Risk Factors For Significant Fibrosis Research Articles

From NAFLD to MASLD: When metabolic comorbidity matters

Introduction and ObjectivesIn a recent development, a cohort of hepatologists has proposed altering the nomenclature of non-alcoholic fatty liver disease (NAFLD) to metabolic-associated steatotic liver disease (MASLD), accompanied by modified diagnostic criteria. Our objective was to investigate the effect of the revised definition on identifying significant hepatic fibrosis. Patients and MethodsFrom Jan 2009 to Dec 2022, a total of 428 patients with biopsy-proven hepatic steatosis were diagnosed with NAFLD. Patients were classified into subgroups according to MASLD and Cryptogenic-SLD diagnostic criteria. The clinical pathological features were compared between these two groups. Risk factors for significant fibrosis were analysed in the MASLD group. In total, 329 (76.9 %) patients were diagnosed with MASLD, and 99 (23.1 %) were diagnosed with Cryptogenic-SLD. ResultsThose with MASLD exhibited a higher degree of disease severity regarding histology features than Cryptogenic-SLD. The prevalence of significant fibrosis increased from 13 % to 26.6 % for one and two criteria present to 42.5 % for meeting three or more cardiometabolic risk factor (CMRF) criteria (p = 0.001). ALB (aOR:0.94,95 %CI:0.90-1.00; p = 0.030), lower levels of PLT (aOR:0.99, 95 %CI:0.99-1.00; p < 0.001), and more metabolic comorbidities (aOR:1.42,95 %CI:1.14-1.78; p = 0.012) were independent risk factors of significant fibrosis in MASLD. ConclusionsThe new nomenclature of MASLD and SLD is more applicable to identifying significant fibrosis than NAFLD. Patients with three or more cardiometabolic risk factors are at higher risk of fibrosis.

Perlemakan Hati Non-Alkoholik dan Risiko Fibrosis Hati pada Pasien Hepatitis B Kronik

Introduction. Prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing throughout the world due to sedentary lifestyle and dietary habit, including in patients with chronic hepatitis B (CHB). In several studies, advanced of liver disease were more likely observed among those CHB patients with NAFLD. NAFLD might increase the risk of liver disease progression in CHB patients, but prior investigations were still limited. This study aimed to determine the association between NAFLD and risk of liver fibrosis in CHB patients. Methods. All patients with positive serum hepatitis B surface antigen in the Hepatobilier Data Registry, Cipto Mangunkusumo Hospital, were included in this study. Based on abdominal ultrasonography, patients were divided into two group (group I: non-NAFLD – hepatitis B patients vs. group II: NAFLD – hepatitis B patients). Data demographic and clinical examination were collected. Significant liver fibrosis was defined as stage liver fibrosis above 7 kPa (≥ F2). Logistic regression was used to identify NAFLD as risk factor for significant fibrosis. Variables were expressed as prevalence odd ratio (POR) with 95% CI. P values &lt;0.05 were considered statistically significant. Results. Among 130 hepatitis B patients, 45 patients (34.6%) were diagnosed with NAFLD. Of 45 patients in group II, 36 patients (80%) had significant liver fibrosis. It was observed that a higher percentage of patients in group II were HBeAg negative compared to those in group I (66.7% vs. 35.9%; p=0.038). Furthermore, group II also displayed higher levels of liver stiffness compared to group I (12.22 (8.6 kPa) vs. 8.57 (7.8 kPa); p 0.016). In multivariate analysis, NAFLD was significantly associated with significant liver fibrosis (POR: 5.87; CI95%: 2.48 – 13.86; p &lt; 0.001) after adjusted with HBeAg status. Conclusion. NAFLD associated with the higher risk of liver fibrosis in patients with hepatitis B. Modification of lifestyle and potential therapeutic intervention may help in reducing the progression of liver fibrosis.

THU-469 - Risk factors for significant fibrosis in non-obese Asian patients with NAFLD

THU-469 - Risk factors for significant fibrosis in non-obese Asian patients with NAFLD

Elevated coffee consumption is associated with a lower risk of elevated liver fibrosis biomarkers in patients treated for chronic hepatitis B (ANRS CO22 Hepather cohort)

Patients chronically infected with hepatitis B virus (HBV) are at high risk of liver fibrosis, cirrhosis and liver cancer, despite recent therapeutic advances. It is therefore crucial to find non-pharmaceutical options for liver fibrosis prevention in this population. Using cross-sectional data from the ANRS CO22 Hepather cohort, we aimed to identify socio-demographic and modifiable risk factors for significant fibrosis in chronic HBV patients. Logistic regression or Firth's penalized maximum likelihood logistic regression (according to outcome prevalence) multivariable models were used to test for associations between explanatory variables and significant fibrosis, as assessed by three non-invasive markers: aspartate aminotransferase to platelet ratio index (APRI), FIB-4, and gamma glutamyltransferase to platelet ratio (GPR). Analyses were stratified by HBV treatment status. The study population comprised 2065 untreated and 1727 treated chronic HBV patients. Elevated coffee consumption was consistently associated with a lower risk of elevated fibrosis biomarkers in all three treated-participant models, suggesting a dose-response relationship (adjusted odds ratios for ≥3 cups/day versus 0 cups/day: 0.16, 0.35 and 0.62, p≤0.002, according to APRI, FIB-4 and GPR, respectively). Other modifiable risk factors included tobacco and alcohol use. Elevated coffee consumption was consistently associated with a lower risk of significant liver fibrosis, as assessed by three non-invasive markers in treated chronic HBV patients. This result can be immediately used in real-world situations, as increasing coffee consumption may be beneficial for patients at risk of advanced liver disease.

Liver Fibrosis in Asians With Metabolic Dysfunction–Associated Fatty Liver Disease

This study aimed to evaluate risk factors associated with liver fibrosis in metabolic dysfunction-associated fatty liver disease (MAFLD). A cross-sectional study of 967 Korean patients with MAFLD involved a cohort from a health screening program during the years 2015-2018. The patients were classified into 4 MAFLD subgroups: group 1 (overweight). group 2 (obese), group 3 (lean/normal weight with metabolic abnormalities), and group 4 (diabetes). Liver fibrosis was assessed based on liver stiffness measurement (LSM) value using 2-dimensional real-time magnetic resonance elastography. We investigated differences in liver fibrosis according to MAFLD subgroup classification and determined the risk factors for significant fibrosis. The mean age was 50.8 years, and 869 (90%) patients were male. The mean value of LSM in magnetic resonance elastography was 2.48 ± 0.47 kPa. Significant fibrosis (LSM ≥2.97 kPa) was observed in 66 (6.8%) of 967 patients. The proportion of significant fibrosis in MAFLD group 1, group 2, group 3, and group 4 was 1.3%, 5.5%, 6.4%, and 18.9%, respectively (P < .001). Multivariable analysis indicated that the risk factors for significant fibrosis were serum ferritin ≥300 ng/mL (odds ratio [OR], 1.96; 95% confidence interval [CI], 1.10-3.49; P= .023), Fibrosis-4 ≥1.3 (OR, 2.97; 95% CI, 1.68-5.24; P < .001), homeostatic model assessment of insulin resistance ≥2.0 (OR, 2.60; 95% CI, 1.25-5.43; P= .011), metabolic syndrome (OR, 2.53; 95% CI, 1.31-4.88; P= .006), and MAFLD group 4 (OR, 6.93; 95% CI, 1.96-24.51; P= .003). However, the etiology of liver disease was not statistically associated with liver fibrosis. Liver fibrosis in patients with MAFLD varies according to subgroup classification based on diabetes, body mass index, and metabolic risk factors.

Development and validation of a noninvasive clinical scoring system to predict significant fibrosis in patients with nonalcoholic fatty liver disease

BackgroundThe aims of this study were to identify risk factors for significant fibrosis (SF) by assessing physical and laboratory parameters and develop and validate a clinical score and nomogram for the prediction of SF in patients with nonalcoholic fatty liver disease (NAFLD). MethodsThis retrospective study included 225 patients with histologically confirmed NAFLD who were divided into two cohorts using 10-fold cross validation for model training and validation. The clinical score and nomogram were used to predict the NAFLD outcome. ResultsThe model for predicting SF (stage ≥ 2) including the free T4/free T3 ratio, low-density lipoprotein cholesterol, homeostatic model assessment for insulin resistance (HOMA-IR), percentage of appendicular skeletal muscle mass and aspartate aminotransferase (AST) level in the training and validation cohorts yielded an area under the receiver operator characteristic curve (AUROC) of 0.79 and 0.78, respectively. The AUROC of the combined clinical score for the prediction of SF was 0.82 (95% CI, 0.75–0.89) at a cutoff value of 3 points, with a sensitivity (SE) of 77.19%, specificity (SP) of 82.88%, positive predictive value (PPV) of 63.77%, and negative predictive value (NPV) of 90.30%. The nomogram had good performance in quantitatively predicting the risk probability of SF. ConclusionOur study showed that a noninvasive clinical scoring system using easily available physical and laboratory variables can identify patients with NAFLD with or without SF with a high degree of accuracy. Application of this system may decrease the need for staging liver biopsy specimens and allow early identification and intervention in these high-risk patients.

Risk factors for significant fibrosis differently affect patients with non-alcoholic liver disease depending on gender

Background: Several risk factors are involved in non-alcoholic fatty liver disease (NAFLD) progression, but whether their role is different in males (M) and females (F) is unclear. The aim of this study is to verify whether NAFLD-related risk factors differently affect the disease according to gender.

Changes in Circulating Lysyl Oxidase-Like-2 (LOXL2) Levels, HOMA, and Fibrosis after Sustained Virological Response by Direct Antiviral Therapy.

Background: we aimed to assess the influence of metabolic syndrome on fibrosis regression (using liver-stiffness measurement (LSM) and serological scores) and the relationship with the expression of lysyl oxidase-like-2 as a potential goal of antifibrotic therapy. Methods: We included 271 patients treated with Direct Antiviral Therapy (DAAs) in our hospital who achieved a sustained virological response (SVR); physical examination, blood tests, and LSM were made at baseline (B) and 24 months (24 M) after SVR. Hemodynamic studies and transjugular liver biopsies were performed on 13 patients. Results: At B, 68 patients were F1 (25.1%); F2 n = 59 (21.7%); F3 n = 44 (16.05%); and 100 were F4 (36.9%). Although the LSM (absolute value) improved in 82% of patients (n = 222), it progressed in 17.5% of patients (n = 48). At 24 M, 48 patients met the metabolic syndrome (MetS) criteria and there was an increase in patients with a BMI of >25 kg/m2 (p < 0.001). At B and 24 M, a BMI of >25 kg/m2 is a risk factor for significant fibrosis or steatosis at 24 M (p < 0.05) and progression on LSM (p < 0.001), as well as MetS at B and 24 M (OR 4.1 IC (1.4–11.7), p = 0.008; and OR 5.4 IC (1.9–15.4), p = 0.001, respectively). Regarding the correlation between LSM and the liver biopsy, we found that only six out of 13 patients had a matching LSM and biopsy. We found a statistically significant decrease in LOXL2 levels at 24 M with respect to B (p < 0.001) with higher serological value in patients with elastography of >9 kPa vs. <9 kPa (p = 0.046). Conclusion: Regression of LSM was reached in 82% of patients. Downregulated LOXL2 was demonstrated post-SVR, with overexpression in cirrhotic patients being a potential therapy goal in selected patients.

Brief Report: HIV/HBV Coinfection is a Significant Risk Factor for Liver Fibrosis in Tanzanian HIV-Infected Adults.

In sub-Saharan Africa, the burden of liver disease associated with chronic hepatitis B virus (HBV) and HIV is unknown. We characterized liver disease using aspartate aminotransferase-to-platelet ratio index (APRI) and FIB-4 in patients with HIV, HBV, and HIV/HBV coinfection in Tanzania. Using a cross-sectional design, we compared the prevalence of liver fibrosis in treatment-naive HIV monoinfected, HBV monoinfected, and HIV/HBV-coinfected adults enrolled at Management and Development for Health (MDH)-supported HIV treatment clinics in Dar es Salaam, Tanzania. Risk factors associated with significant fibrosis (APRI >0.5 and FIB-4 >1.45) were examined. Two hundred sixty-seven HIV-infected, 165 HBV-infected, and 63 HIV/HBV-coinfected patients were analyzed [44% men, median age 37 (interquartile range 14), body mass index 23 (7)]. APRI and FIB-4 were strongly correlated (r = 0.78, P < 0.001, R = 0.61). Overall median APRI scores were low {HIV/HBV [0.36 (interquartile range 0.4)], HIV [0.23 (0.17)], HBV [0.29 (0.15)] (P < 0.01)}. In multivariate analyses, HIV/HBV coinfection was associated with APRI >0.5 [HIV/HBV vs. HIV: odds ratio (OR) 3.78 (95% confidence interval: 1.91 to 7.50)], [HIV/HBV vs. HBV: OR 2.61 (1.26 to 5.44)]. HIV RNA per 1 log10 copies/mL increase [OR 1.53 (95% confidence interval: 1.04 to 2.26)] and HBV DNA per 1 log10 copies/mL increase [OR 1.36 (1.15, 1.62)] were independently associated with APRI >0.5 in HIV-infected and HBV-infected patients, respectively. HIV/HBV coinfection is an important risk factor for significant fibrosis. Higher levels of circulating HIV and HBV virus may play a direct role in liver fibrogenesis. Prompt diagnosis and aggressive monitoring of liver disease in HIV/HBV coinfection is warranted.

Liver fibrosis and fatty liver in Asian HIV-infected patients.

Little is known about the importance of liver fibrosis and fatty liver in HIV-monoinfected individuals without hepatitis virus co-infection, particularly among the Asian population. To evaluate prevalence and risk factors for liver fibrosis and fatty liver in Asian HIV-monoinfected individuals. Eighty asymptomatic HIV-monoinfected individuals (tested negative for HBV/HCV) were compared with 160 matched HIV-uninfected healthy controls. Transient elastography and proton-magnetic resonance spectroscopy ((1) H-MRS) were performed to measure liver stiffness and hepatic steatosis respectively. Blood samples were analysed for metabolic profiles and markers of steatohepatitis (e.g. cytokeratin-18). All HIV-infected individuals (mean ± s.d. age 54 ± 11 years, male 93%, Chinese 94%; diagnosis median duration 8 (IQR 4-13 years) were stable on anti-retrovirals (PI-based 58.7%, NNRTI-based 25.0% integrase-inhibitors 16.3%); diabetes, dyslipidaemia, and metabolic syndrome were common. Fatty liver disease was detected in 28.7%. There was significantly higher degree of liver stiffness [4.9 (IQR 4.1-6.2) kPa vs. 4.2 (IQR 3.6-5.0) kPa, P < 0.001], and greater proportions developed significant fibrosis (7.0 kPa, 14.3% vs. 3.1%, P = 0.001) and cirrhosis (10.3 kPa, 5.2% vs. 0.6%, P = 0.040) compared with controls. HIV infection was an independent risk factor for significant fibrosis (adjusted OR 4.00, 95% CI 1.29-12.41, P = 0.016). HIV-infected individuals with fatty liver had excessive liver stiffness and fibrosis. Two cases of asymptomatic hepatocellular carcinoma were detected. HIV-monoinfected patients are at risk for liver fibrosis and cirrhosis. HIV-related mechanisms and fatty liver disease may play important roles. Screening and intervention to prevent severe outcomes should be considered.

Elevated AST-to-platelet ratio index is associated with increased all-cause mortality among HIV-infected adults in Zambia.

We investigated the association between significant liver fibrosis, determined by AST-to-platelet ratio index (APRI), and all-cause mortality among HIV-infected patients prescribed antiretroviral therapy (ART) in Zambia. Among HIV-infected adults who initiated ART, we categorized baseline APRI scores according to established thresholds for significant hepatic fibrosis (APRI ≥1.5) and cirrhosis (APRI ≥2.0). Using multivariable logistic regression we identified risk factors for elevated APRI including demographic characteristics, body mass index (BMI), HIV clinical and immunological status, and tuberculosis. In the subset tested for hepatitis B surface antigen (HBsAg), we investigated the association of hepatitis B virus co-infection with APRI score. Using Kaplan-Meier analysis and Cox proportional hazards regression we determined the association of elevated APRI with death during ART. Among 20 308 adults in the analysis cohort, 1027 (5.1%) had significant liver fibrosis at ART initiation including 616 (3.0%) with cirrhosis. Risk factors for significant fibrosis or cirrhosis included male sex, BMI <18, WHO clinical stage 3 or 4, CD4(+) count <200 cells/mm(3) , and tuberculosis. Among the 237 (1.2%) who were tested, HBsAg-positive patients had four times the odds (adjusted odds ratio, 4.15; 95% CI, 1.71-10.04) of significant fibrosis compared HBsAg-negatives. Both significant fibrosis (adjusted hazard ratio 1.41, 95% CI, 1.21-1.64) and cirrhosis (adjusted hazard ratio 1.57, 95% CI, 1.31-1.89) were associated with increased all-cause mortality. Liver fibrosis may be a risk factor for mortality during ART among HIV-infected individuals in Africa. APRI is an inexpensive and potentially useful test for liver fibrosis in resource-constrained settings.

Prevalence and risk factors for significant liver fibrosis among HIV-monoinfected patients

BackgroundHIV-monoinfected patients may be at risk for significant liver fibrosis, but its prevalence and determinants in these patients are unknown. Since HIV-monoinfected patients do not routinely undergo liver biopsy, we evaluated the prevalence and risk factors of significant hepatic fibrosis in this group using the aspartate aminotransferase (AST)-to-platelet ratio index (APRI).MethodsWe conducted a cross-sectional study among HIV-infected patients negative for hepatitis B surface antigen and hepatitis C antibody in the Penn Center for AIDS Research Adult/Adolescent Database. Clinical and laboratory data were collected from the database at enrollment. Hypothesized determinants of significant fibrosis were modifiable risk factors associated with liver disease progression, hepatic fibrosis, or hepatotoxicity, including immune dysfunction (i.e., CD4 T lymphocyte count <200 cells/mm3, HIV viremia), diseases associated with hepatic steatosis (e.g., obesity, diabetes mellitus), and use of antiretroviral therapy. The primary outcome was an APRI score >1.5, which suggests significant hepatic fibrosis. Multivariable logistic regression identified independent risk factors for significant fibrosis by APRI.ResultsAmong 432 HIV-monoinfected patients enrolled in the CFAR Database between November 1999 and May 2008, significant fibrosis by APRI was identified in 36 (8.3%; 95% CI, 5.9 - 11.4%) patients. After controlling for all other hypothesized risk factors as well as active alcohol use and site, detectable HIV viremia (adjusted OR, 2.56; 95% CI, 1.02 - 8.87) and diabetes mellitus (adjusted OR, 3.15; 95% CI, 1.12 - 10.10) remained associated with significant fibrosis by APRI.ConclusionsSignificant fibrosis by APRI score was found in 8% of HIV-monoinfected patients. Detectable HIV viremia and diabetes mellitus were associated with significant fibrosis. Future studies should explore mechanisms for fibrosis in HIV-monoinfected patients.

Epidemiology of chronic hepatitis B infection in France: risk factors for significant fibrosis – results of a nationwide survey

Epidemiological data concerning hepatitis B are scarce in France. To describe epidemiological, clinical, virological and histological features of HBsAg-positive patients followed at non-academic hospitals in France. Clinical, biological, virological and histological data of all HBsAg-positive consecutive patients observed from April 1, 2001 to May 31, 2002 in participating centres were recorded prospectively. Multivariate analyses of factors associated with significant fibrosis and cirrhosis were performed. Nearly 1166 HBsAg-positive patients were seen in the 58 centres: 671 males and 495 females from metropolitan France (32%) and from outside metropolitan France (68%); mean age 41 +/- 15 years. Twenty-nine percent of patients were probable HBsAg inactive carriers, while 50% had chronic hepatitis; 43% of these were HBeAg-positive and 57% HBeAg-negative. Liver biopsy had been performed in 558 (51%) patients; 205 (17.6%) patients had cirrhosis. By multivariate analysis, factors associated with significant fibrosis were: age >40 years (P < 0.05), HBeAg-negative status (P < 0.02) and histological activity (P < 0.0001). Factors associated with cirrhosis: age (P < 0.0001), platelet count <150 000/mm(3) (P < 0.0001) and viral co-infection (P < 0.03). HBV infection represents a significant workload for hepatogastroenterologists at non-academic hospitals in France.

Clinical Outcomes of Living Donor Liver Transplantation for Hepatitis C Virus (HCV)-Positive Patients

Whether hepatitis C virus recurrence occurs earlier and with greater severity for living donor liver transplantation (LDLT) than for deceased donor liver transplantation (DDLT) has recently become a subject of debate. We retrospectively evaluated clinical outcomes for a cohort of 91 HCV-positive patients who underwent LDLT at Kyoto University with a median follow-up period of 25 months. Overall 5-year patient survival for HCV patients was similar to that for non-HCV patients (n=209) who underwent right-lobe LDLT at our institute (69% vs. 71%). Survival rate of patients without HCC (n=34) tended to be better than that of patients with HCC (n=57) (82% vs. 60%, P=0.069). According to annual liver biopsy, rate of fibrosis progression to stage 2 or more (representing significant fibrosis) was 39% at 2 years after LDLT. Univariate analysis showed that female recipient and male donor represented significant risk factors for significant fibrosis. Progression to severe recurrence (defined as the presence of liver cirrhosis (F4) in a liver biopsy and/or the development of clinical decompensation) was observed in five patients. Postoperative patient survival was similar for HCV-positive and -negative recipients in our adult LDLT series. Rates of progression to severe disease due to HCV recurrence seemed comparable between our LDLT recipients and DDLT recipients described in the literature. Although longer-term follow-up is required, our results suggest that LDLT can produce acceptable outcomes also for patients suffering from HCV-related cirrhosis.