Transient Elastography Values Research Articles

Enhanced liver fibrosis score is stable after withdrawal in patients with heavy alcohol consumption: A pilot study.

Enhanced liver fibrosis (ELF) score is an accurate, noninvasive test for assessing the severity of liver fibrosis in chronic liver disease, including alcohol-related liver disease. However, whether the ELF score changes during alcohol withdrawal is unknown. This pilot study assessed changes in the ELF score during withdrawal in patients with a history of excessive alcohol intake. In this prospective study, ELF was performed on day 0 (D0, at the beginning of hospitalization), at day 7 (D7, on discharge from hospital), and at follow-up visits on days 30 (D30) and 90 (D90). Transient elastography (TE) was also assessed on days 4 (D4) and D30. The study included 35 patients (71% male) with a mean alcohol intake of 139 g/day. On D30 and D90, 8 and 13 patients had resumed alcohol consumption (mean intake of 90 and 80 g/day, respectively). In patients who remained abstinent, the mean ELF score was 8.93 on D0, 9.14 on D30 (p = 0.32), and 9.27 on D90 (p = 0.14). In patients who resumed alcohol, mean ELF score was 9.7 on D0, 10.05 on D30 (p = 0.09), and 9.71 on D90 (p = 0.12). ELF score was comparable over the first months after withdrawal, although there was a slight increase in the first week (mean ELF score increased from 9.24 on D0 to 9.74 on D7, p < 0.001). Mean TE value was 7.9 kPa on D4 and 8.1 kPa on D30 (p = 0.84) in patients who resumed alcohol consumption, and 8.3 and 7.5 kPa (p = 0.03) on D4 and D30, respectively, in abstinent patients. The ELF score is stable during the first months after withdrawal and thus appears to be a useful tool to assess liver fibrosis or cirrhosis in this setting. Nevertheless, because in the first week there is a transient increase in ELF score, caution in interpretation is warranted.

Quantitative MRCP and metrics of bile duct disease over time in patients with primary sclerosing cholangitis: A prospective study.

Imaging markers of biliary disease in primary sclerosing cholangitis (PSC) have potential for use in clinical and trial disease monitoring. Herein, we evaluate how quantitative magnetic resonance cholangiopancreatography (MRCP) metrics change over time, as per the natural history of disease. Individuals with PSC were prospectively scanned using non-contrast MRCP. Quantitative metrics were calculated using MRCP+ post-processing software to assess duct diameters and dilated and strictured regions. Additionally, a hepatopancreatobiliary radiologist (blinded to clinical details, biochemistry and quantitative biliary metrics) reported each scan, including ductal disease assessment according to the modified Amsterdam Cholangiographic Score (MAS). At baseline, 14 quantitative MRCP+ metrics were found to be significantly different in patients with PSC (N = 55) compared to those with primary biliary cholangitis (N = 55), autoimmune hepatitis (N = 57) and healthy controls (N = 18). In PSC specifically, baseline metrics quantifying the number of strictures and the number and length of bile ducts correlated with the MAS, transient elastography and serum ALP values (p < 0.01 for all correlations). Over a median 371-day follow-up (range: 364-462), 29 patients with PSC underwent repeat MRCP, of whom 15 exhibited quantitative changes in MRCP+ metrics. Compared to baseline, quantitative MRCP+ identified an increasing number of strictures over time (p < 0.05). Comparatively, no significant differences in biochemistry, elastography or the MAS were observed between timepoints. Quantitative MRCP+ metrics remained stable in non-PSC liver disease. Quantitative MRCP+ identifies changes in ductal disease over time in PSC, despite stability in biochemistry, liver stiffness and radiologist-derived cholangiographic assessment (trial registration: ISRCTN39463479).

Metastatic gastric cancer in a 23- year-old female Zambian diagnosed posthumously: A case report

Introduction: Gastric cancer is one of the leading causes of cancer mortality globally and in Zambia, its exact burden is unknown. Here, we present a case of gastric cancer in a young adult that was diagnosed posthumously.&#x0D; Clinical details: A 23-year-old female patient was referred to the largest tertiary care institution in Zambia, the University Teaching Hospital (UTH). She had been followed up at a district hospital. The patient had a three months’ history of ill-health with symptoms of anaemia, abdominal pain and distension. Upon arrival at UTH, she was noted to be very frail, with pallor, tachycardia and gross abdominal distension and a nodular irregular liver, measuring 10cm below the costal margin. A digital rectal examination revealed the presence of melena. She had no jaundice, lymphadenopathy or finger clubbing but had bilateral pedal oedema. A provisional diagnosis of hepatocellular carcinoma complicated by upper gastrointestinal bleeding was made. Subsequent investigations revealed normal alpha fetoprotein, a Transient Elastography value of 75kPa and negative hepatitis B and C serology. Computerised tomography scan showed multiple liver masses with ascites. The patient continued to deteriorate despite supportive management and died on day 10 of admission. A post mortem was done which revealed a primary gastric adenocarcinoma with metastasis to the liver, lungs and pancreas.&#x0D; Conclusion: This is an example of a case of gastric cancer that was not detected while the patient was alive. It illustrates how cases of gastric cancer would be missed by the Zambia National Cancer Registry recording system.

Probiotic supplementation for 24 weeks in patients with non-alcoholic steatohepatitis: the PROBILIVER randomized clinical trial.

Considering the increasing prevalence of non-alcoholic steatohepatitis (NASH) and treatment gaps, this study aimed to evaluate the effect of probiotic supplementation on liver function markers, nutritional status, and clinical parameters. This double-blind, randomized clinical trial (ClinicalTrials.gov ID: NCT0346782) included adult outpatients with biopsy-proven NASH. The intervention consisted of 24 weeks of supplementation with the probiotic mix Lactobacillus acidophilus (1 × 109 CFU) + Lactobacillus rhamnosus (1 × 109 CFU) + Lactobacillus paracasei (1 × 109 CFU) + Bifidobacterium lactis (1 × 109 CFU), or placebo, twice a day. The following parameters were evaluated: demographic and clinical data, transient elastography (FibroScan), liver enzymes, NAFLD fibrosis score, fatty liver index, laboratory assessment, serum concentration of toll-like receptor-4 (sTLR-4) and cytokeratin 18 (CK-18), anthropometric data, dietary intake, and physical activity. Regarding data analysis, the comparison between the groups was based on the delta of the difference of each variable analyzed (value at the end of treatment minus the baseline value) using the t-test for independent samples or the Mann-Whitney U-test. Forty-four patients with NASH completed the trial (51.4 ± 11.6 years). At baseline, 87% of participants had a mild liver fibrosis degree on biopsy, normal values of liver enzymes, transient elastography values consistent with grade 1 fibrosis in both groups, increased waist circumference (WC), a BMI of 30.97 kg/m2, and 76% presented with metabolic syndrome (MetS). After the intervention, no differences were observed between the probiotic and placebo groups in terms of MetS, WC, BMI scores, or liver enzyme levels (p > 0.05 for all). The elastography values remained consistent with grade 1 fibrosis in both groups. Although CK-18 was reduced in both groups, a larger effect size was noted in the probiotic group (D = 1.336). sTLR-4 was also reduced in both groups, with no difference between groups (p = 0.885). Intervention with probiotics in the early stages of NASH demonstrated no significant change in hepatic and clinical parameters. ClinicalTrials.gov, identifier NCT0346782.

The Steatosis-Associated Fibrosis Estimator (SAFE) score for assessing significant liver fibrosis in patients with psoriasis.

There is an urgent need for noninvasive tests to identify patients with psoriasis at risk of significant liver fibrosis. To externally validate the ability of the Steatosis-Associated Fibrosis Estimator (SAFE) score to detect significant liver fibrosis in patients with psoriasis using transient elastography (TE) as a reference. We analysed data from 75 patients with psoriasis, including TE, SAFE score, Fibrosis-4 Index (FIB-4) and Nonalcoholic Fatty Liver Disease Fibrosis Score (NFS). Significant liver fibrosis was defined as TE values ≥ 7.1 kPa. Diagnostic accuracy was assessed using the area under the receiver operating characteristic curve (AUROC). Fifteen patients (20%) exhibited significant liver fibrosis. The AUROCs for the SAFE and FIB-4 scores were 0.82 [95% confidence interval (CI) 0.67-0.97] and 0.62 (95% CI 0.45-0.79), respectively. The SAFE score outperformed the FIB-4 Index (P = 0.01) but was comparable with the NFS (P = 0.05) in predicting significant fibrosis. Using thresholds of < 0, 0 to < 100 and ≥ 100, the SAFE score categorized 36, 24 and 15 patients into low, intermediate and high-risk groups for significant fibrosis, respectively. The negative predictive value for excluding significant fibrosis with a SAFE score of < 0 was 94.4%, and the positive predictive value for diagnosing significant fibrosis with a SAFE score of > 100 was 53.3%. The duration of psoriasis, joint involvement and methotrexate treatment did not affect the diagnostic ability of the SAFE score whereas age of the patient did. The SAFE score demonstrated good accuracy in assessing clinically significant fibrosis among patients with psoriasis. This score should prove valuable for risk stratification and patient management in dermatology practice.

Liver transient elastography values in healthy South African children

BackgroundTransient elastography (TE) is a rapid noninvasive ultrasound-based technology that measures liver stiffness as a surrogate for liver fibrosis and controlled attenuation parameter (CAP) as a measure of liver steatosis. However, normal ranges in children are not well defined in all populations. The aim of this study was to determine transient elastography values in healthy South African children.MethodsFrom April 2019 to December 2021, children were recruited from the HIV negative control group of a cohort study. Only children neither overweight nor obese, without evidence of liver disease, no medical condition or medication associated with hepatic steatosis or fibrosis and normal metabolic profile were included in this cross-sectional analysis. Clinical data, anthropometry and blood samples were collected on the same day as transient elastography with controlled attenuation parameter was performed.Results104 children (median age 12.8 years [IQR 11.4–14.8, range 7.9–17.7 years]; 59 [57%] boys) were included. Liver stiffness was positively correlated with age (Pearson’s r = 0.39, p < 0.001). Median liver stiffness in boys (5.2 kPa [5th to 95th percentiles 3.6 to 6.8 kPa]) was greater than in girls (4.6 kPa [5th to 95th percentiles 3.6 to 6.1 kPa; p = 0.004]), but there was no difference by ethnicity. Median CAP was 179dB/m (5th to 95th percentiles 158 to 233dB/m). There was a positive correlation between CAP and body mass index (BMI) z-score, but no difference by age, sex, ethnicity or pubertal status.ConclusionLiver stiffness values increase with age and are higher in healthy South African boys than girls, whereas CAP values vary with BMI, but not with age or sex.

Bile acid increase during bulevirtide treatment of hepatitis D is not associated with a decline in HDV RNA.

Bulevirtide (BLV) is an entry inhibitor blocking entry of HBsAg into hepatocytes by interfering with the bile acid transporter Na+-taurocholate co-transporting polypeptide. We here investigated if bile acid levels before or during BLV treatment would correlate with HDV RNA declines. We studied 20 patients with compensated HDV infection receiving a daily dose of 2mg bulevirtide subcutaneously qd for at least 24 weeks. ALT levels improved in all patients including 13/20 patients showing normal ALT values at treatment Week 24. An HDV RNA drop of at least 50% was evident in 20/20 patients at Week 24 including 10 patients showing a ≥ 2 log HDV RNA decline. Elevated bile acid levels were detected already before treatment in 10 patients and further increased during BLV administration with different kinetics. Baseline bile acids were associated with higher transient elastography values (p= .0029) and evidence of portal hypertension (p= .0004). Bile acid levels before treatment were associated with HDV RNA declines throughout therapy, but not at Week 24 (rho=-0.577; p= .0078; rho=-0.635, p= .0026; rho=-0.577, p= .0077; rho=-0.519, p= .0191; rho=-0.564, p= .0119 and rho=-0.393, p= .087 at treatment Weeks 2, 8, 12, 16, 20 and 24, respectively). However, bile acid increases during treatment were not associated with HDV RNA or ALT declines at any of the time points. BLV-induced increases in bile salts do not correlate with HDV RNA declines suggesting that the inhibitory effects of BLV on NTCP differ between blocking bile acid transport and hindering HBsAg entry. If baseline bile salt levels could be useful to predict virological response remains to be confirmed.

A41 FONTAN ASSOCIATED LIVER DISEASE: THE ROLE OF TRANSIENT ELASTOGRAPHY IN CHILDREN AND ADOLESCENTS

Abstract Background Non-invasive assessment of Fontan Associated Liver Disease (FALD) is of interest, but studies have yielded inconsistent results about the correlation of severity of disease with laboratory values and imaging. Transient elastography (TE) is a non-invasive imaging modality used commonly for liver stiffness measurement (LSM) and in Fontan patients it is hypothesized to reflect not only liver fibrosis but also venous congestion. Purpose To better define the potential role of TE for non-invasive assessment of the severity of FALD. Method This was a retrospective study conducted on patients’ medical records at CHU Sainte-Justine Hospital. Patients less than 18 years of age with FALD who had at undergone at least one LSM by TE between 1998-2021 were included. The relationship between LSM and liver function tests, hepatic ultrasound findings (including a cirrhosis score), cardiac catheterization results and histological fibrosis scores were analyzed. The impact of interventions during cardiac catherization on LSM were also studied. Result(s) A total of 54 patients (36 boys and 18 girls) with FALD were studied. Median age at Fontan surgery was 4.6 years (IQR 4.0 ─ 5.4 years). Higher LSM values significantly correlated with longer time from Fontan, higher total and direct bilirubin and GGT levels, higher INR, longer APTT, lower Factor V, and lower absolute lymphocyte count. Greater LSM was also significantly associated with the presence of heterogenous parenchymal echogenicity, irregular liver contours and greater ultrasonographic cirrhosis scores. Higher TE values were significantly correlated with higher wedged hepatic venous pressure and Fontan pressure. After catherization interventions that addressed stenoses, there was a statistically significant reduction in mean LSM (24.9±3.63 kPa vs 15.8±4.6 kPa, p=0.005). After closure of significant pulmonary collaterals, mean LSM tended to increase, but this difference did not reach statistical significance (19.1±1.9 kPa vs 24.6±3.5 kPa, p=0.2). At liver biopsy, significant direct correlation was found between LSM and the grade of sinusoidal fibrosis and LSM. TE with values &amp;gt;20 kPa were found to have higher grades of sinusoidal fibrosis, while values &amp;lt;20kPa had higher grades of sinusoidal dilatation. Conclusion(s) This study showed that TE allows to identify patients with higher cholestatic parameters, more severe liver fibrosis at biopsy and sonographic signs suggestive of cirrhosis. Moreover, it confirmed that liver congestion significantly contributes to LSM values. Interestingly, catheter interventions addressing pulmonary stenoses led to the improvement of TE measurements, giving hope for the reduction of hepatic venous congestion in these patients, which might have an effect on their FALD. Finally, the LSM threshold of 20 kPa could be useful clinically as a value above which fibrosis is likely to be significant, while if below could indicate a greater contribution from hepatic congestion. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

A82 PREVALENCE AND NON-INVASIVE SCREENING FOR CYSTIC FIBROSIS RELATED LIVER DISEASE IN A COHORT FOLLOWED AT A CYSTIC FIBROSIS REFERENCE CENTER

Abstract Background The reported prevalence of cystic fibrosis (CF) related liver disease (CFLD) varies widely based on diagnostic criteria but reaches up to 40% in some cohorts. Furthermore, its clinical impact is significant as hepatic involvement is the 3rd leading cause of mortality in CF patients and is associated with a lower life expectancy. Due to the heterogeneous clinical presentation of CFLD, clear diagnostic criteria and non-invasive assessment methods are lacking. Purpose This study aimed to measure the prevalence of CFLD in a cohort of patients followed at a tertiary CF center. Method The files of all patients followed at the CF clinic of the Centre hospitalier de l’Université de Montréal in 2021 were retrospectively reviewed. Imaging reports, histopathology, laboratory values and transient elastography results were assessed. The NIH criteria were used to define CFLD through either presence of one major criteria (abnormal imaging) or two minor criteria (persistently abnormal lab values, hepatosplenomegaly, or transient elastography ≥ 7 kPa). Result(s) 358 patients were included in our study, 56% male with a median age of 36 years. While mean liver tests were within normal limits (ALT 24 U/L, AST 26 U/L, ALP 96 U/L, GGT 29 U/L), 182 patients (51%) had at least one episode of abnormal liver function tests (LFTs), and 85 patients (24%) had persistently abnormal LFTs. CFLD was present in 42 patients (12%), with 39 patients presenting major criteria and 3 patients presenting minor criteria. In addition, 67 patients (19%) had solely hepatic steatosis. Furthermore, clinically significant portal hypertension and esophageal varices were detected in 50% of patients with CFLD who underwent upper endoscopy (n=20). Median transient elastography value was 5.4 kPa (interquartile range 4.25 kPa) in the 51 patients with exam results, and 32% had values ≥ 7 kPa. Fibroscan values correlated well with the presence of major criteria, with an area under the curve (AUROC) of 0.80 (0.68-0.92, p=0.0007), while non-invasive serological markers did not perform as well (Fib4: AUROC 0.70 (0.59-0.81) and APRI: AUROC 0.69 (0.59-0.80)). Conclusion(s) The overall prevalence of CFLD, including hepatic steatosis, was 31% in this cohort. Prompt recognition is important in clinical care in order to prevent hepatic complications from cirrhosis and portal hypertension. The use of Fibroscan seems promising for detecting CFLD. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

Benefits of rilpivirine for liver stiffness in HIV/HCV-coinfected patients

BackgroundRilpivirine (RPV) is an antiretroviral drug characterized by good tolerability and a favorable liver safety profile. Recent research has shown that RPV ameliorates liver fibrosis in animal models of various chronic liver diseases. Our study aimed to analyze the effect of RPV on liver fibrosis by assessing changes in liver stiffness using transient elastography. MethodsRetrospective cohort study of HIV-infected patients who were exposed and not exposed to RPV. The change in liver stiffness during the period between two transient elastography measurements was analyzed and compared for patients exposed and not exposed to RPV. ResultsWe selected 118 RPV-exposed and 118 non-RPV-exposed HIV-infected patients. Median time between transient elastography (TE) measurements was 50 (29–68) months. A repeated-measures general linear model based on the main clinical characteristics revealed a significant decrease in the TE value of −0.8kPa in non-RPV-exposed patients (p=0.254) and −1.6kPa in the RPV-exposed group (p<0.001). The subgroup analysis showed a significant reduction in the TE value only patients cured of hepatitis C (RPV-exposed, −2.8kPa [p<0.001]; non-RPV-exposed, −1.1kPa [p=0.22]). ConclusionRPV-based antiretroviral regimens significantly reduced liver stiffness, as measured by TE, in patients cured of chronic hepatitis C.

Risk of liver fibrosis associated with long-term methotrexate therapy may be overestimated

The risk of significant liver fibrosis from prolonged methotrexate (MTX) exposure has been estimated at around 5%, prompting intensive monitoring strategies. However, the evidence is derived from retrospective studies that under-reported risk factors for liver disease. We evaluated the risk of long-term MTX therapy on liver fibrosis in a longitudinal cohort study using two non-invasive markers. Between 2014-2021, adult patients diagnosed with rheumatoid arthritis (RA) or psoriasis for ≥2 years were recruited prospectively from six UK sites. The MTX group included patients who received MTX for ≥6 months, whereas the unexposed group included those who never received MTX. All patients underwent full liver profiling, with transient elastography (TE) and enhanced liver fibrosis (ELF) marker measurements. A total of 999 patients (mean age 60.8 ± 12 years, 62.3% females) were included. Of 976 with valid TE values, 149 (15.3%) had liver stiffness ≥7.9kPa. Of 892 with a valid ELF, 262 (29.4%) had ELF ≥9.8. Age and BMI were independently associated with elevated liver stiffness and ELF. Neither MTX cumulative dose nor duration was associated with elevated liver stiffness. Diabetes was the most significant risk factor associated with liver stiffness ≥7.9kPa (adjusted odds ratio= 3.19; 95% CI 1.95-5.20; p <0.001). Regular use of non-steroidal anti-inflammatory drugs showed the strongest association with ELF ≥9.8 (odds ratio= 1.76; 95% CI 1.20-2.56; p= 0.003), suggesting the degree of joint inflammation in RA may confound ELF as a non-invasive marker of liver fibrosis. The risk of liver fibrosis attributed to MTX itself might have been previously overestimated; there is a need to consider modifying current monitoring guidelines for MTX. Current guidelines recommend intensive (2-3 monthly) monitoring strategies for patients on long-term methotrexate therapy due to the potential risk of liver fibrosis. Evaluation of the association using two validated non-invasive markers of liver fibrosis, liver stiffness and enhanced liver fibrosis score, in a large cohort of patients with rheumatoid arthritis or psoriasis shows that the reported risk has previously been overestimated. The clinical focus should be to improve patients' metabolic risk factors, diabetes and BMI, that are independently associated with liver stiffness. There is a need to consider modifying current treatment monitoring guidelines for methotrexate.

Normalization of circulating plasma levels of miRNAs in HIV-1/HCV co-infected patients following direct-acting antiviral–induced sustained virologic response

In a previous recent work, we recognized three plasma circulating microRNAs (miRNAs)—miR-100-5p_iso3p:-2, miR-122-5p, and miR-192-5p—that correlate largely with liver fibrosis evolution in human immunodeficiency virus type 1 (HIV-1)/hepatitis C virus (HCV) co-infected patients. Here, we investigated whether levels of these three circulating miRNAs can be associated to liver disease evolution in HIV-1/HCV co-infected patients which have achieved HCV sustained virologic response (SVR) 12 weeks after finishing treatment. Eighty-one chronic HIV-1/HCV co-infected patients were longitudinally recruited at baseline (T0) of DAA therapy and 12 weeks (T12) after finishing therapy. At T0 most of the study patients displayed transient elastography values linked to an advanced stage of liver fibrosis (F0-1 9%, F2 11%, F3 32%, F4 48%). Significant reductions in the levels of circulating miR-100-5p_iso3p:-2, miR-122-5p, and miR-192-5p were detected at T12 in SVR patients, in the overall cohort (P < 0.0001, P < 0.0001, and P = 0.0008, respectively) and in patients with advanced (F3-4) liver fibrosis (p < 0.0001, p < 0.0001, and P = 0.0011, respectively). Of note, no significant reduction in the study miRNA levels was found at T12 in patients who did not achieve SVR (P = 0.8750, P = 0.1250, and P = 0.1260, respectively). HCV-cured patients, in contrast to non-responders, significantly reduced their liver stiffness after two years of achieving SVR (p < 0.0001). DAA-induced SVR is linked with a significant reduction in circulating levels of miR-100-5p_iso3p:-2, miR-122-5p, and miR-192-5p. Our results indicate that miRNA plasma levels may be a useful biomarker of liver damage progression in HIV-1/HCV co-infected individuals that reach DAA-induced SVR.

Accuracy of noninvasive methods for the diagnosis of liver fibrosis in children with chronic viral hepatitis.

Liver biopsy is the reference standard for assessing liver fibrosis. Moreover, it is an invasive procedure. Transient elastography (TE) is an accurate, noninvasive method for evaluating liver stiffness as a surrogate of liver fibrosis. The aspartate aminotransferase to platelet ratio index (APRI) and Hyaluronic acid (HA) are noninvasive alternatives to liver biopsy for detecting hepatic fibrosis. This study aimed to identify the accuracy of APRI, HA, and TE concerning liver biopsy in children with chronic viral hepatitis. This cross-sectional study included 50 children, 5-18years with chronic viral hepatitis B (HBV) or hepatitis C (HCV) who underwent liver biopsy within nine months of laboratory tests, determining APRI & performing TE. Twenty healthy children of age and sex-matching patients were included as a control group for the serum HA levels. The histopathological findings of the studied cases showed seven cases with (F0) fibrosis, 36 cases with mild (F1,2), two children with moderate (F3,4), and five children with severe (F5,6). The median (IQR) of steatosis was 4 (three had HCV). When correlating TE, APRI, and HA values in all cases with their laboratory data, there was a positive correlation between ALT and APRI values (P-value = 0.000), a positive correlation between AST and HA values (P-value = 0.02), and a negative correlation between stiffness and APRI. The sensitivity of HA, APRI, and TE compared to fibrosis detected by histopathology was 60.5, 65.1, and 60.5%, and their specificity was 71.4, 57.1, and 85.7%, respectively. TE was significantly higher in a group with (moderate to severe) fibrosis. APRI, HA, and TE are good indicators of the presence of fibrosis almost with the same accuracy. TE is the only method to differentiate mild cases from those with significant fibrosis.

Benefits of rilpivirine for liver stiffness in HIV/HCV-coinfected patients

BackgroundRilpivirine (RPV) is an antiretroviral drug characterized by good tolerability and a favorable liver safety profile. Recent research has shown that RPV ameliorates liver fibrosis in animal models of various chronic liver diseases. Our study aimed to analyze the effect of RPV on liver fibrosis by assessing changes in liver stiffness using transient elastography. MethodsRetrospective cohort study of HIV-infected patients who were exposed and not exposed to RPV. The change in liver stiffness during the period between two transient elastography measurements was analyzed and compared for patients exposed and not exposed to RPV. ResultsWe selected 118 RPV-exposed and 118 non-RPV-exposed HIV-infected patients. Median time between transient elastography (TE) measurements was 50 (29–68) months. A repeated-measures general linear model based on the main clinical characteristics revealed a significant decrease in the TE value of −0.8kPa in non-RPV-exposed patients (p=0.254) and −1.6kPa in the RPV-exposed group (p<0.001). The subgroup analysis showed a significant reduction in the TE value only patients cured of hepatitis C (RPV-exposed, −2.8kPa [p<0.001]; non-RPV-exposed, −1.1kPa [p=0.22]). ConclusionRPV-based antiretroviral regimens significantly reduced liver stiffness, as measured by TE, in patients cured of chronic hepatitis C.

S1398 Lifestyle Modifications Decrease Hepatic Steatosis in Taiwanese With Metabolic-Associated Fatty Liver Disease

Introduction: Metabolic-associated fatty liver disease (MAFLD) represents a growing global problem and is associated with increasing obesity prevalence. Lifestyle modifications are the currently recommended approaches for MAFLD. Fibroscan device/transient elastography may be used to estimate the degree of liver scarring and steatosis using a controlled attenuation parameter (CAP) value. This study evaluated the short-term effect of lifestyle modifications on transient elastography values in an obese population with MAFLD. Methods: Thirty-two MAFLD patients aged between 18-60 years old who had a body mass index (BMI) of ≧23 kg/m2 with evidence of fatty liver disease by abdominal ultrasound were recruited for this prospective study. All subjects participated in a 3-month program of lifestyle modification. Sequential demographic parameters and biochemical tests were compared before and after program completion. Liver fat and fibrosis changes were measured using transient elastography with CAP and liver stiffness measurements (LSM). Results: The mean age was 38.7 years old. The body weight (88.09 kg vs. 80.35 kg), body mass index (32.24 kg/m2 vs. 29.4 kg/m2), waist (103.19 cm vs. 95.75 cm) and hip circumference (111.67 cm vs. 104.75 cm), and blood pressure (128/78 mmHg vs. 119/71 mmHg) significantly improved after intervention. Aspartate aminotransaminase (24.06 U/L vs. 18.91 U/L), alanine aminotransaminase (33 U/L vs. 23.72 U/L), creatinine (0.75 mg/dL vs. 0.70 mg/dL), cholesterol (176.41 mg/dL vs. 166.22 m/dL), gamma-glutamyl transferase (26.59 IU/L vs. 19.81 IU/L), and low-density lipoprotein cholesterol (115.63 mg/dL vs. 103.19 mg/dL) also improved after the 3-month intervention. The average CAP significantly decreased after intervention (297.5 dB/m vs. 255.0 dB/m), however, no significant difference in LSM was observed (5.24 kPa vs. 4.82 kPa) after intervention. (Figure) Conclusion: This study demonstrated that liver fat, assessed by CAP score, significantly reduced after a 3-month structured lifestyle modification program in patients with MAFLD. In addition, weight reduction, which is the major determining factor for MALFD improvement and/or resolution, was achieved with the structured program, and the CAP value may be used to monitor liver steatosis and respond to intervention. It is believed that this is the first study that evaluates the utility of CAP values for monitoring hepatic steatosis in an obese population with MAFLD through exercise and diet modification. (Table)Figure 1.: Controlled Attenuation Parameter (CAP) and Liver Stiffness (LSM) values before and after intervention. Table 1. - Comparison of Parameters and Biochemical Testing Before and After Intervention Pre-intervention Post-intervention Difference p-value Waist (cm) 103.19±13.12 95.75 ± 11.96 -7.44 ± 3.72 < 0.001 Hip (cm) 111.67 ± 10.72 104.75 ± 10.55 -6.92 ± 3.27 < 0.001 Weight (kg) 88.09 ± 20.75 80.35 ± 19.51 -7.74 ± 3.97 < 0.001 WHR 0.92 ± 0.06 0.91 ± 0.05 -0.01 ± 0.02 0.026 Body Fat (%) 37.07 ± 4.18 34.27 ± 4.44 -2.8 ± 1.44 < 0.001 BMI (kg/m2) 32.24 ± 4.98 29.4 ± 4.72 -2.84 ± 1.35 < 0.001 SBP (mmHg) 127.66 ± 15.57 119.09 ± 12.02 -8.56 ± 10.61 < 0.001 DBP (mmHg) 78.03 ± 13.58 71.09 ± 8.29 -6.94 ± 13.23 0.006 Heart rate (BPM) 84.5 ± 11.45 76.03 ± 10.91 -8.47 ± 12.06 < 0.001 HbA1c (%) 5.44 ± 0.54 5.47 ± 0.36 0.03 ± 0.33 0.67 Fasting Glucose (mg/dL) 89.44 ± 8.06 92.22 ± 7.56 2.78 ± 6.59 0.023 AST (U/L) 24.06 ± 8.85 18.91 ± 6.4 -5.16 ± 8.76 0.002 ALT (U/L) 33 ± 20.76 23.72 ± 14.72 -9.28 ± 19.79 0.012 GGT (IU/L) 26.59 ± 18.23 19.81 ± 14.83 -6.78 ± 10.05 0.001 BUN (mg/dL) 11.09 ± 2.23 11.31 ± 2.29 0.22 ± 2.55 0.631 Creatinine (mg/dL) 0.75 ± 0.17 0.70 ± 0.14 -0.05 ± 0.08 0.002 Chol (mg/dL) 176.41 ± 31.32 166.22 ± 32.13 -10.19 ± 24.14 0.023 TG (mg/dL) 122.59 ± 49.11 113.28 ± 61.32 -9.31 ± 46.8 0.269 HDL (mg/dL) 42.88 ± 8.29 43.94 ± 8.86 1.06 ± 4.99 0.238 LDL (mg/dL) 115.63 ± 28.03 103.19 ± 29.83 -12.44 ± 20.59 0.002 HOMA-IR (mg/dL) 2.65 ± 1.61 2.45 ± 1.85 -0.2 ± 1.94 0.564 WHR, waist-hip ratio; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; BPM, beats per minute. HbA1c, hemoglobin A1c; AST, aspartate aminotransferase; ALT, alanine aminotransferase; GGT, gamma-glutamyl transferase; BUN, blood urea nitrogen; Chol, total cholesterol; TG, triglyceride; HDL, high-density lipoprotein; LDL, low-density lipoprotein; HOMA-IR, Homeostatic Model Assessment for Insulin Resistance.

Modifications decrease hepatic steatosis in Taiwanese with metabolic‐associated fatty liver disease

Metabolic-associated fatty liver disease (MAFLD) is a growing global problem associated with increasing obesity prevalence. Lifestyle modifications are currently recommended, including weight reduction, exercise, and diet control. This study evaluated the short-term effect of lifestyle modifications on transient elastography (TE) values in an obese population with MAFLD. Thirty-two MAFLD patients were recruited for this prospective studyand all subjects participated in a 3-month program of lifestyle modification. Sequential demographic parameters and biochemical tests were compared before and after program completion. Liver fat and fibrosis changes were measured using TE with controlled attenuated parameter (CAP)and liver stiffness measurements (LSM). The mean age was 38.7 years old (10 males). The body weight (88.09 kg vs. 80.35 kg), body mass index (32.24 kg/m2 vs. 29.4 kg/m2 ), waist (103.19 cm vs. 95.75 cm), and hip circumference (111.67 cm vs. 104.75 cm), and blood pressure (128/78 mmHg vs. 119/71 mmHg) significantly improved before and after the intervention, respectively. Aspartate aminotransaminase (24.06 U/L vs. 18.91 U/L), alanine aminotransaminase (33 U/L vs. 23.72 U/L), creatinine (0.75 mg/dl vs. 0.70 mg/dl), cholesterol (176.41 mg/dl vs. 166.22 m/dl), gamma-glutamyl transferase (26.59 IU/L vs. 19.81 IU/L), and low-density lipoprotein cholesterol (115.63 mg/dl vs. 103.19 mg/dl) also improved after the 3-month intervention. The average CAP significantly decreased after intervention (297.5dB/m vs. 255.0 dB/m), however, no significant difference in LSM was observed (5.24 kPa vs. 4.82 kPa). The current study suggests that short-term lifestyle modification can effectively improve hepatic steatosis, and TE may serve as a monitoring tool for therapeutic intervention.

Spleen transient elastography predicts actuarial survival after liver transplantation.

Splenic transient elastography (TE) correlates with increased portal pressure. Little data are available in the post liver transplantation (LTx) setting. Three months after LTx, we performed splenic TE in 125 LTx recipients. Mean splenic TE values were 29.4 (±6.3; range, 21.6-49.2) kPa. Splenic TE correlated with reduced time to development until persistent ascites (30 events, OR =1.082, 95% CI: 1.034-1.133; P=0.001), hepatorenal syndrome (8 events, OR =1.109, 95% CI: 1.015-1.211; P=0.022) and hepatic encephalopathy (16 events, OR =1.136, 95% CI: 1.066-1.211; P=0.000). In Cox univariate analysis, splenic TE served as a predictor of actuarial survival free of liver (OR =1.114, 95% CI: 1.050-1.182; P<0.001) and remained an independent risk factor associated with reduced actuarial survival free of LTx in multivariate analysis (OR =1.103, 95% CI: 1.026-1.186; P=0.008). Splenic TE measurement at 3 months after LTx serves as a robust predictor of survival in LTx recipients.

Non-Alcoholic Fatty Liver Disease in Long-Term Type 2 Diabetes: Role of rs738409 PNPLA3 and rs499765 FGF21 Polymorphisms and Serum Biomarkers.

Fibroblast growth factor 21 (FGF21) signaling and genetic factors are involved in non-alcoholic fatty liver disease (NAFLD) pathogenesis. However, these factors have rarely been studied in type 2 diabetes mellitus (T2D) patients from admixed populations such as in those of Brazil. Therefore, we aimed to evaluate rs738409 patanin-like phospholipase domain-containing protein (PNPLA3) and rs499765 FGF21 polymorphisms in T2D, and their association with NAFLD, liver fibrosis, and serum biomarkers (FGF21 and cytokeratin 18 levels). A total of 158 patients were included, and the frequency of NAFLD was 88.6%, which was independently associated with elevated body mass index. Significant liver fibrosis (≥F2) was detected by transient elastography (TE) in 26.8% of NAFLD patients, and was independently associated with obesity, low density lipoprotein, and gamma-glutamyl transferase (GGT). PNPLA3 GG genotype and GGT were independently associated with cirrhosis. PNPLA3 GG genotype patients had higher GGT and AST levels; PNPLA3 GG carriers had higher TE values than CG patients, and FGF21 CG genotype patients showed lower gamma-GT values than CC patients. No differences were found in serum values of FGF21 and CK18 in relation to the presence of NAFLD or liver fibrosis. The proportion of NAFLD patients with liver fibrosis was relevant in the present admixed T2D population, and was associated with PNPLA3 polymorphisms.

MO481: Novel Predictors of CKD in Metabolic Fatty Liver Disease Patients: Steatosis Vs Fibrosis. A Prospective Study Using Transient Elastography With Controlled Attenuation Parameter

Abstract BACKGROUND AND AIMS Recent data have proven that NAFLD (nonalcoholic fatty liver disease) and NASH (nonalcoholic steatohepatitis) increase the risk of CKD. Changing the concept of NAFLD to MAFLD (metabolic dysfunction associated fatty liver disease) changes the data of inclusion of patients in the new category and also the relationship with CKD. Our study aimed to explore this relation using liver steatosis and liver fibrosis assessments by transient elastography (TE) with controlled attenuation parameter (CAP). METHOD We prospectively evaluated 402 diabetic patients with MAFLD and high CKD risk using TE with CAP (FibroScan®). CKD was defined according to Kidney Disease Improving Global Outcomes (KDIGO) 2012 guidelines. Inclusion criteria: patients &amp;gt;18 years old and the presence of MALFD. Exclusion criteria: pregnancy, ascites, outliers, known chronic liver disease, decompensated liver disease, cardiac pacemaker, end-stage renal disease, heart failure, unreliable or invalid TE and CAP measurements, AST and ALT levels &amp;gt;5 times the upper limit of normal. Transient elastography was performed with the FibroScan® device. To discriminate between fibrosis and steatosis stages, we used the TE and CAP cut-off values from a published multicentric trial compared with biopsy. Logistic regression and stepwise multiple logistic regression were used to evaluate the factors associated with CKD. In addition, ROC analysis was used to assess the performance of CAP and TE in predicting CKD. The study was conducted &amp;gt;1 year period. RESULTS The prevalence of CKD in our group was 60.8%. Patients with CKD had higher mean LSM and CAP values than those without CKD (LSM 8.64 ± 4.30 versus 8.03 ± 6.57; P = .04 and CAP 320.09 ± 57.12 versus 306.29 ± 61.21; P = .04). We found that hepatic steatosis was a better predictor of CKD than fibrosis. Univariate regression showed that CAP values &amp;gt; 353 dB/m were predictive of CKD, and multivariate regression analysis (after adjustment according to sex, BMI, LDLc, HDLc and fasting glucose) showed that CAP values &amp;gt;353 dB/m were more strongly associated with the presence of CKD compared with LSM (fibrosis) values. CONCLUSION In patients with MAFLD, CAP-assessed steatosis appears to be a better predictor of CKD compared with LSM-assessed hepatic fibrosis.

Non-invasive tests for liver fibrosis assessment in patients with chronic liver diseases: a prospective study

There is an urgent need of non-invasive tests (NITs) for monitoring treatment response and disease progression in chronic liver disease. Liver stiffness (LS) evaluated by transient elastography (TE), shear wave elastography (SWE), and magnetic resonance elastography (MRE) and serum markers e.g. APRI and FIB-4 scores were assessed at baseline and the 1-year follow-up. In all, 89 chronic hepatitis C virus (HCV) patients with sustained virological response and 93 non-alcoholic fatty liver disease (NAFLD) patients were included. There was a significantly strong correlation among imaging techniques. Using MRE as the reference standard, the area under the receiver operating characteristics curves for TE, SWE, APRI, and FIB-4 in detecting stage1–4 fibrosis were 0.88–0.95, 0.87–0.96, 0.83–0.89, and 0.79–0.92, respectively. In chronic HCV patients, the values of TE, SWE, MRE, APRI and FIB-4 significantly decreased from baseline to the 1-year follow-up. Liver steatosis did not significantly change over time. In NAFLD, compared to obese patients, non-obese patients had less LS and steatosis at baseline, and these values did not show significant changes at the 1-year follow-up. Our study suggests that the current NITs have a good correlation and accuracy in monitoring the treatment outcomes in patients with chronic liver diseases.