Higher Risk Of Liver Fibrosis Research Articles

The effect of weight gain and metabolic dysfunction-associated steatotic liver disease on liver fibrosis progression and regression in people with HIV.

People with HIV (PWH) have high risk of liver fibrosis. We investigated the effect of weight gain and metabolic dysfunction-associated steatotic liver disease (MASLD) on liver fibrosis dynamics. Multicenter cohort study. Fibrosis progression was defined as development of significant fibrosis (liver stiffness measurement [LSM]≥8 kPa), or transition to cirrhosis (LSM≥13 kPa), for those with significant fibrosis at baseline. Fibrosis regression was defined as transition to LSM<8 kPa, or to LSM<13 kPa for those with cirrhosis at baseline. MASLD was defined as hepatic steatosis (controlled attenuation parameter >248 dB/m) with at least one metabolic abnormality. A continuous-time multi-state Markov model was used to describe transitions across fibrosis states. Among 1183 PWH included from three centres (25.2% with viral hepatitis coinfection), baseline prevalence of significant fibrosis and MASLD was 14.4% and 46.8%, respectively. During a median follow-up of 2.5 years (interquartile range 1.9-3.5) the incidence rate of fibrosis progression and regression was 2.8 (95% CI, 2.3-3.4) and 2.2 (95% CI, 1.9-2.6) per 100 person-years, respectively. In Markov model, weight gain increased the odds of fibrosis progression (odds ratio [OR] 3.11, 95% CI 1.59-6.08), whereas weight gain (OR 0.30, 95% CI 0.10-0.84) and male sex (OR 0.32, 95% CI 0.14-0.75) decreased the odds of fibrosis regression. On multivariable Cox regression analysis, predictors of fibrosis progression were weight gain (adjusted hazard ratio [aHR] 3.12, 95% CI 1.41-6.90) and MASLD (aHR 2.72, 95% CI 1.05-7.02). Fibrosis transitions are driven by metabolic health variables in PWH, independently of viral hepatitis coinfection and antiretroviral class therapy.

Metabolic Dysfunction–Associated Fibrosis 5 (MAF-5) Score Predicts Liver Fibrosis Risk and Outcome in the General Population With Metabolic Dysfunction

There is an unmet need for noninvasive tests to improve case-finding and aid primary care professionals in referring patients at high risk of liver disease. A metabolic dysfunction-associated fibrosis (MAF-5) score was developed and externally validated in a total of 21,797 individuals with metabolic dysfunction in population-based (National Health and Nutrition Examination Survey 2017-2020, National Health and Nutrition Examination Survey III, and Rotterdam Study) and hospital-based (from Antwerp and Bogota) cohorts. Fibrosis was defined as liver stiffness ≥8.0 kPa. Diagnostic accuracy was compared with FIB-4, nonalcoholic fatty liver disease fibrosis score (NFS), LiverRisk score and steatosis-associated fibrosis estimator (SAFE). MAF-5 was externally validated with liver stiffness measurement ≥8.0 kPa, with shear-wave elastography ≥7.5 kPa, and biopsy-proven steatotic liver disease according to Metavir and Nonalcoholic Steatohepatitis Clinical Research Network scores, and was tested for prognostic performance (all-cause mortality). The MAF-5 score comprised waist circumference, body mass index (calculated as kg / m2), diabetes, aspartate aminotransferase, and platelets. With this score, 60.9% was predicted at low, 14.1% at intermediate, and 24.9% at high risk of fibrosis. The observed prevalence was 3.3%, 7.9%, and 28.1%, respectively. The area under the receiver operator curve of MAF-5 (0.81) was significantly higher than FIB-4 (0.61), and outperformed the FIB-4 among young people (negative predictive value [NPV], 99%; area under the curve [AUC], 0.86 vs NPV, 94%; AUC, 0.51) and older adults (NPV, 94%; AUC, 0.75 vs NPV, 88%; AUC, 0.55). MAF-5 showed excellent performance to detect liver stiffness measurement ≥12 kPa (AUC, 0.86 training; AUC, 0.85 validation) and good performance in detecting liver stiffness and biopsy-proven liver fibrosis among the external validation cohorts. MAF-5 score >1 was associated with increased risk of all-cause mortality in (un)adjusted models (adjusted hazard ratio, 1.59; 95% CI, 1.47-1.73). The MAF-5 score is a validated, age-independent, inexpensive referral tool to identify individuals at high risk of liver fibrosis and all-cause mortality in primary care populations, using simple variables.

Breaking new ground: MASLD vs. MAFLD-which holds the key for risk stratification?

The classification and nomenclature of non-alcoholic fatty liver disease (NAFLD) has been the subject of ongoing debate in the medical community. Through the introduction of metabolic dysfunction-associated fatty liver disease (MAFLD) and the later release of metabolic dysfunction-associated steatotic liver disease (MASLD), the limitations associated with NAFLD are intended to be addressed. Both terminologies incorporate the metabolic component of the disease by providing diagnostic criteria that relies on the presence of underlying metabolic risk factors. An epidemiologic cross-sectional study of individuals who had undergone abdominal ultrasound and vibration-controlled transient elastography (VCTE) as part of a routine check was performed. We evaluated clinical, anthropometric, and biochemical variables to determine the metabolic profile of each subject. The study included a total of 500 participants, 56.8% (n = 284) males and 43.2% (n = 216) females, with a mean age of 49 ± 10years. 59.4% (n = 297) were diagnosed with MAFLD and MASLD, 10.2% (n = 51) were diagnosed only with MASLD and 30.4% (n = 152) were not diagnosed with either MAFLD or MASLD. The differences in prevalence were mainly based on the detection of individuals with a BMI < 25kg/m2, where MASLD captures the largest number (p < 0.001). Although MASLD has a higher capture of lean patients compared to MAFLD, patients with MAFLD and MASLD have a worse metabolic profile than those with only MASLD. Our results provide evidence that MAFLD better identifies patients likely to have a higher risk of liver fibrosis and of disease progression.

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 maleand 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 alsounderscores the importance of early detection and management of liver fibrosis in patients with diabetes.

Liver fibrosis in pars cohort study: A large-scale study on the prevalence and correlated factors

Backgrounds and study aimsThe fibrosis-4 (FIB-4) is a non-invasive scoring system for estimating liver fibrosis severity as a biomarker of chronic liver disease. We aimed to estimate the prevalence and severity of chronic liver disease at the community level using FIB-4. Patients and methodsThis cross-sectional study was conducted using the Pars Cohort database collected in Valashar, Fars province, Iran. Participants were divided into three groups based on their FIB-4 scores: low risk of liver fibrosis (FIB < 1.45), intermediate cases (1.45 ≤ FIB-4 ≤ 3.25), and high risk of liver fibrosis (FIB-4 > 3.25). ResultsIn total, 9269 individuals with a mean age of 52.65 years were enrolled in the study, of which 4278 (46.2 %) were male. Among all participants, 7853 (84.7 %) were in the low-risk, and 65 (0.7 %) were in the high-risk groups. In the final ordinal regression model, male gender, being a farmer or rancher, living in rural areas, history of opioid use, history of jaundice, no history of diabetes, history of depression, and positive HBs Ag were independently associated with higher FIB-4 scores. ConclusionOur study revealed that males, individuals residing in rural areas, and those engaged in farming and ranching occupations face a heightened risk of liver fibrosis. These findings emphasize the need for future programs for early detection and effective management of liver fibrosis in these at-risk populations.

Self-awareness of hepatitis C infection in the United States: A cross-sectional study based on the National Health Nutrition and Examination Survey.

Hepatitis C virus (HCV) is a global health issue with an estimated prevalence of 2.4 to 3 million people in the US and 58 million worldwide. Previous reports from the US have shown that close to half of those with the infection are unaware of their status. Although the current therapy for HCV is very effective, the primary barrier has been the inability to diagnose a large fraction of those infected. We studied public awareness of HCV in the US using National Health Nutrition and Examination Survey data from 2013 to 2020. Our aim was to measure awareness of infection in individuals with HCV and identify possible barriers to diagnosis. In total, 206 individuals with HCV were included in the weighted analysis. The weighted awareness of infection was 60.1%, suggesting that over 0.8 million are unaware nationally. Awareness was significantly low in the Mexican American and Asian populations. Non-US citizens and non-US-born individuals also had poor awareness. The transaminases were more elevated in those unaware of the infection, suggesting their higher risk of liver fibrosis. Although the proportion of infected people aware of their illness has been rising, over 0.8 million are still unaware of their infection and their risk of liver damage. We believe policy measures focused on further intense screening and educational campaigns, particularly in high-risk groups, are vital in realizing the World Health Organization's goal of eliminating HCV as a global health threat.

Association of fat-to-muscle ratio with non-alcoholic fatty liver disease: a single-centre retrospective study

ObjectivesSarcopenia is a known risk factor for non-alcoholic fatty liver disease (NAFLD). Studies evaluating the association between the fat-to-muscle ratio (FMR) and NAFLD are limited. Therefore, the aim of our...

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.

Association between Major Adverse Cardiovascular Events and the Liver Fibrosis Score in Patients with and without Coronary Artery Disease: From the FU-CCTA Registry.

The liver fibrosis score reflects the degree of hepatic scarring and has been reported to be associated with cardiovascular disease. Using a coronary artery computed tomography angiography registry at the Fukuoka University Hospital (FU-CCTA registry), we investigated the association between major adverse cardiovascular events (MACEs) and the liver fibrosis score (fibrosis-4 index (FIB-4I)) in 612 patients who underwent CCTA to screen for coronary artery disease and performed a prognosis survey for up to 5 years. The primary endpoint was MACEs (all-cause mortality, acute myocardial infarction, ischemic stroke, coronary revascularization). FIB-4I in all patients and in patients with hypertension (HTN) was significantly higher in the MACE group than in the non-MACE group. The event-free survival rate of MACEs targeting only patients with HTN was significantly lower in patients with a high risk of liver fibrosis (FIB-4I values of 2.67 or higher) than in those with a low or intermediate risk (less than 2.67). However, no significant difference was observed in all patients or in patients without HTN. Finally, FIB-4I and body mass index were independent factors associated with MACEs in patients with HTN. In conclusion, the liver fibrosis score may be an independent predictor of MACEs in hypertensive patients undergoing CCTA.

Liver fibrosis is associated with an increased risk of non-fatal myocardial infarction.

Liver fibrosis is a risk factor for liver-related adverse outcomes and cardiovascular disease (CVD). Recently, the non-invasive Hepamet fibrosis score (HFS) has been validated as a tool capable to identify with good diagnostic accuracy subjects with advanced liver fibrosis. It is unsettled whether HFS is capable to identify individuals at higher risk of CVD. To investigate whether individuals with liver fibrosis measured with HFS have higher risk of myocardial infarction (MI) in adults participating in the CATAnzaro MEtabolic RIsk factors (CATAMERI) study. Participants (n = 2948) were divided into three groups according to HFS: low risk of fibrosis (<0.12); intermediate risk of fibrosis (≥0.12 to <0.47); high risk of fibrosis (≥0.47). The association between the liver fibrosis risk and MI was analysed by a logistic regression analysis. As compared with those having the lowest risk (5.3%), a higher proportion of subjects with moderate or high risk of liver fibrosis had MI (12.9% and 24.4%, respectively; p < 0.001). In a logistic regression analysis, individuals at increased risk of liver fibrosis exhibited a threefold increased risk of having MI as compared to those with low risk (OR 3.18; 95% CI 1.31-7.70) independently of confounders including smoking, cholesterol, triglycerides, anti-hypertensive, lipid-lowering and glucose-lowering therapies. In this cross-sectional study, individuals with higher values of HFS show a higher risk of MI, suggesting that HFS may be a useful tool to identify not only individuals with liver fibrosis but also those at the increased risk of CVD.

Liver fibrosis markers and all cause mortality in people with type 2 diabetes: A population based study (The Ayrshire Diabetes Outcomes Cohort (ADOC) Study).

To describe the distribution of the biomarker scores Fibrosis-4 (FIB4), nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS), and aspartate aminotransferase to platelet ratio index (APRI), and the associations between risk categories and all-cause mortality. This was a retrospective cohort study of 12 589 patients, with follow-up from January 2012 until November 2021. The cut-off points used to identify low risk were: FIB4 <1.3 if aged <65 years or <2.0 if aged ≥65 years; NFS < -1.455 if aged <65 years or <0.12 if aged ≥ 65 years; APRI <1 (independent of age). High-risk cut-off points were FIB4 >2.67, NFS >0.676 and APRI ≥1 (all independent of age). Multivariable Cox regression analysis was performed to assess the association between liver fibrosis scores and all-cause mortality. The mean ± standard deviation age was 65.2 ± 12.1 years, 54.5% were men and the median (interquartile range) diabetes duration was 5.8 (2.8-9.3) years. The prevalence of high-risk categories was 6.1% for FIB4, 23.5% for NFS and 1.6% for APRI. During a median follow-up of 9.8 years, 3925 patients (31.1%) died, resulting in a crude mortality rate of 40.4 per 1000 person-years. The overall adjusted all-cause mortality hazard ratios (95% confidence intervals [CIs]) in the high- compared with low-fibrosis-risk groups were 3.69 (1.95-2.75) for FIB4, 2.32 (2.88-4.70) for NFS, and 3.92 (2.88-5.34) for APRI. Stratified adjusted all-cause mortality hazard ratios for individuals under 65 years and people over 65 years of age at cohort entry were 3.89 (95% CI 2.99-5.05) and 1.44 (95% CI 1.28-1.61) for FIB4, 2.50 (95% CI 1.89-3.18) and 1.35 (95% CI 1.24-1.48) for NFS and 3.74 (95% CI 2.73-5.14) and 1.64 (95% CI 1.24-2.17) for APRI. All three fibrosis risk scores were positively associated with all-cause mortality in people with type 2 diabetes, with higher relative risks in younger than older people. Effective interventions are required to minimize excess mortality in people at high risk of liver fibrosis.

Association between liver fibrosis and decreased myocardial mechano-energetic efficiency in individuals with different degree of glucose tolerance

AimDecreased myocardial mechano-energetic efficiency (MEEi) is associated with NAFLD and poorer prognosis in liver cirrhosis. We aim to investigate the association between liver fibrosis severity and MEEi in individuals participating in the CATAnzaro MEtabolic RIsk factors (CATAMERI) study. MethodsMyocardial MEEi, assessed by an echocardiography-derived measure, and fibrosis severity, estimated by the fibrosis-4 index (FIB-4), were evaluated in 2383 subjects with different degree of glucose tolerance. Participants were divided into four groups according to FIB-4 index values: lowest risk of fibrosis (<1.3); low risk of fibrosis (≥1.3 to < 1.67); moderate risk of fibrosis (≥1.67 to < 2.67); high risk of fibrosis (≥2.67). ResultsSubjects with higher risk of liver fibrosis displayed a graded decrease in myocardial MEEi compare to those with the lowest risk of liver fibrosis. In a multivariable regression analysis, FIB-4 index was independently associated with MEEi (β = -0.080, P < 0.001), along with total cholesterol (β = -0.067, P = 0.01), hsCRP (β = -0.081, P < 0.001), sex (β = -0.099, P < 0.001), glucose tolerance status (β = -0.109, <0.001) and HOMA-IR index (β = -0.143, P < 0.001). ConclusionCompromised myocardial MEEi is already reported in individuals with high risk of hepatic fibrosis suggesting that its assessment may help to identify among subjects with NAFLD those with worst prognosis.

Cleaning up alpha-1 antitrypsin deficiency related liver disease.

Alpha-1 antitrypsin deficiency (AATD) is one of the most common genetic disorders arising due to mutations in alpha-1 antitrypsin (AAT) gene affecting primarily the lung and the liver. This review summarizes the pathophysiology and clinical manifestation of different AATD genotypes and discusses the recent therapeutic developments. The focus is on the severe, rare homozygous Pi∗ZZ and the common heterozygous Pi∗MZ genotype. Pi∗ZZ individuals harbor an up to 20 times higher risk of liver fibrosis and cirrhosis than noncarriers and liver transplantation is currently the only available therapeutic option. AATD constitutes a proteotoxic disorder arising from hepatic AAT accumulation and the currently most promising data come from a phase 2, open-label trial of fazirsiran, a hepatocyte-targeted siRNA. Pi∗MZ subjects display an increased risk of advanced liver disease and at the latter stage, a faster deterioration than individuals without AAT mutation. Although the fazirsiran data offer a glimpse of hope to AATD patients, a consensus on appropriate study endpoint, a careful patient selection as well as monitoring of long-term safety will be essential for an approval.

Blood pressure stratification for predicting liver fibrosis risk in metabolic dysfunction associated fatty liver disease

Introduction and ObjectivesThe optimal blood pressure (BP) range for patients with metabolic dysfunction-associated fatty liver disease (MAFLD) is currently unknown. This study aimed to explore the relationship between stratified BP levels and MAFLD progression. Patients and MethodsThe data of adults who underwent yearly health check-ups were screened to establish both a cross-sectional and a 6-year longitudinal cohort of individuals with MAFLD. BP was classified into the following categories optimal, normal, high-normal, and hypertension. Liver fibrosis was diagnosed with fibrosis-4 (FIB-4) score, nonalcoholic fatty liver disease fibrosis score (NFS), and aspartate aminotransferase-to-platelet ratio index (APRI). ResultsA total of 10,232 individuals were included in the cross-sectional cohort. In the MAFLD population, individuals with liver fibrosis had significantly higher BP levels and hypertension prevalence (P < 0.001) than those without. Furthermore, liver fibrosis score was significantly associated with BP levels (P < 0.001). In the 6-year longitudinal cohort of 3661 individuals with MAFLD without liver fibrosis, the incidence rates of liver fibrosis increased with increasing BP levels as follows optimal=11.20%, normal=13.90%, high-normal=19.50%, hypertension=26.20% (log-rank 22.205; P < 0.001). Cox regression analysis showed that both baseline high-normal BP (hazard ratio [HR], 1.820; P=0.019) and hypertension (HR, 2.656; P < 0.001) were predictive of liver fibrosis. ConclusionsBP stratification may be useful in predicting the progression of MAFLD. Individuals having MAFLD with concurrent hypertension or high-normal BP are at a higher risk of liver fibrosis. These findings may provide a criteria for early intervention of MAFLD to prevent liver fibrosis.

Liver Fibrosis and Hearing Loss in an Older Mediterranean Population: Results from the Salus in Apulia Study.

Aging is the main negative prognostic factor for various chronic diseases, such as liver fibrosis, and clinical disorders such as hearing loss. This study aimed to investigate the association between age-related hearing loss (ARHL) and age-related central auditory processing disorder (CAPD), and the risk for liver fibrosis in a cross-sectional study on an aging population. Liver fibrosis risk was judged on the fibrosis-4 (FIB-4) score. Peripheral ARHL was evaluated with pure tone audiometry using a calibrated audiometer. The pure tone average (PTA), calculated as a threshold ≤ 40 dB (HL) in the better ear, was measured at the frequencies 0.5-4 kHz. For age-related CAPD assessment, we employed the Synthetic Sentence Identification with an Ipsilateral Competitive Message test (SSI-ICM). General linear Logistic regression models were used to estimate the association. The increase in the PTA 0.5-2 kHz (coefficient: 0.02, SE: 0.01, CI 95%: 0.01 to 0.03) was directly associated with a higher risk of liver fibrosis (FIB-4 ≥ 2.67). Moreover, the reduction in SSI (coefficient: -0.02, SE: 0.01, CI 95%: -0.03 to -0.01) was inversely associated with FIB-4 values &lt; 2.67. Our results show an association between liver fibrosis and both ARHL and CAPD, linked by the typical consequence of aging. We also assume a role of inflammatory responses and oxidative stress.

Associations between neck circumference and markers of dysglycemia, non-alcoholic fatty liver disease, and dysmetabolism independent of Body Mass Index in an Emirati population.

AimNeck circumference (NC) is quick and easy to measure and may be a useful surrogate marker for body composition. We investigated NC as a potential marker of dysglycemia, MetS, and NAFLD.Methods674 individuals were recruited at the Imperial College London Diabetes Centre in a study of sleep apnea prevalence. Of these, 547 (Age 46 ± 11.4 years, Body Mass Index (BMI) 31 ± 6 kg/m2, 279 (51%) female, 113 normal glucose tolerance (NGT), 108 Prediabetes, 326 Type 2 diabetes (T2DM)) met all inclusion criteria for analysis. NC was measured at the thyroid cartilage, and collar size was recorded. Analysis was performed using univariate and multivariate linear regression.ResultsAdjusted for BMI, sex, and age, NC was 0.65 ± 0.3 cm greater in prediabetes (p = 0.0331), and 1.07 ± 0.28 cm greater in T2DM, compared with NGT (p = 0.0002). Adjusting for BMI, sex, and glycemic status, 1-cm increase in NC was associated with a 1.04 ± 1.01 U/L (p <0.0001) increase in ALT and, additionally, correcting for statin use, a 0.03 ± 0.01 mmol/L reduction in HDL (p <0.0001) and a 0.1 ± 0.02 increase in TC : HDL. A 1 cm increase in NC was associated with a 1.15 ± 1.02% (p <0.0001) increase in 10-year AHA cardiovascular risk in individuals over 40 years old and a 0.16 ± 0.02 (p <0.0001) increase in NAFLD fibrosis score. The neck circumference was associated with the hazard of new onset of deranged ALT adjusted for age, sex, glycemic status, and BMI (hazard ratio 1.076 (95% CI 1.015–1.14, p = 0.0131) and with the incidence of Fatty Liver Index associated with high probability of NAFLD (hazard ratio 1.153 (95% CI 1.019–1.304), p = 0.0239).ConclusionNC is associated with dysglycemia, components of the MetS, and factors predictive of NAFLD, but does not appear to independently predict subsequent progression to high risk of liver fibrosis in this predominantly diabetic population.

Distribution of FIB-4 index in the general population: analysis of 75,666 residents who underwent health checkups

BackgroundFatty liver is frequently found in a general population, and it is critical to detect advanced fibrosis. FIB-4 index is considered a useful marker for evaluating liver fibrosis but the distribution of FIB-4 index in the general population remains unknown.MethodsThis cross-sectional study included residents who underwent ultrasonography at health checkups in Hiroshima or Iwate prefectures. The distribution of FIB-4 index in the total study population (N = 75,666) as well as in non-alcoholic fatty liver disease (NAFLD) populations (N = 17,968) and non-drinkers without fatty liver populations (N = 47,222) was evaluated. The distribution of aspartate aminotransferase (AST) levels, alanine aminotransferase (ALT) levels was also evaluated.ResultsThe mean FIB-4 index in the total study population was 1.20 ± 0.63. FIB-4 index ≥ 2.67, which indicates a high risk of liver fibrosis, was found in 16.4% of those aged ≥ 70 years. In the NAFLD population, 58.1% of those in their 60 s and 88.1% of those ≥ 70 years met the criteria for referral to hepatologists by using the recommended FIB-4 index cutoff value (≥ 1.3). The mean FIB-4 index in the NAFLD population (1.12 ± 0.58) was significantly lower than in the non-drinkers without fatty liver (1.23 ± 0.63, p < 0.0001). The non-drinkers without fatty liver tended to have higher AST relative to ALT levels (60.0% with AST/ALT > 1.0), whereas the results in the NAFLD population were opposite (14.8% with AST/ALT > 1.0). AST > ALT resulted in a higher FIB-4 index in non-drinkers without fatty liver due to the nature of FIB-4 index formula.ConclusionsThe cutoff value of FIB-4 index (≥ 1.3) for triaging the elderly people with fatty liver for referral to hepatologists should be reconsidered to avoid over-referral. Due to the impact of age and characteristics of AST/ALT ratios, there is no prospect of using FIB-4 index for primary screening for liver fibrosis in a general population of unknown presence or absence of liver disease, even though it can be easily calculated using routine clinical indices. It is desired to develop a non-invasive method for picking up cases with advanced fibrosis latent in the general population.

Alcohol Consumption and Risk of Liver Fibrosis in People Living With HIV: A Systematic Review and Meta-Analysis.

ObjectivesIt is unclear if a high level of alcohol consumption is a risk factor for liver fibrosis for people living with HIV (PLWH). This study systematically summarizes the risk relationship between different alcohol consumption and the incidence of liver fibrosis among PLWH.MethodsWe identified potential studies by searching the PubMed, Embase, Web of Science Library, and CNKI databases up to September 26th, 2021. Observation studies in PLWH that evaluated the relationship between alcohol consumption and the risk of liver fibrosis and estimated the effect of alcohol with pooled odds ratios (pooled ORs) and 95% confidence intervals (CIs) were included.ResultsThere were total 15 studies included in data analysis. Three studies were set up as cohort studies and the other twelve were cross-sectional studies. Our study was based on 22,676 individuals and 2,729 liver fibrosis cases from 15 studies. Alcohol abuse is a significant risk factor of liver fibrosis (pooled OR = 2.25, 95% CI: 1.59-3.17, p < 0.05) among PLWH. Daily alcohol consumption > 50 g can elevate the risk of liver fibrosis (pooled OR = 3.10, 95% CI: 2.02-4.73, p < 0.05) among PLWH. However, high-risk alcohol consumption determined by AUDIT-C (AUDIT-C ≥ 4) had little or no effect on subsequent liver fibrosis risk. Further, alcohol consumption > 50 g is also a risk factor to liver fibrosis in PLWH co-infected with HCV (pooled OR = 2.48, 95% CI: 1.62-3.80, p < 0.05) and in HIV mono-infected (pooled OR = 1.85, 95% CI: 1.00-3.43, p < 0.05).ConclusionAlcohol consumption is associated with an increased risk of liver fibrosis in PLWH. HCV co-infection with alcohol abuse could possibly induce a higher risk of liver fibrosis than HIV mono-infected patients.Systematic Review RegistrationPROSPERO, identifier (CRD42021272604).

Genotype-phenotype correlates in Joubert syndrome: A review.

Joubert syndrome (JS) is a genetically heterogeneous primary ciliopathy characterized by a pathognomonic cerebellar and brainstem malformation, the “molar tooth sign,” and variable organ involvement. Over 40 causative genes have been identified to date, explaining up to 94% of cases. To date, gene‐phenotype correlates have been delineated only for a handful of genes, directly translating into improved counseling and clinical care. For instance, JS individuals harboring pathogenic variants in TMEM67 have a significantly higher risk of liver fibrosis, while pathogenic variants in NPHP1, RPGRIP1L, and TMEM237 are frequently associated to JS with renal involvement, requiring a closer monitoring of liver parameters, or renal functioning. On the other hand, individuals with causal variants in the CEP290 or AHI1 need a closer surveillance for retinal dystrophy and, in case of CEP290, also for chronic kidney disease. These examples highlight how an accurate description of the range of clinical symptoms associated with defects in each causative gene, including the rare ones, would better address prognosis and help guiding a personalized management. This review proposes to address this issue by assessing the available literature, to confirm known, as well as to propose rare gene‐phenotype correlates in JS.

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.