Prognostic Value of Non-Invasive Fibrosis and Steatosis Tools, Hepatic Venous Pressure Gradient (HVPG) and Histology in Nonalcoholic Steatohepatitis

Abstract

Background & AimsNon-invasive diagnostic methods for liver fibrosis predict clinical outcomes in viral hepatitis and nonalcoholic fatty liver disease (NAFLD). We specifically evaluated prognostic value of non-invasive fibrosis methods in nonalcoholic steatohepatitis (NASH) against hepatic venous pressure gradient (HVPG) and liver histology.MethodsThis was a retrospective cohort study of 148 consecutive patients who met the following criteria: transjugular liver biopsy with HVPG measurement; biopsy-proven NASH; absence of decompensation; AST-to-Platelets Ratio Index (APRI), fibrosis-4 (FIB-4), NAFLD fibrosis score, ultrasound, hepatic steatosis index and Xenon-133 scan available within 6 months from biopsy; a minimum follow-up of 1 year. Outcomes were defined by death, liver transplantation, cirrhosis complications. Kaplan–Meier and Cox regression analyses were employed to estimate incidence and predictors of outcomes, respectively. Prognostic value was expressed as area under the curve (AUC).ResultsDuring a median follow-up of 5 years (interquartile range 3-8), 16.2% developed outcomes, including 7.4% who died or underwent liver transplantation. After adjustment for age, sex, diabetes, the following fibrosis tools predicted outcomes: HVPG >10mmHg (HR=9.60; 95% confidence interval [CI] 3.07-30.12), histologic fibrosis F3-F4 (HR=3.14; 1.41-6.95), APRI >1.5 (HR=5.02; 1.6-15.7), FIB-4 >3.25 (HR=6.33; 1.98-20.2), NAFLD fibrosis score >0.676 (HR=11.9; 3.79-37.4). Prognostic value was as follows: histologic fibrosis stage, AUC=0.85 (95% CI 0.76-0.93); HVPG, AUC=0.81 (0.70-0.91); APRI, AUC=0.89 (0.82-0.96); FIB-4, AUC=0.89 (0.83-0.95); NAFLD fibrosis score, AUC=0.79 (0.69-0.91). Neither histologic steatosis nor non-invasive steatosis methods predicted outcomes (AUC<0.50).ConclusionsNon-invasive methods for liver fibrosis predict outcomes of patients with NASH. They could be used for serial monitoring, risk stratification and targeted interventions.

Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: Systematic review and meta‐analysis

“…A total of 844 studies were identified in our primary search, five of which were included in this meta‐analysis (http://onlinelibrary.wiley.com/doi/10.1002/hep.29085/suppinfo). These five studies reported on 1,495 patients with 17,452 PYF (Table ; http://onlinelibrary.wiley.com/doi/10.1002/hep.29085/suppinfo). All five were cohort studies that used existing databases or cohorts of patients.…”

“…Studies were excluded from this meta‐analysis for the following reasons: (1) was not a cohort design (i.e., meta‐analysis/review, cross‐sectional, case‐control), (2) participants did not have histologically confirmed diagnosis of NAFLD, (3) participants with other causes of liver disease were not excluded and/or NAFLD patient‐specific information was not available, or (4) fibrosis stage–specific mortality data were not available. If fibrosis stage–specific mortality data were not available, then the study investigators contacted the primary authors to obtain unpublished data, which were provided for four of the five included studies …”

Liver fibrosis scores predict liver disease mortality in the United States population

“…Hepatic steatosis on ultrasound and elevated liver enzyme activities as noninvasive markers of fatty liver or nonalcoholic steatohepatitis have been examined in relation to disease outcome, including mortality . However, few prospective studies of fibrosis scores have been well‐powered to predict liver disease mortality and other long‐term adverse hepatic outcomes . A previous analysis of the NHANES III population with mortality follow‐up through 2006 found higher overall and cardiovascular disease mortality in association with three of the same fibrosis scores among persons with suspected NAFLD .…”

A Review of Western and Traditional Chinese Medical Approaches to Managing Nonalcoholic Fatty Liver Disease

“…Sumida et al found that FIB-4 had a negative predictive value of 98% at a cutoff of <1.45 but a positive predictive value of 53% at a cutoff of >3.25, indicating that implementation of the FIB-4 index would spare more than 50% of patients with NAFLD from undergoing liver biopsy [35]. A recent retrospective study showed that APRI, FIB-4, and the NAFLD fibrosis score were predictive of clinical outcomes and had similar prognostic performance to histologic fibrosis stage in patients with NASH [36]. …”

“…Study designs of trials are important and, unfortunately, many TCM clinical studies used insensitive methods to evaluate the severity of NAFLD, such as measuring AST and ALT levels [14]. Future TCM trials should use noninvasive serologic methods or liver biopsy to evaluate the severity of NAFLD [36]. In addition, many TCM studies on NAFLD suffer from selection, performance, detection, and reporting biases and lack homogenous clinical data [77].…”