Elevated Serum Alanine Aminotransferase Research Articles

Roselle (Hibiscus sabdariffa L.) calyx water extract ameliorates isoniazid and rifampicin induced liver and renal injuries in rats

Introduction: Roselle (Hibiscus sabdariffa L.) calyces possess natural antioxidants that may provide therapeutic benefits. This study aimed to investigate the protective effects of Roselle calyx water extract against isoniazid (INH) and rifampicin (RIF) induced liver and renal toxicities.Methods: Male Wistar rats (150-250 g) were designated into five groups: control group, INH-RIF group that was treated with INH-RIF at the toxic doses (50-100 mg/kg for 4 weeks, followed by 100-200 mg/kg for 2 weeks), and Roselle groups that were treated daily with Roselle extract at the doses 62.5, 125, and 250 mg/kg, respectively prior to INH-RIF administration. Blood samples were withdrawn weekly for 6 weeks before removing rats’ livers and kidneys for tissue malondialdehyde (MDA) and histopathological analysis.Results: The results showed all rats in the INH-RIF group experienced marked elevations of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, creatinine, and tissue MDA levels compared to the controls (P<0.05). In contrast, these biomarkers were maintained at near-normal levels in Roselle extract groups. Significant inflammation and cellular degeneration were found in the liver and renal tissues of the INH-RIF group, which were noticeably reduced with Roselle extract pre-treatment at the dose of 250 mg/kg.Conclusion: It is concluded that Roselle calyx extract can provide protection against liver and renal toxicities induced by INH-RIF administration in rats.

Potassium bromate-induced nephrotoxicity and potential curative role of metformin loaded on gold nanoparticles.

Potassium bromate (KBrO3) is classified by the International Agency for Research on Cancer as a carcinogenic compound, where it causes renal tumors. The present study investigated the potential curative effect of metformin loaded on gold nanoparticles (MET AuNPs) in attenuating KBrO3-induced nephrotoxicity. Rats were divided into eight groups (control, MET, AuNPs, MET AuNPs, KBrO3, KBrO3/MET, KBrO3/AuNPS, and KBrO3/MET AuNPs). KBrO3 administration resulted in a significant elevation in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total protein (TP), albumin (Alb), total bilirubin (TB), direct bilirubin (DB), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), creatinine, urea, uric acid. Also, KBrO3 significantly increased renal malondialdehyde (MDA), protein carbonyl (PC), and nitric oxide (NO) levels and reduced the activities of antioxidant molecules superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), and Reduced glutathione (GSH). It also caused damaged DNA spots in comet assay and increased inflammatory IL-6 and apoptotic markers (caspase 3, Bax) while antiapoptotic Bcl-2 was significantly reduced. MET, AuNPS, MET AuNPS reduced the extent of renal damage induced by KBrO3 as indicated by decreased (AST, ALT, ALP, Alb, TP, TB, DB, creatinine, urea, uric, Lipid profile). MET, AuNPS, MET AuNPS showed a good curative effect against KBrO3-induced nephrotoxicity and MET AuNPS group showed better results compared with monotherapy.

Correlation analysis between ICG-R15 and modified Scheuer score in liver tissues of patients with hepatitis B e antigen-positive/negative chronic hepatitis B

Objective: To analyze the correlation between indocyanine green retention rate at 15 minutes (ICG-R15) and modified Scheuer score in liver tissues of patients with hepatitis B e antigen-positive/negative chronic hepatitis B (CHB), and further explore the indocyanine green clearance test (ICGCT) applied value in judging the progress of CHB-related liver disease. Methods: 407 HBeAg (+) / HBeAg (-) CHB inpatients with normal or slightly elevated serum alanine aminotransferase (ALT) [< 2 times the upper limit of normal (ULN)] and modified Scheuer score were collected, and divided into mild liver disease group (M group, 131 cases, modified Scheuer score < G2S2) and progressive liver disease group (A group, 276 cases, modified Scheuer score≥G2 and / or S2). Furthermore, the groups were sub-divided into HBeAg (+) - M group, HBeAg (-) - M group, HBeAg (+) - A group and HBeAg (-) - A group. The correlation between ICG-R15 and modified Scheuer score was analyzed retrospectively. The data were analyzed by SPSS 24.0 software. Results: Basic clinical characteristics: Among the 407 CHB cases with normal or mildly elevated serum ALT, 171 were HBeAg(+) CHB and 236 were HBeAg(-) CHB. The baseline mean serum HBV DNA was higher in HBeAg(+) CHB patients [(6.06 ± 1.95) log10IU/ml] than HBeAg(-) CHB patients [(3.60±1.37)log10IU/ml (P = 0.000)]. Included patients ICG-R15 detection characteristics: (1) The baseline mean value of ICG-R15 was not statistically significant between the two groups of HBeAg(+) CHB and HBeAg(-) CHB, and was basically within the normal range (< 10%); (2) Comparison of ICG-R15 baseline mean value among the subgroups showed that the patients in the HBeAg(+)-A group/HBeAg(-)-A group were higher than the HBeAg(+)-M group/HBeAg(-)-M group patients, and the difference was statistically significant (P = 0.013/P = 0.000). Included patients' correlation analysis between ICG-R15 and modified Scheuer score: (1) ICG-R15 and modified Scheuer score had shown weak positive correlation with inflammatory activity grade (g) in HBeAg (+) / HBeAg (-) CHB (r = 0.237, P = 0.002); r = 0.244, P = 0.000); (2) There was a weak positive correlation between ICG-R15 and fibrosis stage (s) in HBeAg (+) / HBeAg (-) CHB (r = 0. 254, P = 0; r = 0.225, P = 0.001). Included patients ICG-R15 predictive value for the severity of liver histological progression: when the cut-off value of ICG-R15 was 5.1%, the area under the receiver operating characteristic curve from M group to A group was 0.601 (P = 0.001) for predicting HBeAg (+) / HBeAg (-) CHB patients. Conclusion: ICG-R15 is positively correlated with the modified Scheuer score of liver tissue in HBeAg (+)/HBeAg (-) CHB patients with normal or slightly elevated ALT. In addition, when the cut-off value of ICG-R15 was 10%, it could not accurately reflect the effective hepatocyte reserve function of HBeAg (+) / HBeAg (-) CHB patients with normal or slightly elevated ALT. Importantly, when the cut-off value of ICG-R15 is 4.0% ~ 5.0%, it may have predictive value for liver disease progression to modified Scheuer score ≥ G2 and / or ≥S2 in HBeAg (+) / HBeAg (-) CHB patients with normal or slightly elevated ALT.

Inhibition of Oxidative Stress and ALOX12 and NF-κB Pathways Contribute to the Protective Effect of Baicalein on Carbon Tetrachloride-Induced Acute Liver Injury.

This study investigates the protective effect of baicalein on carbon tetrachloride (CCl4)-induced acute liver injury and the underlying molecular mechanisms. Mice were orally administrated baicalein at 25 and 100 mg/kg/day for 7 consecutive days or ferrostatin-1 (Fer-1) at 10 mg/kg was i.p. injected in mice at 2 and 24 h prior to CCl4 injection or the vehicle. Our results showed that baicalein or Fer-1 supplementation significantly attenuated CCl4 exposure-induced elevations of serum alanine aminotransferase and aspartate aminotransferase, and malondialdehyde levels in the liver tissues and unregulated glutathione levels. Baicalein treatment inhibited the nuclear factor kappa-B (NF-κB) pathway, activated the erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway in liver tissues, and markedly improved CCl4-induced apoptosis, inflammation and ferroptosis in liver tissues exposed with CCl4. In vitro, baicalein treatment improved CCl4 -induced decreases of cell viabilities and knockdown of Nrf2 and arachidonate 12-lipoxygenase (ALOX12) genes partly abolished the protective effect of baicalein on CCl4 -induced cytotoxicity in HepG2 cells. In conclusion, our results reveal that baicalein supplementation ameliorates CCl4-induced acute liver injury in mice by upregulating the antioxidant defense pathways and downregulating oxidative stress, apoptosis, inflammation and ferroptosis, which involved the activation of Nrf2 pathway and the inhibition of ALOX12 and NF-κB pathways.

Lactobacillus acidophilus LA14 Alleviates Liver Injury.

ABSTRACTAlthough the probiotic Lactobacillus acidophilus LA14 is used worldwide, its effect on liver diseases remains unelucidated. Here, 32 rats were divided into four groups, gavaged with L. acidophilus LA14 (3 × 109 CFU) or phosphate-buffered saline for 7 days, and then intraperitoneally injected with d-galactosamine or saline. After 24 h, blood, liver, ileum, and feces samples were collected for liver injury, inflammation, intestinal barrier, gut microbiota, metabolome, and transcriptome analyses. Pretreatment with L. acidophilus LA14 alleviated the d-galactosamine-induced elevation of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and bile acids; mitigated the histological injury to the liver and gut; and suppressed the inflammatory cytokines macrophage inflammatory protein 1α (MIP-1α), MIP-3α, and MCP-1. L. acidophilus LA14 also ameliorated the d-galactosamine-induced dysbiosis of the gut microbiota and metabolism, such as the enrichment of Bacteroides sp. strain dnLKV3 and the depletion of Streptococcus, butanoic acid, and N-acetyl-d-glucosamine. The underlying mechanism of L. acidophilus LA14 included prevention of not only the d-galactosamine-induced upregulation of infection- and tumor-related pathways but also the d-galactosamine-induced downregulation of antioxidation-related pathways during this process, as reflected by the liver transcriptome and proteome analyses. Furthermore, the administration of L. acidophilus LA14 to healthy rats did not alter the tested liver indicators but significantly enriched the beneficial Lactobacillus and Bifidobacterium species, promoted metabolism and regulated pathways to improve immunity. The ability of L. acidophilus LA14 to alleviate liver injury was further confirmed with an acetaminophen-induced mouse model. These results might provide a reference for future studies on the application of L. acidophilus LA14 for the prevention of liver injury.IMPORTANCE The probiotic Lactobacillus acidophilus LA14 is widely used, but its effect on liver diseases has not been elucidated. We explored the protective effect of L. acidophilus LA14 on the liver using rats with d-galactosamine-induced liver injury. Pretreatment with L. acidophilus LA14 alleviated the d-galactosamine-induced elevation of serum ALT, AST, ALP, and bile acids, mitigated the histological injury to the liver and gut, and suppressed the inflammatory cytokines MIP-1α, MIP-3α, and MCP-1. These effects were correlated with the modulations of the gut microbiome, metabolome, and hepatic gene expression induced by L. acidophilus LA14. Moreover, the ability of L. acidophilus LA14 to alleviate liver injury was further confirmed with an acetaminophen-induced mouse model. These results might provide a reference for future studies on the application of L. acidophilus LA14 for the prevention of liver injury.

Ameliorative Effects of Aspergillus awamori against the Initiation of Hepatocarcinogenesis Induced by Diethylnitrosamine in a Rat Model: Regulation of Cyp19 and p53 Gene Expression.

Hepatocellular carcinoma (HCC) is the most common cancer in humans. Despite advances in its treatment, liver cancer remains one of the most difficult cancers to treat. This study aimed to investigate the ameliorative action and potential mechanism of Aspergillus awamori (ASP) administration against the initiation process of liver carcinogenesis induced by diethylnitrosamine (DEN) in male Wistar rats. Seventy-two male rats were divided equally into eight groups as follows, Group 1: untreated control; Group 2: DEN (200 mg/kg bw) intra-peritoneally for the initiation of HCC; Groups 3–5: DEN + ASP at a dose of 1, 0.5, and 0.25 mg/kg bw and groups 6–8: ASP at a dose of 1, 0.5, and 0.25 mg/kg bw. Supplementation of A. awamori significantly lightened the adverse impacts induced by DEN via restoring the leukogram to normal, lowering the elevated serum aspartate aminotransferase (AST), alanine transaminase (ALT), and γ-glutamyl transferase (GGT), and alkaline phosphatase (ALP). Furthermore, it enhanced the hepatic antioxidant capacity through increasing the reduced glutathione (GSH) level and catalase (CAT) activity with a marked reduction in malondialdehyde (MDA) level. In addition, it decreased the positive GST-P foci. Likewise, a significant alteration of DEN-associated hepatocarcinogenesis occurred through inhibiting cytochrome P450 (Cyp19) and activating p53 gene expression. In conclusion, supplementation of A. awamori counteracts the negative effects of DEN, inhibits the early development of GST-P-positive foci and could be used as a new alternative strategy for its chemo-preventive effect in liver cancer. To the best of our knowledge, the present study is the first to report the hepato-protective effect of A. awamori in induced hepatocarcinogenesis.

Antioxidative and hepatoprotective activities of a novel polysaccharide (LSAP) from Lepista sordida mycelia

A novel alkali-soluble polysaccharide from Lepista sordida (LSAP) mycelia with antioxidative and hepatoprotective activities was characterized. The weight-average molecular weight and number-average molecular weight of LSAP were 1.442×103 and 6.05×102kDa, respectively. LSAP was consisted of glucose (57.9%), xylose (31.8%), and small amounts of rhamnose, arabinose, galactose, glucuronic acid, and galacturonic acid (1.2%–3.1%). The FT-IR and 2D NMR confirmed that LSAP was composed of Xylp, Araf, 4-O-Me-α-D-GlcpA, (1→4)-linked β-D-Glcp, and (1→4)-α-D-GalA, and β-glycosidic linkages between these sugar units. LSAP displayed notable effects on 1,1-dephenyl-2-picryhydrazyl (DPPH) radical scavenging, hydrogen peroxide scavenging, lipid peroxidation inhibitory ability, reducing power and Fe2+ chelating property. These biological effects were further verified by suppressing CCl4-induced oxidative liver damage in mice at doses of 100 and 200mg/kg. Administration of LSAP in mice prior to CCl4 significantly prevented the CCl4-induced elevation in serum alanine aminotransferase, aspartate aminotransferase, and hepatic malondialdehyde. Mice treated with LSAP demonstrated to increase activities in superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the liver. We also found out that LSAP prevented CCl4-induced oxidative liver histological alteration. LSAP may exert hepatoprotective effects against CCl4-induced damage through antioxidant mechanisms in model mice.

Genetic variants associated with serum alanine aminotransferase levels among patients with hepatitis C virus infection: A genome-wide association study.

Information on genetic variants associated with elevated serum alanine aminotransferase (ALT) levels remains limited. A genome-wide association study was performed to identify single-nucleotide polymorphisms (SNPs) associated with ALT levels. The ALT-associated SNP was further evaluated for hepatocellular carcinoma (HCC) risk. A cohort of 892 anti-HCV seropositive patients was used for genome-wide SNP array to examine the associations with baseline ALT levels. SNPs <10-5 were further tested for associations with serial ALT levels then validated in 486 anti-HCV seropositives. Multinomial logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals of SNPs associated with ALT. The SNP was evaluated for HCC risk by using Cox's proportional hazards models. After quality control, 803 participants with 564,464 SNPs were included in the analysis. Of these, 12 SNPs were associated with ALT (p<10-5 ). Among the participants, 158 (19.7%) had ALT persistently ≤15 U/L, 327 (40.7%) ever >15 U/L but never >45 U/L, and 318 (39.6%) ever >45 U/L during follow-up. The rs568800 was associated with serial ALT levels, and this was replicated in the external population significantly (p<.05). The A allele (vs C) of rs568800 was associated with ALT >15 U/L but ≤45 U/L and ALT >45 U/L, with the adjusted ORs of 1.41 (1.11-1.78) and 1.86 (1.34-2.60), respectively. The adjusted HRs for HCC were 2.09 (0.90-4.89) for AC and 2.64 (1.13-6.17) for AA (CC as a reference). In conclusion, the rs568800 was associated with serum ALT levels and HCC risk. Clinical utility should be evaluated among patients who have received antivirals.

The role of SAMM50 in non-alcoholic fatty liver disease: from genetics to mechanisms.

Non‐alcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation. SAMM50 encodes Sam50, a mitochondrial outer membrane protein involved in the removal of reactive oxygen species, mitochondrial morphology and regulation of mitophagy. Certain single nucleotide polymorphisms of SAMM50 have been reported to be correlated with NAFLD. However, the contribution of SAMM50 polymorphisms to the occurrence and severity of fatty liver in the Chinese Han cohort has rarely been reported. Here, we investigated the association between SAMM50 polymorphisms (rs738491 and rs2073082) and NAFLD in a Chinese Han cohort, as well as the mechanistic basis of this association. Clinical information and blood samples were collected from 380 NAFLD cases and 380 normal subjects for the detection of genotypes and biochemical parameters. Carriers of the rs738491 T allele or rs2073082 G allele of SAMM50 exhibit increased susceptibility to NAFLD [odds ratio (OR) = 1.39; 95% confidence interval (CI) = 1.14–1.71, P = 0.001; OR = 1.31; 95% CI = 1.05–1.62, P = 0.016, respectively] and are correlated with elevated serum triglyceride, alanine aminotransferase and aspartate aminotransferase levels. The presence of the T allele (TT + CT) of rs738491 (P < 0.01) or G allele (AG + GG) of rs2073082 (P = 0.03) is correlated with the severity of fatty liver in the NAFLD cohort. In vitro studies indicated that SAMM50 gene polymorphisms decrease its expression and SAMM50 deficiency results in increased lipid accumulation as a result of a decrease in fatty acid oxidation. Overexpression of SAMM50 enhances fatty acid oxidation and mitigates intracellular lipid accumulation. Our results confirm the association between the SAMM50 rs738491 and rs2073082 polymorphisms and the risk of fatty liver in a Chinese cohort. The underlying mechanism may be related to decreased fatty acid oxidation caused by SAMM50 deficiency.

Incidences and Determinants of Functional Cure During Entecavir or Tenofovir Disoproxil Fumarate for Chronic Hepatitis B.

Long-term incidences and baseline determinants of functional cure (hepatitis B surface antigen [HBsAg] seroclearance) during entecavir (ETV) or tenofovir disoproxil fumarate (TDF) treatment are incompletely understood. This is an international multicenter cohort study of treatment-naive patients with chronic hepatitis B who started ETV or TDF treatment without baseline cancer. Patients were observed for HBsAg seroclearance until death or loss to follow-up. We calculated the incidences and explored the baseline determinants of HBsAg seroclearance using competing risk regression. The analysis included 4769 patients (median age, 50 years; 69.05% male), with a median follow-up of 5.16 years (26 614.47 person-years). HBsAg clearance occurred in 58 patients, yielding a 10-year cumulative incidence of 2.11% (95% confidence interval, 1.54%-2.88%) and an annual rate of 0.22% (.17%-.28%). Baseline predictors included low-level viremia with hepatitis B virus DNA <2000 IU/mL (adjusted subdistribution hazard ratio, 3.14 [95% confidence interval, 1.80-5.49]), elevated serum alanine aminotransferase >200 U/L (3.68 [2.07-6.53]), serum bilirubin (1.11 per mg/dL; [1.06-1.17 mg/dL]), and fatty liver (1.84 [1.03-3.29]). HBsAg seroclearance rarely occurs in patients with chronic hepatitis B treated with ETV or TDF and is associated with low-level viremia, alanine aminotransferase flare, bilirubin level, and fatty liver.Functional cure of hepatitis B virus infection rarely occurred at an average annual rate of 0.22% during first-line oral antiviral treatment, with higher chances observed in patients with low-level viremia, high-level aminotransferase flare, elevation of serum bilirubin, and fatty liver.

Characterization of liver injury induced by a pyrrolizidine alkaloid in rats

BackgroundPyrrolizidine alkaloids (PAs) are common phytotoxins. PA intoxication is reported to cause severe acute liver damage, typically known as hepatic sinusoidal obstruction syndrome (HSOS), but it remains obscure whether the acute liver damage may progress into chronic liver disease characterized by hepatic fibrosis. PurposeThis study aims to characterize the biochemical markers of liver injury and histological features of regressive and progressive liver fibrosis, and to examine changes in hepatic gene expression that may underpin mechanisms of fibrogenesis in rats induced by retrorsine (RTS), a representative toxic PA. Study design/methodsRats were gavaged with RTS via two dosing regimens, i.e. a single dose of 40 mg/kg (Group 1) and two doses of 40 mg/kg and 20 mg/kg on day 0 and day 7 (Group 2), respectively. Rats receiving one (Group 3) or two (Group 4) doses of vehicle served as negative controls. The animals were followed for up to 16 weeks by serum biochemical analyses and histological examination, and gene expression assays of liver tissues. ResultsAcute liver injury on day 2 manifested as HSOS, characterized by sinusoidal dilation, endothelial cell damage, and elevated serum alanine aminotransferase activity and bilirubin levels. In Group 1, mild liver fibrosis developed at sinusoids and perisinusoidal space surrounding the central veins at week 1 and 2, and thereafter, all liver injury resolved gradually. In Group 2, liver fibrosis progressed within the 16-week observation period. No apparent liver injury was observed in Groups 3 and 4. Compared with negative control groups, RTS induced myofibroblastic activation, TGF-β1 signaling, and changes in expression of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1). These dynamic changes differed in Groups 1 and 2, corresponding with the regression and progression of liver fibrosis, respectively, in these groups. ConclusionThis study has provided in-vivo proof of concept that “one hit” and “two hits” of RTS lead to acute resolving liver injury and chronic progressive liver fibrosis, respectively. These animal models may serve as powerful tools for studying RTS toxicology and related preventive and therapeutic strategies and as positive controls for studying other PA- and non-PA-induced liver injury.

Zingiber roseum Rosc. rhizome: A rich source of hepatoprotective polyphenols

Zingiber roseum is native to Bangladesh and widely used in folk medicine. This present study was designed to assess the ameliorative potential of Zingiber roseum rhizome extract in carbon tetrachloride (CCl4) induced hepatotoxicity in mice model. Seven phenolic compounds were identified and quantified by HPLC analysis in the plant extract, including quercetin, myricetin, catechin hydrate, trans-ferulic acid, trans-cinnamic acid, (-) epicatechin, and rosmarinic acid. Hepatotoxicity was induced by administrating a single intraperitoneal injection of CCl4 (10 mL/kg) on 7th day of treatment. The results revealed that plant extract at all doses (100, 200 and 400 mg/kg) significantly reduced (p < 0.05) the elevated serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) concentrations, and these effects were comparable to that of standard drug silymarin. Histopathological examination also revealed the evidence of recovery from CCL4 induced cellular damage when pretreated with Z. roseum rhizome extract. The in-vivo hepatoprotective effects were further investigated by the in-silico study of the aforementioned compounds with liver-protective enzymes such as superoxide dismutase (SOD), peroxiredoxin, and catalase. The strong binding affinities (ranging from −7.3359 to −9.111 KCal/mol) between the phenolic compounds (except trans-cinnamic acid) and oxidative stress enzymes inhibit ROS production during metabolism. The compounds were also found non-toxic in computational prediction, and a series of biological activities like antioxidant, anticarcinogen, cardio-protectant, hepato-protectant have been detected.

NLRP3 deficiency did not attenuate NASH development under high fat calorie diet plus high fructose and glucose in drinking water

NOD-like receptor protein 3 (NLRP3) promotes the inflammatory response during progression of nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH). This study aimed to further delineate the role of NLRP3 in NASH development by abolishing its expression in mice. A high-fat and calorie diet plus high fructose and glucose in drinking water (HFCD-HF/G) was used to establish NASH in both wild-type (WT) and NLRP3 knock-out (KO) mice. Hepatocellular injury, hepatic steatosis and fibrosis, as well as inflammatory response and insulin resistance in the liver and epidydimal white adipose tissue (eWAT) were determined. Elevated body weight, liver weight and serum alanine transaminase level, increased hepatic triglyceride accumulation and collagen deposition, and worsened systemic insulin resistance were observed in Nlrp3−/− mice compared to WT mice under HFCD-HF/G feeding. Upregulated hepatic transcription of tumor necrosis factor-α (TNF-α) and monocyte chemotactic protein-1 (MCP-1), and enhanced infiltration of inducible nitric oxide synthase-positive (iNOS+) M1 macrophages were also documented in HFCD-HF/G-fed Nlrp3−/− mice in comparison to HFCD-HF/G-fed WT mice. Moreover, transcription of TNF-α and MCP-1 and infiltration of iNOS+ M1 macrophages were increased in the liver of Nlrp3−/− mice under control diet. NLRP3 deficiency did not attenuate, but instead aggravated NASH development under HFCD-HF/G feeding. The worsened extent of NASH might be attributed to enhanced hepatic MCP-1 expression and M1 macrophage infiltration in Nlrp3−/− mice. Our study points to additional caution when NLRP3 blockade is considered as a therapeutic strategy in the treatment of human NASH.

Coronavirus Disease 2019 and Liver Injury: A Retrospective Analysis of Hospitalized Patients in New York City

Background and AimsCoronavirus disease 2019 (COVID-19) is a global threat, affecting more than 100 million people and causing over 2 million deaths. Liver laboratory test abnormalities are an extrapulmonary manifestation of COVID-19, yet characterization of hepatic injury is incomplete. Our objective was to further characterize and identify causes of liver injury in patients with COVID-19.MethodsWe conducted a retrospective cohort study of 551 patients hospitalized with COVID-19 at NewYork-Presbyterian Hospital/Columbia University Irving Medical Center between March 1, 2020 and May 31, 2020. We analyzed patient demographics, liver laboratory test results, vital signs, other relevant test results, and clinical outcomes (mortality and intensive care unit admission).ResultsAbnormal liver laboratory tests were common on hospital admission for COVID-19 and the incidence increased during hospitalization. Of those with elevated serum alanine aminotransferase and/or alkaline phosphatase activities on admission, 58.2% had a cholestatic injury pattern, 35.2% mixed, and 6.6% hepatocellular. Comorbid liver disease was not associated with outcome; however, abnormal direct bilirubin or albumin on admission were associated with intensive care unit stay and mortality. On average, patients who died had greater magnitudes of abnormalities in all liver laboratory tests than those who survived. Ischemic hepatitis was a mechanism of severe hepatocellular injury in some patients.ConclusionsLiver laboratory test abnormalities are common in hospitalized patients with COVID-19, and some are associated with increased odds of intensive care unit stay or death. Severe hepatocellular injury is likely attributable to secondary effects such as systemic inflammatory response syndrome, sepsis, and ischemic hepatitis.

Intrahepatic cholestasis of pregnancy

Die Schwangerschaftscholestase („intrahepatic cholestasis of pregnancy“, ICP) ist die häufigste schwangerschaftsspezifische Lebererkrankung. Das Leitsymptom Juckreiz sowie eine begleitende Serumkonzentrationserhöhung von Gallensäuren und/oder der Alaninaminotransferase (ALT) sind wegweisend in der Diagnosestellung. Die mütterliche Prognose ist gut. Das fetale Outcome ist abhängig von der Gallensäurenkonzentration. Die ICP ist dabei sowohl mit Frühgeburt als auch mit intrauterinem Fruchttod (IUFT) assoziiert. Dieser ist Folge einer akuten fetalen Asphyxie, nicht einer chronischen uteroplazentaren Dysfunktion. Ein prädiktives Monitoring, z. B. durch Kardiotokographie (CTG) oder Ultraschall gibt es nicht. Eine medikamentöse Therapie mit Ursodeoxycholsäure (UDCA) bessert den Juckreiz, aber beeinflusst das fetale Outcome nicht nachweislich. Eine Entbindungsindikation ist in Abhängigkeit von Gallensäurenkonzentration und Gestationsalter gegeben. In Folgeschwangerschaften besteht ein hohes Wiederholungsrisiko.

Moringa oleifera Lam. leaf extract mitigates carbon tetrachloride-mediated hepatic inflammation and apoptosis via targeting oxidative stress and toll-like receptor 4/nuclear factor kappa B pathway in mice

Carbon tetrachloride (CCl4) is a hepatotoxin that triggers liver damage. This study aimed to evaluate the protective effect of phytochemicals detected in Moringa oleifera Lam. leaf extract (MOLE) on CCl4-induced hepatotoxicity in mice. Phytochemicals, total phenolics, and total flavonoids were detected in MOLE. MOLE markedly decreased the elevation of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in consistence with the ameliorating effect on CCl4-induced histopathological abnormalities. Moreover, MOLE significantly alleviated the decrease in the antioxidant defense mechanism induced by CCl4. The suppressing effect of MOLE on the boosted inflammatory pathway triggered by CCl4 was detected by measuring the protein levels of nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB-p65), toll-like receptor 4 (TLR4), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1β, and IL-8 as well as the relative expressions of nuclear factor kappa B (NF-κB), TNF-α, IL-1β, and TLR4 genes. Apoptosis and genotoxicity induced by CCl4 were significantly alleviated by MOLE. MOLE co-administration modulated TLR4/NF-κB pathway as presented by the suppressed gene expression of TLR4 and NF-κB as well as by the reduced protein expression of TLR4 and NF-κB-p65. In conclusion, MOLE has a multifarious protective role against hepatotoxicity through control of oxidative stress and modulation of TLR4/NF-κB.

Potential Predictors of Poor Prognosis among Severe COVID-19 Patients: A Single-Center Study.

Background Timely detection of the progression of the highly contagious coronavirus disease (COVID-19) is of utmost importance for management and intervention for patients in intensive care (ICU). Aim This study aims to better understand this new infection and report the changes in the various laboratory tests identified in critically ill patients and associated with poor prognosis among COVID-19 patients admitted to the ICU. Methods This was a retrospective study that included 160 confirmed SARS-CoV-2-positive patients. Results Elevated serum ferritin, D-dimer, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and nonconjugated bilirubin levels were present in 139 (96%), 131 (96%), 107 (68%), 52 (34%), and 89 (70%) patients, respectively. Renal parameters were abnormal in a significant number of cases with elevated creatinine and blood urea nitrogen in 93 (62%) and 102 (68%) cases, respectively. Hematological profiles revealed lower red blood cell count, hemoglobin, eosinophils, basophils, monocytes, and lymphocytes in 90 (57%), 103 (65%), 89 (62%), 105 (73%), 35 (24%), and 119 (83%) cases, respectively. The neutrophil count was found to increase in 71.3% of the cases. There was significantly higher mortality (83%) among patients older than 60 years (p=0.001) and in female patients (75%) (p=0.012). Patients with lung diseases had a poor outcome compared to patients with other comorbidities (p=0.002). There was a significant association between elevated D-dimer levels and increased mortality (p=0.003). Elevated levels of AST, creatinine, blood urea nitrogen, and bilirubin were significantly associated with unfavorable outcomes. Conclusion Different parameters can be used to predict disease prognosis, especially the risk of poor prognosis. Accurate diagnosis and monitoring of disease progression from the early stages will help in reducing mortality and unfavorable outcomes.

Antioxidant effects of gum arabic on gentamycin-induced hepatotoxicity in rats

Background Gum arabic (GA) is an exudate obtained from Acacia senegal and A. seyal, and it contains a large amount of nonviscous soluble fiber. Experimental studies revealed its strong antioxidant properties. Gentamycin-induced hepatotoxicity has been reported in experimental animals. Gentamycin induces hepatoxicity mainly by generating free radicals and enhancing oxidative stress. Aim This study aimed to investigate the involvement of oxidative stress and the alteration of the oxidant–antioxidant balance in gentamycin-induced hepatotoxicity. In addition, this study explored the possible protection that can be afforded by GA, given its antioxidant potential. Materials and methods Forty adult male Albino rats’ weighing was used in this study. The animals were randomly divided into four groups. Group I served as control, which received normal mouse diet. Group II orally received GA through a gastric feeding tube for 8 days. Group III received a daily intraperitoneal injection of gentamycin. Group IV received gentamycin intraperitoneally plus orally for 8 days. Results The results of this study revealed significant elevation of serum alanine transaminase, hepatic malondialdehyde level, glutathione peroxidase, and glutathione S-transferase activities and reduction of hepatic Reduced Glutathione (GSH) and glutathione reductase activities in gentamycin-treated animals. Administration of GA with gentamycin intake restored the altered parameters to their normal values, whereas hepatic glutathione peroxidase and glutathione S-transferase activities were enhanced further. Conclusion This study demonstrated the antioxidant effect of GA and its protective role against gentamycin-induced hepatocyte injury. More studies are warranted to further reveal the underlying mechanisms of the antioxidant properties of GA, especially at the structural and molecular levels.

The association between serum alanine aminotransferase and hypertension: A national based cross-sectional analysis among over 21 million Chinese adults

BackgroundInconsistent results were found in the association between serum alanine aminotransferase (ALT) and hypertension among population-based studies. This study evaluated the association between ALT and hypertension among Chinese reproductive-age population by utilizing registration data from National Free Pre-pregnancy Checkups Project in 2016–2017.MethodsThe 21,103,790 registered participants were eligible for analysis, including women who were 20–49 years old and men who were 20–59 years old with available data for ALT and blood pressure (BP). Logistic regression was conducted to estimate odds ratio (OR) for the association between ALT and hypertension as a binary outcome. Linear regression was used to examine the association between ALT and BP as a continuous outcome.ResultsIn total, 4.21% of the participants were hypertensive, and 11.67% had elevated ALT (> 40 U/L). Hypertension prevalence was 3.63% and 8.56% among participants with normal and elevated ALT levels. A strong linear relationship was found between serum ALT levels and the odds of hypertension after adjustment for potential confounders. The multivariable-adjusted ORs for hypertension were 1, 1.22 (1.21, 1.22), 1.67 (1.65 1.68), 1.78 (1.76, 1.80), and 1.92 (1.90, 1.94) in participants with ALT levels of ≤ 20, 20.01–40, 40.01–60, 60.01–80, and > 80 U/L, respectively. Systolic and diastolic BPs rose by 1.83 and 1.20 mmHg on average, for each 20 U/L increase in ALT (P for trend < 0.001). The association was consistent among subgroups and tended to be stronger among populations who are overweight (body mass index ≥ 24 kg/m2) (χ2 = 52,228, P < 0.001), alcohol drinking (χ2 = 100,730, P < 0.001) and cigarette smoking (χ2 = 105,347, P < 0.001).ConclusionsOur cross-sectional analysis suggested a linear association between serum ALT and hypertension or BP, which indicated that abnormal liver metabolism marked by elevated serum ALT could play a role in hypertension or elevated BP condition.

Association between Dietary Patterns and Serum Hepatic Enzyme Levels in Adults with Dyslipidemia and Impaired Fasting Plasma Glucose.

We investigated the association between dietary patterns and serum hepatic enzyme levels in adults with dyslipidemia and impaired fasting glucose in Taiwan. A total of 15,005 subjects (5452 men and 9553 women) aged 35–69 years were selected. Two major dietary patterns were identified by principal component analysis: Western dietary pattern and Mediterranean dietary pattern. Subjects in the highest quartile (Q4) of the Western dietary pattern showed an increased risk of elevated serum alanine aminotransferase (ALT) levels (OR: 1.24, 95% CI: 1.06–1.45, p-trend = 0.01). Fur-thermore, in the highest quartile of the Western dietary pattern, subjects with high waist circum-ference were observed to have a greater risk for developing abnormal serum ALT levels compared to those in the lowest quartile (Q1) (OR: 1.43, 95% CI: 1.04–1.97, p-trend = 0.01). In the highest quartile of the Western dietary pattern, only women were at an increased risk for having abnormal serum ALT levels (OR: 1.28, 95% CI: 1.04–1.59, p-trend = 0.03). By contrast, in the highest quartile of the Mediterranean dietary pattern, only men were at a reduced risk for having abnormal serum gamma-glutamyl transferase (GGT) levels (OR: 0.72, 95% CI: 0.53–0.97, p-trend = 0.048). We report a positive association between the Western dietary pattern and abnormal serum ALT levels.