A Novel Algorithm for Streamlining Diagnosis of Advanced Liver Fibrosis in CHB Patients with Concurrent Hepatic Steatosis.
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ABSTRACT:
SUBMITTER: Xu X
PROVIDER: S-EPMC10851070 | biostudies-literature | 2024 Feb
REPOSITORIES: biostudies-literature
Publications
A Novel Algorithm for Streamlining Diagnosis of Advanced Liver Fibrosis in CHB Patients with Concurrent Hepatic Steatosis.
Xu Xiaoming X Rui Fajuan F Ni Wenjing W Wu Chao C Shi Junping J Li Jie J
Journal of clinical and translational hepatology 20240129 2
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Project description:Chronic liver disease (CLD) is associated with tissue-destructive fibrosis. Considering that common mechanisms drive fibrosis across etiologies, and that steatosis is an important cofactor for pathology, we performed RNA sequencing on liver biopsies of patients with different fibrosis stages, resulting from infection with hepatitis C virus (HCV) (with or without steatosis) or fatty liver disease. In combination with enhanced liver fibrosis score correlation analysis, we reveal a common set of genes associated with advanced fibrosis, as exemplified by those encoding the transcription factor ETS-homologous factor (EHF) and the extracellular matrix protein versican (VCAN). We identified 17 fibrosis-associated genes as candidate EHF targets and demonstrated that EHF regulates multiple fibrosis-associated genes, including VCAN, in hepatic stellate cells. Serum VCAN levels were also elevated in advanced fibrosis patients. Comparing biopsies from patients with HCV with or without steatosis, we identified a steatosis-enriched gene set associated with advanced fibrosis, validating follistatin-like protein 1 (FSTL1) as an exemplar of this profile. In patients with advanced fibrosis, serum FSTL1 levels were elevated in those with steatosis (versus those without). Liver Fstl1 mRNA levels were also elevated in murine CLD models. We thus reveal a common gene signature for CLD-associated liver fibrosis and potential biomarkers and/or targets for steatosis-associated liver fibrosis.
| S-EPMC6124454 | biostudies-literature
Project description:To determine whether chemotherapy treatment at least 6 months prior to the detection of hepatic steatosis is associated with advanced hepatic fibrosis. Demographics, comorbid conditions, and laboratory data for cancer patients with hepatic steatosis were reviewed. The primary end point of this study was a low probability of fibrosis as calculated by the AST-to-platelet ratio index (APRI)-a surrogate for the absence of histologic bridging fibrosis and/or cirrhosis. Of 279 patients, 117 (41.9 %) were treated with chemotherapy and 197 (66.3 %) had a low probability of fibrosis by APRI. A smaller proportion of patients treated with chemotherapy had a low probability of hepatic fibrosis compared with untreated patients (64.1 vs. 75.3 %, p = 0.04). On multivariable analysis, chemotherapy treatment was a negative predictive factor for a low probability of fibrosis (OR 0.366 [95 % CI 0.184-0.708], p < 0.01). Among chemotherapy-treated patients, 75 (64.1 %) had a low probability of fibrosis. There were no differences in chemotherapy duration (mean 7.8 vs. 7.5 cycles) and interval from last dose to steatosis diagnosis (24.3 vs. 21.4 months) between patients with and without a low probability of fibrosis. A smaller proportion of patients treated with irinotecan or 5-fluorouracil had a low probability of fibrosis (37.3 vs. 66.7 %, p = 0.04). On multivariable analysis, irinotecan or 5-fluorouracil treatment was a negative predictive factor for low probability of fibrosis (OR 0.277 [95 % CI 0.091-0.779], p = 0.02). Prior chemotherapy treatment, especially with 5-fluorouracil or irinotecan, is a negative predictor for the absence of advanced hepatic fibrosis among patients with steatosis.
| S-EPMC4419370 | biostudies-literature
Project description:PurposeThe 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.MethodsBetween 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.ResultsAC 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).ConclusionAC 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.
| S-EPMC10915114 | biostudies-literature
Project description:BackgroundNonalcoholic fatty liver disease (NAFLD) and subsequent progression to fibrosis is increasingly prevalent in people with HIV (PWH). We used noninvasive methods to stratify risk and identify associated factors of advanced fibrosis in PWH with NAFLD.MethodsWe conducted a retrospective study of PWH in our clinic from 2005 to 2022. We used liver imaging or biopsy reports to identify cases of hepatic steatosis after excluding specified etiologies. We used the Fibrosis-4 (FIB-4), NAFLD Fibrosis (NFS), and body mass index, aspartate transaminase/alanine transaminase ratio, and diabetes score scores to stratify fibrosis. We used logistic regression to identify factors associated with advanced fibrosis.ResultsAmong 3959 PWH in care, 1201 had available imaging or liver biopsies. After exclusions, 114 of 783 PWH had evidence of hepatic steatosis (14.6%). Most were male (71.1%), with a median age of 47 years, and median body mass index of 30.1 kg/m2. Approximately 24% had lean NAFLD (ie, body mass index < 25 kg/m2). Based on the FIB-4 and NFS, 34 (29.8%) and 36 (31.6%) had advanced fibrosis, whereas 1 in 4 had low risk of fibrosis based on FIB-4, NFS, and BARD scores. In adjusted analysis using FIB-4, advanced fibrosis was associated with age > 45 years (adjusted odds ratio, 6.29; 95% confidence interval, 1.93-20.50) and hypoalbuminemia (adjusted odds ratio, 9.45; 95% confidence interval, 2.45-32.52) in addition to elevated transaminases and thrombocytopenia, whereas using the NFS did not identify associations with advanced fibrosis.ConclusionsWe found 14.6% of PWH had NAFLD, with 1 in 3 having advanced fibrosis. Our study provides practical insights into fibrosis risk stratification in HIV primary care settings.
| S-EPMC10878060 | biostudies-literature
Project description:Metabolic dysfunction-associated fatty liver disease (MAFLD), formerly known as nonalcoholic fatty liver disease, is the most prevalent liver disorder worldwide. Historically, its diagnosis required biopsy, even though the procedure has a variable degree of error. Therefore, new non-invasive strategies are needed. Consequently, this article presents a thorough review of biopsy-free scoring systems proposed for the diagnosis of MAFLD. Similarly, it compares the severity of the disease, ranging from hepatic steatosis (HS) and nonalcoholic steatohepatitis (NASH) to fibrosis, by contrasting the corresponding serum markers, clinical associations, and performance metrics of these biopsy-free scoring systems. In this regard, defining MAFLD in conjunction with non-invasive tests can accurately identify patients with fatty liver at risk of fibrosis and its complications. Nonetheless, several biopsy-free scoring systems have been assessed only in certain cohorts; thus, further validation studies in different populations are required, with adjustment for variables, such as body mass index (BMI), clinical settings, concomitant diseases, and ethnic backgrounds. Hence, comprehensive studies on the effects of age, morbid obesity, and prevalence of MAFLD and advanced fibrosis in the target population are required. Nevertheless, the current clinical practice is urged to incorporate biopsy-free scoring systems that demonstrate adequate performance metrics for the accurate detection of patients with MAFLD and underlying conditions or those with contraindications of biopsy.
| S-EPMC8792949 | biostudies-literature
Project description:BackgroundThe systemic immune-inflammation index (SII) is a novel marker of inflammation, and hepatic steatosis and fibrosis are associated with inflammation. This study aimed to investigate the possible relationship between SII and hepatic steatosis and fibrosis.MethodsThe datasets from the National Health and Nutrition Examination Survey (NHANES) 2017-2020 were used in a cross-sectional investigation. Multivariate linear regression models were used to examine the linear connection between SII and controlled attenuation parameter (CAP) and liver stiffness measurement (LSM). Fitted smoothing curves and threshold effect analysis were used to describe the nonlinear relationship.ResultsThis population-based study included a total of 6,792 adults aged 18-80 years. In a multivariate linear regression analysis, a significant positive association between SII and CAP was shown [0.006 (0.001, 0.010)]. This positive association in a subgroup analysis was maintained in men [0.011 (0.004, 0.018)] but not in women. Furthermore, the association between SII and CAP was nonlinear; using a two-segment linear regression model, we found an inverted U-shaped relationship between SII and CAP with an inflection point of 687.059 (1,000 cells/µl). The results of the multiple regression analysis showed that the relationship between SII and LSM was not significant (P = 0.263).ConclusionsOur findings imply that increased SII levels are linked to hepatic steatosis, but SII is not linked to liver fibrosis. To confirm our findings, more large-scale prospective investigations are needed.
| S-EPMC9520084 | biostudies-literature
Project description:BackgroundThe rising prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) has led to an increased occurrence of steatotic liver grafts (SLG) in liver transplantation (LT). However, the implications of SLG on post-transplant de novo hepatic steatosis (PTHS) and advanced fibrosis (≥F3) remain uncertain. This study aimed to characterize PTHS and ≥ F3 using magnetic resonance imaging (MRI) in patients who underwent LT for non-MASLD indications and to examine their relationship with SLG.MethodsPost-LT patients with implant biopsy fat content data were recruited for MRI assessments. MRI-proton density fat fraction (MRI-PDFF) and MR elastography (MRE) were performed using a 1.5 Tesla Optima 450 W MR scanner with a 3D volumetric sequence. PTHS and ≥ F3 were defined as MRI-PDFF ≥5% and MRE ≥3.64 kPa, respectively. SLG was defined as implant biopsy fat content ≥5%.ResultsA total of 292 patients (70.5% men, median age at LT: 51.9 years, 22.6% with SLG) were recruited. The majority (73.6%) were transplanted for hepatitis B virus (HBV)-related complications. MRI performed at a median of 12.2 years post-LT identified PTHS in 27.4 and 10.6% of patients. PTHS was independently associated with SLG (OR 2.067, 95% CI 1.082-3.951), central obesity (OR 3.952, 95% CI 1.768-8.832), and hypertension (OR 2.510, 95% CI 1.268-4.966). In contrast, ≥F3 was associated with sex, change in BMI, and abnormal liver biochemistry but not with PTHS or SLG.ConclusionMRI identified a high prevalence of PTHS, which was associated with SLG and metabolic risk factors among Chinese patients transplanted for non-MASLD indications. Advanced graft fibrosis was not associated with PTHS or SLG.
| S-EPMC11782125 | biostudies-literature
Project description:Non-alcoholic fatty liver disease (NAFLD) is strongly associated with dyslipidemia, and the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) is a more comprehensive indicator of lipids. This study aimed to investigate the association between NHHR and hepatic steatosis and liver fibrosis. The 2017-2020 national health and nutrition examination survey (NHANES) dataset was used for the cross-sectional survey. NHHR was calculated by lipid profiling, and the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) were determined by vibration-controlled transient elastography (VCTE). Multiple linear regression models were used to test the linear association between NHHR and hepatic steatosis and liver fibrosis. Fitted smoothing curves and threshold effect analysis were used to describe the nonlinear relationships. This population-based study included 6575 adults (≥ 18 years). After adjusting for covariates, we found a U-shaped association between NHHR and hepatic steatosis, with a breakpoint of 1.26. There was a negative association on the left side of the breakpoint (OR [95% CI] - 24.31 [- 43.92, - 4.70]) and a positive association on the right side of the breakpoint (OR [95% CI] 3.82 [2.05, 5.59]). There was no significant association between NHHR and liver fibrosis. In addition, subgroup analyses and interaction tests showed stable results. In summary, NHHR has a U-shaped association with hepatic steatosis and no significant association with liver fibrosis. Keeping NHHR below 1.26 may be an effective option to reduce the risk of hepatic steatosis. NHHR is a more efficient and cost-effective marker for NAFLD surveillance that can be utilized in future clinical practice.
| S-EPMC11897350 | biostudies-literature
Project description:Advanced chronic liver disease (aCLD) represents a major public health concern. aCLD is more prevalent and severe in the elderly, carrying a higher risk of decompensation. We aimed at understanding how aging may impact on the pathophysiology of aCLD in aged rats and humans and secondly, at evaluating simvastatin as a therapeutic option in aged animals. aCLD was induced in young (1 month) and old (16 months) rats. A subgroup of aCLD-old animals received simvastatin (5 mg/kg) or vehicle (PBS) for 15 days. Hepatic and systemic hemodynamic, liver cells phenotype and hepatic fibrosis were evaluated. Additionally, the gene expression signature of cirrhosis was evaluated in a cohort of young and aged cirrhotic patients. Aged animals developed a more severe form of aCLD. Portal hypertension and liver fibrosis were exacerbated as a consequence of profound deregulations in the phenotype of the main hepatic cells: hepatocytes presented more extensive cell-death and poorer function, LSEC were further capillarized, HSC over-activated and macrophage infiltration was significantly increased. The gene expression signature of cirrhosis significantly differed comparing young and aged patients, indicating alterations in sinusoidal-protective pathways and confirming the pre-clinical observations. Simvastatin administration for 15-day to aged cirrhotic rats improved the hepatic sinusoidal milieu, leading to significant amelioration in portal hypertension. This study provides evidence that aCLD pathobiology is different in aged individuals. As the median age of patients with aCLD is increasing, we propose a real-life pre-clinical model to develop more reliable therapeutic strategies. Simvastatin effects in this model further demonstrate its translational potential.
| S-EPMC6675529 | biostudies-literature
Project description:BackgroundMetabolic syndrome (MetS) is a group of factors associated with increased risks of cardiovascular disease and overall mortality. Nonalcoholic fatty liver disease (NAFLD) is a common disorder that has been shown to cause hepatic steatosis and fibrosis. The relationship between NAFLD and MetS appears to be bidirectional, but very few studies have examined the role of MetS in hepatic steatosis and fibrosis. The present study investigated the relationships between MetS and its components and the severity of hepatic fibrosis and steatosis, and fibrosis independent of steatosis.MethodsThe study was a cross-sectional population-based survey of 4,678 National Health and Nutrition Examination Survey participants from 2017 to 2018 in the United States. Hepatic fibrosis and steatosis were measured using liver elastography. The MetS components were assessed using demographic, examination, laboratory, and self-reported data.ResultsUsing survey-weighted population estimates, 26% of the population had steatosis, 7.5% had fibrosis, and 3.3% had fibrosis without steatosis. The adjusted odds ratio for any level of steatosis was 4.12 times higher (95% confidence interval [CI], 3.16-5.37) and any level of fibrosis was 3.34 times higher (95% CI, 2.26-4.94) among participants with MetS than those without. The adjusted odds ratio for fibrosis without steatosis is 2.67 times higher (95% CI, 1.47-4.87) among participants with MetS than those without.ConclusionThe presence of MetS significantly increases the risk of hepatic fibrosis and steatosis, providing evidence for MetS to be considered an additional independent risk factor for hepatic fibrosis together with other known etiologies.
| S-EPMC8987451 | biostudies-literature