The thyroid gland and liver share a complex bidirectional relationship that is fundamental to metabolic regulation and hormonal homeostasis. Thyroid hormones (THs) regulate hepatic lipid handling, glucose metabolism, mitochondrial function, and energy balance, while the liver governs TH transport, activation, metabolism, and clearance. Increasing evidence links thyroid dysfunction with metabolic dysfunction-associated steatotic liver disease (MASLD), fibrosis progression, and adverse metabolic outcomes. This narrative review provides an updated synthesis of the mechanistic, clinical, and therapeutic aspects of thyroid-liver interactions and their implications for clinical practice. A comprehensive review of mechanistic, clinical, translational, and therapeutic studies examining thyroid dysfunction, liver disease, thyroid hormone sensitivity, and emerging thyroid hormone-based therapies was conducted. Thyroid dysfunction contributes to MASLD, dyslipidemia, insulin resistance, and hepatic injury, whereas liver disease alters TH metabolism and complicates the interpretation of thyroid function tests, including the occurrence of nonthyroidal illness syndrome. Emerging evidence suggests that reduced intrahepatic TH signaling and altered tissue-level hormone sensitivity play central roles in steatosis and fibrosis progression. Clinically, recognition of these interactions may improve the interpretation of thyroid abnormalities in liver disease and support risk stratification in metabolic liver disorders. The development of liver-targeted thyroid hormone receptor-β agonists, including resmetirom, represents a major therapeutic advance with potential to reshape management strategies for metabolic dysfunction-associated steatohepatitis (MASH). However, important controversies remain regarding the diagnostic utility of thyroid hormone sensitivity indices, long-term safety of thyromimetics, and the role of thyroid hormone replacement in liver-directed therapy, highlighting the need for robust prospective studies.

Portal vein thrombosis (PVT) is a rare complication following percutaneous liver biopsy, with an incidence below 0.4% in large multicenter series. We report a 51-year-old male with common variable immunodeficiency (CVID), chronic liver enzyme elevation, and preoperative imaging consistent with cirrhotic morphology, who developed acute abdominal pain within minutes of ultrasound-guided liver biopsy. Notably, biopsy demonstrated only mild steatosis with portal chronic inflammation and no significant fibrosis-a discordance from imaging attributed to CVID-associated nodular regenerative hyperplasia and biopsy sampling error. Contrast-enhanced CT on the day of the procedure showed heterogeneous left lobe enhancement consistent with a transient hepatic attenuation difference (THAD) secondary to focal portal venous obstruction, with a subsegmental filling defect in segment 3 on portal venous phase imaging. Repeat CT on postprocedure day 1 demonstrated thrombus extension into the left main portal vein; MRCP excluded biliary complications and hemobilia. The patient was treated with intravenous heparin transitioned to oral apixaban, with symptomatic improvement and normalization of liver function tests. A formal hypercoagulable evaluation was not performed given the provoked clinical context and normal INR, and no postdischarge imaging was available to assess recanalization; both are acknowledged as limitations. This case illustrates the convergence of multiple risk factors-abnormal hepatic vascular architecture from CVID-related liver disease, endothelial injury from needle passage, and potential hemostatic agent migration-in the pathogenesis of postbiopsy PVT, and underscores the importance of prompt vascular imaging and anticoagulation in patients presenting with acute abdominal pain following liver biopsy.

Dittrichia viscosa (L.) is widely recognized in alternative medicine in the Mediterranean area for its therapeutic purposes. This study evaluates the acute and subacute toxicity of polar and non-polar extracts of D. viscosa when administered orally or applied topically. Toxicity tests were conducted at a dose of 2000 mg/kg on Wistar rats over 14 days for acute toxicity and 28 days for subacute toxicity. Parameters assessed included body weight, behavioral observations, hematological analysis, serum biochemistry, and histopathological examinations. No significant toxic effects were observed after a single administration of 2000 mg/kg of D. viscosa extracts. Furthermore, during the 28-day sub-acute toxicity study, daily doses of 2000 mg/kg were well-tolerated without inducing mortality, clinical signs of toxicity, or significant changes in behavior, body weight, or physiological status in either male or female rats. Hematological parameters remained stable, and there were no disruptions in liver function enzymes, glucose, or creatinine levels, confirming normal hepatic and renal function. These findings suggest that D. viscosa extracts are non-toxic and safe for oral and dermal use.

Hyperammonaemia is a potentially reversible cause of encephalopathy that can mimic focal neurological syndromes. A man in his 60s presented with light-headedness, vomiting and abdominal pain. He developed acute aphasia and right-sided weakness within 24 hours, and although serial CT brain imaging and CT angiography were normal, conscious level deteriorated rapidly, such that he required intubation and mechanical ventilation. MRI brain demonstrated symmetrical basal ganglia T1 hyperintensity. Metabolic investigation identified hyperammonaemia (147 µmol/L). He was treated with lactulose, rifaximin and continuous veno-venous haemofiltration with biochemical and neurological improvement and resolution of neurological deficits. In the absence of overt liver failure, small bowel bacterial overgrowth was considered the most likely cause although potential additional contributory factors were also identified. This case highlights the need to measure ammonia early in otherwise unexplained encephalopathy, even when liver function tests are normal.

Accurate diagnostic tests are essential for effective screening and treatment. However, individual biomarkers often fail to provide sufficient diagnostic accuracy, as they typically capture only one aspect of the complex disease process. Combining multiple biomarkers, each capturing a distinct mechanism, can help construct more informative diagnostic tests. In practice, logistic regression is used as the default to combine biomarkers, but it can perform poorly when biomarker distributions exhibit skewness or differ across disease groups. Nonparametric methods provide more flexibility but generally require large sample sizes that are infrequently available in biomedical research. We propose a novel framework called transformation discriminant analysis which combines biomarkers through the likelihood ratio function to construct theoretically optimal diagnostic scores. Transformation discriminant analysis (TDA) balances between flexibility and efficiency. It can accommodate a wide range of distributional shapes and disease-specific dependence structures while remaining fully parametric. This allows for likelihood inference and strong performance even in small-sample settings. We evaluate TDA through simulations and benchmark its performance against commonly used methods. Finally, we illustrate its utility in constructing an optimal diagnostic test for hepatocellular carcinoma, a disease with no single ideal biomarker. An open-source R implementation is provided for reproducibility and broader application.