UNASSIGNED: Hepatotoxicity is the foremost issue for clinicians and the primary reason for pharmaceutical product recalls. A biomarker is a measurable and quantifiable attribute used to evaluate the efficacy of a treatment or to diagnose a disease. There are various biomarkers which are used for the detection of liver disease and the intent of liver damage.
UNASSIGNED: This review aims to investigate the current state of hepatotoxicity biomarkers and their utility in clinical settings. Using hepatic biomarkers, the presence of liver injury, its severity, prognosis, causative agent, and type of hepatotoxicity can all be determined.
UNASSIGNED: Relevant published articles up to 2022 were systematically retrieved from MEDLINE/PubMed, SCOPUS, EMBASE, and WOS databases using keywords such as drug toxicity, hepatotoxicity biomarkers, biochemical parameters, and nonalcoholic fatty liver disease.
UNASSIGNED: In clinical trials and everyday practice, biomarkers of drug-induced liver injury are essential for spotting the most severe cases of hepatotoxicity. Hence, developing novel biomarker approaches to enhance hepatotoxicity diagnosis will increase specificity and/or identify the person at risk. Importantly, early clinical studies on patients with liver illness have proved that some biomarkers such as aminotransferase, bilirubin, albumin, and bile acids are even therapeutically beneficial.
UNASSIGNED: By assessing the unique signs of liver injury, health care professionals can rapidly and accurately detect liver damage and evaluate its severity. These measures contribute to ensuring prompt and effective medical intervention, hence reducing the risk of long-term liver damage and other major health concerns.

The objective of this manuscript is to examine the current literature on non-alcoholic fatty liver disease (NAFLD) biomarkers and their correlation with cardiovascular disease (CVD) outcomes and cardiovascular risk scores.
There has been a growing appreciation for an independent link between NAFLD and CVD, culminating in a scientific statement by the American Heart Association in 2022. More recently, studies have begun to identify biomarkers of the three NAFLD phases as potent predictors of cardiovascular risk. Despite the body of evidence supporting a connection between hepatic biomarkers and CVD, more research is certainly needed, as some studies find no significant relationship. If this relationship continues to be robust and readily reproducible, NAFLD and its biomarkers may have an exciting role in the future of cardiovascular risk prediction, possibly as risk-enhancing factors or as components of novel cardiovascular risk prediction models.

Increasing interest in developing antifibrotic therapies became a paramount priority due to the globally raised incidence of deaths secondary to hepatic cirrhosis. This work deals with the development of innovative antifibrotic pirfenidone -loaded lecithin core nanocapsules. This with the intention to target the liver and to increase the drug bioavailability, reducing drug liver toxicity, and studying the associated hepatic microenvironment changes. PFD-loaded lecithin nanocapsules (PFD-LENCs) were prepared using the natural lipoid S45 for its dual benefits of being both a lipid and an amphiphilic surfactant. The selected formulation exhibited in vitro sustained drug release up to 24 h compared to free PFD, which is consistent with the studied pharmacokinetic profile. The studied cytotoxicity of PFD as well as PFD-LENCs exhibited negligible cytotoxicity in normal oral epithelial cells. For exploring the capability of the PFD-LENCs in reaching the liver; in vivo tracing using CLSM, in vivo biodistribution to the vital organs were conducted and electron microscopic examination for depicting nanoparticles in liver tissue was performed. Results revealed the capability of the prepared fluorescent LENC2 in reaching the liver, PFD-LENCs detection in the Disse space of the liver and the significant accumulation of PFD-LENCs in liver tissue compared to the other tested organs. The assessment of the necro-inflammatory, antioxidant and the anti-fibrotic effect of PFD-LENCs (50 & 100 mg/kg) exhibited a significant decrease of liver enzymes, TNF-α, TGF-β, Col-1, α-SMA, and TIMP-1, and a significant increase of catalase enzyme and MMP2 compared to free PFD. EM studies, revealed often detection of dendritic cells in PFD-LENCs (100 mg/kg) treated mice and abnormal collagen structure which can represent an adjunct contribution to the antifibrotic mechanism of PFD-LENCs. In conclusion, the development of this innovative PFD loaded lecithin nanocapsules achieved a targeting ability to the liver, controlled drug release, thereby increase the PFD therapeutic value in downregulating hepatic fibrosis in adjunct with the reduction of liver toxicity.

Lomitapide is a microsomal triglyceride transfer protein inhibitor for patients with homozygous familial hypercholesterolaemia. Due to its mechanism of action, potential hepatic effects of lomitapide are of clinical interest. This study aimed to determine the long-term hepatic safety of lomitapide.
Data were aggregated from the pivotal phase 3 and extension phase clinical trial with lomitapide (median 5.1 years; serum total bilirubin, transaminases, cytokeratin-18 [CK-18] and enhanced liver fibrosis [ELF] score, fat-soluble vitamins and essential fatty acids), 8-year data from the Lomitapide Observational Worldwide Evaluation Registry (LOWER) and real-world evidence from a cohort of patients treated with lomitapide in Italy (hepatic elastography, and FIB-4 score for hepatic fibrosis).
In the phase 3 trial and the LOWER registry, any asymptomatic excursions in liver transaminase levels were not associated with elevations in bilirubin, and no Hy\'s law cases were detected in up to 8 years follow-up. There were no clinically relevant increases among hepatic biomarkers CK-18, CK-18 fragments or ELF score and fat-soluble vitamins and essential fatty acids remained above normal levels. In 34 patients treated in Italy with lomita pide for more than 9  years, elevations in hepatic fat were mild-to-moderate; hepatic stiffness remained normal, and the mean FIB-4 score remained below the fibrosis threshold value of 2.67.
These data indicate that the hepatic safety of lomitapide remains favourable with no clinically significant elevations in hepatic biomarkers and hepatic stiffness remained normal for more than 9 years follow-up. PHASE 3 TRIAL: NCT00730236; extension phase: NCT00943306; LOWER: NCT02135705.

Chikungunya infection leads to acute/chronic polyarthritis/polyarthralgia causing long-term morbidity among patients. Prognosis of post-chikungunya chronic arthritis (PCA) is of utmost necessity for proper disease management. Arthritic and hepatic biomarkers were evaluated among chikungunya patients without arthritis, with acute arthritis and with post-chikungunya chronic arthritis in the study. Serum levels of arthritic [CRP (C-reactive protein), anti cyclic-citrullinated-peptide (anti-CCP) antibody, soluble interleukin-2 receptor (sIL-2R), cartilage oligomeric matrix protein (COMP)] and hepatic [ALT (alanine aminotransferase), AST (aspartate aminotransferase), ALP (alkaline phosphatase), albumin and bilirubin] biomarkers of 167 chikungunya positive patients were determined by sandwich-ELISA/immunoturbidimetry/auto-analyser. 167 chikungunya-patients and 102 healthy controls were genotyped to understand role of CRP-rs3093059/rs3091244, IL-2R-rs743777 and COMP-rs144778694 polymorphisms towards chikungunya virus (CHIKV) infectivity and arthralgic manifestation. CRP, anti-CCP antibody, IL-2R and COMP levels significantly increased among PCA patients. Concentrations of AST, ALT, AST/ALT-ratio, bilirubin and ALP increased among arthritic chikungunya patients. Principal component analysis differentiated PCA groups from acute (AA) and non-arthritic groups. Patients with IL-2R-rs743777-GA, G-allele and COMP-rs144778694-GA genotypes were susceptible to chikungunya infection. Moreover, patients with CRP-rs3093059-CT, rs3091244-TT, IL-2R-rs743777-GA and COMP-rs144778694-AA genotypes were significantly protected from arthralgia, whereas, COMP-rs144778694-GA genotype was susceptible towards it. Patients with certain genotypes of CRP, IL-2R and COMP demonstrated significantly higher biomarker serum-levels among patients suffering from AA with/without PCA. Thus, both serum biomarker levels and polymorphic genotypes of infected patients play decisive role in development of PCA.

UNASSIGNED: Fasciolosis is a cosmopolitan parasitic disease of food-producing animals and is typically caused by digenetic trematodes, Fasciola gigantica and Fasciola hepatica. It has a direct negative impact on the liver and consequently affects liver metabolism. It has indirect effects, including lowered milk production and effects on quality and general health conditions leading to extensive economic losses. This study aimed to focus on the link between clinical fasciolosis and some biochemical analysis of the hepatic profile of cattle in Chad.
UNASSIGNED: This study was initiated in response to emerging complaints from dairy cattle owners detecting a bitter milk cream and butter taste. Furthermore, those animals had shown poor health conditions by presenting with diarrhea. Preliminary surveillance for possible causes was performed, including fecal and serum biochemical analyses and clinical observation to diagnose the possible disease.
UNASSIGNED: The results obtained, including the finding of parasite stages during the coprological examination, confirmed the role of fasciolosis. The independent sample t-test indicated highly significantly altered values of all biochemical liver indicators in the infected animals. All animals were treated with two doses of rafoxanide (3 mg/kg b.w.) S/C, at 21 days intervals, with vitamin supplements, mineral mixtures, and food additives. Surprisingly, the main complaint was restored after treatment. This is another evident clue of fasciolosis. To the best of our knowledge, this is the first recent study that diagnosed fasciolosis in Chad.
UNASSIGNED: This study emphasized the importance of fasciolosis, its negative impact on milk taste, and the necessity for veterinary advice regarding routine examination and prophylactic measures, especially before autumn, to minimize economic losses. However, regardless of the small sample size, this study could serve as a cornerstone for future studies on evaluating the accurate epidemiological status of fasciolosis in Chad. This study reported a close association between the alteration of liver enzymes and total protein levels in fasciolosis and the bitter milk cream taste, which could be used as a diagnostic tool for fasciolosis.

Growth hormone (GH) replacement alters the peripheral interconversion of thyroxine (T4) and triiodothyronine (T3). However, little is known about the clinical impact of these alterations. We aimed to compare changes observed in the serum T3:T4 ratio with known biological markers of thyroid hormone action derived from different peripheral tissues.
We prospectively studied twenty GH deficient men before and after GH replacement in a tertiary referral endocrine center. Serum biochemical measurements included insulin like growth factor-1 (IGF-1), thyroid hormones (free & total T3, free & total T4 and reverse T3) and TSH. Changes in thyroid hormone concentration were compared to alterations in hepatic and bone biomarkers of thyroid hormone action.
GH replacement provoked a decline in serum free T4 concentration (-1.09 ± 1.99 pmol/L; p = 0.02) and an increase in free T3 (+0.34 ± 0.15 pmol/L; p = 0.03); therefore, the free T3:free T4 ratio increased from 0.40 ± 0.02 to 0.47 ± 0.02 (p = 0.002). Sex hormone binding globulin (SHBG) level was unchanged. However, a decline in serum ferritin (-26.6 ± 8.5 ng/mL; p = 0.005) correlated with a fall in freeT4. Alterations in lipid profile, including a rise in large HDL sub-fractions and Lp (a) (+2.1 ± 21.1 nmol/L; p = 0.002) did not correlate with thyroid hormone levels. Significant increases were recorded in serum bone turnover markers - procollagen type 1 amino-terminal propeptide +57.4%; p = 0.0009, osteocalcin +48.6%; p = 0.0007; c-terminal telopeptides of type 1 collagen +73.7%; p = 0.002. Changes in bone formation markers occurred in parallel with fluctuations in thyroid hormone.
GH-induced alterations in the thyroid axis are associated with complex, tissue specific effects on thyroid hormone action. Modulation of bone turnover markers suggests that GH may improve the biological action of thyroid hormone on bone.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with abnormal liver function tests. We hypothesized that early altered liver biochemistries at admission might have different clinical relevance than subsequent changes during hospitalization. A single-center retrospective study was conducted on 540 consecutive hospitalized patients, PCR-diagnosed with SARS-CoV-2. Liver test abnormalities were defined as the elevation of either gamma-glutamyltransferase (GGT), alanine aminotransferase (ALT), or aspartate aminotransferase (AST), above the upper limit of normality set by our laboratory. Linear mixed models (LMM) evaluated longitudinal associations, incorporating all available follow-up laboratory chemistries. By the end of the follow-up period, 502 patients (94.5%) were discharged (109 (20.5%) died). A total of 319 (64.3%) had at least one abnormal liver test result at admission. More prevalent were elevated AST (40.9%) and GGT (47.3%). Abnormalities were not associated with survival but with respiratory complications at admission. Conversely, LMM models adjusted for age and sex showed that longitudinal increases during hospitalization in ferritin, GGT, and alkaline phosphatase (ALP), as well as a decreased albumin levels, were associated with reduced survival. This dual pattern of liver damage might reconcile previous conflicting reports. GGT and ALP trajectories could be useful to determine who might need more surveillance and intensive care.

Polyethylene glycols (PEGs) are commonly employed as excipients in preclinical studies and in vitro experiments to dissolve poorly hydrosoluble drugs. Their use is generally considered safe in both animals and humans; however, limited data is available concerning the safety of PEGs when administered parenterally. The results of our investigation demonstrate that PEG-400 can have an irritant effect on serosal surfaces and causes subcapsular hepatocellular necrosis in mice when administered intraperitoneally at a high dose (4 mL/kg). Accordingly, levels of serum biomarkers of liver injury need to be carefully interpreted in studies where PEG is administered intraperitoneally and always in association with the results of the histological assessment.