patients admitted with AH, in a Hepatology Department were evaluated and followed up to 6 months. CPT, MI, MELD and GASH were calculated and the respective scores were analyzed using ROC curves, and compared with Clarke-Pearson method. Results: 76 patients were admitted, 60 men, with a mean age of 50±10 years, hepatic cirrhosis (liver biopsy or clinical evidence of portal hypertension) in 82%. The present episode was the first hepatic decompensation in 71%. 47 patients had severe AH, with a MI32, 9 were treated with corticosteroids and 36 with pentoxifilin. One month mortality was 14.5%, and at 6 months mortality was 26.3%, being infection the main cause of death (90%) followed by renal failure (RF) in 5% and gastrointestinal bleeding in 5%. One month mortality associated with RF, coagulation impairment and lactic dehydrogenase levels (multivariate analysis). AUROC to assess mortality were: GASH9 = 0.732, MELD20 = 0.731, CPT12 = 0.692 and MI32 = 0.670; no statistical differences between indices. Percentage of patients correctly classified was: GASH 67.1%, MELD 60.5%, MI 50% and CPT 47.4%. Six months mortality associated to infection, RF and coagulation impairment (multivariate analysis). AUROC: GASH9 = 0.723, MELD20 = 0.695, MI32 = 0.691 and CPT12 = 0.689; no statistical differences between indices. Percentage of patients correctly classified was: GASH 71.0%, MELD 64.5%, MI 59.2% and CPT 56.6%. Conclusion: AH presentation was the first manifestation of hepatic disease in the majority of patients, with a high mortality (26% at 6 months). Infection was the main cause of death. Comparing several risk stratification scores available, all scores performed equally, with a moderate prognostic acuity.
947 FEASIBILITY AND PERFORMANCE OF THE LIVER STIFFNESS (LSM) MEASUREMENT FOR THE DIAGNOSIS OF FIBROSIS IN NAFLD A. Mahmoudi1 , G. Nkontchou1 , M. Lemoine1 , J. Reboul Marty2 , N. Ganne Carrie1 , V. Grando Lemaire1 , J.C. Trinchet1 , M. Beaugrand1 . 1 Liver Unit, 2 Public Health, Hˆ opital Jean Verdier, Assistance PubliqueHˆopitaux de Paris, UPRES EA 3409, UFR SMBH, Universit´e Paris, Bondy, France E-mail: [email protected] LMS has been validated as a non invasive tool for the evaluation of liver diseases But information’s are still limited concerning it’s feasibility and performances in patients with NAFLD and the possible influence of inflammation and or steatosis on the results. This study was aimed at assessing these different points. Patients and Methods: We studied 137 patients (74 male, mean age: 55±12 yrs) referred for liver biopsy and presenting with the metabolic syndrome and liver enzyme abnormalities. Alcohol consumption >20 g/day, HCV or HBV infection or others causes of liver diseases were excluded in all cases. LSM by Fibroscan (Echosens Paris) was performed by experienced operator not aware of any biological or histological results. The measure was considered valid if 8 acquisitions were recorded by the success to rate >50%. All liver biopsies were coded according to the Brunt classification staging taking in account fibrosis (F0−F4), Activity (A0-A4), steatosis (S1-S3). Results: LSM failed in 45 patients (32%). The rate of failure was closely related to obesity. Among the 92 remaining patients, all had NAFLD or NASH with the following fibrosis score: F0 = 4, F1 = 27, F2 = 28, F3 = 27 and F4 = 10. The main values LSM (95% CI) were respectively F0: 5.37 kPa (3.66−7.09), F1: 7.21 kPa (6.10−8.32), F2: 10.45 kPa (8.60−12.27); F3: 13.71 kPa (9.72−17.7); F4: 26.77 kPa (22.65−30.88). In univariate analysis the stage of fibrosis (p < 0.0001) and the degree of activity was correlated to LSM. Steatosis was not. In multivariate analysis, only the stage of fibrosis was correlated to LSM F0−F1/F2, F3, F4: 0.77 and for cirrhosis F0−F1−F2−F3/F4: 0.97.
08. ALCOHOLIC LIVER DISEASE, NAFLD AND DRUG-INDUCED LIVER DISEASE Conclusion: In patients with NAFLD and NASH, LSM when possible (2/3 cases) allow a reliable assessment of liver fibrosis especially in advanced stage. Steatosis and or inflammation don’t seem to have any influence on LSM. 948 IDENTIFICATION OF BIOMARKERS THAT MEASURE DISEASE ACTIVITY IN PATIENTS WITH NONALCOHOLIC FATTY LIVER DISEASE R. Malik, M. Lai, K. Bhaskar, I. Nasser, M. Curry, D. Schuppan, N. Afdhal. Liver Center, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA, USA E-mail: [email protected] Background and Aims: We characterised a group of patients with nonalcoholic fatty liver disease (NAFLD) to determine the predictive value of serum markers to identify histological NASH. Methods: We assessed demographic, serological, radiological and histological variables on 95 consecutive patients with NAFLD. Diagnostic criteria for NAFLD included subjects who drank less than175g alcohol per week, had a negative hepatitis serology and greater than 10% lipid content on liver biopsy. The serum markers assessed were CK18, hyaluronic acid, TIMP 1, and YKL 40. Results are given as mean + standard deviation of the sample. Results: The NAFLD cohort was initially statified according to the degree of necroinflammation into simple steatosis [NAS 1−3] vs NASH [NAS 4−8]. A high NAS score (NAS 4−8) was associated with type 2 diabetes and high serum ALT levels. Serum CK 18 levels were significantly higher in patients with NASH (394+53u/L) compared to patients with simple steatosis (194+26u/L – p < 0.05). The markers of liver fibrogenesis showed no significant difference between groups. Serum CK 18 performed the best at identifying patients with NASH yielding an AUC of 0.8, with a cut-off value 350u/L giving a PPV of 84% and NPV of 81%. Subsequently, we stratified the same population according to the degree of fibrosis (metavir F0 vs F1−F4). Liver fibrosis was associated with advanced age, high BMI, type 2 diabetes and a high NAS score. Serum CK 18, hyaluronic acid and YKL 40 levels were all significantly higher in patients with fibrosis (372+49u/Lcf 206+31u/L for CK 18 (p < 0.05), 64+11 ng/ml cf 20+2.5 ng/ml for HA (p < 0.05) and 125+13 ng/ml cf 79+10 ng/ml for YKL 40 (p < 0.05). A high NAS score performed best at identifying patients with fibrosis yielding an AUC of 0.9. Conclusion: CK 18 levels can be used as a surrogate biomarker to identify patients at risk of disease progression in NAFLD. 949 IMPACT OF NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) ON CHRONIC HEPATITIS B (CH B) AND C (CH C) A.A. Markova1 , S.S. Dragneva1 , K. Antonov1 , D. Jelev1 , O. Kosseva1 , R. Ivanova2 , A. Gegova2 , L. Mateva1 . 1 Clinic of Gastroenterology, University Hospital “St. Ivan Rilski”, Sofia, Bulgaria, 2 Department of Pathology, Medical University, Sofia, Bulgaria E-mail: [email protected] It is well known that NAFLD, obesity, insulin resistance (IR), diabetes mellitus (DM), and older age correlated with the progression of liver fibrosis and cirrhosis in CH C. The impact of NAFLD overlap in CH B is not well established. Aim: In this study we investigated the prevalence of parameters of the metabolic syndrome (MetS), IR, and NAFLD in CH C and CH B, and their impact on the liver fibrosis. Methods: The parameters of MetS, insulin, HOMA-IR, degree of steatosis/NASH were investigated in total of 700 patients with chronic viral hepatitis – CH B (n = 334) and genotype 1 CH C (n = 366). Glucose and insulin were also assessed on baseline and during OGTT (60 and 120 min.) in 100 cases with CH B and 100 – CH C.
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Results: Liver steatosis was found more frequently in CH C 62% versus 48% in CH B (p < 0.01), predominantly in cases with metabolic syndrome (96% for CH B and 89% CH C, p < 0.001). In 70% of the cases with CH B and severe steatosis (>66%) HBV DNA was negative or <10,000 copies/ml. There was positive correlation between histological staging and glucose and insulin (CH C p < 0.001 and CH B p < 0.05). The advanced liver fibrosis (F3−F4) was also associated with moderate or severe steatosis or NASH in CH C and HBsAg caries (with negative or minimal HBVDNA) as well as with glucose levels, HOMA-IR, and degree of hyperinsulinaemia during OGTT as well as the presence of DM (p < 0.001), but not with other components of metabolic syndrome. We found nonsignificant differences in BMI, serum cholesterol, HDL-C, LDL-C triglycerides and blood sugar, as well as the degree of serum insulin levels and HOMA-IR index between the both groups. In conclusion NAFLD in both viral hepatitis B and C genotype 1 depends on insulin resistance and metabolic syndrom. Liver steatosis is more common in patients with CH C, but more severe in nonactive CH B. Insulin resistance and DM are associated with more advanced liver fibrosis in both hepatitis.
950 TOLERANCE AND EFFICACY OF THE MARS SYSTEM IN PATIENTS WITH SEVERE ALCOHOLIC HEPATITIS NON-RESPONDERS TO STEROIDS: A PILOT STUDY J. Boitard1 , A. Louvet1,2 , B. Bismuth1 , S. Dharancy1,2 , F. Wartel1 , V. Canva-Delcambre1 , P. Deltenre1 , B. Jude3 , F. Fourrier4 , P. Mathurin1,2 . 1 Service des Maladies de L’Appareil Digestif, Hˆ opital Huriez, Lille, France; 2 INSERM U795, Hˆopital Swynghedauw, Lille, France, 3 Laboratoire D’Hemostase, Hˆ opital Cardiologique, Lille, France, 4 Service de Reanimation Polyvalente, Hˆ opital Salengro, Lille, France E-mail: [email protected] 40% of patients treated with steroids for severe alcoholic hepatitis (SAH) do not benefit from this treatment and require new strategy. It has been suggested that the molecular adsorbent recirculating system (MARS) may improve liver function and survival. Aim: analyse the safety and efficacy of MARS in patients with SAH non responders to steroids. Methods: 19 non-responders were selected and treated with MARS. Steroids were interrupted once non-response was diagnosed (defined by absence of decrease in bilirubin after 7 days of treatment or Lille model >0.45). Each non-responder treated with MARS was compared to one control non-responder from our data-base matched on age, gender, creatinine, PT and bilirubin selected without knowledge of survival. Results: 38 patients were included: 19 treated with MARS and 19 paired non-responders. At baseline, there was no significant difference between MARS and control groups for male gender (68.4 vs 68.4%), age (50.8±1.8 vs 51.1±1.4years), encephalopathy (45.6 vs 44.8%), AST (329±185 IU/l vs 149±18 IU/l), bilirubin (213±25 vs 192±22 mg/l), creatinine (10.4±2 vs 12.5±2 mg/l), albumin (26±1.7 vs 26.3±1.5g/l), PT (26.7±1.6 vs 25±2s), Maddrey function (84±5 vs 80±9) and Lille model (0.73±0.08 vs 0.78±0.06). As planned, the median number of MARS sessions was 3 (95% CI: 2−3, range 1−3). Fibrinogen before MARS was 1.5±0.2g/l. In terms of safety, fibrinolysis occurred in 6 out of the first 8 patients treated with MARS. In the following 11 patients, during each session, we systematically administered 10 mg/kg/hr Exacyl® (tranexamic acid). The decrease of fibrinogen after the first session was drastically lower in the patients treated with Exacyl® (−16±3% vs −76±12%, p < 0.001) and coagulation disorders were no longer observed (75 vs 0%, p = 0.0005). On overall patients, each session of MARS induced a significant relative decrease in bilirubin (−18±4%, −6±4%, −15±5%) and creatinine (−20±6%, −13.5±7%, −5±9%) but worsened PT (+19±6%, +11±4%, +16±6%). Patients treated with MARS had similar 1 and 2-month survival than controls: 52.6±11 vs 52.6±11% and 42.1±11 vs 31.5±10.7%. In a sensitivity analysis restricted on patients treated with Exacyl® , there was
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945 HISTOLOGICAL DEFINITIONS OF NON-ALCOHOLIC STEATOHEPATITIS IN A COHORT OF MORBIDLY OBESE PATIENTS SUBMITTED TO BARIATRIC SURGERY: COMPARISON OF TWO CLASSIFICATIONS AND METABOLIC CORRELATES M.V. Machado1 , A. Costa2 , J. Coutinho3 , F. Carepa3 , N. Alves3 , H. Cortez-Pinto1,4 . 1 Departamento de Gastrenterologia e Hepatologia, 2 Departamento de Anatomia Patol´ ogica, 3 Departamento de Cirurgia, Hospital de Santa Maria, Lisboa, Portugal, 4 Unidade de Nutri¸ca˜ o e Metabolismo, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal E-mail: [email protected] Background and Aims: Histological definition of non-alcoholic steatohepatitis (NASH), in morbidly obese patients, is controversial, being the most accepted classifications the one proposed by Matteoni et al. (MC) and the NAFLD Activity Score (NAS). We aimed to compare both classifications, analyzing factors related to NASH. Methods: Morbidly obese patients submitted to bariatric surgery were consecutively and prospectively recruited. Other causes of liver disease and alcohol intake >20 g/day were excluded. Surgical liver biopsies were evaluated using Matteoni et al. (MC) and the NAFLD Activity Score (NAS). Results: 40 patients, 3 men; age: 42±12 years; body mass index (BMI): 47±9 kg/m2 . Steatosis (>5%), was present in 95%; fibrosis in 97.5%, severe in 10%, one patient presenting with unexpected hepatic cirrhosis. With MC, NASH was diagnosed in 4 patients, simple steatosis in 18 patients, and 16 patients were classified in the controversial group 2 (steatosis plus inflammation without criteria of NASH). With NAS, definitive diagnosis of NASH was made in 8 patients, exclusion of NASH in 21 patients, 11 remaining unclassified. Inter-rater agreement between both classifications, when categorized in 3 subgroups, definitive NASH (NAS 5/MC 3 and 4), unclassified (NAS 3−4/MC 2) and exclusion of NASH (NAS < 3/MC 1), was 0.77 (p = 0.123). Group 2 of MC occurred in all subgroups of NAS. NASH diagnosed by either MC or NAS associated to increases in aminotransferases levels, hypertriglyceridaemia, a higher HOMA and a greater number of metabolic syndrome features (p < 0.05). All patients with NASH (MC or NAS) had evidence of insulin resistance (HOMA 3) and criteria for metabolic syndrome (3 features) (p < 0.05). Both classifications associated to steatosis severity, but only MC NASH with fibrosis severity. Conclusion: MC and NAS classifications presented only a moderate agreement in respect to the diagnosis of NASH. Using NAS score, NASH was two fold more frequent than if MC was applied. MC correlated better to the severity of hepatic fibrosis, the main factor associated to more advanced disease, however a more significant percentage of patients are left on a rather undefined group of NAFLD. Applying either classification, NASH associated strongly with metabolic disturbances, in morbidly obese. 946 PREDICTION OF MORTALITY IN PATIENTS WITH ALCOHOLIC HEPATITIS: COMPARISON OF PROGNOSTIC SCORES M.V. Machado, J. Nunes, H. Cortez-Pinto, F. Ramalho, E. Monteiro. Departamento de Gastroenterologia E Hepatologia, Hospital de Santa Maria, Lisbon, Poland E-mail: [email protected] Background: Severity stratification in patients with alcoholic hepatitis (AH), allow us to predict mortality risk and to guide our clinical management. Although there are several prognostic models, information is lacking concerning the comparison of their prognostic value. Aims: 1) To evaluate mortality, its causes, and related risk factors in patients with AH. 2) To compare Child-Pugh-Turcotte (CPT), modified
Maddrey Index (MI), MELD and Glasgow Alcoholic Hepatitis Score (GASH), as mortality predictors. Methods: From 2002 to 2006 all patients admitted with AH, in a Hepatology Department were evaluated and followed up to 6 months. CPT, MI, MELD and GASH were calculated and the respective scores were analyzed using ROC curves, and compared with Clarke-Pearson method. Results: 76 patients were admitted, 60 men, with a mean age of 50±10 years, hepatic cirrhosis (liver biopsy or clinical evidence of portal hypertension) in 82%. The present episode was the first hepatic decompensation in 71%. 47 patients had severe AH, with a MI32, 9 were treated with corticosteroids and 36 with pentoxifilin. One month mortality was 14.5%, and at 6 months mortality was 26.3%, being infection the main cause of death (90%) followed by renal failure (RF) in 5% and gastrointestinal bleeding in 5%. One month mortality associated with RF, coagulation impairment and lactic dehydrogenase levels (multivariate analysis). AUROC to assess mortality were: GASH9 = 0.732, MELD20 = 0.731, CPT12 = 0.692 and MI32 = 0.670; no statistical differences between indices. Percentage of patients correctly classified was: GASH 67.1%, MELD 60.5%, MI 50% and CPT 47.4%. Six months mortality associated to infection, RF and coagulation impairment (multivariate analysis). AUROC: GASH9 = 0.723, MELD20 = 0.695, MI32 = 0.691 and CPT12 = 0.689; no statistical differences between indices. Percentage of patients correctly classified was: GASH 71.0%, MELD 64.5%, MI 59.2% and CPT 56.6%. Conclusion: AH presentation was the first manifestation of hepatic disease in the majority of patients, with a high mortality (26% at 6 months). Infection was the main cause of death. Comparing several risk stratification scores available, all scores performed equally, with a moderate prognostic acuity.
947 FEASIBILITY AND PERFORMANCE OF THE LIVER STIFFNESS (LSM) MEASUREMENT FOR THE DIAGNOSIS OF FIBROSIS IN NAFLD A. Mahmoudi1 , G. Nkontchou1 , M. Lemoine1 , J. Reboul Marty2 , N. Ganne Carrie1 , V. Grando Lemaire1 , J.C. Trinchet1 , M. Beaugrand1 . 1 Liver Unit, 2 Public Health, Hˆ opital Jean Verdier, Assistance PubliqueHˆopitaux de Paris, UPRES EA 3409, UFR SMBH, Universit´e Paris, Bondy, France E-mail: [email protected] LMS has been validated as a non invasive tool for the evaluation of liver diseases But information’s are still limited concerning it’s feasibility and performances in patients with NAFLD and the possible influence of inflammation and or steatosis on the results. This study was aimed at assessing these different points. Patients and Methods: We studied 137 patients (74 male, mean age: 55±12 yrs) referred for liver biopsy and presenting with the metabolic syndrome and liver enzyme abnormalities. Alcohol consumption >20 g/day, HCV or HBV infection or others causes of liver diseases were excluded in all cases. LSM by Fibroscan (Echosens Paris) was performed by experienced operator not aware of any biological or histological results. The measure was considered valid if 8 acquisitions were recorded by the success to rate >50%. All liver biopsies were coded according to the Brunt classification staging taking in account fibrosis (F0−F4), Activity (A0-A4), steatosis (S1-S3). Results: LSM failed in 45 patients (32%). The rate of failure was closely related to obesity. Among the 92 remaining patients, all had NAFLD or NASH with the following fibrosis score: F0 = 4, F1 = 27, F2 = 28, F3 = 27 and F4 = 10. The main values LSM (95% CI) were respectively F0: 5.37 kPa (3.66−7.09), F1: 7.21 kPa (6.10−8.32), F2: 10.45 kPa (8.60−12.27); F3: 13.71 kPa (9.72−17.7); F4: 26.77 kPa (22.65−30.88). In univariate analysis the stage of fibrosis (p < 0.0001) and the degree of activity was correlated to LSM. Steatosis was not. In multivariate analysis, only the stage of fibrosis was correlated to LSM F0−F1/F2, F3, F4: 0.77 and for cirrhosis F0−F1−F2−F3/F4: 0.97.
08. ALCOHOLIC LIVER DISEASE, NAFLD AND DRUG-INDUCED LIVER DISEASE Conclusion: In patients with NAFLD and NASH, LSM when possible (2/3 cases) allow a reliable assessment of liver fibrosis especially in advanced stage. Steatosis and or inflammation don’t seem to have any influence on LSM. 948 IDENTIFICATION OF BIOMARKERS THAT MEASURE DISEASE ACTIVITY IN PATIENTS WITH NONALCOHOLIC FATTY LIVER DISEASE R. Malik, M. Lai, K. Bhaskar, I. Nasser, M. Curry, D. Schuppan, N. Afdhal. Liver Center, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA, USA E-mail: [email protected] Background and Aims: We characterised a group of patients with nonalcoholic fatty liver disease (NAFLD) to determine the predictive value of serum markers to identify histological NASH. Methods: We assessed demographic, serological, radiological and histological variables on 95 consecutive patients with NAFLD. Diagnostic criteria for NAFLD included subjects who drank less than175g alcohol per week, had a negative hepatitis serology and greater than 10% lipid content on liver biopsy. The serum markers assessed were CK18, hyaluronic acid, TIMP 1, and YKL 40. Results are given as mean + standard deviation of the sample. Results: The NAFLD cohort was initially statified according to the degree of necroinflammation into simple steatosis [NAS 1−3] vs NASH [NAS 4−8]. A high NAS score (NAS 4−8) was associated with type 2 diabetes and high serum ALT levels. Serum CK 18 levels were significantly higher in patients with NASH (394+53u/L) compared to patients with simple steatosis (194+26u/L – p < 0.05). The markers of liver fibrogenesis showed no significant difference between groups. Serum CK 18 performed the best at identifying patients with NASH yielding an AUC of 0.8, with a cut-off value 350u/L giving a PPV of 84% and NPV of 81%. Subsequently, we stratified the same population according to the degree of fibrosis (metavir F0 vs F1−F4). Liver fibrosis was associated with advanced age, high BMI, type 2 diabetes and a high NAS score. Serum CK 18, hyaluronic acid and YKL 40 levels were all significantly higher in patients with fibrosis (372+49u/Lcf 206+31u/L for CK 18 (p < 0.05), 64+11 ng/ml cf 20+2.5 ng/ml for HA (p < 0.05) and 125+13 ng/ml cf 79+10 ng/ml for YKL 40 (p < 0.05). A high NAS score performed best at identifying patients with fibrosis yielding an AUC of 0.9. Conclusion: CK 18 levels can be used as a surrogate biomarker to identify patients at risk of disease progression in NAFLD. 949 IMPACT OF NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) ON CHRONIC HEPATITIS B (CH B) AND C (CH C) A.A. Markova1 , S.S. Dragneva1 , K. Antonov1 , D. Jelev1 , O. Kosseva1 , R. Ivanova2 , A. Gegova2 , L. Mateva1 . 1 Clinic of Gastroenterology, University Hospital “St. Ivan Rilski”, Sofia, Bulgaria, 2 Department of Pathology, Medical University, Sofia, Bulgaria E-mail: [email protected] It is well known that NAFLD, obesity, insulin resistance (IR), diabetes mellitus (DM), and older age correlated with the progression of liver fibrosis and cirrhosis in CH C. The impact of NAFLD overlap in CH B is not well established. Aim: In this study we investigated the prevalence of parameters of the metabolic syndrome (MetS), IR, and NAFLD in CH C and CH B, and their impact on the liver fibrosis. Methods: The parameters of MetS, insulin, HOMA-IR, degree of steatosis/NASH were investigated in total of 700 patients with chronic viral hepatitis – CH B (n = 334) and genotype 1 CH C (n = 366). Glucose and insulin were also assessed on baseline and during OGTT (60 and 120 min.) in 100 cases with CH B and 100 – CH C.
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Results: Liver steatosis was found more frequently in CH C 62% versus 48% in CH B (p < 0.01), predominantly in cases with metabolic syndrome (96% for CH B and 89% CH C, p < 0.001). In 70% of the cases with CH B and severe steatosis (>66%) HBV DNA was negative or <10,000 copies/ml. There was positive correlation between histological staging and glucose and insulin (CH C p < 0.001 and CH B p < 0.05). The advanced liver fibrosis (F3−F4) was also associated with moderate or severe steatosis or NASH in CH C and HBsAg caries (with negative or minimal HBVDNA) as well as with glucose levels, HOMA-IR, and degree of hyperinsulinaemia during OGTT as well as the presence of DM (p < 0.001), but not with other components of metabolic syndrome. We found nonsignificant differences in BMI, serum cholesterol, HDL-C, LDL-C triglycerides and blood sugar, as well as the degree of serum insulin levels and HOMA-IR index between the both groups. In conclusion NAFLD in both viral hepatitis B and C genotype 1 depends on insulin resistance and metabolic syndrom. Liver steatosis is more common in patients with CH C, but more severe in nonactive CH B. Insulin resistance and DM are associated with more advanced liver fibrosis in both hepatitis.
950 TOLERANCE AND EFFICACY OF THE MARS SYSTEM IN PATIENTS WITH SEVERE ALCOHOLIC HEPATITIS NON-RESPONDERS TO STEROIDS: A PILOT STUDY J. Boitard1 , A. Louvet1,2 , B. Bismuth1 , S. Dharancy1,2 , F. Wartel1 , V. Canva-Delcambre1 , P. Deltenre1 , B. Jude3 , F. Fourrier4 , P. Mathurin1,2 . 1 Service des Maladies de L’Appareil Digestif, Hˆ opital Huriez, Lille, France; 2 INSERM U795, Hˆopital Swynghedauw, Lille, France, 3 Laboratoire D’Hemostase, Hˆ opital Cardiologique, Lille, France, 4 Service de Reanimation Polyvalente, Hˆ opital Salengro, Lille, France E-mail: [email protected] 40% of patients treated with steroids for severe alcoholic hepatitis (SAH) do not benefit from this treatment and require new strategy. It has been suggested that the molecular adsorbent recirculating system (MARS) may improve liver function and survival. Aim: analyse the safety and efficacy of MARS in patients with SAH non responders to steroids. Methods: 19 non-responders were selected and treated with MARS. Steroids were interrupted once non-response was diagnosed (defined by absence of decrease in bilirubin after 7 days of treatment or Lille model >0.45). Each non-responder treated with MARS was compared to one control non-responder from our data-base matched on age, gender, creatinine, PT and bilirubin selected without knowledge of survival. Results: 38 patients were included: 19 treated with MARS and 19 paired non-responders. At baseline, there was no significant difference between MARS and control groups for male gender (68.4 vs 68.4%), age (50.8±1.8 vs 51.1±1.4years), encephalopathy (45.6 vs 44.8%), AST (329±185 IU/l vs 149±18 IU/l), bilirubin (213±25 vs 192±22 mg/l), creatinine (10.4±2 vs 12.5±2 mg/l), albumin (26±1.7 vs 26.3±1.5g/l), PT (26.7±1.6 vs 25±2s), Maddrey function (84±5 vs 80±9) and Lille model (0.73±0.08 vs 0.78±0.06). As planned, the median number of MARS sessions was 3 (95% CI: 2−3, range 1−3). Fibrinogen before MARS was 1.5±0.2g/l. In terms of safety, fibrinolysis occurred in 6 out of the first 8 patients treated with MARS. In the following 11 patients, during each session, we systematically administered 10 mg/kg/hr Exacyl® (tranexamic acid). The decrease of fibrinogen after the first session was drastically lower in the patients treated with Exacyl® (−16±3% vs −76±12%, p < 0.001) and coagulation disorders were no longer observed (75 vs 0%, p = 0.0005). On overall patients, each session of MARS induced a significant relative decrease in bilirubin (−18±4%, −6±4%, −15±5%) and creatinine (−20±6%, −13.5±7%, −5±9%) but worsened PT (+19±6%, +11±4%, +16±6%). Patients treated with MARS had similar 1 and 2-month survival than controls: 52.6±11 vs 52.6±11% and 42.1±11 vs 31.5±10.7%. In a sensitivity analysis restricted on patients treated with Exacyl® , there was