Use of non-invasive diagnostic tools for metabolic dysfunction-associated steatohepatitis: A qualitative exploration of challenges and barriers.

BACKGROUND AND AIMS: Non-invasive tests (NITs) are underutilized for diagnosis and risk stratification in metabolic dysfunction-associated steatotic liver disease (MASLD), despite good accuracy. This study aimed to identify challenges and barriers to the use of NITs in clinical practice. METHODS: We conducted a qualitative exploratory study in Germany, Italy, United Kingdom and United States. Phase 1 participants (primary care physicians, hepatologists, diabetologists, researchers, healthcare administrators, payers and patient advocates; n = 29) were interviewed. Phase 2 participants (experts in MASLD; n = 8) took part in a group discussion to validate and expand on Phase 1 findings. Finally, we triangulated perspectives in a hybrid deductive/inductive thematic analysis. RESULTS: Four themes hindering the use of NITs emerged: (1) limited knowledge and awareness; (2) unclear referral pathways for patients affected by liver conditions; (3) uncertainty over the value of NITs in monitoring and managing liver diseases; and (4) challenges justifying system-level reimbursement. Through these themes, participants perceived a stigma associated with liver diseases, and primary care physicians generally lacked awareness, adequate knowledge and skills to use recommended NITs. We identified uncertainties over the results of NITs, specifically to guide lifestyle intervention or to identify patients that should be referred to a specialist. Participants indicated an ongoing need for research and development to improve the prognostic value of NITs and communicating their cost-effectiveness to payers. CONCLUSIONS: This qualitative study suggests that use of NITs for MASLD is limited due to several individual and system-level barriers. Multi-level interventions are likely required to address these barriers.

FIB-4 index is associated with mortality in critically ill patients with alcohol use disorder: Analysis from the MIMIC-IV database.

BACKGROUND: The relationship between fibrosis-4 (FIB-4) index and all-cause mortality in critically ill patients with alcohol use disorder (AUD) is unclear. The present study aimed to investigate the predictive ability of FIB-4 for all-cause mortality in critically ill AUD patients and the association between them. METHODS: A total of 2528 AUD patients were included using the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. FIB-4 was calculated for each patient using the existing formula. The patients were equally divided into four groups based on the quartiles of FIB-4. Multivariate logistic regression and Cox proportional hazard model were used to evaluate the association of FIB-4 with in-hospital mortality, 28-day mortality and 1-year mortality. Kaplan-Meier curves were used to analyse the incidence of 28-day mortality among four groups. RESULTS: FIB-4 was positively associated with 28-day mortality of AUD patients with hazard ratio (HR) of 1.354 [95% confidence interval (CI) 1.192-1.538]. There were similar trends in the in-hospital mortality [odds ratio (OR): 1.440, 95% CI (1.239-1.674)] and 1-year mortality [HR: 1.325, 95% CI (1.178-1.490)]. CONCLUSION: Increased FIB-4 is associated with greater in-hospital mortality, 28-day mortality and 1-year mortality in critically ill AUD patients.

A simple CD4+ T cells to FIB-4 ratio for evaluating prognosis of BCLC-B hepatocellular carcinoma: a retrospective cohort study.

INTRODUCTION: Immunotherapy has become a new therapy for advanced hepatocellular carcinoma (HCC); however, its treatment results are considerably different. CD4+ T cells (CD4+) are the key to immunotherapy, but patients with HCC that have low CD4+ are rarely observed for clinical evidence. Hepatitis B virus-related HCC is often accompanied by cirrhosis and portal hypertension; therefore, CD4+ tend to be relatively low in number. TACE is the standard treatment for Barcelona Clinic Liver Cancer (BCLC)-B HCC, which may further reduce the number of CD4 + . METHODS: This retrospective cohort study further reduced CD4+ by including patients with human immunodeficiency virus (HIV) to observe the relationship between CD4+ and Chronic hepatitis B virus (CHB) induced HCC. A total of 170 BCLC-B HCC patients (42 HIV+) were included. Univariate and multivariate analyses, and artificial neural networks (ANNs) were used to evaluate the independent risk factors for the two-year survival. RESULTS: The statistical analysis of the two-year survival rate showed that the main factors influencing survival were liver function and immune indices, including CD4+, platelet, alanine aminotransferase, aspartate aminotransferase, aspartate aminotransferase-to-platelet ratio index, and fibrosis-4 (FIB-4) (P < 0.05). Compared with that in other indices, in logistic and ANN multivariate analysis, CD4 + -to-FIB-4 ratio (CD4+/FIB-4) had the highest importance with 0.716 C-statistic and 145.93 cut-off value. In terms of overall survival rate, HIV infection was not a risk factor (P = 0.589); however, CD4+/FIB-4 ≤ 145.93 significantly affected patient prognosis (P = 0.002). CONCLUSION: HIV infection does not affect the prognosis of BCLC-B HCC, but CD4+ have a significant predictive value. CD4+ played a vital role in HCC and this deserves the attention from physicians. Further, the CD4+/FIB-4 is a clinically valuable effective prognostic indicator for these patients.

Validation of magnetic resonance elastography plus fibrosis-4 for significant fibrosis in nonalcoholic fatty liver disease.

BACKGROUND AND AIM: MEFIB (the combination of magnetic resonance elastography [MRE] ≥ 3.3 kPa and fibrosis-4 (FIB-4) ≥ 1.6) is useful for detecting patients with significant fibrosis (fibrosis stage ≥ 2) having nonalcoholic fatty liver disease (NAFLD). However, age-dependent thresholds of FIB-4 have been proposed, and it remains unclear whether MEFIB could be applied with the same FIB-4 threshold in a different cohort. Therefore, in this study, we examined the best threshold of FIB-4 and validated the utility of MEFIB. METHODS: This study included 105 biopsy-proven NAFLD patients with contemporaneous MRE assessment. The primary outcome was a diagnostic accuracy for significant fibrosis. RESULTS: The median (interquartile range) age was 65 (58-72) years, and significant fibrosis was 76.2% (80/105). FIB-4 of 2.1 was defined as the best threshold for significant fibrosis in the cohort. The area under the receiver operating characteristics curves (AUROCs) of the combination of MRE and FIB-4 (MRE ≥ 3.3 kPa + FIB-4 ≥ 1.6: 0.80, MRE ≥ 3.3 kPa + FIB-4 ≥ 2.1: 0.84) were higher than those of each index alone (MRE ≥ 3.3 kPa: 0.76, FIB-4 ≥ 1.6: 0.72, and FIB-4 ≥ 2.1: 0.77), but AUROCs of MRE ≥ 3.3 kPa + FIB-4 ≥ 1.6 and MRE ≥ 3.3 kPa + FIB-4 ≥ 2.1 were equivalent (P = 0.3). CONCLUSIONS: MEFIB is useful for detecting patients with significant fibrosis and could be utilized in a different cohort without changing the threshold of FIB-4, and it may then be used as a two-step screening strategy.

Direct antiviral agent treatment leads to rapid and significant fibrosis regression after HCV eradication.

Limited data are currently available regarding fibrosis progression after hepatitis C virus (HCV) eradication. The goal of the present study was to evaluate the effects of HCV eradication on liver stiffness measurements (LSMs), aspartate aminotransferase/platelet ratio index (APRI) scores, fibrosis-4(FIB-4) scores, chitinase-3-like protein 1 (CHI3L1) levels and Golgi protein 73 (GP73) levels in patients with chronic hepatitis C (CHC). One hundred and two patients who received direct antiviral agents (DAAs) therapy at Peking University First Hospital participated in the present study. Clinical information and serum samples were collected at baseline, at the end of treatment (EOT), and at the weeks 12, 24 and 48 after treatment (W12, W24 and W48, respectively). Of the 102 patients, 51 had mild-to-moderate fibrosis (F1/F2), and 51 had advanced fibrosis (F3/F4). The LSMs improved for all patients at the EOT, with observed changes of 2.85 kPa, and the decrease continued to W12. However, a more pronounced improvement was noted for the advanced fibrosis (F3/F4) patients, with a change of 3.6 kPa from baseline to the EOT. Significant decreases between the baseline and EOT measurements were observed in the APRI and FIB-4 scores [0.64 (0.39-1.21) vs. 0.35 (0.26-0.52), p<0.001; 2.53 (1.30-3.91) vs. 1.87 (0.89-2.5), p<0.001], after which the values decreased until W12, with no significant difference observed. Serum CHI3L1 and GP73 levels were profoundly decreased at the EOT compared with those at baseline [134.07 (154.49) vs. 103.75 (98.04), p=0.025; 98.24 (64.76) vs. 88.91 (50.89), p=0.002]. DAA treatments could significantly improve liver fibrosis of CHC patients as evidenced by decreased liver stiffness, APRI scores and FIB-4 scores. Improvements in liver fibrosis markers (especially serum CHI3L1 and GP73) were prominent in patients with advanced fibrosis, indicating that serum CHI3L1 and GP73 could be noninvasive markers for monitoring fibrosis in CHC patients. Significance Statement The prospective cohort evaluated the effect of direct antiviral agents (DAAs) on fibrosis regression after hepatitis C virus (HCV) eradication of Chinese people in the real-world study. This study highlighted that rapid and significant fibrosis regression rather than reduction in inflammation was achieved with DAA treatment, and this regression could be detected as early as the end of treatment. We found the serum CHI3L1 and GP73 levels can be used to monitor changes in fibrosis in CHC patients.

Association of FIB-4 index and clinical outcomes in critically ill patients with acute kidney injury: a cohort study.

BACKGROUND: The relationship between fibrosis-4 (FIB-4) index and clinical outcomes in patients with acute kidney injury (AKI) is unclear. We aimed to investigate the association between FIB-4 index and all-cause mortality in critically ill patients with AKI. METHODS: We used data from the Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC-III) database (v1.4). The FIB-4 score was calculated using the existing formulas. logistic regression model, and Cox proportional hazards model were used to assessed the relationship between the FIB-4 index and in-hospital,28-day and 90-day mortality, respectively. RESULTS: A total of 3592 patients with AKI included in the data analysis. 395 (10.99%) patients died during hospitalization and 458 (12.74%) patients died in 28-day. During the 90-day follow-up, 893 (22.54%) patients were dead. An elevated FIB-4 value was significantly associated with increased in-hospital mortality when used as a continuous variable (odds ratio [OR] 1.183, 95% confidence interval [CI] 1.072-1.305, P = 0.002) and as a quartile variable (OR of Q2 to Q4 1.216-1.744, with Q1 as reference). FIB-4 was positively associated with 28-day mortality of AKI patients with hazard ratio (HR) of 1.097 (95% CI 1.008, 1.194) and 1.098 (95% 1.032, 1.167) for 90-day mortality, respectively. CONCLUSION: This study demonstrated the FIB-4 index is associated with clinical outcomes in critically ill patients with acute kidney injury.

Noninvasive Measurements Predict Liver Fibrosis Well in Hepatitis C Virus Patients After Direct-Acting Antiviral Therapy.

BACKGROUND: Short-time usage of direct-acting antiviral agents (DAA) limited knowledge regarding histological outcomes and predictive values of noninvasive measurements in patients with hepatitis C virus (HCV) after sustained virologic response (SVR) with DAA. AIMS: This study aimed to indicate histological changes and assess predictive value of noninvasive measurements for fibrosis in these patients. METHODS: HCV patients who achieved SVR by DAA were identified. Pre- and post-SVR clinical and histological data were collected. RESULTS: Of patients, 83% (33/40), 38% (15/40) and 83% (33/40) achieved inflammation improvement, fibrosis regression and histological improvement, respectively. Liver stiffness measurements (LSM), APRI, and FIB-4 could predict post-SVR fibrosis well without significant differences. Areas under receiver operating characteristic curves of LSM, APRI, and FIB-4 were 0.78, 0.81, and 0.87 for post-SVR advanced fibrosis (≥ F4) and 0.86, 0.86, and 0.85 for post-SVR cirrhosis (≥ F5), respectively. Pre-SVR LSM, APRI, and FIB-4 values were significantly lower in patients with fibrosis regression (P = 0.003-0.012), while FIB-4 was significantly lower in patients with histological improvement (P = 0.012-0.033). Patients with higher pre-SVR Ishak scores tended to have bigger decline in APRI (P = 0.025) and FIB-4 (P = 0.024) after SVR. CONCLUSIONS: DAA could improve liver inflammation and fibrosis of HCV patients in a short time after SVR. LSM, APRI, and FIB-4 predict fibrosis well even after SVR by DAA. Most of the cutoff values for advanced fibrosis (≥ F4) and cirrhosis (≥ F5) of these noninvasive measurements decreased significantly after SVR, maybe because of the inflammation improvement.

Diagnostic performance of three non-invasive fibrosis scores (Hepamet, FIB-4, NAFLD fibrosis score) in NAFLD patients from a mixed Latin American population.

INTRODUCTION AND AIMS: Several non-invasive scoring systems have been developed and validated worldwide to predict the risk of liver fibrosis in nonalcoholic fatty liver disease (NAFLD). However, information about the performance of these systems in Latin American populations is scarce. Our aim was to evaluate the performance of the Hepamet Fibrosis Score, Fibrosis-4 (FIB-4) and the NAFLD Fibrosis Score (NFS) in a mixed Latin American group of NAFLD patients. METHODS: Clinical, laboratory and liver biopsy data collected from 379 biopsy-proven NAFLD patients from Latin American tertiary health centers were reviewed. Histological fibrosis stages were classified using the Kleiner score. Accuracy was determined, and new fibrosis score thresholds were calculated to better compare the performances of non-invasive tests and to explore their usefulness in excluding fibrosis. RESULTS: The distribution of fibrosis stages among the sample population was as follows: F0 (45%), F1 (27%), F2 (8%), F3 (16%) and F4 (4%). Using modified thresholds, the areas under the ROC curves (AUROC) for Hepamet and FIB-4 (0.73 and 0.74, respectively) to detect significant fibrosis were higher than that of NFS (0.58). However, the AUROCs of the three scores were not significantly different in advanced fibrosis and cirrhosis. To exclude fibrosis, we calculated lower cutoffs than standard thresholds for Hepamet, FIB-4 and NFS with similar performances. CONCLUSION: Thresholds of non-invasive fibrosis scores (Hepamet, FIB-4 and NFS) can be modified to maximize diagnostic accuracy in Latin American patients with NAFLD.

ALBI score combined with FIB-4 index to predict post-hepatectomy liver failure in patients with hepatocellular carcinoma.

Post-hepatectomy liver failure (PHLF) is a potentially life-threatening complication following liver resection. Hepatocellular carcinoma (HCC) often occurs in patients with chronic liver disease, which increases the risk of PHLF. This study aimed to investigate the ability of the combination of liver function and fibrosis markers (ALBI score and FIB-4 index) to predict PHLF in patients with HCC. Patients who underwent hepatectomy for HCC between August 2012 and September 2022 were considered for inclusion. Multivariable logistic regression analysis was used to identify factors associated with PHLF, and ALBI score and FIB-4 index were combined based on their regression coefficients. The performance of the combined ALBI-FIB4 score in predicting PHLF and postoperative mortality was compared with Child-Pugh score, MELD score, ALBI score, and FIB-4 index. A total of 215 patients were enrolled in this study. PHLF occurred in 35 patients (16.3%). The incidence of severe PHLF (grade B and grade C PHLF) was 9.3%. Postoperative 90-d mortality was 2.8%. ALBI score, FIB-4 index, prothrombin time, and extent of liver resection were identified as independent factors for predicting PHLF. The AUC of the ALBI-FIB4 score in predicting PHLF was 0.783(95%CI: 0.694-0.872), higher than other models. The ALBI-FIB4 score could divide patients into two risk groups based on a cut-off value of - 1.82. High-risk patients had a high incidence of PHLF of 39.1%, while PHLF just occurred in 6.6% of low-risk patients. Similarly, the AUCs of the ALBI-FIB4 score in predicting severe PHLF and postoperative 90-d mortality were also higher than other models. Preoperative ALBI-FIB4 score showed good performance in predicting PHLF and postoperative mortality in patients undergoing hepatectomy for HCC, superior to the currently commonly used liver function and fibrosis scoring systems.

FIB-4 and APRI for cirrhosis detection in a privately insured national cohort.

Background and Aims: Non-invasive laboratory-based fibrosis indices have been proposed as a tool for population-based screening for advanced fibrosis. We aimed to examine the performance of fibrosis indices at the time of and prior to cirrhosis diagnosis. Methods: We included adult patients with cirrhosis diagnosis codes in a privately insured database (Optum) from 2010-2018 with 1:4 birth year-matched controls without cirrhosis diagnosis codes. We analyzed aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis-4 index (FIB-4) up to 30 months prior to the entry of cirrhosis diagnosis codes. Cut-offs of <1 and ≥2 were used for APRI and <1.3 and ≥2.67 were used for FIB-4. Results: We included 10,650 patients with cirrhosis (median age 62 years), who were predominantly white (57.8%) and male (51.9%). The most common etiologies of cirrhosis were non-alcoholic steatohepatitis (23.8%), hepatitis C (23.0%), and alcohol-related liver disease (20.5%). At the time of cirrhosis diagnosis (±3 months), 9.3% of patients with cirrhosis had APRI ≥2 and 41.3% had a FIB-4 ≥2.67 compared to 1.2% and 8.9% in control patients, respectively. In the periods spanning 3-12, 12-21, and 21-30 months prior to cirrhosis diagnosis, APRI was ≥2 in 9.4%, 6.6%, and 6.5% of patients, respectively; FIB-4 was ≥2.67 in 42.1%, 37.1%, and 34.3% of patients, respectively. The sensitivity and specificity of APRI at the time of cirrhosis diagnosis were 9.3% and 98.8%, respectively, while the sensitivity and specificity of FIB-4 were 41.3% and 91.0%, respectively. Lower cut-off values for APRI and FIB-4 showed similar performance. Conclusions: Existing non-invasive fibrosis makers are suboptimal when used for advanced fibrosis identification, missing over half of patients with cirrhosis at the time of and prior to clinical diagnosis. Impact and implications: Commonly available laboratory-based indices, including APRI and FIB-4, have been proposed to rule in or rule out advanced fibrosis in the general population. In a study of a large privately insured cohort from the US, FIB-4 and APRI were not sufficient for screening for advanced fibrosis at the time of or prior to clinical diagnosis. While performance for screening out advanced fibrosis was better, a significant percentage of patients with cirrhosis have lab indices below threshold values. Future studies to develop laboratory-based algorithms to help stratify liver fibrosis for population-based screening are warranted.

Fibrosis score 4 index has an independent relationship with coronary artery diseases in patients with metabolic-associated fatty liver disease.

BACKGROUND: Metabolic-associated fatty liver disease (MAFLD), one of the most common liver diseases, is detected in patients with concomitant hepatic steatosis and Type 2 Diabetes (T2D). We looked into the relationship between Fibrosis-4 (FIB-4) index and coronary artery diseases (CAD) in patients with MAFLD, to further look into the efficiency of FIB-4 in screening for CAD among patients with MAFLD. METHOD: In this study, we included 1664 patients with MAFLD (T2D, who also had hepatic steatosis) during 2012-2022 and divided them into 2 groups; CAD and non-CAD. Demographic, Anthropometric indices, liver function tests, lipid profile and FIB-4 index of all patients were evaluated and compared. RESULT: Among the 1644 patients (all have MAFLD), 364(21.4%) had CAD. Patients with MAFLD and CAD were more probable to be hypertensive, have longer duration of diabetes and be older (with p-values < 0.001). After adjustment for confounding factors, in a multivariable logistic regression model, FIB4 showed a significant independent relationship with concomitant MAFLD and CAD. Upper Tertile FIB-4 had an odds ratio of 3.28 (P-value = 0.002) to predict CAD. Furthermore, in Receiver Operating Characteristic (ROC) Curve analysis with the maximum Youden Index, a FIB-4 cut-off of 0.85 (AUC = 0.656, 95% CI 0.618-0.693, P < 0.001) noted to predict CAD in patients with MAFLD. CONCLUSION: This study showed that the FIB-4 score independently correlates with CAD in patients with MAFLD.

Prevalence of High and Moderate Risk of Liver Fibrosis Among Patients With Diabetes at a Noncommunicable Diseases (NCD) Clinic in a Primary Healthcare Center in Northern India.

Background Diabetes is a known entity that contributes to increased incidence and progress of liver fibrosis. Despite the integration of nonalcoholic fatty liver disease (NAFLD) into the NP-NCD program (National Programme for Prevention and Control of Cancer, Diabetes, Cardiovascular Diseases, and Stroke [NPCDCS]), screening individuals in primary healthcare settings for liver fibrosis remains uncommon. The objective of this study was to determine the prevalence of the risk of liver fibrosis in individuals with diabetes. Methodology The secondary data analysis was conducted among patients with diabetes attending the noncommunicable diseases (NCD) clinic at the Primary Health Center (PHC) Najafgarh, Delhi, from January 2023 to June 2023. We used the Fibrosis-4 (FIB-4) score to assess the risk of liver fibrosis. The data analysis was carried out using Stata 17.0 software (StataCorp, College Station, TX). Results Out of 394 individuals screened, 158 (39.5%) were male and 236 (60.5%) were female. Among the study participants, 64.9% (95% confidence interval [CI] 60.0%-69.7%) were of low risk, 30.5% (95% CI 25.9%-35.3%) were of intermediate risk, and 4.6% (95% CI 2.7%-7.1%) were of high risk of developing liver fibrosis based on FIB-4 scoring. The increased risk was associated with increased age, duration of diabetes, and dyslipidemia. Conclusions The prevalence of high risk of liver fibrosis among patients with diabetes was 4.6% (95% CI 2.7%-7.1%), whereas an intermediate risk of developing liver fibrosis was observed in 30.5%. The study advocates integrating these screening tools into primary healthcare settings, alleviating the strain on larger healthcare facilities. It also underscores the importance of early detection and management of liver fibrosis in patients with diabetes.

Comparison of Liver Fibrosis and Function Indices with Extracellular Volume Using Dual-energy CT: A Retrospective Study.

BACKGROUND: Dual-Energy Computed Tomography (DECT) enables the direct measurement of iodine accumulation in the extracellular space. OBJECTIVE: To compare measures of liver fibrosis and function with Extracellular Volume (ECV) from iodine/water images using DECT. METHODS: Data was obtained from 119 consecutive patients who underwent abdominal DECT. A region of interest was set in the right lobe of the liver, pancreas, spleen, and aorta on iodine density images. ECV was calculated using the following formula: ECV = (1 - hematocrit) × [iodine concentration in the liver (or pancreas, spleen) / iodine concentration in the aorta]. The severity of liver fibrosis was estimated using the aminotransferase/platelet ratio index (APRI) and the Fibrosis-4 (FIB-4) index. Liver function was assessed by the Child-Pugh classification and albumin-bilirubin (ALBI) grade. Data were analyzed by the Spearman rank correlation coefficient, one-way analysis of variance, and post hoc analysis. RESULTS: The correlation between ECV and fibrosis indices (APRI and FIB-4) was only significant, with a weak magnitude for liver ECV quantification at the equilibrium phase (r=0.25 and r=0.20, respectively). The correlations between liver function index and ECV quantification were more robust than with fibrosis index. The highest correlations (r=0.50) were found between ALBI grade and liver ECV at the equilibrium phase. Liver ECV values at the equilibrium phase had a significant difference between ALBI grade 1 vs. 2 and grade 1 vs. 3. CONCLUSION: Liver ECV quantification by DECT is more suitable for evaluating liver function than liver fibrosis severity.

On-Treatment Changes in FIB-4 and 1-Year FIB-4 Values Help Identify Patients with Chronic Hepatitis B Receiving Entecavir Therapy Who Have the Lowest Risk of Hepatocellular Carcinoma.

Noninvasive fibrosis indices can help stratify the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) receiving nucleos(t)ide analogue (NA) therapy. We investigated the predictive performance of on-treatment changes in FIB-4 (△FIB-4) and 1-year FIB-4 values (FIB-4 12M) for HCC risk in patients with CHB receiving entecavir therapy. We included 1325 NA-naïve patients with CHB treated with entecavir, retrospectively, from January 2007 to August 2012. A combination of △FIB-4 and FIB-4 12M was used to stratify the cumulative risk of HCC into three subgroups each in the noncirrhotic and cirrhotic subgroups with p < 0.0001 by using the log-rank test (noncirrhotic: the highest risk (n = 88): FIB-4 12M ≥ 1.58/△FIB-4 ≥ 0 (hazard ratio (HR): 40.35; 95% confidence interval (CI): 5.107-318.7; p <0.0001) and cirrhotic: the highest risk (n = 89): FIB-4 12M ≥2.88/△FIB-4 ≥0 (HR: 9.576; 95% CI: 5.033-18.22; p < 0.0001)). Patients with noncirrhotic CHB treated with entecavir who had a FIB-4 12M < 1.58 or FIB-4 12M ≥ 1.58/△FIB-4 < 0 exhibited the lowest 5-year HCC risk (0.6%). A combination of on-treatment changes in FIB-4 and 1-year FIB-4 values may help identify patients with CHB receiving entecavir therapy with the lowest risk of HCC.

Predicting Liver Fibrosis in the Hepatitis C Population: Concordance Analysis Between Noninvasive Scoring Systems and Percutaneous Liver Biopsy.

Background Due to the slow progression of many chronic liver diseases, including hepatitis C, it is not practical or safe to monitor disease progression by serial liver biopsies. Noninvasive laboratory scoring systems based on routine laboratory tests are appealing surrogate markers of liver fibrosis for the staging and monitoring of chronic liver diseases such as hepatitis C. Methods We explored the accuracy of three scoring systems: the fibrosis-4 score (FIB-4), the aspartate aminotransferase to platelet ratio index (APRI score), and the aspartate aminotransferase to alanine aminotransferase ratio (AAR) in 496 patients with chronic hepatitis C virus (HCV) infection who had undergone percutaneous liver biopsy at a viral hepatitis clinic in Shreveport, Louisiana. Results For FIB-4, the area under the receiver operating characteristic curve (AUROC) for hepatic fibrosis stages ≥ 1, ≥ 2, ≥ 3, and 4 (cirrhosis) ranged from 0.74 (95% CI, 0.678 - 0.802) to 0.802 (95% CI, 0.751 - 0.854). At a cutoff value of 1.45, FIB-4 was 82% sensitive for advanced fibrosis or cirrhosis (stage 3 or 4) but was only 58% specific for these findings. Increasing the FIB-4 cutoff value to 3.25 reduced the sensitivity for detecting advanced fibrosis or cirrhosis to 39%, but this higher cutoff was 92% specific for these findings. Corresponding AUROCs for the APRI and AAR scores were inferior to FIB-4. Conclusion The FIB-4 index outperformed APRI and AAR in our HCV infected population in predicting severe fibrosis or cirrhosis.

Direct-acting antiviral agents do not increase the incidence of hepatocellular carcinoma development: a prospective, multicenter study.

BACKGROUND: While achieving sustained virological response (SVR) following interferon-based or direct-acting antiviral agent (DAA) treatments reduces the incidence of hepatocellular carcinoma (HCC), an increase in unexpected early occurrence or recurrence of HCC after hepatitis C virus elimination by DAA treatments has been reported. We prospectively investigated the incidence and risk factors of HCC after DAA treatment in a large multicenter cohort in Japan. METHODS: Patients with chronic hepatitis C with or without cirrhosis who were treated with DAAs and obtained SVR were enrolled. DAAs were administered for 3 or 6 months. A total of 2552 patients were enrolled. RESULTS: Of these, 70 patients (2.7%) developed HCC. The 12-, 24-, and 36-month cumulative HCC incidences were 1.3%, 2.9%, and 4.9% in all patients; 2.5%, 5.2%, and 10.0% in those with cirrhosis; and 0.9%, 2.1%, and 2.9% in those without cirrhosis, respectively. Multivariate analysis revealed age, sex, gamma-glutamyl transpeptidase level, and fibrosis-4 index to be independent factors associated with HCC. Patients with these four factors had an approximately six-to-sevenfold increased risk for HCC development. Five patients with large and early tumor occurrence did not receive contrast imaging examinations before treatment. CONCLUSION: Although the results of our prospective study suggested that achieving SVR by DAA treatment reduces the incidence of HCC, HCC development still occurs. Careful follow-up is important in patients with risk factors.