Risk Factor For Liver Damage Research Articles

PFHpA alters lipid metabolism and increases the risk of metabolic dysfunction-associated steatotic liver disease in youth-a translational research framework.

To address the growing epidemic of liver disease, particularly in pediatric populations, it is crucial to identify modifiable risk factors for the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Per- and polyfluoroalkyl substances (PFAS) are persistent ubiquitous chemicals and have emerged as potential risk factors for liver damage. However, their impact on the etiology and severity of MASLD remains largely unexplored in humans. This study aims to bridge the gap between human and in vitro studies to understand how exposure to perfluoroheptanoic acid (PFHpA), one of the emerging PFAS replacements which accumulates in high concentrations in the liver, contributes to MASLD risk and progression. First, we showed that PFHpA plasma concentrations were significantly associated with increased risk of MASLD in obese adolescents. Further, we examined the impact of PFHpA on hepatic metabolism using 3D human liver spheroids and single-cell transcriptomics to identify major hepatic pathways affected by PFHpA. Next, we integrated the in vivo and in vitro multi-omics datasets with a novel statistical approach which identified signatures of proteins and metabolites associated with MASLD development triggered by PFHpA exposure. In addition to characterizing the contribution of PFHpA to MASLD progression, our study provides a novel strategy to identify individuals at high risk of PFHpA-induced MASLD and develop early intervention strategies. Notably, our analysis revealed that the proteomic signature exhibited a stronger correlation between both PFHpA exposure and MASLD risk compared to the metabolomic signature. While establishing a clear connection between PFHpA exposure and MASLD progression in humans, our study delved into the molecular mechanisms through which PFHpA disrupts liver metabolism. Our in vitro findings revealed that PFHpA primarily impacts lipid metabolism, leading to a notable increase of lipid accumulation in human hepatocytes after PFHpA exposure. Among the pathways involved in lipid metabolism in hepatocytes, regulation of lipid metabolism by PPAR-a showed a remarkable activation. Moreover, the translational research framework we developed by integrating human and in vitro data provided us biomarkers to identify individuals at a high risk of MASLD due to PFHpA exposure. Our framework can inform policies on PFAS-induced liver disease and identify potential targets for prevention and treatment strategies.

Meta-analysis of Risk Factors for Liver Damage in Newly Diagnosed Patients with Hyperthyroidism

Meta-analysis of Risk Factors for Liver Damage in Newly Diagnosed Patients with Hyperthyroidism

Hepatobiliary System Effects And Clinical Features of Sars-Cov-2 Infection; Case-Control Study

Introduction: Pandemic caused by SARS-CoV-2 infection has been an important health problem worldwide for the last 3 years. The pathogenesis and consequences of liver injury developed in COVID-19 disease are still unclear. We investigated the prevalence of liver function tests (LFTs) abnormalities in COVID-19 patients, their relationship with drugs, the difference between severe and non-severe COVID-19 patients, and the results of the course of LFTs among patients hospitalized in intensive care units and clinics. Methods: 389 patients who applied to Eskişehir City Hospital between March 2020 and October 2020 were included in the study. Demographic data of RT-PCR (+) patients and RT-PCR (-) control groups (age, gender, comorbidities, symptoms), laboratory parameters, radiological examinations, follow-ups in the clinics and intensive care units, drugs used for the infection were collected retrospectively. All patients with COVID-19 were classified as severe cases or mild to moderate cases groups. Results: Abnormal LFTs were found in 115 (35.2%) of 321 patients with RT-PCR(+), and in 10 (14.7%) of 68 patients in the PCR(-) control group. LFTs at the time of hospitalization were 10.3%, 22.7%, 4.9%, 11.4% and 1.2% in the patient group, respectively; in the control group, it was 1.9%, 2.9%, 2%, 3.3%, 0.8% (p=0.610, p=0.00, p=0.269, p=0.198, p=0.158). There was a significant increase in LFTs in patients who received antibiotics (Levofloxacin, Ceftriaxone, Clarithromycin, Tazobactam, Carbapenem), low molecular weight heparins and antiviral (favipravir) treatments (p=0.001, p=0.001, p=0.001). While the increase in LFTs were significant in the mild (40.2%; 8.2%) and severe groups (41.2%; 5.2%), the number of patients with elevated LFTs in the control group was low (0.5%). Conclusion: Liver damage is common in SARS-CoV-2 infection, but it is quite mild. Patients with severe COVID-19 have a higher frequency of abnormal LFTs than those with mild disease. Disease severity, pre-existing liver disease, and advanced age are risk factors for liver damage. Drug-induced liver injury, systemic inflammatory response syndrome, and hypoxia-induced liver injury may be the main etiological factors for liver injury in COVID-19.

Incidence of and risk factors for liver damage in patients with HIV-1 mono-infection receiving antiretroviral therapy.

The study aimed to investigate the incidence of and risk factors for liver damage in patients with human immunodeficiency virus type-1 (HIV-1) mono-infection receiving antiretroviral therapy (ART). We retrospectively analyzed the clinical data of patients who were diagnosed with HIV-1 infection and initiated ART from January to December 2017. Among them, 382 patients with HIV-1mono-infection and normal baseline liver function were included in the analysis. The incidence of liver damage at each follow-up point, and possible risk factors for liver damage were evaluated via COX regression survival analyses. The overall incidence of liver damage (grade I-IV) was 27.23% (interquartile range [IQR]: 26.38%-28.72%). Grade I liver damage was most common and accounted for 22.13% of cases (IQR: 21.06%-24.04%), while grade II liver damage accounted for 3.40% of cases (IQR: 3.19%-4.26%). COX regression and survival analyses revealed that baseline body mass index (BMI), alanine aminotransferase (ALT) level, CD4+ T cell count, HIV-1 viral load, and the antiretroviral regimen were significantly correlated with the occurrence of liver damage. Moreover, baseline ALT levels and HIV-1 viral load were identified as independent risk factors for liver damage in patients with HIV-1mono-infection. Liver damage is common in patients with HIV-1mono-infection undergoing ART. Patients with risk factors for liver damage should be well-informed before the initiation of ART, and liver function should be closely monitored during ART even in patients with normal liver function before ART.

COVID-19’lu Hastalarda Gastrointestinal Semptomlar ve Karaciğer Hasarı

Introduction: Gastrointestinal and hepatic symptoms may be seen before respiratory symptoms in Coronavirus disease 2019 (COVID19). The purpose of the present study was to evaluate the relationship between liver damage and observed symptoms and laboratory parameters. Materials and Methods: Patients followed-up with diagnoses of COVID-19 between March and August 2020 were included in the study. Clinical characteristics and laboratory parameters were compared according to liver damage status. Results: Four hundred and thirteen COVID-19 cases were included. The prevalence of gastrointestinal symptoms was 19.8%, the most common being nausea/vomiting, abdominal pain, and diarrhea (10.4%, 6.1%, and 2.9%, respectively). CT-confirmed pneumonia, intensive care requirement, and mean length of hospitalization differed significantly depending on liver damage status (p< 0.001, p= 0.006, p= 0.002, respectively). Significant differences were determined between the groups with and without liver damage in terms of all the laboratory parameters examined, apart from white blood cell, neutrophil, lymphocyte, neutrophil:lymphocyte ratio (NLR), total bilirubin, and partial thromboplastin time (PTT) (p< 0.05). Significant associations were present between alanine aminotransferase lev- els and all other laboratory parameters apart from NLR and PTT (p< 0.001). Aspartate aminotransferase (OR: 1.22, CI: 1.16-1.28) and albumin (OR: 2.28, CI: 1.12-4.63) were identified as significant independent risk factors for liver damage in patients with COVID-19. Conclusion: Gastrointestinal symptoms are not uncommon in COVID-19 patients. Liver damage may be associated with progression to intensive care and systemic inflammation.

Analysis of liver injury factors in 332 patients with COVID-19 in Shanghai, China.

Objective: We analyzed clinical parameters and risk factors for coronavirus disease 2019 (COVID-19)-related liver damage.Results: Of the 332 COVID-19 patients, 306 and 26 were included in the non-critical and critical groups, respectively. The median time from onset to admission was 4.0 (2.0–8.0) days. Of the 332 COVID-19 patients, 98 (29.5%) were admitted with liver injury. The rates of aspartate transaminase, γ-glutamyl transpeptidase, and total bilirubin abnormalities were higher in the critical group than in the non-critical group. The patient’s sex, COVID-19 severity, and a low liver CT density strongly correlated with liver injury (ORs: 2.936, 6.543, and 3.387, respectively). Statistical analysis on drug administration after admission showed that the usage rates of lopinavir/ritonavir, glucocorticoids, and thymopeptides were significantly higher in the abnormal group than the normal groups (p<0.05).Conclusions: Though not severe, the liver injury among COVID-19 patients was pervasive. Being male, COVID-19 severity, low CT density, and medications may be risk factors for liver damage. Following recovery, liver function gradually returns to normal.Methods: This retrospective study screened 332 confirmed COVID-19 patients from January 20 to March 13, 2020. Liver indicators were evaluated on admission. The risk factors, medications, and the dynamic change of liver functions were analyzed.

Iron overload as a risk factor for hepatic ischemia-reperfusion injury in liver transplantation: Potential role of ferroptosis.

Hepatic ischemia-reperfusion (I/R) injury is a major problem in liver transplantation (LT). Although hepatocyte cell death is the initial event in hepatic I/R injury, the underlying mechanism remains unclear. In the present study, we retrospectively analyzed the clinical data of 202 pediatric living donor LT and found that a high serum ferritin level, a marker of iron overload, of the donor is an independent risk factor for liver damage after LT. Since ferroptosis has been recently discovered as an iron-dependent cell death that is triggered by a loss of cellular redox homeostasis, we investigated the role of ferroptosis in a murine model of hepatic I/R injury, and found that liver damage, lipid peroxidation, and upregulation of the ferroptosis marker Ptgs2 were induced by I/R, and all of these manifestations were markedly prevented by the ferroptosis-specific inhibitor ferrostatin-1 (Fer-1) or α-tocopherol. Fer-1 also inhibited hepatic I/R-induced inflammatory responses. Furthermore, hepatic I/R injury was attenuated by iron chelation by deferoxamine and exacerbated by iron overload with a high iron diet. These findings demonstrate that iron overload is a novel risk factor for hepatic I/R injury in LT, and ferroptosis contributes to the pathogenesis of hepatic I/R injury.

P-Chloro-diphenyl diselenide attenuates plasma lipid profile changes and hepatotoxicity induced by nonionic surfactant tyloxapol in rats

Tyloxapol is a nonionic surfactant oligomer inductor of dyslipidemia, which in turn is a risk factor for liver damage. Selenium-based compounds have emerged as promising therapeutic candidates for treating different experimental disorders. This study investigated the effects of p-chloro-diphenyl diselenide (p-ClPhSe)2 on toxicity induced by Tyloxapol in rats. Plasma lipid profile, hepatic functionality and oxidative stress parameters were evaluated in adult male Wistar rats treated with (p-ClPhSe)2 (10 mg/kg; oral administration by gavage) for seven days and exposed to a single Tyloxapol injection (400 mg/kg; intraperitoneal route) 30 min after the last (p-ClPhSe)2 treatment. Tyloxapol exposure increased the plasma levels of total cholesterol, triacylglycerol, non-HDL-cholesterol and the calculated cardiac risk index (CRI). The plasma activities of alanine and aspartate aminotransferase (ALT and AST, liver function markers) were increased in rats exposed to Tyloxapol, which demonstrates a hepatic lipotoxicity. In the liver, reactive oxygen species (ROS) content was enhanced and the non-protein sulfhydryl (NPSH) levels were decreased by Tyloxapol. The data revealed that repeated treatment with (p-ClPhSe)2 reduced plasma lipid alterations and hepatotoxicity induced by Tyloxapol. Although (p-ClPhSe)2 did not reduce ROS levels increased by Tyloxapol, it increased NPSH content in the liver. Pearson’s correlation coefficient revealed a positive relationship between the levels of hepatic NPSH and plasma HDL. HDL is known by eliciting antioxidant activity; therefore, the improvement in HDL function could be suggested as a therapeutic target. In conclusion, the results demonstrate the protective effects of (p-ClPhSe)2 on the hepatic lipotoxicity induced by Tyloxapol in rats.

Clinical significance of elevated liver transaminases in HIV-infected patients.

: Elevation of liver transaminases is common in patients infected with the HIV. Although this is usually an incidental finding during regular work-up, HIV-infected patients with transaminase elevations require additional visits for laboratory studies and clinical assessments, and often undergo interruptions and changes in antiretroviral therapy (ART). Alanine aminotransferase is present primarily in the liver, thus being a surrogate marker of hepatocellular injury. Aspartate aminotransferase is present in the liver and other organs, namely cardiac and skeletal muscle, kidney and brain. Serum levels of both liver transaminases predict liver-related mortality. Moreover, serum fibrosis biomarkers based on alanine aminotransferase and aspartate aminotransferase predict all-cause mortality. In a busy clinical setting, a diagnostic approach to elevated liver transaminases could be complicated given the frequency and nonspecificity of this finding. Indeed, HIV-infected individuals present multiple risk factors for liver damage and chronic elevation of transaminases, including coinfection with hepatitis B and C viruses, alcohol abuse, hepatotoxicity due to ART, HIV itself and frequent metabolic comorbidities leading to nonalcoholic fatty liver disease. This review provides an update on epidemiology of elevated liver transaminases, summarizes the main etiologic contributors and discusses the prognostic significance and a pragmatic approach to this frequent finding in the clinical practice of HIV medicine. With the aging of the HIV-infected population following the successful implementation of ART in Western countries, liver-related conditions are now a major comorbidity in this setting. As such, clinicians should be aware of the frequency, clinical significance and diagnostic approach to elevated liver transaminases.

Liver damage in patients living with HIV on antiretroviral treatment with normal baseline liver function and without HBV/HCV infection: an 11-year retrospective cohort study in Guangxi, China

ObjectiveTo characterise the association between duration of exposure to antiretroviral treatment (ART) and liver damage in HIV patients with an initially normal baseline liver function and without hepatitis B virus...

Chemical Induced Liver Injury: Types, Mechanisms and Biomarkers

Liver is a primary organ involved in biotransformation of foods and drugs. Liver diseases are a major worldwide problem; Hepatic disorders are mainly caused by toxic chemicals, e.g. - alcohol, carbon tetra chloride, anticancer agent, analgesic, anti-inflammatory drugs, anti-tuberculosis agent and heavy metals. Various risk factors for liver damage include age, gender, alcoholism, nutrition and genetic polymorphisms of cytochrome P450 have also been considered. The present review enumerate various hepatic diseases, risk factors and chemicals induced hepatic injury via different mechanical pathway as well as numerous biochemical changes viz. serum biomarkers, proteomics biomarkers, genomic biomarkers, metabolic biomarkers and micro RNA. This review could be immensely useful for researchers especially for pharmacologists, toxicologist working on hepatotoxicity and drug research organization.

The Effect of Protracted Exposure to Radiation on Liver Injury: A Cohort Study of Industrial Radiographers in Xinjiang, China.

Background: At present, a large number of studies indicate that high dose ionizing radiation exposure is an important risk factor for liver damage. Whether protracted exposure to low external doses of ionizing radiation could induce liver injury is unclear. The aim of this study was to assess the risk of liver injury following protracted exposure to occupational radiation compared to a group of unexposed workers. Methods: A three-year cohort study was initiated in Xinjiang, China in 2010 and included 508 industrial radiographers and 2156 unexposed workers. The incidence of liver injury was assessed clinically based on the evaluation of alanine aminotransferase (ALT) and aspartate transaminase (AST) levels. Logistic regression was used to examine whether radiation is a risk factor for liver injury. Results: Compared with the unexposed group, protracted radiation exposure was found to be a risk factor for liver injury. Sex, age at baseline and alcohol consumption were not associated with liver injury. However, hypertension was a risk factor for liver injury. The association between cumulative recorded radiation dose and liver injury was not found in this study. Conclusions: These findings indicate that protracted exposure to radiation is a risk factor for liver injury.

Interaction Effects of AFB1 and MC-LR Co-exposure with Polymorphism of Metabolic Genes on Liver Damage: focusing on SLCO1B1 and GSTP1

AFB1 and MC-LR are two major environmental risk factors for liver damage worldwide, especially in warm and humid areas, but there are individual differences in health response of the toxin-exposed populations. Therefore, we intended to identify the susceptible genes in transport and metabolic process of AFB1 and MC-LR and find their effects on liver damage. We selected eight related SNPs that may affect liver damage outcomes in AFB1 and MC-LR exposed persons, and enrolled 475 cases with liver damage and 475 controls of healthy people in rural areas of China. The eight SNPs were genotyped by PCR and restriction fragment length polymorphism. We found that SLCO1B1 (T521C) is a risk factor for liver damage among people exposed to high AFB1 levels alone or combined with MC-LR, and that GSTP1 (A1578G) could indicate the risk of liver damage among those exposed to high MC-LR levels alone or combined with high AFB1 levels. However, GSTP1 (A1578G) could reduce the risk of liver damage in populations exposed to low MC-LR levels alone or combined with high AFB1 levels. In conclusion, SLCO1B1 (T521C) and GSTP1 (A1578G) are susceptible genes for liver damage in humans exposed to AFB1 and/or MC-LR in rural areas of China.

Statins are not a risk factor for liver damage associated with intravenous glucocorticoid pulse therapy for Graves' orbitopathy.

Acute liver damage (ALD) is associated with high-dose intravenous (iv) glucocorticoid (GC) (ivGC) pulse therapy in ~1% of patients for Graves' orbitopathy (GO). It has been proposed that statins may increase the risk of ALD. Here we investigated the frequency of ALD according to the assumption of statins in a large retrospective cohort study. We studied 1076 consecutive patients with GO given ivGC. ALD was defined as an increase in alanine aminotransferase ≥300U/l. At the time of ivGC, 62 patients were taking statins and 1014 were not. The frequency of ALD has been reported to be 1.2 cases/100,000 statins users and 1300/100,000 in GO patients given ivGC. Thus, the expected frequency of ALD in patients given both statins and ivGC is 1560/100,000. Transferring these data to our series, one would have expected at least 0.96 cases of ALD (~one case), in the 62 patients given both ivGC and statins. However, no cases of ALD were observed in patients given statins, and the previously reported 14 cases of ALD in this series were seen in patients who were not taking statins. The lack of observation of cases of ALD in patients given ivGC and statins is quite reassuring. Although caution should be applied to any patient candidate to ivGC treatment and this should be particularly accurate in patients given statins, our findings somehow justify the use of ivGC in patients under statins, although further studies in larger cohorts are needed to confirm our conclusions.

Ischemia-Reperfusion Injury in Fatty Liver Is Mediated by Activated NADPH Oxidase 2 in Rats.

Liver ischemia-reperfusion (I/R) injury is a severe complication of liver surgery, and steatosis is a risk factor for liver damage. Reactive oxygen species generated by nicotinamide adenine dinucleotide phosphate oxidase (NOX) contribute to liver dysfunction. Here we examined the role of NOX in I/R injury of fatty livers. Rats were fed a methionine and choline-deficient diet to induce a fatty liver. Rats then underwent surgically induced partial hepatic ischemia followed by reperfusion. The overall survival rate after I/R was lower in rats with fatty livers than with normal livers (P < 0.01). Necrotic area and the concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG), TNFα, and IL-6 were higher in fatty liver tissue than in normal liver tissue (P < 0.01). The number of p47phox-positive cells was significantly higher in fatty liver tissue than in normal liver tissue after reperfusion and peaked 24 hours after reperfusion. The number of TLR-4 positive cells was significantly higher in fatty liver tissue than in normal liver tissue after reperfusion and peaked 4 and 24 hours after reperfusion coupled with a decreased number of high-mobility group box 1-positive hepatocytes. Apocynin significantly improved the survival rate, necrotic area, and concentrations of 8-hydroxy-2'-deoxyguanosine, TNFα, and IL-6 (P < 0.01). The protective effect of apocynin on fatty livers was greater than on normal livers. Ischemia-reperfusion injury was associated with increased high-mobility group box 1, TLR4, and NOX2. Inhibition of NOX activity improved oxidative stress and may prevent I/R injury in fatty liver.

Modulatory effects of Acanthopanax koreanum Nakai on oxidative stress induced by combination of alcohol and high‐fat diet in C57BL/6j mice.

Excess alcohol consumption is liked to a high risk of liver problem, which can develop into steatohepatitis and liver cirrhosis in modern society. A high‐fat (HF) diet can also lead to the progression of fatty liver. Therefore the role of alcohol as a risk factor for liver damage may be clearly demonstrated by a combination of both alcohol and HF diet. We tested this hypothesis by using Acanthopanax koreanum Nakai (AK) as a model compound. C57BL/6j mice (8‐week‐old; n=56) were randomly divided into seven groups for four weeks; normal control (NC), ethanol control (EC), EC + high fat diet (EF), EC + 1% AK (ECL), EC + 3% AK (ECH), EF + 1% AK (EFL), and EF + 3% AK (EFH). AK was provided in the diet and 50% (v/v) ethanol was provided by gavage. ADH had no significant difference among all groups. Hepatic ALDH activities were significantly increased in the EH compared with the NC, whereas the ECH showed a tendency of increase in ALDH activity compared with the EC. CYP2E1 was significantly increased in both the EC and the EF compared with the NC. ECH tended to decrease CYP2E1 protein expression compared with the EC and the EFL and EFH showed a tendency to decrease compared with the EF. Peroxisomal catalase (CAT) and glutathione reductase (GR) had a tendency to decrease in the EC; CAT and GR decreased significantly in the HF than in the NC. The AK treatment groups (ECH and EFH) showed a tendency to increase in CAT and GR. Taken together, the results support the hypothesis that combination of alcohol and high‐fat diet provide better animal model for testing the alcohol‐induced oxidative stress. Based on this animal model, the results suggest that AK administration in particularly at a high dose may have protective effects against hepatic injury via anti‐oxidative function.

Local recurrence and complications after percutaneous radiofrequency ablation of hepatocellular carcinoma: a retrospective cohort study focused on tumor location.

We conducted a retrospective cohort study to investigate the predisposing factors for local recurrence and complications after percutaneous radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC). HCC patients (n＝397) consecutively treated with RFA (256 males, 141 females, median age 69 years) were enrolled. In these patients, 1,455 nodules (median size 17mm) were ablated. Predisposing factors for overall recurrence and local recurrence in the context of tumor location and complications were examined. Local recurrence was observed for 113 of the 1,455 nodules. The 1-, 3- and 5-year local recurrence rates were 2.2%, 7.4% and 9.5%, respectively. A multivariate Cox proportional hazard analysis revealed that large tumor size (＞2cm), tumor location (adjacent to the major portal branch or hepatic vein), and small ablated margin (＜3mm) were independent predisposing factors for local recurrence after RFA (HR＝1.70-2.81). Tumor location (adjacent to the major portal branch, hepatic vein, or diaphragm) was also revealed as a risk factor for liver damage due to RFA. HCC adjacent to the major portal vein or hepatic vein was associated with a higher risk for local recurrence and for complications;therefore, special precautions are necessary when applying RFA to HCC near vessels even when the tumors are located at an easy-to-puncture site.

PNPLA3 I148M polymorphism is associated with elevated alanine transaminase levels in Mexican Indigenous and Mestizo populations

The patatin like phospholipase domain-containing (PNPLA3) I148M variant is the strongest genetic factor associated with elevated alanine transaminase (ALT) levels in different populations, particularly in Hispanics who have the highest 148M risk allele frequency reported to date. It has been suggested that Indigenous ancestry is associated with higher ALT levels in Mexicans. The aim of the present study was to assess the frequency of the PNPLA3 148M risk allele in Mexican indigenous and Mestizo individuals, and to examine its association with serum ALT levels. The study included a total of 1624 Mexican individuals: 919 Indigenous subjects from five different native groups and 705 Mexican Mestizo individuals (141 cases with ALT levels ≥ 40 U/L and 564 controls with ALT <40 U/L). The I148M polymorphism was genotyped by TaqMan assays. The frequency of elevated ALT levels in Indigenous populations was 18.7%, and varied according to obesity status: 14.4% in normal weight, 19.9% in overweight and 24.5% in obese individuals. The Mexican indigenous populations showed the highest reported frequency of the PNPLA3 148M risk allele (mean 0.73). The M148M genotype was significantly associated with elevated ALT levels in indigenous individuals (OR = 3.15, 95 % CI 1.91-5.20; P = 7.1 × 10(-6)) and this association was confirmed in Mexican Mestizos (OR = 2.24, 95% CI 1.50-3.33; P = 8.1 × 10(-5)). This is the first study reporting the association between M148M genotype and elevated ALT levels in Indigenous Mexican populations. The 148M allele risk may be considered an important risk factor for liver damage in Mexican indigenous and Mestizo populations.

Possible Hepatoprotective Effects of Lacidipine in Irradiated DOCA-Salt Hypertensive Albino Rats

Calcium channel blockers are increasingly used for the treatment of hypertension. Hypertension is an important risk factor for liver damage and several other circulatory abnormalities. The aim of this study was to determine the effects of lacidipine in a irradiation-induced hepatocellular damage model in Deoxyc Orticosterone Acetate (DOCA)-salt-induced hypertensive model in rats. In this study, animals were divided into five groups as follows: control (Group 1), hypertensive (Group 2), irradiated (Group 3), irradiated and hypertensive (Group 4) and irradiated, hypertensive and lacidipine-treated (Group 5). At the end of the experiment, the livers were removed and its homogenates were biochemically examined. Significant differences were found between values of all groups (p < 0.05). Group 3 and particularly Group 4 showed significant increase in lipid peroxidation and Nitric Oxide (NO) and serum tumor necrosis factor-alpha (TNF-alpha) with a significant reduction in serum level of alanine amine transferase (ALT) enzyme and in superoxide dismutase in red blood cells lysates. Lacidipine-treated group (5) showed a significant reduction in elevated systolic blood pressure together with a great protection of ALT and SOD enzymes from the destructive effects of irradiation and hypertension. Additionally, this CCB reduces hepatic NO and serum TNF-alpha levels that were increased in groups (2,3,4). The present study suggests that lacidipine has some important protective effects on liver of hypertensive irradiated albino rats.

Association of the I148M/PNPLA3 variant with elevated alanine transaminase levels in normal-weight and overweight/obese Mexican children

Background and aimsNon-alcoholic fatty liver disease (NAFLD) and elevated alanine transaminase (ALT) levels are common in obese Hispanic adults and children. Recently, a PNPLA3 gene variant (I148M) was strongly associated with NAFLD and higher ALT levels in obese adults, including Hispanics. The aims of this study were to estimate the frequency of elevated ALT levels, and to address the influence of obesity and PNPLA3/I148M on ALT levels in a general population sample of Mexican school-aged children. MethodsA total of 1037 non-related Mexican children aged 6 to 12years were genotyped for the I148M variant. Anthropometric, clinical and metabolic parameters were collected from all participants. ResultsElevated ALT levels (>35U/L) were more frequent in obese (26.9%) and overweight (9.3%) than in normal weight children (2.2%). The M148M genotype was significantly associated with elevated ALT levels in this population (OR=3.7, 95% CI 2.3–5.9; P=3.7×10−8), and children carrying the M148M genotype showed significantly lower HDL cholesterol levels and BMI z-core (P=0.036 and 0.015, respectively). On stratifying by BMI percentile, this genotype conferred a much greater risk of elevated ALT levels in normal weight (OR=19.9, 95% CI 2.5–157.7; P=0.005) than overweight and obese children (OR=3.4, 95% CI 1.3–8.9; P=0.014 and OR=3.1, 95% CI 1.7–5.5; P=1.4 x10−4, respectively). ConclusionsThe I148M PNPLA3 variant is strongly associated with elevated ALT levels in normal weight and overweight/obese Mexican children. Thus, the M148M genotype may be considered as an important risk factor for liver damage in this population.