NASH Patients Research Articles

SAT-431 - A New Method including the Quantification of Circulating Mirnas Allows the Efficient Identification of Nash Patients at Risk who should be Treated

SAT-431 - A New Method including the Quantification of Circulating Mirnas Allows the Efficient Identification of Nash Patients at Risk who should be Treated

Non-alcoholic fatty liver disease and type 2 diabetes mellitus: the liver disease of our age?

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that might affect up to one-third of the adult population in industrialised countries. NAFLD incorporates histologically and clinically different non-alcoholic entities; fatty liver (NAFL, steatosis hepatis) and steatohepatitis (NASH-characterised by hepatocyte ballooning and lobular inflammation ± fibrosis) might progress to cirrhosis and rarely to hepatocellular cancer. NAFL increasingly affects children (paediatric prevalence is 4.2%-9.6%). Type 2 diabetes mellitus (T2DM), insulin resistance (IR), obesity, metabolic syndrome and NAFLD are particularly closely related. Increased hepatic lipid storage is an early abnormality in insulin resistant women with a history of gestational diabetes mellitus. The accumulation of triacylglycerols in hepatocytes is predominantly derived from the plasma nonesterified fatty acid pool supplied largely by the adipose tissue. A few NAFLD susceptibility gene variants are associated with progressive liver disease, IR, T2DM and a higher risk for hepatocellular carcinoma. Although not approved, pharmacological approaches might be considered in NASH patients.

Peripheral and Hepatic Vein Cytokine Levels in Correlation with Non-Alcoholic Fatty Liver Disease (NAFLD)-Related Metabolic, Histological, and Haemodynamic Features.

BackgroundHaemodynamic impairment, inflammatory mediators and glucose metabolism disturbances have been implicated in the pathogenesis of Non-Alcoholic Fatty Liver Disease (NAFLD).AimTo investigate the cytokine profile in NAFLD patients in peripheral (P) and hepatic venous (HV) blood and to compare with histology, haemodynamic and metabolic parameters.Methods40 obese patients with an indication for a transjugular liver biopsy were enrolled. Besides an extended liver and metabolic work-up, interleukin (IL) 1B, IL4, IL6, IL10, IL23, tumour necrosis factor (TNF) α and interferon (INF) γ were measured in plasma obtained from P and HV blood by means of multiplex immunoassay. The T helper (Th)1/Th2, the macrophage M1/M2 and the IL10/IL17a ratios were calculated.ResultsA decrease of the P-IL10/IL17-ratio and an increase of the P-M1/M2-ratio (p<0.05) were observed in NASH versus no-NASH patients. A P-M1/M2-ratio increase was detected also in patients with portal hypertension in comparison with patients without it (p<0.05). Moreover diabetic patients showed an increase of the P-Th1/Th2-ratio in comparison with non-diabetic ones (p<0.05). The P-M1/M2 ratio positively correlated with steatosis grade (r = 0.39, p = 0.02) and insulin (r = 0.47, p = 0.003). The HV-M1/M2 ratio positively correlated with fasting insulin and Hepatic Venous Pressure Gradient (r = 0.47, p = 0.003). IL6 correlated with the visceral fat amount (r = 0.36, p = 0.02). The P- and HV-IL10/IL17 ratios negatively correlated with fasting insulin (respectively r = -0.4, p = 0.005 and r = 0.4, p = 0.01).ConclusionsA proinflammatory cytokine state is associated with more disturbed metabolic, histological, and haemodynamic features in NAFLD obese patients. An increase of the M1/M2 ratio and a decrease of the IL10/IL17 ratio play a key role in this process.

Roles of hepatic progenitor cells activation, ductular reaction proliferation and Notch signaling in morbid obesity.

Hepatic progenitor cells (HPCs) activation, proliferative ductular reaction (DR), replicative arrest and Notch signaling have been demonstrated in a variety of human liver diseases. The relationships are poorly understood in morbid obesity. We investigated factors responsible for the HPCs/DR, replicative arrest and Notch signaling in non-NASH and NASH groups. Cytokeratin 7 (and 19), p21, CD34, Ki67 and different Notch receptors and ligands immunohistochemical stained biopsies from morbid obese patients with non-NASH (n=10) and NASH (n=25) were studied. These results were correlated with clinicopathological variables. NASH patients presented with abnormal liver function tests and had higher HbA1c percentage. Strong association between HPCs and DR was seen (r=0.785, p<0.000). BMI, interface activity and replicative arrest were associated with HPCs expansion and DR in NASH patients. A strong association between CD34 with HPCs and DR was found in non-NASH patients. In NASH group, Notch 3 was important in bile ductular proliferation; whereas Notch 4 was associated with sinusoidal neovessels proliferation and Kupffer cell activation. HPCs and DR played an important role in hepatic regeneration in fatty liver disease of morbid obesity. An altered replication pathway in NASH promotes HPCs activation and DR. Notch-3 and Notch-4 were significantly different between non-NASH and NASH groups.

Prevalencia de la esteatosis hepática no alcohólica en población con hipertransaminasemia y grado de adecuación del diagnóstico registrado en atención primaria

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of elevated transaminases in adults. AimDetermine the prevalence of NASH in patients with sustained hypertransaminasemia, and Know the adequacy of the registered in Primary Care (AP) diagnosis. Material and methods1) Cross-sectional study with a random sample of patients with elevated alanine aminotransferase (ALT) held (ALT> 32 for ≥6 months), ruling out other causes of liver disease, according to clinical, laboratory and ultrasound scan criteria in AP and 2) cross-sectional description of all cases diagnosed with NASH recorded (K76 - ICD10) with diagnostic adequacy analysis according to standard criteria. Results290 patients were analyzed: 76 were diagnosed as NASH (26.1%), 44 women (57.9%). Multivariate analysis adjusted for age and sex showed no association between NASH and male gender (OR: 0.5; CI95%: 0.3-0.9), diabetes mellitus (DM) (OR: 2.42; CI95%: 1.2-4.9) and hypertension blood pressure (HBP) (OR: 3.07; CI 95% 1.6-5.6). Of the 209 diagnosed with NASH record: 51 (24.4%) met the criteria for NASH. The rest had insufficient records. Highlights: 53.1% lacked sustained hypertransaminasemia; 48% of viral serology; 11% supported and 53.1% abdominal ultrasound registration of alcohol. ConclusionsSevere NASH is frequent among patients with sustained hypertransaminasemia. The DM and hypertension significantly increase the risk of NASH. The diagnosis of NASH is recorded without considering all criteria and mainly NASH made by ultrasonography. They should unify diagnostic criteria in the register of NASH.

Understanding the Role of Liver Disease in Decisions About Bariatric Surgery

Introduction: Chronic hepatitis C (HCV) infection and nonalcoholic fatty liver disease (NAFLD) commonly affect patients considering bariatric surgery as a treatment option for obesity. The effect of liver disease in bariatric surgical outcomes is unclear. The aim of this study is to understand current protocols used by bariatric surgeons at academic training centers when evaluating patients with chronic liver disease for bariatric surgery. Methods: Using the Fellowship Council website, 32 bariatric fellowship program coordinators were emailed a 21 question multiple-choice survey with ability to free text additional comments, and asked to forward survey to bariatric surgeons in their program. Results: There were a total of 24 respondents to the survey of the 32 bariatric surgery fellowship programs emailed. The respondents were predominantly male (75%) and academic (95.8% from academic centers), with a median of 13 (1, 23) years experience. Almost all surgeons surveyed (95.65%) would perform bariatric surgery in morbidly obese patients with NASH, while the majority (65.2%) would perform bariatric surgery even in patients with cirrhosis. The majority of respondents (82.61%) would perform surgical weight loss procedures on morbidly obese patients who have chronic HCV without evidence of cirrhosis. Those reluctant to perform surgeries in patients with chronic HCV infection, cited the following reasons: requirement of no viral load prior to surgery, concern for liver failure, and degree of portal hypertension. In both NASH and HCV patients, sleeve gastrectomy and roux-en-Y gastric bypass were the two most commonly preferred surgeries, however, gastric banding was also cited as surgical option in NASH. Surgical complications experienced by the respondents included progressive postoperative liver failure, liver hematoma and abscess secondary to liver laceration, perioperative bleeding and wound infection. Conclusion: The majority of bariatric surgeon respondents report that they would perform bariatric surgery in patients with underlying liver disease, including chronic HCV, even in the setting of cirrhosis. Sleeve gastrectomy and roux-en-Y gastric bypass are the two most commonly performed procedures, but some respondents pointed out the advantages of sleeve gastrectomy in the pre-transplant population. There is still no firm consensus on which type of weight loss surgery is the best in this patient population, and studies comparing gastric bypass to sleeve gastrectomy are needed.

Factors affecting post-embolization fever and liver failure after trans-arterial chemo-embolization in a cohort without background infective hepatitis- a prospective analysis.

BackgroundTransarterial-chemo-embolization (TACE) is used for palliation of unresectable hepatocellular carcinoma (HCC). We studied the tolerability of TACE in a cohort of patients with NASH and alcoholic cirrhosis related HCC.MethodsOf 290 patients with HCC (July 2011 - December 2014), 84 underwent TACE. They were monitored for post-TACE complications: postembolization fever (PEF), nausea and vomiting (NV), abdominal pain, infection, acute hepatic decompensation (AHD) and acute kidney injury (AKI).Results84 patients [90.5 % males, 89.2 % cirrhotics, 89.2 % nodular HCC, median age 63 (34–84) years] underwent 111 TACE sessions. All were Child class A [69.4 % sessions (n = 77)] or B; ascites and portal vein invasion was present in 18 (16.2 %) and 15 (13.6 %), respectively.42 (38.2 %) TACE procedures resulted in complications [PEF 28 (25.2 %), NV 4 (3.6 %), abdominal pain 9 (8.1 %), infection 7 (6.3 %), AHD 13 (11.7 %), AKI 3 (2.7 %)]. There were no immediate post-TACE deaths.On univariate analysis elevated serum bilirubin (p = 0.046) and low serum albumin (p = 0.035) predicted PEF while low serum albumin (p = 0.021) and low platelet counts (p = 0.041) predicted AHD. In the multivariate model, factors with p < 0.200 on univariate analysis and factors derived from the previous literature were considered covariates. Female gender (p = 0.029, OR = 1.412), ascites (p = 0.030, OR = 1.212), elevated serum bilirubin (p = 0.007, OR = 4.357) and large tumour size (p = 0.036, OR = 3.603) were independent risk factors for PEF. Tumour diameter >5 cm (p = 0.049, OR = 2.410) and elevated serum bilirubin (p = 0.036, OR = 1.517) predicted AHD.ConclusionIn NASH and alcoholic cirrhosis related HCC patients pre-procedure serum bilirubin, ascites, tumour size and female gender predicted PEF post-TACE. Tumours larger 5 cm with elevated bilirubin predicted AHD post-TACE.

Lysosomal Acid Lipase Activity: A Tool for the Detection and Management of Fatty Liver Disease?

Lysosomal Acid Lipase Activity: A Tool for the Detection and Management of Fatty Liver Disease?

Association of Serum Cytokeratin-18 Fragment Concentration in Patients with Different Types of Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is one of the most common forms of chronic liver diseases worldwide. The prevalence of NAFLD was 15% in the Asian population. In a study, NASH was observed in 42.4% of NAFLD cases in Bangladesh. It is a serious clinical problem because of its worldwide distribution and potential adverse sequel. Cytokeratin-18 fragment is a marker of hepatocyte apoptosis. Measurement of serum cytokeratin-18 fragment concentration is a noninvasive, quick and simple procedure that can be carried out easily in peripheral hospital. It can be very much helpful for early detection and frequent monitoring of disease progression and response to therapy. This cross sectional study was conducted in the Department of Clinical Pathology in collaboration with Department of Hepatology and Department of Pathology, BSMMU, Dhaka from March 2014 to February 2015. Forty patients who fulfilled the criteria of NAFLD were determined in our study. The concentration of serum CK-18 fragment was measured to evaluate its association in different types of NAFLD by enzyme linked immune sorbent assay (ELISA). In this study, we observed that the serum CK-18 fragment concentration was increased in relation to Nonalcoholic fatty liver disease Activity Score (NAS) (r=+0.7134, P<0.05). To assess diagnostic performance of CK-18 fragment were used receiver-operator characteristic (ROC) curve. The area under ROC was 0.918 for identification of NASH. Using a cutoff value of 150 U/L the sensitivity and specificity of CK-18 fragment were 85.7% and 80.8% respectively. The positive predictive value, negative predictive value and accuracy of CK-18 fragment were 66.67%, 90.91% and 80.00% respectively. Our data revealed that serum CK-18 fragment was strongly associated with Nonalcoholic fatty liver disease Activity Score (NAS). Serum CK-18 fragment may be a useful noninvasive tool for assessing NASH in patients with NAFLD.

Abstract #274: Elevated Ast and Alt Results and an Ast/Alt Ratio Between 0.7 and 1.0 Linked to an Increased Risk of Nash in Patients with Diabetes

Abstract #274: Elevated Ast and Alt Results and an Ast/Alt Ratio Between 0.7 and 1.0 Linked to an Increased Risk of Nash in Patients with Diabetes

Nonalcoholic fatty liver disease is an independent risk factor for atherosclerosis in young adult men

IntroductionThe possible cause of accelerated atherosclerosis in NAFLD may be the relationship with the MetS and its components. Our primary goal was to evaluate the relationship between NAFLD and subclinical atherosclerosis in adult male patients between 20 and 40 years of age. Moreover, we aimed to investigate the changes in this association according to the presence or absence of MetS. MethodSixty-one male patients with biopsy-proven NAFLD and 41 healthy male volunteers were enrolled. In order to exclude any interference of confounding factors, we studied a specifically selected group with no additional cardiovascular risk. PWV, CIMT and FMD levels were measured in all patients and controls. ResultsThe levels of cf-PWV were significantly higher in SS and NASH patients compared to the control group (P < 0.001); no significant difference was found between SS and NASH patients (P > 0.05). We found significantly decreased FMD levels in patients with SS and NASH compared with control subjects (P < 0.001). Subjects with NASH had significantly greater CIMT measurements than the SS and controls (P = 0.026, P < 0.001, respectively). Although, NAFLD patients with MetS had increased cf-PWV and CIMT and reduced FMD compared to healthy subjects (P < 0.05), no significant difference existed between NAFLD with Mets and NAFLD without MetS in terms of cf-PWV, CIMT and FMD (P > 0.05) ConclusionThe present study showed that the presence of NAFLD leads to increased risk of endothelial dysfunction and atherosclerosis in adult male patients, independent of MetS.

Low- and high-density lipoprotein subclasses in subjects with nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is associated with increased cardiometabolic risk. Although dyslipidemia represents a key factor in this disease, its impact on serum levels of distinct lipoprotein subfractions is largely unknown. To assess the full low-density lipoprotein (LDL) and high-density lipoprotein (HDL) profiles in patients with NAFLD. Seven LDL and 10 HDL subfractions were assessed by gel electrophoresis (Lipoprint, Quantimetrix Corporation, USA) in men with biopsy proven NAFLD (simple steatosis [n = 17, age, 34 ± 7 years] and nonalcoholic steatohepatitis [NASH; n = 24, age, 32 ± 6 years]). Exclusion criteria included robust alcohol consumption, infection with hepatitis B or C virus, body mass index ≥ 40 kg/m(2), diabetes mellitus, and hypertension. Compared with simple steatosis, NASH patients had similar body mass index, homeostasis model assessment of insulin resistance index and plasma lipids, with increased levels of both aspartate aminotransferase and alanine transaminase. NASH subjects had lower levels of larger LDL1 (10 ± 4 vs 13 ± 4%, P = .010) and increased smaller LDL3 and LDL4 particles (9 ± 5 vs 5 ± 5%, P = .017 and 3 ± 3 vs 1 ± 2%, P = .012, respectively). No changes were found in the HDL subclass profile. By multiple regression analysis, we found that NASH was associated only with increased levels of LDL3 (P = .0470). The increased levels of small, dense LDL3 and LDL4 in NASH may help to at least partly explain the increased risk for atherosclerosis and cardiovascular diseases in these patients.

908 Comparison of Transient Elastography and Shear Wave Elastography As Markers for Cirrhosis: Experience at a Tertiary Care Center

Background and Aims: Fibroscan (Echosens,France) is a new non invasive tool for measuring liver stiffness and steatosis. It has mainly developed to evaluate chronic liver disease in adult, but usefulness and appropriate inspection method in children has not been established. We report our experience of Fibroscan to evaluate liver stiffness and steatosis in children. Methods: Pediatric patients diagnosed or suspected to have liver disease were evaluated for controlled attenuation parameter (CAP) and elasticity value (E value) using Fibroscan from August 2013 to November 2014. Results: In total, 20 procedures were performed for 19 patients (14 male, average age 11.5 year). CAP was 100 to 348 dB/m, and E value was 3.2 to 21.3 kPa. E values were higher than 10 kPa in three patients, one after receiving liver transplantation, one post Fontan procedure and one Alstrom syndrome. Liver biopsy was performed in four of them (2 Non-alcoholic steatohepatitis:NASH), 1 congenital liver fibrosis, 1 Wilson's disease) at almost the same time and E value was correlated with histological fibrosis stage (F 1-2) in them. CAP and the degree of steatosis in the liver tissue were correlated in NASH patients. After treatment not only the blood data such as transaminase and HOMA-IR but also CAP and E value of the patient of NASH were improved (CAP 323 to 299 dB/m, E value 7.7 to 4.5 kPa). Conclusion: Fibroscan might be useful for evaluating and following up liver stiffness and steatosis of children with liver disease as well as adult.

P1020 : Effects of ursodeoxycholic acid and pioglitazone long therapy on hepatocytes changes in NASH patients

P1020 : Effects of ursodeoxycholic acid and pioglitazone long therapy on hepatocytes changes in NASH patients

906 Evaluating Liver Stiffness and Steatosis in Children Using FibroScan

Background and Aims: Fibroscan (Echosens,France) is a new non invasive tool for measuring liver stiffness and steatosis. It has mainly developed to evaluate chronic liver disease in adult, but usefulness and appropriate inspection method in children has not been established. We report our experience of Fibroscan to evaluate liver stiffness and steatosis in children. Methods: Pediatric patients diagnosed or suspected to have liver disease were evaluated for controlled attenuation parameter (CAP) and elasticity value (E value) using Fibroscan from August 2013 to November 2014. Results: In total, 20 procedures were performed for 19 patients (14 male, average age 11.5 year). CAP was 100 to 348 dB/m, and E value was 3.2 to 21.3 kPa. E values were higher than 10 kPa in three patients, one after receiving liver transplantation, one post Fontan procedure and one Alstrom syndrome. Liver biopsy was performed in four of them (2 Non-alcoholic steatohepatitis:NASH), 1 congenital liver fibrosis, 1 Wilson's disease) at almost the same time and E value was correlated with histological fibrosis stage (F 1-2) in them. CAP and the degree of steatosis in the liver tissue were correlated in NASH patients. After treatment not only the blood data such as transaminase and HOMA-IR but also CAP and E value of the patient of NASH were improved (CAP 323 to 299 dB/m, E value 7.7 to 4.5 kPa). Conclusion: Fibroscan might be useful for evaluating and following up liver stiffness and steatosis of children with liver disease as well as adult.

P1072 : The interaction between visceral adipose and hepatic tissue affects liver injury in NAFL and NASH patients

P1072 : The interaction between visceral adipose and hepatic tissue affects liver injury in NAFL and NASH patients

Su1013 Prevalence and Outcomes of Incidental Hepatocellular Carcinoma Among Liver Transplant Recipients: A Study From United Nation of Organ Sharing (UNOS) Database

respectively), about 5.8% (N=2319) received SLK (6, 9, and 5% in groups I-III respectively). Of LTA, 22%, 14%, and 64% were performed for group I-III respectively. Similar respective figures of all SLK were 23, 20, and 57% respectively (Figure). Frequency of SLK increased from about 4% in 2002 to about 7% in 2011. Trends for group I-III were 4 to 5.8%, 4 to 10%, and 4 to 8% respectively. SLK for NASH+CC (group II, n=477) compared to1842 non-NASH SLK (group II+III) were older, more likely to be females, diabetics, andCaucasians, and have higher body mass index. Five year respective outcomes after SLK comparing group I-III were 78 vs. 76 vs. 66% for liver graft, 79 vs. 72 vs. 65% for kidney graft, and 81 vs. 77 vs. 69% for patient survival, Log Rank P<0.0001 for all. Comparing groups I and II, outcomes were similar for liver graft (P=0.29) and patient survival (p=0.14) but worse for group II on kidney graft (P=0.01). Diabetics compared to non-diabetics had worse five year kidney survival for non-NASH SLK (67 vs. 71%, P=0.044). Similar respective figures among group II were 69 vs. 78%, P=0.017. Patients receiving SLK for NASH or CC (group II) were 29%more likely to lose kidney graft [1.29 (1.002-1.67]) compared to non-NASH transplants after controlling for recipient characteristics and kidney donor risk index. Other strong predictors were black race [1.32 (1.06-1.63] and dialysis [1.26 (1.07-1.49)]. Conclusion: Frequency of SLK transplants is increasing among NASH patients requiring liver transplantation. SLK recipients for NASH have worse renal outcomes independent of associated diabetes. Studies are needed to examine mechanisms of renal pathology in NASH and to develop strategies to improve renal outcomes in NASH patients receiving SLK.

Su1054 Smoking Is Not Associated With Nonalcoholic Fatty Liver Disease: A Population-Based Study From the National Health and Nutrition Examination Survey, 2001-2006

in the NASH group (2.4% vs. 1.0%, OR=2.49, p<0.001), whereas the incidence of acute renal failure (p=0.12) and sepsis/septic shock (p=0.86) was not significantly different. Patients with NASH had significantly lower adjusted mortality (4.3% vs. 9.2%, OR 0.38; p<0.001). Conclusion NASH patients who were admitted with STEMI were younger and more likely to have features of metabolic syndrome. Although transfusion requirements were increased, gastrointestinal bleeding was not more frequent in these patients. Acute liver failure and hepatic encephalopathy infrequently complicated the hospitalization for STEMI. Surprisingly patients with NASH had much lower mortality from STEMI than patients without NASH.

Visceral Adipose Tissue in NAFLD and NASH Patients is Closely Associated with Liver Injury

Visceral Adipose Tissue in NAFLD and NASH Patients is Closely Associated with Liver Injury

Nonalcoholic Steatohepatitis: Involvement of the Telomerase and Proinflammatory Mediators.

Nonalcoholic steatohepatitis or NASH is an excessive accumulation of fat in hepatocytes accompanied by inflammation and hepatic injury. Proinflammatory molecules such as IL-17, CCL20, S100A8, S100A9, and S100A8/A9 have been shown to be implicated in many types of cancer. Telomerase activity has been found to be associated with chronic inflammation and cancer. NASH can progress to fibrosis then cirrhosis and finally to hepatocellular carcinoma (HCC). Our objective is to try to find a relation between inflammation and the progression of NASH into HCC. We found that there was a significant elevation in the telomerase activity, detected by real-time PCR, between NASH and fibrotic NASH in the liver biopsies of patients. The expression of S100A8, S100A9, S100A8/A9, CCL20, and IL-17, detected by ELISA, is significantly increased in NASH patients with fibrosis in comparison with controls. But, in NASH patients, S100A9, S100A8/A9, and IL-17 only are significantly elevated in comparison with controls. The same, on the mRNA level, expression of IL-17, detected by RT-PCR, is significantly elevated in NASH patients in comparison with controls. Therefore, there is a direct link between the expression of IL-17, CCL20, telomerase, S100A8, and S100A9 in the fibrotic condition and the progression towards cancer.