Risk Factors For Hepatic Fibrosis Research Articles

The systemic inflammation response index as a risk factor for hepatic fibrosis and long-term mortality among individuals with metabolic dysfunction-associated steatotic liver disease

Background and aimsThe systemic inflammation response index (SIRI) is associated with various diseases with inflammatory components, but its relationship with the progression of hepatic fibrosis and survival outcomes in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) is still unclear. This study was designed to investigate the potential associations between the SIRI and advanced hepatic fibrosis (AHF) as well as between the SIRI and long-term outcomes in individuals with MASLD. Methods and resultsA prospective cohort study was conducted using data gathered from the National Health and Nutrition Examination Survey (NHANES) spanning from 2005 to 2016. Weighted binary logistic regression, the Cox proportional hazards model, and time-dependent receiver operating characteristic (ROC) analyses were employed to assess the relationships among the SIRI, AHF, and mortality in patients with MASLD. Our study included a total of 5126 patients with MASLD. A higher SIRI was significantly associated with increased odds of AHF (OR 1.55, 95% CI 1.22, 1.96). According to the survival analyses, a higher SIRI was associated with greater all-cause (HR 1.19, 95% CI 1.15, 1.22) and cardiovascular mortality (HR 1.25, 95% CI 1.19, 1.32) after adjustment. The time-dependent ROC analysis indicated that the SIRI had a modest predictive value for discriminating MASLD individuals at higher versus lower mortality risk over 3-year, 5-year, and 10-year follow-up. ConclusionsThe SIRI is a promising tool for identifying MASLD individuals at risk of progressing to AHF and for predicting mortality outcomes.

Prevalence of Hepatitis C Viral Infection among Diabetes Mellitus Patients in Qassim Region, Saudi Arabia

The worldwide prevalence of Diabetes Mellitus (DM) associated with Hepatitis C Virus (HCV) infection are reported with higher rates of morbidity and mortality. The frequency of HCV is approximately 3-4 million cases each year and in parallel the incidence of DM is increasing alarmingly. World Health Organization (WHO) has specified that DM will be the 7th leading cause of mortality by 2030. The increasing association between HCV and DM has been indicated by some significant reports recently. HCV infection leads to hepatic steatosis and rapid insulin resistance, which in turn upsurges the risk factors for hepatic fibrosis and hepatocellular carcinoma. This study is designed to examine the association between HCV and DM, and different risk factors associated with HCV infection in Qassim region, Kingdom of Saudi Arabia (KSA). A total of 634 blood samples were obtained from diabetic and non-diabetic patients. These blood samples were first screened for HCV infection by enzyme-linked immunosorbent assay (ELISA) and positive samples were again confirmed by TaqMan HCV quantitative test and the viral load in different samples was estimated. The HCV prevalence was identified as 2.5% in diabetic patients with a positive association between HCV and DM (RR= 1.24, OR= 1.77) which is not significant statistically. However, the HCV prevalence among diabetic females was significantly different from males (p<0.05). The behavioural factors had no significant impact to acquire HCV infection. This study indicated a positive association between HCV and DM. Gender was an association factor in the HCV and DM status. Further studies with larger sample size is significant to properly assess the temporal relationship between HCV and DM.

Comparison of the severity of metabolic, liver and cardiovascular damage in NAFLD patients attending the hepatology clinic over the last three decades

Background and aimsNAFLD prevalence is increasing worldwide. Aim: to assess whether severity of hepatic, metabolic and cardiovascular (CV) disease changed over time. Methods422 NAFLD patients (388 biopsy proven and 34 clinical cirrhosis) diagnosed between 1990 and 2021 and subdivided according to decade of presentation. Metabolic parameters, early atherosclerosis (carotid plaques at Doppler ultrasound), severity of liver damage (NAS score, NASH, significant fibrosis (≥2) and cirrhosis) and PNPLA3 genotyping were assessed. ResultsNo difference in age, sex and prevalence of dyslipidemia and hypertension was found across decades (p for trend), whereas a higher prevalence of diabetes (p = 0.02), obesity (p<0.001), histological severe steatosis (p<0.001), NASH (p<0.001), fibrosis ≥2 (p<0.001), cirrhosis (p<0.001) and carotid plaques (p = 0.05) was observed in the last decade compared to the others. A higher prevalence of PNPLA3 GG polymorphism was found over time (p = 0.02). In the whole cohort, age, metabolic alterations and PNPLA3 G homozygosity were independent risk factors for hepatic fibrosis and carotid plaques, independently of the decade considered. ConclusionOver the past 10 years compared to previous decades, NAFLD patients presented to observation with more severe liver disease and subclinical atherosclerosis, paralleling the spread of diabetes and obesity. PNPLA3 unfavorable genotype became more prevalent over time.

Association between congenital heart disease and parenteral nutrition-associated liver disease in neonates: A retrospective cohort study.

Infants receiving parenteral nutrition (PN) are at increased risk of PN-associated liver disease (PNALD), which can lead to hepatic fibrosis. Congenital heart disease (CHD) represents a risk factor for hepatic fibrosis, so this study sought to better understand whether infants with CHD were at elevated risk of PNALD when receiving long-term PN. This study includes a retrospective cohort of infants at a level IV neonatal intensive care unit from 2010 to 2020 who received long-term PN during the first 8 weeks of life. A time-varying Cox survival model was used to model risk of PNALD between infants with and without CHD, adjusted for demographics, surgical intervention, and PN exposure, using a 5000-iteration bootstrap estimation. Secondary analyses evaluated risk against discrete CHD diagnoses, and sensitivity analysis was performed on the magnitude and quantity of direct bilirubin laboratory measurements making up the PNALD definition. Neonates with CHD were found to be at higher risk for PNALD during or soon after long-term PN exposure. A pattern of increasing association strength with increasing bilirubin threshold suggests infants with CHD may also experience higher degrees of injury. This work offers a step in understanding how diagnoses can be factored into neonate PN prescription. Future work will explore modifications in lipid profiles and timing to mitigate risk in patients with CHD.

Risk factors in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease, with a global prevalence estimated at approximately 25%. NAFLD is also the leading cause of liver cirrhosis, hepatocellular carcinoma, and death. Additionally, the risk of cardiovascular disease increases with greater NAFLD severity. The liver- and cardiovascular disease-related mortality incident rate ratios among the NAFLD population were 0.77 and 4.79 per 1,000 person-years, respectively. We intend to discuss the risk factors associated with NAFLD in terms of development and progression. Obesity or higher body mass index is closely associated with NAFLD in a dose-dependent manner, but growing evidence suggests that central obesity plays a more important role in the development of NAFLD. Saturated fat and fructose have been reported to be closely related to NAFLD. Fructose intake promotes lipogenesis and impairs mitochondria fat oxidation. The presence of type 2 diabetes is the most powerful predictive risk factor for hepatic fibrosis in patients with NAFLD. Single nucleotide polymorphism is not only associated with the prevalence of NAFLD but also associated with increased liver disease mortality. Obstructive sleep apnea, intestinal dysbiosis, and sarcopenia are associated with the development of NAFLD.

The emerging role of DEAD/H-box helicases in hepatitis B virus infection.

DEAD/H-box helicases are an essential protein family with a conserved motif containing unique amino acid sequences (Asp-Glu-Ala-Asp/His). Current evidence indicates that DEAD/H-box helicases regulate RNA metabolism and innate immune responses. In recent years, DEAD/H-box helicases have been reported to participate in the development of a variety of diseases, including hepatitis B virus (HBV) infection, which is a significant risk factor for hepatic fibrosis, cirrhosis, and liver cancer. Furthermore, emerging evidence suggests that different DEAD/H-box helicases play vital roles in the regulation of viral replication, based on the interaction of DEAD/H-box helicases with HBV and the modulation of innate signaling pathways mediated by DEAD/H-box helicases. Besides these, HBV can alter the expression and activity of DEAD/H-box helicases to facilitate its biosynthesis. More importantly, current investigation suggests that targeting DEAD/H-box helicases with appropriate compounds is an attractive treatment strategy for the virus infection. In this review, we delineate recent advances in molecular mechanisms relevant to the interplay of DEAD/H-box helicase and HBV and the potential of targeting DEAD/H-box helicase to eliminate HBV infection.

Decreased Serum zinc, selenium, and vitamin E as possible risk factors of hepatic fibrosis in non-alcoholic fatty liver disease.

The incidence of non-alcoholic fatty liver disease (NAFLD) has been significantly growing in recent years. Although the pathophysiology of fibrosis progression in NAFLD is not yet known, oxidative stress and inflammation have been known to have a major role in the development of NASH. Understanding the impact of micronutrients in NAFLD could potentially help us better understand NAFLD pathogenesis. Assessing the serum levels of Zn, Se, and Vitamin E and their relation to the development of hepatic fibrosis in NAFLD patients. This study included 80 NAFLD patients and 40 healthy controls. All of the patients were subjected to abdominal ultrasound and FibroScan examination (to estimate hepatic fibrosis and steatosis degree), and the serum levels of Zn, Se, and vitamin E were evaluated. A statistically significant difference in the serum levels of Zn and Se was observed between the NAFLD group and the control group (P-value = 0.04 and 0.05, respectively). The serum levels of Zn and Se were independently related to the presence of hepatic fibrosis in NAFLD. However, serum vitamin E was not related to the severity of NAFLD. Furthermore, no significant difference in the levels of Zn, Se, and vitamin E was observed between the different groups of NAFLD patients categorized according to the degree of steatosis and the control group. Reduced serum levels of Zn and Se can be considered a possible risk factor for hepatic fibrosis in NAFLD. Deficiency in these micronutrients could play a role in the pathogenesis of NAFLD.

Hepatic Fibrosis and Steatosis in Metabolic Syndrome.

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.

TGF-Β1 & PNPLA3 Genetic Variants and the Risk of Hepatic Fibrosis and HCC in Egyptian Patients with HCV-Related Liver Cirrhosis.

Objective:The clinical outcomes of hepatitis C virus (HCV) infection and its sequelae including liver cirrhosis and hepatocellular carcinoma (HCC) are greatly affected by host genetic factors; however, the possible mechanisms are still largely unclear. This work aimed to assess transforming growth factor-β1 (TGF-β1), and patatin-like phospholipase domain containing-protein 3 (PNPLA3) genetic variants as risk factors for hepatic fibrosis and hepatocellular carcinoma (HCC) in Egyptian patients with HCV-related liver cirrhosis. Methods:Seventy HCV-related liver cirrhosis patients (Total cirrhosis) who were divided into two groups; 34 patients with HCC (HCC group), and 36 patients without HCC (LC group) and 20 healthy volunteers (control group) were included. Routine laboratory investigations and imaging studies were determined. TGF-β1 (Arg25Pro; 915G>C) and PNPLA3 (I148M; C>G) variants were evaluated using real-time polymerase chain reaction (real-time PCR). Results:HCC group showed a significantly higher GG genotype distribution of TGF-β1 (Arg25Pro) than the LC group (P= 0.008, OR: 7.083, CI 95%: 1.422 – 35.282). The distributions of GG genotype (P= 0.047) and G allele (P= 0.002, OR: 4.395, CI 95%: 1.622 – 11.911) of PNPLA3 (I148M) were significantly higher in total cirrhosis patients than controls. Conclusion:TGF-β1 (Arg25Pro) GG variant may be associated with HCC risk in HCV-related liver cirrhosis patients, while PNPLA3 (I148M) GG variant may be associated with cirrhosis development but not HCC risk in HCV-related liver cirrhosis patients.

Association of Nonalcoholic Hepatic Fibrosis with Body Composition in Female and Male Psoriasis Patients.

Psoriasis has been associated with increased frequency of hepatic diseases. Psoriasis severity, obesity, insulin resistance, aspartate aminotransferase level, platelet count, and alcohol use are significant predictors for advanced fibrosis in psoriasis patients. Although psoriasis patients also present body composition changes (e.g., higher overall body fat, visceral fat and sarcopenia), and these have recently been reported as risk factors for hepatic fibrosis, to date, body composition has not been prospectively investigated in psoriasis in the context of liver fibrosis. In this study anthropometric assessment (body weight and body mass index (BMI)), body composition analysis (body fat%, visceral fat scores and muscle mass%), and liver stiffness measurements (using transient elastography [TE]) were done in 52 psoriasis patients undergoing methotrexate therapy. Fourteen patients (26.9%) had advanced (F3–F4) liver fibrosis. There was no correlation between the patients’ liver stiffness values and the cumulative MTX doses. On the other hand, patients with higher BMI values, total body fat% and visceral fat scores were significantly more likely to present with higher hepatic stiffness values. BMI was a significant predictor of hepatic fibrosis in both genders. In males, body fat% (R = 0.578, p = 0.002) and, especially, visceral fat scores (R = 0.716, p < 0.001) had statistically significant correlation with stiffness scores, while in females only visceral fat scores were statistically significant predictors of the liver stiffness values (R = 0.452, p = 0.023), and body fat% was not (R = 0.187, p = 0.382). Our results suggest that anthropometric data should be assessed differently in female and male psoriasis patients when evaluating liver fibrosis risk.

Considerations of Ultrasound Scanning Approaches in Non-alcoholic Fatty Liver Disease Assessment through Acoustic Structure Quantification

Non-alcoholic fatty liver disease (NAFLD) is a risk factor for hepatic fibrosis and cirrhosis. Acoustic structure quantification (ASQ), based on statistical analysis of ultrasound echoes, is an emerging technique for hepatic steatosis diagnosis. A standardized measurement protocol for ASQ analysis was suggested previously; however, an optimal ultrasound scanning approach has not been concluded thus far. In this study, the suitability of scanning approaches for the ASQ-based evaluation of hepatic steatosis was investigated. Hepatic fat fractions (HFFs; liver segments VIII, III and VI) of 70 living liver donors were assessed with magnetic resonance spectroscopy. A clinical ultrasound machine equipped with a 3-MHz convex transducer was used to scan each participant using the intercostal, epigastric and subcostal planes to acquire raw data for estimating two ASQ parameters (Cm2 and focal disturbance [FD] ratio) of segments VIII, III and VI, respectively. The parameters were plotted as functions of the HFF for calculating the values of the correlation coefficient (r) and probability value (p). The diagnostic performance of the parameters in discriminating between the normal and steatotic (≥5 and ≥10%) groups was also compared using receiver operating characteristic (ROC) curves. The Cm2 and FD ratio values measured using the epigastric and subcostal planes did not correlate with the severity of hepatic steatosis. However, intercostal imaging exhibited a higher correlation between the ASQ parameters and HFF (r = −0.64, p < 0.001). The diagnostic performance of Cm2 and FD ratio in detecting hepatic steatosis using intercostal imaging was also satisfactory (areas under ROC curves >0.8). Intercostal imaging is an appropriate scanning approach for ASQ analysis of the liver.

Evaluation of elastography combined with serological indexes for hepatic fibrosis in patients with chronic hepatitis B.

AIMTo investigate the value of ultrasound elastography combined with serological indexes in diagnosing liver fibrosis and assessing its severity.METHODSA total of 338 chronic hepatitis B (CHB) patients were divided into a disease group (patients with hepatic fibrosis) and control group (subjects without hepatic fibrosis). The disease group was further divided into S1-S4 according to the degree of fibrosis. Independent risk factors for hepatic fibrosis were analyzed using multivariate logistic regression. The diagnostic values of hepatic fibrosis from different indicators were compared using receiver operating characteristic (ROC) curves. The combination of elastography and serological indexes was explored to assess the severity of hepatic fibrosis.RESULTSThe multivariate logistic regression analysis results revealed that shear wave velocity (SWV), hyaluronic acid (HA), type IV collagen (CIV) and aspartate aminotransferase-to-platelet ratio index (APRI) significantly affected the occurrence of hepatic fibrosis. The ROC curve revealed that the accuracy of the diagnosis of hepatic fibrosis for SWV and HA were 87.3% and 84.8%, respectively. The accuracy of SWV combined with HA was 88.9%. The multiple linear regression analysis revealed that SWV, aspartate aminotransferase (AST)/alanine aminotransferase (ALT), HA, CIV, APRI and fibrosis index based on the 4 factor (FIB-4) were screened as statistically significant independent factors. The established regression equation was: Fibrosis level = -4.046 + 1.024 × SWV + 1.170 × AST/ALT + 0.011 × HA + 0.020 × CIV + 0.719 × APRI + 0.379 × FIB-4.CONCLUSIONSWV combined with serological indexes can improve the accuracy of diagnosis for CHB hepatic fibrosis. Serum indexes can help diagnose the degree of hepatic fibrosis.

Caffeine affects HFD-induced hepatic steatosis by multifactorial intervention.

The incidence of nonalcoholic fatty liver disease (NAFLD) is considered a risk factor for hepatic fibrosis. Therefore, there is critical need to develop novel cheap and effective therapeutic approaches to prevent and reverse NAFLD. Caffeine is commonly consumed beverage and has antioxidant and anti-inflammatory activities. This study examined whether caffeine can ameliorate liver injury induced by high-fat diet (HFD) feeding. Four groups of rats were used and treated for 16 weeks as follows: control group, rats were fed a standard diet; HFD group, rats were fed HFD; and caffeine 20 and caffeine 30 groups, rats were fed HFD for 16 weeks in addition to different doses of caffeine (20 or 30 mg/kg, respectively) for last 8 weeks. The HFD-induced liver injury is determined biochemically by evaluating serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, bilirubin, triglycerides, cholesterol, and high-density lipoprotein-cholesterol and by histopathological examination. Tissue malondialdehyde, total nitrate/nitrite, and glutathione concentration were also measured. Real-time reverse transcription polymerase chain reaction technique was used to determine the expression of lipogenic enzyme genes. Caffeine treatment significantly decreased the elevated serum ALT, AST, and bilirubin and increased the reduced albumin level. Interestingly, the hepatic mRNA expression of Fatty acid synthase and acetyl CoA carboxylase was decreased by caffeine, while the protein expression of hepatic carnitine palmitoyltransferase 1 and proliferation-activated receptor α was increased. Furthermore, caffeine reduced tissue lipid peroxidation and oxidative stress. These effects suggest that caffeine could improve HFD-induced hepatic injury by suppressing inflammatory response and oxidative stress and regulating hepatic de novo lipogenesis and β-oxidation.

Mice Lacking Liver‐Specific [beta]‐Catenin Develoop Steatohepatitis and Fibrosis After Iron Overload

Background &amp; aimsIron overload disorders such as hereditary hemochromatosis and iron‐loading anemias are a common cause of morbidity from liver diseases and are risk factors for hepatic fibrosis and hepatocellular carcinoma (HCC). Once iron‐induced damage occurs, treatment options are limited, partly because of the lack of animal models recapitulating human disease, since mice do not exhibit fibrosis or HCC following chronic iron overload.MethodsA high iron containing diet was fed to normal mice to assess any effect on Wnt signaling. Iron overload diet was also administered to liver‐specific β‐catenin knockout (KO) and control (CON) mice for three months. To ameliorate an oxidant‐mediated component of tissue injury, N‐Acetyl‐L‐(+)‐cysteine (NAC) was added to drinking water of mice on iron overload diet.ResultsKO on iron diet (KO+Fe) exhibited remarkable steatosis, inflammation, hepatic fibrosis, regenerating nodules, and sequelae associated with increased oxidative stress. We also noted increased activation of AKT and NFkB pathways in KO+Fe. Addition of NAC to drinking water protected KO+Fe from hepatic steatosis, injury and fibrosis, and suppressed phosphorylation of AKT and NFkB.ConclusionsWe provide evidence that lack of hepatic b‐catenin predisposes mice to hepatic injury and fibrosis following iron overload thus phenocopying disease in patients. This is chiefly due to lack of antioxidant response in the absence of b‐catenin demonstrating its role in hepatic redox homeostasis. Lastly, antioxidant therapy may have a chemopreventive role in the management of chronic iron overload.

Abstract 17110: Risk Factors for Hepatic Fibrosis in Children and Adolescents After Fontan Operation

Introduction: Congestive hepatopathy is increasingly recognized as a complication of Fontan physiology. Prospective data regarding the incidence of hepatopathy and risk factors for its development are lacking. Methods: Liver biopsies were obtained as part of a routine program of comprehensive end-organ evaluation offered to all patients &gt;10 years after Fontan operation (FO) through the Single Ventricle Survivorship Program. Evaluation included cardiac catheterization and contemporaneous percutaneous liver biopsy. Quantitative determination of hepatic fibrosis was performed using Sirius red staining for collagen with automated calculation of percent positive staining per slide. Patient specific characteristics, echocardiographic findings, and hemodynamic measures were assessed and evaluated as potential risk factors for collagen deposition using Pearson correlation. Differences in collagen deposition (%CD) between subgroups were assessed using the student t-test. Results: The cohort consisted of 67 patients (36 male) at mean age of 17.3 ±4.5 years and mean time from Fontan of 14.9 ±4.5 years. Right ventricular morphology was present in 37 subjects; 30 with hypoplastic left heart syndrome. Mean %CD by Sirius red staining was 23.8 ±9.5% (range 8.7-49.4%) as compared to 2.6 ±0.3% in controls. There was significant correlation between time from Fontan and degree of Sirius red staining (r=0.33, p=0.006). Serum liver enzymes and platelet count did not correlate with %CD. The median inferior vena cava (IVC) pressure was 13 mmHg (range 6-24 mmHg) and did not correlate with %CD. There was no difference in %CD between those with a measured IVC pressure ≥13 mmHg versus those with a pressure &lt;13 mmHg. There was no difference in %CD based on ventricular morphology or severity of atrioventricular valve insufficiency. Conclusion: In this cohort of predominantly asymptomatic children and adolescents electively evaluated after FO, all exhibited evidence for hepatic fibrosis as measured by collagen deposition in the liver. Time from FO was the only factor in this cohort that was significantly associated with collagen. These findings demonstrate that liver fibrosis is an inherent feature of Fontan physiology and that the degree of fibrosis increases over time.

Non-Alcoholic Steatohepatitis (NASH): Risk Factors in Morbidly Obese Patients.

The aim was to investigate the prevalence of non-alcoholic steatohepatitis (NASH) and risk factors for hepatic fibrosis in morbidly obese patients submitted to bariatric surgery. This retrospective study recruited all patients submitted to bariatric surgery from January 2007 to December 2012 at a reference attendance center of Southern Brazil. Clinical and biochemical data were studied as a function of the histological findings of liver biopsies done during the surgery. Steatosis was present in 226 (90.4%) and NASH in 176 (70.4%) cases. The diagnosis of cirrhosis was established in four cases (1.6%) and fibrosis in 108 (43.2%). Risk factors associated with NASH at multivariate analysis were alanine aminotransferase (ALT) >1.5 times the upper limit of normal (ULN); glucose ≥ 126 mg/dL and triglycerides ≥ 150 mg/dL. All patients with ALT ≥1.5 times the ULN had NASH. When the presence of fibrosis was analyzed, ALT > 1.5 times the ULN and triglycerides ≥ 150 mg/dL were risk factors, furthermore, there was an increase of 1% in the prevalence of fibrosis for each year of age increase. Not only steatosis, but NASH is a frequent finding in MO patients. In the present study, ALT ≥ 1.5 times the ULN identifies all patients with NASH, this finding needs to be further validated in other studies. Moreover, the presence of fibrosis was associated with ALT, triglycerides and age, identifying a subset of patients with more severe disease.

Amelioration of hypercholesterolemia-induced hepatic changes with red grape juice: A histopathological study.

Hypercholesterolemia was confirmed as a risk factor for hepatic fibrosis, as well atherosclerosis and coronary heart disease. This biochemical and histoplathological study was conducted to investigate the possible protective effect of red grape against hepatic injury induced by a high-cholesterol diet (HCD). Thirty male Wister rats were randomly divided into three groups (n=10): the control received saline, the induction group was fed HCD, and the treated group was fed a HCD and 0.4 ml of 100% red grape juice (RGJ) for 13 weeks. After the animals were sacrificed, liver tissue samples were taken to be processed for light and electron microscopy examination. The administration of the RGJ and HCD significantly decreased the animals' blood glucose, insulin, cholesterol, triglycerides, Low Density Lipoprotein levels and increased their High Density Lipoprotein level compared to the rats fed the HCD alone. It also decreased the periportal (macro- and microvesicular) steatosis, fibrosis, lymphocytic infiltration and blood sinusoidal congestion that were observed in HCD-fed rats alone. The RGJ reduced the number of activated myofibrobasts. This was confirmed by a reduction in the expression of alpha smooth muscle actin and desmin. The RGJ increased, although not significantly, the expression of endothelial Nitric Oxide Synthetase. The administration of RGJ succeeded in alleviating the biochemical and, to some extent, the histopathological changes induced by the high cholesterol diet. Consumption of fresh RGJ or its pharmaceutical preparations is advised especially for those who are used to eat a high fat diet.

Association of tyrosine with insulin resistance in hepatitis C virus-related chronic liver disease

Insulin resistance (IR) increases during the early stages of hepatitis C virus (HCV)-related chronic liver disease and is a sign of poor prognosis as well as a risk factor for hepatic fibrosis and hepatocellular carcinoma. We aimed to determine the factors affecting IR in HCV-related chronic liver disease. We retrospectively examined 71 patients with HCV-related chronic liver disease and analyzed various parameters, including amino acids, as possible predictors of IR. IR was assessed using the Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR). Amino acids were assayed by examining branched-chain amino acids (BCAA), tyrosine level, and the ratio of BCAA to tyrosine level (BTR). HOMA-IR was significantly correlated with body mass index, platelet count, prothrombin time, hemoglobin, total bilirubin, total protein, albumin, total cholesterol, fasting glucose, BTR (r = -0.46, P = 0.0001) and tyrosine (r = 0.55, P < 0.0001). However, BCAA were not significantly correlated with HOMA-IR (r = -0.21, P = 0.082). In multivariate analysis, only two factors were identified as independent parameters contributing to a HOMA-IR of 2.5 or more: total cholesterol (odds ratio [OR], 6.511; 95% confidence interval [95% CI], 1.554-27.284; P = 0.010) and tyrosine (OR, 4.839; 95% CI, 1.087-21.549; P = 0.039). Serum tyrosine levels may be associated with IR in patients with HCV-related chronic liver disease.

Risk factors for hepatic fibrosis in CHB patients

Risk factors for hepatic fibrosis in CHB patients

The common adiponutrin variant as a general risk factor for hepatic fibrosis: Elastography-based study in patients with chronic liver diseases

The common adiponutrin variant as a general risk factor for hepatic fibrosis: Elastography-based study in patients with chronic liver diseases