Severe hepatic steatosis promotes increased liver stiffness in the early stages of metabolic dysfunction-associated steatotic liver disease.

BACKGROUND & AIMS: The predictors of progression from steatosis to more advanced stages of metabolic dysfunction-associated steatotic liver disease (MASLD) remain unclear. We evaluated the association between the quantity of hepatic steatosis and longitudinal changes in liver stiffness measurements (LSMs) using magnetic resonance elastography (MRE) in patients with MASLD. METHODS: We retrospectively analysed patients with MASLD who underwent at least two serial MRE and magnetic resonance imaging-based proton density fat fraction (MRI-PDFF) examinations at least 1 year apart. Fine-Gray competitive proportional hazard regression was used to identify LSM progression and regression factors. RESULTS: A total of 471 patients were enrolled. Factors linked to LSM progression were steatosis grade 3 (MRI-PDFF ≥17.1%, adjusted hazard ratio [aHR] 2.597; 95% confidence interval [CI] 1.483-4.547) and albumin-bilirubin grade 2 or 3 (aHR 2.790; 95% CI 1.284-6.091), while the only factor linked to LSM regression was % decrease rate of MRI-PDFF ≥5% (aHR 2.781; 95% CI 1.584-4.883). Steatosis grade 3 correlated with a higher incidence rate of LSM progression than steatosis grade 1 (MRI-PDFF <11.3%) in patients with LSM stage 0 (<2.5 kilopascal [kPa]), and a % annual decrease rate of MRI-PDFF ≥5% correlated with a higher incidence rate of LSM regression than that of MRI-PDFF >-5% and <5% in patients with LSM stage 1 or 2-4 (≥2.5 kPa). CONCLUSIONS: Severe hepatic steatosis was linked to significant LSM progression in patients with MASLD and low LSM (<2.5 kPa).

Advanced fibrosis leads to overestimation of steatosis with quantitative ultrasound in individuals without hepatic steatosis.

PURPOSE: The effect of hepatic fibrosis stage on quantitative ultrasound based on the attenuation coefficient (AC) for liver lipid quantification is controversial. The objective of this study was to determine how the degree of fibrosis assessed by magnetic resonance (MR) elastography affects AC based on the ultrasound-guided attenuation parameter according to the grade of hepatic steatosis, using magnetic resonance imaging (MRI)-derived proton density fat fraction (MRIderived PDFF) as the reference standard. METHODS: Between February 2020 and April 2021, 982 patients with chronic liver disease who underwent AC and MRI-derived PDFF measurement as well as MR elastography were enrolled. Multiple regression was used to investigate whether AC was affected by the degree of liver stiffness. RESULTS: AC increased as liver stiffness progressed in 344 patients without hepatic steatosis (P=0.009). In multivariable analysis, AC was positively correlated with skin-capsule distance (P<0.001), MR elastography value (P=0.037), and MRI-derived PDFF (P<0.001) in patients without hepatic steatosis. In 52 of 982 patients (5%), the correlation between AC and MRIderived PDFF fell outside the 95% confidence interval for the regression line slope. Patients with MRI-derived PDFF lower than their AC (n=36) had higher fibrosis-4 scores, albumin-bilirubin scores, and MR elastography values than patients with MRI-derived PDFF greater than their AC (n=16; P=0.018, P=0.001, and P=0.011, respectively). CONCLUSION: AC is affected by liver fibrosis (MR elastography value ≥6.7 kPa) only in patients without hepatic steatosis (MRI-derived PDFF <5.2%). These values should be interpreted with caution in patients with advanced liver fibrosis.

Multivariable Quantitative US Parameters for Assessing Hepatic Steatosis.

Background Because of the global increase in the incidence of nonalcoholic fatty liver disease, the development of noninvasive, widely available, and highly accurate methods for assessing hepatic steatosis is necessary. Purpose To evaluate the performance of models with different combinations of quantitative US parameters for their ability to predict at least 5% steatosis in patients with chronic liver disease (CLD) as defined using MRI proton density fat fraction (PDFF). Materials and Methods Patients with CLD were enrolled in this prospective multicenter study between February 2020 and April 2021. Integrated backscatter coefficient (IBSC), signal-to-noise ratio (SNR), and US-guided attenuation parameter (UGAP) were measured in all participants. Participant MRI PDFF value was used to define at least 5% steatosis. Four models based on different combinations of US parameters were created: model 1 (UGAP alone), model 2 (UGAP with IBSC), model 3 (UGAP with SNR), and model 4 (UGAP with IBSC and SNR). Diagnostic performance of all models was assessed using area under the receiver operating characteristic curve (AUC). The model was internally validated using 1000 bootstrap samples. Results A total of 582 participants were included in this study (median age, 64 years; IQR, 52-72 years; 274 female participants). There were 364 participants in the steatosis group and 218 in the nonsteatosis group. The AUC values for steatosis diagnosis in models 1-4 were 0.92, 0.93, 0.95, and 0.96, respectively. The C-indexes of models adjusted by the bootstrap method were 0.92, 0.93, 0.95, and 0.96, respectively. Compared with other models, models 3 and 4 demonstrated improved discrimination of at least 5% steatosis (P < .01). Conclusion A model built using the quantitative US parameters UGAP, IBSC, and SNR could accurately discriminate at least 5% steatosis in patients with CLD. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Han in this issue.

Diagnostic Accuracy of Two-Dimensional Shear Wave Elastography for Liver Fibrosis: A Multicenter Prospective Study.

Chronic liver disease (CLD) leads to the development of hepatocellular carcinoma, which is one of the leading causes of cancer-related deaths globally.1 Liver fibrosis is the most important prognostic factor for hepatocellular carcinoma development and prognosis in CLD, and accurate staging of liver fibrosis is pivotal in clinical practice.2 Although liver biopsy is the gold standard for evaluating liver fibrosis, liver biopsy has several limitations including invasiveness, sampling error, and intraobserver and interobserver reproducibility.3 To resolve these problems, several noninvasive methods for evaluating liver fibrosis have been developed using serum fibrosis markers, ultrasound-based modalities, and magnetic resonance imaging-based modalities.4.

Utility of Ultrasound-Guided Attenuation Parameter for Grading Steatosis With Reference to MRI-PDFF in a Large Cohort.

BACKGROUND & AIMS: Ultrasound-guided attenuation parameter (UGAP) is recently developed for noninvasive evaluation of steatosis. However, reports on its usefulness in clinical practice are limited. This prospective multicenter study analyzed the diagnostic accuracy of grading steatosis with reference to magnetic resonance imaging-based proton density fat fraction (MRI-PDFF), a noninvasive method with high accuracy, in a large cohort. METHODS: Altogether, 1010 patients with chronic liver disease who underwent MRI-PDFF and UGAP were recruited and prospectively enrolled from 6 Japanese liver centers. Linearity was evaluated using intraclass correlation coefficients between MRI-PDFF and UGAP values. Bias, defined as the mean difference between MRI-PDFF and UGAP values, was assessed by Bland-Altman analysis. UGAP cutoffs for pairwise MRI-PDFF-based steatosis grade were determined using area under the receiver-operating characteristic curve (AUROC) analyses. RESULTS: UGAP values were shown to be normally distributed. However, because PDFF values were not normally distributed, they were log-transformed (MRI-logPDFF). UGAP values significantly correlated with MRI-logPDFF (intraclass correlation coefficient = 0.768). Additionally, Bland-Altman analysis showed good agreement between MRI-logPDFF and UGAP with a mean bias of 0.0002% and a narrow range of agreement (95% confidence interval [CI], -0.015 to 0.015). The AUROCs for distinguishing steatosis grade ≥1 (MRI-PDFF ≥5.2%), ≥2 (MRI-PDFF ≥11.3%), and 3 (MRI-PDFF ≥17.1%) were 0.910 (95% CI, 0.891-0.928), 0.912 (95% CI, 0.894-0.929), and 0.894 (95% CI, 0.873-0.916), respectively. CONCLUSIONS: UGAP has excellent diagnostic accuracy for grading steatosis with reference to MRI-PDFF. Additionally, UGAP has good linearity and negligible bias, suggesting that UGAP has excellent technical performance characteristics that can be widely used in clinical trials and patient care. (UMIN Clinical Trials Registry, Number: UMIN000041196).

Type IV Collagen 7S Is the Most Accurate Test For Identifying Advanced Fibrosis in NAFLD With Type 2 Diabetes.

This study aimed to examine whether the diagnostic accuracy of four noninvasive tests (NITs) for detecting advanced fibrosis in nonalcoholic fatty liver disease (NAFLD) is maintained or is inferior to with or without the presence of type 2 diabetes. Overall, 874 patients with biopsy-proven NAFLD were enrolled. After propensity-score matching by age, sex, and the prevalence of dyslipidemia, 311 patients were enrolled in each group of with or without diabetes. To evaluate the effect of diabetes, we compared the diagnostic accuracy of the fibrosis-4 (FIB-4) index, the NAFLD fibrosis score (NFS), the aspartate aminotransferase to platelet ratio index (APRI), and type IV collagen 7S (COL4-7S) in patients with NAFLD with and without diabetes. The areas under the receiver operating characteristic curve (AUROC) for identifying advanced fibrosis in patients without diabetes were 0.879 for the FIB-4 index, 0.851 for the NFS, 0.862 for the APRI, and 0.883 for COL4-7S. The AUROCs in patients with diabetes were 0.790 for the FIB-4 index, 0.784 for the NFS, 0.771 for the APRI, and 0.872 for COL4-7S. The AUROC of COL4-7S was significantly larger than that of the other NITs in patients with NAFLD with diabetes than in those without diabetes. The optimal high and low cutoff points of COL4-7S were 5.9 ng/mL and 4.8 ng/mL, respectively. At the low cutoff point, the accuracy of COL4-7S was better than that of the other NITs, especially in patients with diabetes. Conclusion: COL4-7S measurement might be the best NIT for identifying advanced fibrosis in NAFLD, especially in NAFLD with diabetes.

Hereditary hemorrhagic telangiectasia: how to efficiently detect hepatic abnormalities using ultrasonography.

INTRODUCTION: Hereditary hemorrhagic telangiectasia (HHT) is a multiorgan genetic angiodysplastic affection characterized by visceral vascular malformations. It affects mainly the brains, lungs, gastrointestinal tract, and nasal mucosa. Unlike those organs, hepatic involvement, although very frequently occurring, is insufficiently recognized, mainly because of the complex vascular structure of this organ. Thus, treating HHT patients requires a solid understanding of these hepatic anomalies. It is especially important for any general clinicians to be able to recognize clinical findings in HHT, which leads to a high suspicion of HHT and have an index of suspicion for liver abnormalities of HHT. For this purpose, keen awareness of clinical as well as hepatic sonographic (US) findings is paramount. AIM: The aim of this review is to summarize previously reported findings on the hepatic US through a thorough analysis of related articles, and to (a) determine the role of US in the diagnosis of hepatic involvement in HHT patients and (b) propose the most simple and easy way to detect HHT-related abnormalities during routine US examinations. CONCLUSION: Hepatic US serves to diagnose the detailed complex hepatic changes typical of HHT, and contributes to increased diagnostic confidence of hepatic changes in HHT patients, with the most simple way not to overlook HHT-related abnormalities being to find hepatic artery dilatation.

A Data Mining-based Prognostic Algorithm for NAFLD-related Hepatoma Patients: A Nationwide Study by the Japan Study Group of NAFLD.

The prognosis of patients with nonalcoholic fatty liver disease-related hepatocellular carcinoma (NAFLD-HCC) is intricately associated with various factors. We aimed to investigate the prognostic algorithm of NAFLD-HCC patients using a data-mining analysis. A total of 247 NAFLD-HCC patients diagnosed from 2000 to 2014 were registered from 17 medical institutions in Japan. Of these, 136 patients remained alive (Alive group) and 111 patients had died at the censor time point (Deceased group). The random forest analysis demonstrated that treatment for HCC and the serum albumin level were the first and second distinguishing factors between the Alive and Deceased groups. A decision-tree algorithm revealed that the best profile comprised treatment with hepatectomy or radiofrequency ablation and a serum albumin level ≥3.7 g/dL (Group 1). The second-best profile comprised treatment with hepatectomy or radiofrequency ablation and serum albumin levels <3.7 g/dL (Group 2). The 5-year overall survival rate was significantly higher in the Group 1 than in the Group 2. Thus, we demonstrated that curative treatment for HCC and serum albumin level >3.7 g/dL was the best prognostic profile for NAFLD-HCC patients. This novel prognostic algorithm for patients with NAFLD-HCC could be used for clinical management.

The novel cutoff points for the FIB4 index categorized by age increase the diagnostic accuracy in NAFLD: a multi-center study.

BACKGROUND: The FIB4 index is clinically useful, but because its formula includes age, the appropriate cutoff point may differ by age group. Here, new FIB4 index cutoff points were validated using cohort data from 14 hepatology centers in Japan. METHODS: The FIB4 index was determined in biopsy-confirmed NAFLD patients (n = 1050) who were divided into four groups: ≤ 49, 50-59, 60-69, and ≥ 70 years. ROC analysis predicted advanced fibrosis in each age group; low and high cutoff points were defined by a sensitivity and specificity of 90%. The new and conventional cutoffs were compared for detecting advanced fibrosis. RESULTS: The modified low and high cutoff points were 1.05 and 1.21 in ≤ 49 years, 1.24 and 1.96 in 50-59 years, 1.88 and 3.24 in 60-69 years, and 1.95 and 4.56 in ≥ 70 years. In ≥ 60 years, the false-negative rate was increased using the modified high cutoff point, and the high cutoff point was better with the conventional cutoff point. The new proposed low and high cutoff points are 1.05 and 1.21 in ≤ 49 years, 1.24 and 1.96 in 50-59 years, 1.88 and 2.67 in 60-69 years, and 1.95 and 2.67 in ≥ 70 years; these cutoff points improved the accuracy of advanced fibrosis diagnosis. CONCLUSIONS: FIB4 index cutoff points for predicting advanced fibrosis in NAFLD increased with age. Cutoff points modified by age improved the diagnostic accuracy of estimations of advanced liver fibrosis using the FIB4 index.

Correction to: The novel cutoff points for the FIB4 index categorized by age increase the diagnostic accuracy in NAFLD: a multi-center study.

The coauthor Masashi Yoneda's affiliation has been incorrectly published in the original publication of the article. The correct affiliation is provided in this correction.

Hepatocellular carcinoma in Japanese patients with nonalcoholic fatty liver disease and alcoholic liver disease: multicenter survey.

BACKGROUND: In Japan, the prevalence of hepatocellular carcinoma (HCC) associated with nonviral liver disease, especially with nonalcoholic fatty liver disease (NAFLD-HCC) and alcoholic liver disease (ALD-HCC), has been increasing. Clarification of the clinical features of NAFLD-HCC and ALD-HCC is needed. We performed a large retrospective multicenter survey to clarify the clinical course of these two types of HCC. METHODS: Clinical characteristics, survival, and recurrence were examined in 532 patients with ALD-HCC and 209 patients with NAFLD-HCC who were diagnosed between January 2000 and December 2013. RESULTS: The ALD-HCC patients were predominantly male and were younger than the patients with NAFLD-HCC. Lifestyle-related diseases were significantly more common in the NAFLD-HCC group, but the prevalence of cirrhosis was significantly higher in the ALD-HCC group. The histological diagnosis of NAFLD-HCC showed a gender difference (F4; 72.7 % in the females vs. 37.6 % in the males). The characteristic features of HCC including histology, survival rate, and recurrence rate were quite similar in the NAFLD-HCC and ALD-HCC groups: 5-year survival rates 49.1 vs. 43.7 %; 5-year recurrence rates 69.6 vs. 65.4 %, respectively. However, the risk factors for recurrence differed between the two groups: des-gamma-carboxy prothrombin was a risk factor in NAFLD-HCC and α-fetoprotein was a risk factor in ALD-HCC. CONCLUSIONS: Although the characteristic features underlying these two diseases are different, the two HCC groups showed a similar clinical course. The recurrence rates of the two HCC groups were relatively high. We found that critical tumor markers for recurrence differed between the two diseases.

Simple scoring system for predicting cirrhosis in nonalcoholic fatty liver disease.

AIM: To investigate a simple noninvasive scoring system for predicting liver cirrhosis in nonalcoholic fatty liver disease (NAFLD) patients. METHODS: A total of 1048 patients with liver-biopsy-confirmed NAFLD were enrolled from nine hepatology centers in Japan (stage 0, 216; stage 1, 334; stage 2, 270; stage 3, 190; stage 4, 38). The weight and height of the patients were measured using a calibrated scale after requesting the patients to remove their shoes and any heavy clothing. Venous blood samples were obtained in the morning after the patients had fasted overnight for 12 h. Laboratory evaluation was performed in all patients. Statistical analysis was conducted using SPSS version 12.0. Continuous variables were expressed as mean ± SD. RESULTS: The optimal cutoff value of platelet count, serum albumin, and aminotransferase/alanine aminotransferase ratio (AAR) was set at < 15.3 10(4)/µL, < 4.0 g/dL, and > 0.9, respectively, by the receiver operating characteristic curve. These three variables were combined in an unweighted sum (platelet count = 1 point, serum albumin = 1 point, AAR = 1 point) to form an easily calculated composite score for predicting cirrhosis in NAFLD patients, called the PLALA (platelet, albumin, AAR) score. The diagnosis of PLALA ≥ 2 had sufficient accuracy for detecting liver cirrhosis in NAFLD patients. CONCLUSION: The PLALA score may be an ideal scoring system for detecting cirrhosis in NAFLD patients with sufficient accuracy and simplicity to be considered for clinical use.

Effective control of relapsing disseminated intravascular coagulation in a patient with decompensated liver cirrhosis by recombinant soluble thrombomodulin.

A 70-year-old Japanese man was hospitalized for expanding purpura and chronic disseminated intravascular coagulation (DIC) caused by decompensated liver cirrhosis. As there are no effective treatments for chronic DIC caused by liver cirrhosis, we decided to administer recombinant human soluble thrombomodulin (rhsTM) after he provided informed consent. The DIC was rapidly improved; however, the purpura and coagulopathy recurred after two months, and repeated rhsTM treatments were required. The rhsTM treatment sufficiently controlled the coagulopathy for two years, without any complications, including bleeding. This is the first report demonstrating that rhsTM can be administered safely and repeatedly to a patient with decompensated liver cirrhosis, and that it appears to be associated with a favorable outcome.

Augmented hepatic Toll-like receptors by fatty acids trigger the pro-inflammatory state of non-alcoholic fatty liver disease in mice.

AIM: There is considerable evidence that intestinal microbiota are involved in the development of metabolic syndromes and, consequently, with the development of non-alcoholic fatty liver disease (NAFLD). Toll-like receptors (TLRs) are essential for the recognition of microbiota. However, the induction mechanism of TLR signals through the gut-liver axis for triggering the development of non-alcoholic steatohepatitis (NASH) or NAFLD remains unclear. In this study, we investigated the role of palmitic acid (PA) in triggering the development of a pro-inflammatory state of NAFLD. METHODS: Non-alcoholic fatty liver disease was induced in mice fed a high fat diet (HFD). The mice were killed and the expression of TLRs, tumor necrosis factor (TNF), interleukin (IL)-1ß, and phospho-interleukin-1 receptor-associated kinase 1 in the liver and small intestine were assessed. In addition, primary hepatocytes and Kupffer cells were treated with PA, and the direct effects of PA on TLRs induction by these cells were evaluated. RESULTS: The expression of inflammatory cytokines such as TNF, IL-1ß, and TLR-2, -4, -5, and -9 was increased in the liver, but decreased in the small intestine of HFD-fed mice in vivo. In addition, the expression of TLRs in primary hepatocytes and Kupffer cells was increased by treatment with PA. CONCLUSION: In the development of the pro-inflammatory state of NAFLD, PA triggers the expression of TLRs, which contribute to the induction of inflammatory cytokines through TLR signals by intestinal microbiota.

Survey of non-B, non-C liver cirrhosis in Japan.

AIM: The aim of this survey was to reveal clinical features for each etiology of non-B, non-C liver cirrhosis (NBNC LC) in Japan. METHODS: In a nationwide survey of NBNC LC in Japan at the 15th General Meeting of the Japan Society of Hepatology, 6999 NBNC LC patients were registered at 48 medical institutions. Epidemiological and clinical factors were investigated. RESULTS: The percentage of NBNC LC among LC patients was 26%. NBNC LC patients were categorized into 11 types according to etiological agents: non-alcoholic steatohepatitis (NASH), 14.5%; alcoholic liver disease (ALD), 55.1%; fatty liver disease (FLD), except NASH, ALD, and other known etiology, 2.5%; primary biliary cirrhosis, 8.0%; other biliary cirrhosis, 0.8%; autoimmune hepatitis, 6.8%; metabolic disease, 0.6%; congestive disease, 0.8%; parasitic disease, 0.2%; other known etiology, 0.2%; and unknown etiology, 10.5%. Compared with previous surveys, the percentage of ALD remained unchanged, whereas that of NASH increased. The mean age and percentage of females were significantly higher in NASH patients than in ALD and FLD patients. Prevalence of diabetes mellitus was significantly higher in NASH and FLD patients than in ALD ones. Prevalence of hepatocellular carcinoma (HCC) in NBNC LC patients was 35.9%. Among NASH, ALD and FLD patients, 50.9%, 34.3% and 54.5% had HCC, respectively. Positivity of hepatitis B core antibody was significantly higher in HCC patients than in those without HCC (41.1% vs 24.8%). CONCLUSION: This survey determined the etiology of NBNC LC in Japan. These results should contribute new ideas toward understanding NBNC LC and NBNC HCC.

Modification of a simple clinical scoring system as a diagnostic screening tool for non-alcoholic steatohepatitis in Japanese patients with non-alcoholic fatty liver disease.

AIMS/INTRODUCTION: We reinvestigated the clinical usefulness of the modified NAFIC scoring system, modified by changing the weightage assigned to the fasting serum insulin level based on the importance of hyperinsulinemia in the pathogenesis of non-alcoholic steatohepatitis (NASH), in Japanese patients with non-alcoholic fatty liver disease (NAFLD) who had undergone liver biopsy. MATERIALS AND METHODS: The NAFIC score is conventionally calculated as follows: serum ferritin ≥200 ng/mL (female) or ≥300 ng/mL (male), 1 point; serum fasting insulin ≥10 µU/mL, 1 point; and serum type IV collagen 7 s ≥5.0 ng/mL, 2 points. A total of 147 patients with NAFLD who had undergone liver biopsies were included in the estimation group. To validate the modified scoring system, 355 patients from nine hepatology centers in Japan were also enrolled. RESULTS: In the estimation group, 74 (50.3%) patients were histologically diagnosed as having NASH, whereas the remaining 73 (49.7%) were diagnosed as not having NASH. As the percentage of NASH patients increased not only among participants with serum insulin levels greater than 10 µU/mL, but also in those with serum levels greater than 15 µU/mL, we advocated use of the modified NAFIC score, as follows: serum fasting insulin 10-15 µU/mL, 1 point and ≥15 µU/mL, 2 points. The modified NAFIC score showed improved sensitivity and negative predictive value for the diagnosis of NASH. This finding was also confirmed in the validation group. CONCLUSIONS: The modified NAFIC scoring system could be a clinically useful diagnostic screening tool for NASH.

Noninvasive scoring systems in patients with nonalcoholic fatty liver disease with normal alanine aminotransferase levels.

BACKGROUND: The severity of liver fibrosis must be estimated to determine the prognosis, for surveillance, and for optimal treatment of nonalcoholic fatty liver disease (NAFLD). However, the severity of hepatic fibrosis tends to be underestimated in patients with normal ALT. METHODS: We investigated histological data and scoring systems (FIB-4 index, NAFLD fibrosis score, BARD score, and AST/ALT ratio) of 1,102 liver-biopsy-confirmed NAFLD patients. RESULTS: A total of 235 NAFLD patients with normal ALT were estimated to exist. The ratio of advanced fibrosis (stage 3-4) was seen in 16.1 % of subjects with normal ALT. Scoring systems, especially the FIB-4 index and NAFLD fibrosis score, were clinically very useful (AUROC >0.8), even in patients with normal ALT. Furthermore, with resetting of the cutoff values, the FIB-4 index (>1.659) and NAFLD fibrosis score (>0.735) were found to have a higher sensitivity and higher specificity for the prediction of advanced fibrosis, and all of these scoring systems (FIB-4 index, NAFLD fibrosis score, BARD score, and AST/ALT ratio) had higher negative predictive values (>90.3 %). By using the resetting cutoff value, liver biopsy could have been avoided in 60.4 % (FIB-4), 66.4 % (NAFLD fibrosis score), 51.9 % (BARD score), and 62.1 % (AST/ALT ratio). CONCLUSIONS: We reset the cutoff values of numerous non-invasive scoring systems to improve their clinical usefulness in the prediction of liver fibrosis in NAFLD patients with normal ALT, and these non-invasive scoring systems with the reset cutoff values could be of substantial benefit to reduce the number of liver biopsies performed.

Validation of the FIB4 index in a Japanese nonalcoholic fatty liver disease population.

BACKGROUND: A reliable and inexpensive noninvasive marker of hepatic fibrosis is required in patients with nonalcoholic fatty liver disease (NAFLD). FIB4 index (based on age, aspartate aminotransferase [AST] and alanine aminotransferase [ALT] levels, and platelet counts) is expected to be useful for evaluating hepatic fibrosis. We validated the performance of FIB4 index in a Japanese cohort with NAFLD. METHODS: The areas under the receiver operating characteristic curves (AUROC) for FIB4 and six other markers were compared, based on data from 576 biopsy-proven NAFLD patients. Advanced fibrosis was defined as stage 3-4 fibrosis. FIB4 index was assessed as: age (yr) × AST (IU/L)/(platelet count (10(9)/L) × âˆšALT (IU/L)) RESULTS: Advanced fibrosis was found in 64 (11%) patients. The AUROC for FIB4 index was superior to those for the other scoring systems for differentiating between advanced and mild fibrosis. Only 6 of 308 patients with a FIB4 index below the proposed low cut-off point (< 1.45) were under-staged, giving a high negative predictive value of 98%. Twenty-eight of 59 patients with a FIB4 index above the high cut-off point (> 3.25) were over-staged, giving a low positive predictive value of 53%. Using these cutoffs, 91% of the 395 patients with FIB-4 values outside 1.45-3.25 would be correctly classified. Implementation of the FIB4 index in the Japanese population would avoid 58% of liver biopsies. CONCLUSION: The FIB4 index was superior to other tested noninvasive markers of fibrosis in Japanese patients with NAFLD, with a high negative predictive value for excluding advanced fibrosis. The small number of cases of advanced fibrosis in this cohort meant that this study had limited power for validating the high cut-off point.

Platelet count for predicting fibrosis in nonalcoholic fatty liver disease.

BACKGROUND: The severity of liver fibrosis is known to be a good indicator for surveillance, and for determining the prognosis and optimal treatment of nonalcoholic fatty liver disease (NAFLD). However, it is virtually impossible to carry out liver biopsies in all NAFLD patients. The purpose of this study was to investigate the clinical usefulness of measuring the platelet count for predicting the severity of liver fibrosis in a large retrospective cohort of Japanese patients with NAFLD. METHODS: A total of 1,048 patients with liver-biopsy-confirmed NAFLD seen between 2002 and 2008 were enrolled from nine hepatology centers in Japan. Laboratory evaluations were performed for all patients. RESULTS: A linear decrease of the platelet count with increasing histological severity of hepatic fibrosis was revealed. The area under the receiver operating characteristic curve estimating the diagnostic performance of the platelet count for hepatic fibrosis Stage 3 was 0.774 (optimal cutoff value, 19.2 × 10(4)/µl; sensitivity, 62.7%; specificity, 76.3%), and that for Stage 4 was 0.918 (optimal cutoff value, 15.3 × 10(4)/µl; sensitivity, 80.5%; specificity, 88.8%). CONCLUSIONS: The platelet count may be an ideal biomarker of the severity of fibrosis in NAFLD patients, because it is simple, easy to measure and handle, cost-effective, and accurate for predicting the severity of fibrosis. Furthermore, by using the platelet count cutoff value validated in our multiple large trials, efficient recruitment of NAFLD patients may be facilitated.