F4 Patients Research Articles

Erken Evre Karaciğer Fibrozisini Öngörmede Shear Wave Elastografinin Rolü

Aim: We examined the relationship between shear wave elastography (SWE) values and histopathological results in our study. Thus, we found the sensitivity of SWE in demonstrating early fibrosis. Materials and Methods: A total of consecutive 70 patients with chronic hepatitis B were prospectively evaluated. The patients included in fibrosis stages (F) 0, 1, 2, 3 and 4 according to Ishak scoring were examined with SWE. SWE measurements of F2, F3 and F4 patients who were found to have early stage fibrosis were compared with those of F0 and F1 patients. Results: The velocity+SD, and kPa+SD values in the group requiring treatment (F2, F3 and F4) were significantly higher than the group not requiring treatment (F0 and F1 )(p < 0.05). The sensitivity rate of the 1.85 cut-off value for velocity+SD was 53.8%, the positive prediction rate was 80.8%, the specificity rate was 83.3%, and the negative prediction rate was 58.1%. For kPa+SD, the cut-off value of 10.8 had a sensitivity rate of 51.3%, a positive prediction rate of 95.2%, a specificity of 96.7%, and a negative predictive rate of 60.4%. A significant correlation was observed between the fibrosis score and the kPa+SD distribution. Conclusion: SWE can differentiate the patients requiring treatment (F2, F3 and F4) from the patients not requiring treatment.

INCIDENCE OF HEPATOCELLULAR CARCINOMA IN PATIENTS WITH CHRONIC HEPATITIS C GENOTYPE III AND ADVANCED HEPATIC FIBROSIS AFTER TREATMENT WITH DIRECT-ACTING ANTIVIRALS

A prospective study was conducted at the Gastroenterology Department of Nishtar Hospital from August 2020 to August 2022 to evaluate the incidence of hepatocellular carcinoma (HCC) in chronic hepatitis C (CHC) patients with hepatic fibrosis or cirrhosis, genotype III, who achieved sustained viral response (SVR) after treatment with direct-acting antivirals (DAAs). The study included a total of 500 genotype III patients diagnosed with F3 and F4, who received a 3-month or 6-month course of DAA regimens. HCC was diagnosed by performing triphasic MSCT, and staging was done. During the follow-up, 50 out of 500 patients were diagnosed with HCC. The patients diagnosed with HCC were primarily elderly males and had higher levels of AST, AFP, and bilirubin, as well as reduced platelets and albumin levels compared to non-HCC patients. In cirrhotic patients, the incidence of HCC per year was 2.920 per 100 people. Advanced age, male gender, increased AFP, and decreased albumin were among the predictors of HCC incidence in F4 patients. The study findings suggest that CHC patients with fibrosis and cirrhosis who achieve SVR after treatment with DAAs have a reduced incidence of HCC.

Serum biomarkers predictive of cirrhosis in alcoholic liver disease as an alternative to ARFI-SW elastography.

Aspartate aminotransferase to platelet ratio index (APRI) and fibrosis 4 (FIB-4) index are noninvasive biomarkers that evaluate liver stiffness in patients with chronic viral hepatitis and are able to detect advanced hepatic fibrosis and cirrhosis. However, their usefulness in alcoholic liver disease (ALD), when compared with Acoustic Radiation Force Impulse- Shear Wave (ARFI-SW) elastography, is debatable. We sifted the files of all enrolled patients with ALD that were admitted to our Emergency hospital between January 2019 and December 2020. All patients had undergone ARFI-SW elastography, and APRI and FIB-4 scores were calculated. The performance of APRI and FIB-4 scores in the prediction of cirrhotic patients according to ARFI-SW elastography was evaluated. In total, 120 patients with ALD were evaluated. All of them were male and Caucasian, with a mean age of 55.54±12.4 years. The mean ARFI-SW elastography score was 1.57±0.7 m/s, the median APRI score was 0.68 (0.1-11.6) and the median FIB-4 score was 1.8 (0.2-19.4). Stages of liver fibrosis according to ARFI-SW elastography were evaluated as F0-1 in 21 (10.5%), F2 in 35 (26%), F3 in 52 (17.5%), and F4 in 92 (46%) patients. Based on ARFI-SW elastography fibrosis stage classification, we estimated the optimal APRI and FIB-4 scores to predict the presence of liver cirrhosis (F4) by using ROC curve analysis and the Youden index. The optimal APRI score for F4 patients was calculated as >1.52 [area under the curve (AUC) 0.875, 95% CI 0.809-0.919; p<0.001], giving sensitivity (Se) 81.2%, specificity (Sp) 81.4%, positive predictive value (PPV) 76%, and negative predictive value (NPV) 86.1%. The optimal FIB-4 score for F4 patients was calculated as >2.77 (AUC 0.916, 95% CI 0.814-0.922; p<0.001), giving Se 83.8%, Sp 77%, 81.4 77%, and NPV 84.3%. APRI and FIB-4 scores can be used as screening tools in ALD for predicting cirrhosis instead of ARFI-SW elastography measurement, which is neither widely available nor an affordable method. Additional prospective studies are required in the future to confirm this finding.

Impact of Direct-Acting Antiviral Therapy on Liver Fibrosis Regression among People with Chronic HCV Infection: Results from a Real-Life Cohort in Patients Who Achieved Sustained Virological Response.

Background and Objectives: The global prevalence of chronic hepatitis C virus (HCV) infection is 0.8%, affecting around 58 million people worldwide. Treatment with DAAs reduces all-cause HCV mortality by 49-68%. This work aims to determine whether there is liver fibrosis regression (LFR) in patients who achieved Sustained Virological Response (SVR) after treatment with DAAs. Materials and Methods: An analytical, observational, single-center, and cohort study was carried out. The final sample consisted of 248 HCV-infected patients. All started treatment with DAAs between January 2015 and December 2017. Five measurements were performed to determine the fibrotic stage in patients (measured in kilopascals (kPa)) using transient elastography (FibroScan®, Echosens, The Netherlands). Results: Taking the baseline fibrotic stage as a reference, the distribution in subgroups was as follows: 77 F4 patients (31.0%); 55 F3 patients (22.2%); 53 F2 patients (21.4%); and 63 F0/F1 patients (25.4%). There were 40 patients (16.1%) with at least one HCV complication and 13 (5.2%) who developed hepatocellular carcinoma. The overall LFR rate was 77.8% (144 of 185 F2/F3/F4 patients, p = 0.01) at the end of the follow-up period. The highest mean FibroScan® values were observed in patients with: "male gender"; "metabolic syndrome"; "subtype 1a"; "NRP DAA"; "at least one HCV complication"; "death from HCV complications"; and "liver transplantation requirement". Conclusions: Treatment with DAAs achieved high rates of LFR and a decrease in mean FibroScan® values in all subgroups.

Serum retinol-binding protein 4 as a predictor of fibrosis regression and response to direct-acting antiviral drugs in chronic hepatitis C virus patients

BackgroundHepatitis C virus is the underlying cause of chronic hepatitis which frequently progresses to cirrhosis and hepatocellular carcinoma. In addition, HCV is thought to cause steatosis, dyslipidemia, insulin resistance, diabetes, obesity, and cardiovascular events. The aim of this study is to evaluate the role of serum RBP-4 in the prediction of fibrosis regression and the response of treatment among chronic HCV patients receiving direct-acting antiviral agents.MethodsThis study included 40 chronic HCV Egyptian patients, divided into two groups: Naive cases, 20 chronic HCV patients before starting first line of treatment; Relapser cases, 20 chronic HCV patients who were non-responders before starting second line treatment; and 10 healthy subjects as control. Laboratory investigations including complete blood count, full hepatic profile, fibroscan assessment, and retinol-binding protein-4 level at baseline and re-assessed 12 weeks after the end of treatment [sustained virological response SVR12]. Student T test, analysis of variance, chi-square, Tukey’s test, and Pearson correlation coefficient tests were used for statistical analysis.ResultsBaseline retinol-binding protein-4 level was significantly higher in the naïve case group than in the relapser and control groups with a P value of P value of < 0.001. All the naïve patients had 100% SVR12, only 90% of the relapser group achieved SVR12. A significant reduction in retinol-binding protein-4 and fibrosis staging and measurements by fibroscan among all studied patients were noted after receiving direct acting antivirals (P value < 0.001). Retinol-binding protein-4 levels before and after treatment were significantly lower among F4 patients in comparison to those of F1–F3 patients (P value 0.002, 0.009, respectively). The best cutoff value of retinol-binding protein-4 in the prediction of liver cirrhosis (F4) was ≤ 46 pg/ml with sensitivity of 100% and specificity of 66.67%.ConclusionSerum retinol-binding protein-4 was found to be higher in chronic HCV infection with a significant reduction after successful eradication. Its level is much lower in cirrhotic patients [F4]. As a result, retinol-binding protein-4 may have a promising role in assessing direct acting antivirals response, as well as a prognostic value in predicting liver cirrhosis.

Hepatocellular carcinoma incidence in chronic hepatitis C patients according to sustained virological response (SVR) with interferon‐based therapies and baseline characteristics

AbstractIntroductionHepatocellular carcinoma (HCC) is the second most common cause of cancer‐related death worldwide with increasing incidence. Effective antiviral treatment for chronic hepatitis C (CHC) became available in the last 7 years but despite the WHO Hepatitis elimination targets, they are not universally available today in all regions for all the patients, indicating still a bleak outlook for CHC‐associated HCC in the next decades.AimTo assess the HCC incidence in relation to interferon (IFN)‐based antiviral treatment response and baseline characteristics of a large cohort of chronic hepatitis C (CHC) patients from a single institution.MethodsWe retrospectively collected data of CHC patients, who were diagnosed between 1989 and 2011 and treated at the AKH‐University Hospital of Vienna before the introduction of direct‐acting antiviral (DAA) only therapy. We analysed the HCC incidence in patients with a sustained virological response (SVR) and without SVR according to the patients' baseline characteristics.ResultsOur study included 2134 patients, who were treated or not treated with IFN‐based antiviral treatment and had long‐term follow‐up available. The overall HCC incidence in this cohort was 6.2% (132 HCC cases over a median follow‐up period of 9 years). According to the baseline fibrosis stage, the overall HCC incidence was: 1.1% in patients with baseline fibrosis stage F0‐2, 8.2% in F3 and 20.6% in F4 patients. The HCC incidence was significantly higher in non‐SVR and no‐treatment group as compared with SVR patients: 12.4% vs 1.9%, P &lt; .0001, 7.3% vs 1.9%, P &lt; .0001. In multivariate analysis, lower platelet count (odds ratio‐OR = ‐0.1, 95% CI: 0.15‐0.63), for the SVR group and presence of cirrhosis (OR = 3.6, 95% CI: 1.59‐8.17), ALBI grade &gt;=2 (OR = 2.3, 95% CI: 1.0‐5.3) for the non‐SVR group were independently associated with HCC occurrence. For the group of patients with no treatment, the only predictor for HCC was high baseline alpha‐fetoprotein values (OR = 10.2, 95% CI: 2.2‐47.9).ConclusionThe achievement of SVR significantly reduces the risk for HCC occurrence during long‐term follow‐up. However, the risk remains high in successfully treated patients with low platelet count and in patients who did not achieve SVR with more advanced liver disease. These risk factors should be considered in decision‐making of HCC surveillance in this settling.

The Potential Role of Fatigue in Identifying Patients With NASH and Advanced Fibrosis Who Experience Disease Progression

Fatigue is common in patients with advanced liver disease. We investigated fatigue and clinical outcomes among patients with advanced nonalcoholic steatohepatitis (NASH). In this study, patients with biopsy confirmed NASH and bridging fibrosis (F3) or compensated cirrhosis (F4) were followed for up to 2 years. The Chronic Liver Disease Questionnaire for Nonalcoholic Steatohepatitis (CLDQ-NASH) fatigue domain at baseline (range, 1-7; lower score indicating worse fatigue) quantified fatigue. The Cox proportional hazards model was used to study time to liver-related clinical events (progression to histologic cirrhosis or hepatic decompensation in F3, hepatic decompensation in F4). Of the 1679 NASH patients with fibrosis, 802 had F3 and 877 had F4 (58 ± 9 years of age, 40% male, 74% type 2 diabetes). During median follow-up of 16 months (interquartile range, 14-18), 15% (n= 123) of NASH F3 patients experienced liver-related events and 3.5% (n= 31) of NASH F4 patients experienced hepatic decompensation. Mean baseline CLDQ-NASH fatigue score in F3 patients was 4.77 ± 1.36; NASH F3 patients who experienced liver-related events had lower baseline scores: 4.47 ± 1.36 vs 4.83 ± 1.35 (P= .0091). The mean fatigue score in F4 was 4.56 ± 1.44; these scores were lower in patients who decompensated in follow-up: 3.74 ± 1.31 vs 4.59 ± 1.43 (P= .0011). The association of lower fatigue scores and risk of liver-related or decompensation events was significant after adjustment for confounders (adjusted hazard ratio per 1 point in fatigue score in F3, 0.85; 95% confidence interval, 0.74-0.97; P= .02; adjusted hazard ratio in F4, 0.62; 95% confidence interval, 0.48-0.81; P= .0004). Worse fatigue at baseline is associated with a higher risk of adverse clinical events in patients with NASH-related advanced fibrosis and cirrhosis.

Effects of direct-acting antiviral agents on lipid and glucose profile in HCV patients with type 2 diabetes: A real-life Italian experience.

Hepatitis C virus (HCV) infection is associated with an increased risk of type 2 diabetes mellitus (T2DM) and cardiovascular diseases. The impact of HCV eradication on the metabolic profile in diabetic patients treated with direct-acting antiviral agents (DAAs) is not well defined. The aim of our study was to evaluate the effects of DAAs on a lipid and glucose profile in a cohort of diabetic patients with different liver fibrotic stages. T2DM patients with active HCV infection were consecutively enrolled in this prospective trial. Glycolipidic status was assessed, before starting DAA treatment (T0) and at 12 months after the beginning of treatment (T1). Liver fibrotic stage was assessed by FibroScan. In all, 131 patients were enrolled and all of them achieved a sustained virologic response. At baseline, no significant differences were found in lipid and glucose profiles in subgroup analysis by liver fibrosis, HCV genotype, and cardiovascular risk factors. At T1, total cholesterol and low-density lipoprotein cholesterol, but not triglycerides, significantly increased irrespective of liver fibrotic stage and baseline anthropometric and clinical profiles, while glycated hemoglobin significantly decreased only in F4 patients. HCV eradication in diabetic patients is associated with a worsening lipid profile that could impact future cardiovascular risk. A careful global monitoring of cardiovascular risk factors in all diabetic patients after HCV eradication is needed.

A mathematical model by route of transmission and fibrosis progression to estimate undiagnosed individuals with HCV in different Italian regions

BackgroundAlthough an increase in hepatitis C virus (HCV) prevalence from Northern to Southern Italy has been reported, the burden of asymptomatic individuals in different Italian regions is currently unknown.MethodsA probabilistic approach, including a Markov chain for liver disease progression, was applied to estimate current HCV viraemic burden. The model defined prevalence by geographic area using an estimated annual historical HCV incidence by age, treatment rate, and migration rate from the Italian National database. Viraemic infection by age group was estimated for each region by main HCV transmission routes of individuals for stage F0–F3 (i.e. patients without liver cirrhosis and thus potentially asymptomatic) and F4 (patients with liver cirrhosis, thus potentially symptomatic).ResultsBy January 2020, it was estimated that there were 409,184 Italian individuals with HCV (prevalence of 0.68%; 95% CI: 0.54–0.82%), of which 300,171 (0.50%; 95% CI: 0.4–0.6%) were stage F0–F3. Considering all individuals with HCV in stage F0–F3, the geographical distributions (expressed as the proportion of HCV infected individuals by macroarea within the overall estimated number of F0–F3 individuals and prevalence values, expressed as the percentage of individuals with HCV versus the overall number of individuals for each macroarea) were as follows: North 42.1% (0.45%; 95% CI: 0.36–0.55%), Central 24.1% (0.61%; 95% CI: 0.48–0.74%), South 23.2% (0.50%; 95% CI: 0.4–0.61%), and the Isles 10.6% (0.49%; 95% CI: 0.39–0.59%). The population of people who inject drugs accounted for 50.4% of all individuals infected (F0–F3). Undiagnosed individuals (F0–F3) were ~ 15 years younger (⁓ 50 years) compared with patients with stage F4 (⁓ 65 years), with similar age distributions across macroareas. In contrast to what has been reported on HCV epidemiology in Italy, an increasing trend in the proportion of potentially undiagnosed individuals with HCV (absolute number within the F0–F3) from South (23.2%) to North (42.1%) emerged, independent of similar regional prevalence values.ConclusionThis targeted approach, which addresses the specific profile of undiagnosed individuals, is helpful in planning effective elimination strategies by region in Italy and could be a useful methodology for other countries in implementing their elimination plans.

Long-Term Impact of Hepatitis C Virus Eradication on Liver Stiffness in Egyptian Patients.

Methods Liver stiffness measurements (LSM) have been serially assessed 1, 3, and 5 years after HCV clearance in 655 patients who have been treated with DAAs. Results The mean age was 51.44 ± 10 years. 73% of patients were males. 48% were cirrhotics. In noncirrhotics, the mean LSM was significantly decreased from 8.29 ± 2.3 kPa to 4.03 ± 1.0 kPa (p < 0.0001) at the end of the follow-up. Likewise, LSM decreased in cirrhotics from 29.66 ± 14.25 kPa to 22.50 ± 11.16 kPa (p < 0.0001). The proportions of F1, F2, F3, and F4 patients at the baseline were 17.7%, 17.9%, 16.6%, and 47.8%, which became 56.5%, 4.1%, 4.9%, and 34.5%, respectively, with a substantial reversal of cirrhosis in 87 patients (27.7%) at the end of follow-up. Conclusions There was an overall significant regression of liver stiffness in all patients after sustained HCV eradication. Liver stiffness reflecting mild fibrosis (F0–F2) usually improves shortly after treatment, while measurements reflecting advanced fibrosis (F3–F4) take a longer time to regress to lower fibrosis stages.

Comparison between shear wave elastography and serological findings for the evaluation of fibrosis in chronic liver disease.

Aim: In this study, we sought to examine the optimal cutoff values for predicting different stages of liver fibrosis, and to determine the level of agreement between shear wave elastography and aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 index (FIB-4) scores in patients with chronic liver disease. Methodology: A descriptive, cross-sectional study was performed at the Radiology Department of Shaukat Khanum Memorial Hospital Lahore from 1 Jun 2019 until 1 June 2020. FIB-4 and APRI scores were determined by the following formula: FIB-4 = (age × AST) ÷ (platelet count × (√ (ALT)) and APRI = (AST÷AST upper limit of normal) ÷ platelet × 100. Data was analyzed with the help of SPSS version 24.0 and Microsoft Excel 2013. Results: Eighty individuals were conveniently selected, of which 62.5% were men and 37.5% were women. The mean age of the subjects was 43.47 SD ± 13.85 years. APRI and FIB-4 scores predicted F4 patients using the cutoff values of 0.47 (Sn. 72%, Sp. 70%) and 1.27 (Sn. 78%, Sp. 73%), respectively. The cutoff values of 0.46 for APRI and 1.27 for FIB-4 predicted F3–F4 patients (Sn. 74% and 77%; Sp. 76% and 76%), respectively. To predict F1–F4 compared to F0, the cutoff value was 0.34 (Sn. 68%, Sp. 75%) for APRI, while the cutoff value for FIB was 0.87 (Sn. 72%, Sp. 75%). The findings suggest that FIB-4 shows better diagnostic accuracy than APRI. Conclusion: This study provides optimal cutoff values for different groups of fibrosis patients for both serum markers. Also, the diagnostic accuracy of FIB-4 for predicting liver fibrosis was found to be superior to APRI in all disease stages.

Validation of a machine learning approach using FIB-4 and APRI scores assessed by the metavir scoring system: A cohort study

Background and Study AimThe study aim was to improve and validate the accuracy of the fibrosis-4 (FIB-4) and aspartate aminotransferase-to-platelet ratio index (APRI) scores for use in a potential machine-learning (ML) method that accurately predicts the extent of liver fibrosis. Patients and MethodsThis retrospective multicenter study included 69,106 patients with chronic hepatitis C planned for antiviral therapy from January 2010–December 2014 with liver biopsy results. FIB-4 and APRI scores were calculated and their performance for predicting significant liver fibrosis (F3–F4) assessed against the Metavir scoring system. ML was used for feature selection and reduction to identify the most relevant attributes (CfsSubseteval/best first) for prediction. ResultsIn this study, 57,492 (83.2%) patients were F0–F2, and 11,615 (16.8%) patients were F3–F4. The revalidation of FIB-4 and APRI showed lower accuracy and higher disagreement with the biopsy results, with AUCs of 0.68 and 0.58, respectively. FIB-4 diagnosed fewer (14%) F3–F4 patients, and the high specificity and negative predictive values of FIB-4 and APRI reflected the low prevalence of F3–F4 in the study population. Out of 15 attributes, age (>35 years), AFP (>6.5 ng/ml), and platelet count (<150,000/mm3) were the most relevant risk attributes, and patients with one or more of these risk factors were likely to be F3–F4, with a classification accuracy of ≤ 92% and receiver operating characteristics area of 0.74. ConclusionFIB-4 and APRI scores were not very accurate and missed diagnosing most of the F3–F4 patients. ML implementation improved medical decisions and minimized the required clinical data to three risk factors.

Definite and indeterminate nonalcoholic steatohepatitis share similar clinical features and prognosis: A longitudinal study of 1893 biopsy-proven nonalcoholic fatty liver disease subjects.

Histological score systems may not fully capture the essential nonalcoholic steatohepatitis (NASH) features, which is one of the leading causes of screening failure in clinical trials. We assessed the NASH distribution and its components across the fibrosis stages and their impact on the prognosis and their relationship with the concept of metabolic-associated fatty liver disease (MAFLD). Spanish multicenter study including 1893 biopsy-proven nonalcoholic fatty liver disease (NAFLD) patients from HEPAmet registry. NASH was diagnosed by NAS score ≥4 (including steatosis, ballooning and lobular inflammation) and fibrosis by Kleiner score. The presence of MAFLD was determined. Progression to cirrhosis, first episode of decompensated cirrhosis and death were collected during the follow-up (4.7±3.8years). Fibrosis was F0 34.3% (649/1893), F1 27% (511/1893), F2 16.5% (312/1893), F3 15% (284/1893) and F4 7.2% (137/1893). NASH diagnosis 51.9% (982/1893), and its individual components (severe steatosis, ballooning and lobular inflammation), increased from F0 (33.6%) to F2 (68.6%), and decreased significantly in F4 patients (51.8%) (P=.0001). More than 70% of non-NASH patients showed some inflammatory activity (ballooning or lobular inflammation), showing a similar MAFLD rate than NASH (96.2% [945/982] vs. 95.2% [535/562]) and significantly higher than nonalcoholic fatty liver (NAFL) subjects (89.1% [311/349]) (P<.0001). Progression to cirrhosis was similar between NASH (9.5% [51/539]) and indeterminate NASH (7.9% [25/316]), and higher than steatosis (5% [14/263]) (logRank 8.417; P=.015). Death and decompensated cirrhosis were similar between these. The prevalence of steatohepatitis decreased in advanced liver disease. However, most of these patients showed some inflammatory activity histologically and had metabolic disturbances. These findings should be considered in clinical trials whose main aim is to prevent cirrhosis progression and complications, liver transplant and death.

The Effect of Direct Acting Antiviral Therapy for Hepatitis C- Virus Infected Egyptian Patients on Changes in the Parameters of Liver Fibrosis Progression

Hepatitis C Virus (HCV) is a major health care concern worldwide. Egypt shows the highest worldwide HCV prevalence. Fibrosis progression is common in HCV and it is the most important prognostic factor in chronic HCV patients. The aim of this study was to investigate changes in some parameters of liver fibrosis progression after successful HCV eradication by direct acting antiviral (DAA) therapy in Egyptian patients. The study included 100 chronic HCV patients. liver stiffness measurement (LSM) was obtained by Transient elastography (TE) or Fibroscan before starting DAA treatment, after the end of 12 weeks of treatment and after achieving sustained virologic response12 (SVR12). Based on baseline LSM, patients were stratified into F2, F3 and F4 groups (METAVIR), F0-F1 patients were excluded. LSM and laboratory data after the end of treatment and after achieving SVR12 was compared with that baseline values in each fibrosis group. Following DAA treatment, all patients achieved SVR12. Mean baseline LSM dropped from 13.5 to 10.1 (kPa) post SVR12; the maximum change occurred in F2 patients 84.3% versus 84.2%, 43.3% in F3, and F4 patients respectively (p < 0.001). At baseline, 30 patients were in the F4 group; only 11 patients (43.3%) regressed to non-cirrhotic range (<12.5 kPa), while 19 patients (56.7%) were still cirrhotic despite achieving SVR12 (p < 0.001). Patients showed significant improvement in platelets count and decreased ALT enzyme levels after achieving SVR12 (p < 0.001). So, successful eradication of HCV results in significant LSM improvement; the best improvement occurs in F2 and F3 patients.

S1145 Current Hepatocellular Carcinoma Screening Strategies for Nonalcoholic Fatty Liver Disease May Not Be Cost-Effective

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD), the leading cause of liver disease in the U.S., is associated with an increased risk of hepatocellular carcinoma (HCC), with ∼30% of NAFLD-associated HCC cases diagnosed in non-cirrhotic patients. HCC surveillance with twice-yearly (q6m) ultrasound (US) has been advocated for patients with stage 3 fibrosis (F3) and cirrhosis (F4). However, the cost-effectiveness (CE) of screening is unclear, particularly for F3 patients. Previous studies have found screening for F4 patients to be cost-effective, but they may have underestimated the costs associated with HCC treatment. We analyzed the CE of HCC screening in NAFLD incorporating recent HCC treatment cost data. METHODS: We created a novel microsimulation model of NAFLD and HCC natural history and surveillance. In a state-transition framework, 100,000 50-year-old patients progressed through the health states representing the development and growth of HCCs (with an annual HCC risk of 2.6% for F4, 0.02–0.9% for F3), screening for these tumors (comparing q6m US until age 70 to no screening), subsequent treatment, and long-term survival. Transition parameters were derived from published data. Each health state was associated with costs, with HCC treatment costing $130,240–$267,139 per a recent national VA study. We calculated incremental cost-effectiveness ratios (ICER) for several comparisons, determining acceptability of screening using a threshold of $100,000/life-year gained. We evaluated screening scenarios including q6m US for F3, F4 patients with follow-up of positive tests with MRI vs. CT, as well as q6m MRI for surveillance of F3 patients. RESULTS: The F4 NAFLD group screened with q6m US and followed up with MRI had an ICER of $178,270 with 3.2 average months of life gained. The F3 NAFLD group screened with q6m US (followed by MRI) had an ICER of $192,693 to $1,106,1878 and 0.07–2.3 months of life gained (for estimated annual HCC incidence of 0.02%–0.9%.) In the F3 NAFLD group screened with q6m MRI, the ICER was $289,375 with 1.3 months of life gained. CONCLUSION: We found that twice-yearly surveillance with US or MRI was associated with modest life-year gains for NAFLD patients with significant fibrosis, but surveillance was not cost-effective using contemporary willingness-to-pay thresholds. More individualized cost estimates based on HCC risk stratification, particularly among F3 patients, may be warranted.Table 1.: Cost-effectiveness analysis of HCC surveillance among F3 and F4 NAFLD patients by fibrosis stage and screening type

1449-P: The Enhanced Liver Fibrosis (ELF) Score Predicts Adverse Clinical and Patient-Reported Outcomes in Patients with Advanced Fibrosis Due to Nonalcoholic Steatohepatitis (NASH)

Background: ELF score is a non-invasive assessment for NASH fibrosis. We assessed associations between ELF, clinical outcomes and PROs in advanced NASH. Methods: NASH patients with advanced fibrosis (Stage ≥F3) were enrolled in 4 clinical trials of simtuzumab and selonsertib - neither showed efficacy. Liver biopsies, ELF scores, and PROs were collected at baseline and week 48. Disease progression (histologic progression to cirrhosis, hepatic decompensation, listed for or liver transplanted, death) was monitored over time (median 16 months; IQR 14-20 months). Results: Patients (n=2155) with biopsy-proven advanced NASH [ 52.5% F4, 40% male, 78% white, 72% type 2 diabetes, mean baseline ELF 10.4±1.1 (F4: 11.4±1.2 vs. F3: 10.3±1.0, p&amp;lt;0.0001)] were included;16.7% F3-NASH had disease progression (96% progressed to cirrhosis or clinical symptoms); 7.3% F4-NASH experienced clinical events (39% ascites, 24% hepatic encephalopathy). Those who progressed had higher baseline ELF: 10.6 ± 1.0 vs. 9.9 ± 0.9 (F3) and 11.5 ± 1.2 vs. 10.6 ± 1.0 (F4) (both p&amp;lt;0.0001). In F3 and F4 patients, baseline ELF was independently associated with disease progression: adjusted hazard ratio (aHR) = 2.48 (2.11-2.93) and 2.83 (2.20-3.63) per 1 ELF point (p&amp;lt;0.0001). After adjustment for baseline ELF, increases in ELF were associated with disease progression: aHR (F3)=1.47 (1.20-1.80) and (F4)=1.68 (1.21-2.33) per +1 additional ELF point (both p&amp;lt;0.002). ELF scores were associated with PRO impairments- ELF cutoff of 10.43 described 18/23 PRO scores (p&amp;lt;0.05) including all domains of CLDQ-NASH. The average magnitude of PRO impairment was -6.1% of a PRO range in NASH with ELF≥10.43 vs. ELF&amp;lt;10.43. Patients with a decrease in ELF of at least 0.83 points had improvement in 11/23 PROs (all domains of CLDQ-NASH, up to +9.8%, p≤0.05). Conclusions: ELF at baseline and its changes over time are good predictors of adverse clinical and PROs in advanced NASH. Disclosure Z. Younossi: Consultant; Self; AbbVie Inc., Bristol-Myers Squibb, Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., Novo Nordisk Inc., Terns and Viking. Q. Anstee: Consultant; Self; 89Bio, Abbott Laboratories, Acuitas Medical, Allergan/Tobira, AstraZeneca, Axcella, Blade, BNN Cardio, Celgene, Cirius, CymaBay, EcoR1, E3Bio, Eli Lilly &amp; Company Ltd., Galmed, Genentech, Genfit S, Intercept Pharma Europe Ltd., Inventiva, IQVIA, Janssen, Madrigal, MedImmune, Metacrine, NewGene, NGMBio, North Sea Therapeutics, Novartis, Novo Nordisk A/S, Pfizer Ltd., Poxel, ProSciento, Raptor Pha. Research Support; Self; Abbvie, Allergan/Tobira, AstraZeneca, GlaxoSmithKline, Glympse Bio, Novartis Pharma AG, Pfizer Ltd., Vertex. Speaker’s Bureau; Self; Abbott Laboratories, Allergan/Tobira, BMS, Clinical Care Options, Falk, Fishawack, Genfit SA, Gilead, Integritas Communications, Kenes, MedScape. M. Trauner: Advisory Panel; Self; Gilead Sciences, Inc. Research Support; Self; Gilead Sciences, Inc. Speaker’s Bureau; Self; Gilead Sciences, Inc. Other Relationship; Self; Gilead Sciences, Inc. V.W.S. Wong: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Gilead Sciences, Inc. Consultant; Self; AbbVie Inc., Allergan plc., Echosens, Intercept Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Pfizer Inc. M. Camargo: Employee; Self; Gilead Sciences, Inc. L. Henry: None. M. Stepanova: None. M. Romero-Gomez: Consultant; Self; Kaleido Biosciences, Merck &amp; Co., Inc., Novo Nordisk Inc., Siemens Corporation, Zydus Pharmaceuticals, Inc. E. Lawitz: None. R. Myers: None. Funding Gilead Sciences Foundation

Elastography and serum markers of fibrosis versus liver biopsy in 1270 Egyptian patients with hepatitis C.

Chronic hepatitis C (CHC) is a leading cause of liver fibrosis. To compare utility of liver transient elastography, AST-to-platelet ratio index (APRI), fibrosis-4 index (FIB4), Forns Index and Goteborg University cirrhosis index (GUCI) in predicting fibrosis stage assessed by liver biopsy in Egyptian CHC patients. One thousand two-hundred and seventy CHC patients undergoing liver biopsy in preparation for therapy and 40 healthy potential living liver donors had transient elastography and calculation of APRI, FIB4, Forns and GUCI scores on the same day or day preceding the biopsy. Mean age was 39.89 (17-60 years) and most were males (70.7%). All donors had F0 fibrosis, most patients had F1-F2 fibrosis (n = 1011, 79.6%) and 259 (20.4%) had F3-F4 fibrosis. Patients with F3-F4 fibrosis had higher median values of APRI (0.99 vs. 0.46), FIB4 (2.15 vs. 0.95) and Forns (7.34 vs. 4.79) indices, GUCI score (1.16 vs. 0.49) and transient elastography (19.2 vs. 6.2 kPa) (all P = 0.001). For F1 discrimination, AUROC of transient elastography was higher than both Forns and GUCI scores (P = 0.001). APRI, FIB4 and GUCI had lower AUROC than transient elastography for predicting fibrosis stage in F2 and F3 patients (P = 0.001). Transient elastography had the best area under receiver operating characteristic curve for predicting fibrosis stage in F4 patients (P = 0.001). The transient elastography cutoff values (kPa) were F1 (>4.8), F2 (>8.3), F3 (>10.1) and F4 (>13.4). Age, APRI, FIB4, Forns, GUCI and transient elastography were independent predictors of F3-F4 fibrosis. Liver elastography is superior to APRI, FIB4, Forns and GUCI scores in predicting fibrosis in CHC patients.

Diagnostic performance of tomoelastography of the liver and spleen for staging hepatic fibrosis

ObjectivesTo determine the diagnostic performance, cut-off values, and optimal drive frequency range for staging hepatic fibrosis using tomoelastography by multifrequency MR elastography of the liver and spleen.MethodsThis prospective study consecutively enrolled a total of 61 subjects between June 2014 and April 2017: 45 patients with chronic liver disease and proven stage of fibrosis and 16 healthy volunteers. Tomoelastography was performed at 1.5 T using six drive frequencies from 35 to 60 Hz. Cut-off values and AUC were calculated. Shear wave speed (in m/s) of the liver and spleen was assessed separately and in combination as a surrogate of stiffness.ResultsFor compound multifrequency processing of the liver, cut-off and AUC values by fibrosis stage were as follows: F1, 1.52 m/s and 0.89; F2, 1.55 m/s and 0.94; F3, 1.67 m/s and 0.98; and F4, 1.72 m/s and 0.98. Diagnostic performance of the best single drive frequencies (45 Hz, 55 Hz, 60 Hz) was similar (mean AUC = 0.95, respectively). Combined analysis of the liver and spleen slightly improved performance at 60 Hz in F4 patients (mean AUC = 0.97 vs. 0.95, p = 0.03). Full-field-of-view elastograms displayed not only the liver and spleen but also small anatomical structures including the pancreas and major vessels.ConclusionTomoelastography provides full-field-of-view elastograms with unprecedented detail resolution and excellent diagnostic accuracy for staging hepatic fibrosis. Our analysis of single-frequency tomoelastography suggests that scan time can be further reduced in future studies, making tomoelastography easier to implement in clinical routine.Key Points• Tomoelastography provides full-field-of-view elastograms of the abdomen with unprecedented detail resolution and excellent diagnostic accuracy for staging hepatic fibrosis.• Diagnostic performance of single-frequency tomoelastography at higher frequencies (45 Hz, 55 Hz, 60 Hz) and compound multifrequency processing are equivalent for staging hepatic fibrosis.• Combined assessment of hepatic and splenic stiffness slightly improves diagnostic performance for staging hepatic fibrosis.

PGI27 THE BURDEN OF NON-ALCOHOLIC STEATOHEPATITIS (NASH) IN THE EU5 COUNTRIES

NASH is a chronic disease that can progress to end-stage liver disease. This progression is particularly rapid in NASH patients with advanced liver fibrosis (stages F3–F4). This study estimated the disease burden and economic impact of NASH in the adult population of France, Germany, Italy, Spain and the UK. A cost-of-illness methodology applying a prevalence approach was used to estimate the number of adults with NASH (stages F0–F4, hepatocellular carcinoma and liver transplant) in 2018, and the attributable economic and wellbeing costs. Wellbeing costs were estimated using World Health Organisation burden of disease methodology. The analysis and resource-use were based on extensive literature review, and consultation with clinical experts, health economists and patient groups. Epidemiological estimates were derived from two modelling studies (upper and lower bound). Costs were sourced from literature and local fee schedules. The estimated prevalence of NASH ranged from 1.89% to 4.03% across F0–F4 patients. Patients with advanced fibrosis due to NASH (F3–F4) were estimated to range from 0.37% to 0.79% or 0.9–2.0 million adults; of these, only 37.8–39.1% were diagnosed. The proportion of patients with advanced fibrosis due to NASH and a diagnosis therefore comprised between 0.15% and 0.33%. Total economic costs in the EU5 ranged between €6,065 and €13,424 million; of these, direct health system costs ranged from €619 to €1,292 million. Total wellbeing costs ranged from €41,536 to €90,379 million, primarily driven by the high mortality rate of NASH patients. This study found that there was a low rate of diagnosis of advanced liver fibrosis due to NASH in the EU5 countries. There was also a notable variation between the countries in the prevalence of all-stage NASH and its associated economic costs.

1254-P: Increased Health-Care Resource Utilization (HRU) and Costs among Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis (NAFLD/NASH) Patients with Advanced Fibrosis (AF) having Diabetes Mellitus (DM)

Objective: NAFLD/NASH patients with AF (bridging fibrosis/F3 and compensated cirrhosis/F4) have an increased risk of liver disease progression leading to higher costs, which may be compounded by presence of DM. The study evaluated the impact of DM on HRU and associated healthcare costs among NAFLD/NASH-AF patients in the U.S. Methods: Adult NAFLD/NASH-AF patients with available lab results were identified from 2008-2016 Optum Research claims database, to calculate their Fibrosis-4 (FIB-4) score. Using the FIB-4 score, patients were categorized as F3 or F4 (first date of FIB-4 cut-off score marked the index date), and then stratified by DM (ICD codes). Mean annual HRU/costs were obtained via per patient per month values (2016 USD). Results: Among 91,122 NAFLD/NASH patients with FIB-4 scores, 2,482 (2.7%) had F3, among which 36% had DM, and 939 (1.0%) had F4, among which 35% had DM. The mean annual costs of F3 and F4 patients with DM were 12-53% higher than non-DM (Figure) before and after the development of AF. Conclusions: NAFLD/NASH-AF patients with DM had higher mean annual HRU-associated costs compared to those without DM - primarily driven by ambulatory and pharmacy costs. Management options are needed to improve clinical care and optimize healthcare costs among NAFLD/NASH-AF patients with DM. Disclosure S. Gordon: Consultant; Self; Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc. N. Kachru: Employee; Self; Gilead Sciences, Inc. Stock/Shareholder; Self; Gilead Sciences, Inc. A. Ozbay: Employee; Self; Gilead Sciences, Inc. Stock/Shareholder; Self; Gilead Sciences, Inc. R. Wong: Advisory Panel; Self; Gilead Sciences, Inc. Consultant; Self; Gilead Sciences, Inc. Research Support; Self; Gilead Sciences, Inc. Speaker's Bureau; Self; Gilead Sciences, Inc.