Inherited genetic disorders of the liver pose a significant public health burden. Liver transplantation is often limited by the availability of donor livers and the exorbitant costs of immunosuppressive therapy. To overcome these limitations, nucleic acid therapy provides a hopeful alternative that enables gene repair, gene supplementation, and gene silencing with suitable vectors. Though viral vectors are the most efficient and preferred for gene therapy, pre-existing immunity debilitating immune responses limit their use. As a potential alternative, lipid nanoparticle-mediated vectors are being explored to deliver multiple nucleic acid forms, including pDNA, mRNA, siRNA, and proteins. Herein, we discuss the broader applications of lipid nanoparticles, from protein replacement therapy to restoring the disease mechanism through nucleic acid delivery and gene editing, as well as multiple preclinical and clinical studies as a potential alternative to liver transplantation.

Liver diseases in pregnancy can be specific to gestation or only coincidental. In the latter case, the diagnosis can be difficult. Rapid diagnosis of maternal-fetal emergencies and situations requiring specialized interventions are crucial to preserve the maternal liver and guarantee materno-fetal survival. While detailed questioning of the patient and a clinical examination are highly important, imaging is often essential to reach a diagnosis of these liver diseases and lesions. Three groups of liver diseases may be observed during pregnancy: (1) diseases related to pregnancy: intrahepatic cholestasis of pregnancy, pre-eclampsia, eclampsia, hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome, and acute fatty liver of pregnancy; (2) liver diseases that are more frequent during or exacerbated by pregnancy: acute herpes simplex hepatitis, Budd-Chiari syndrome, hemorrhagic hereditary telangiectasia, hepatocellular adenoma, portal vein thrombosis, and cholelithiasis; (3) coincidental conditions, including acute hepatitis, incidental focal liver lesions, metabolic dysfunction-associated steatotic liver disease, cirrhosis, hepatocellular carcinoma, liver abscesses and parasitosis, and liver transplantation. Specific knowledge of the main imaging findings is required to reach an early diagnosis, for adequate follow-up, and to avoid adverse consequences in both the mother and the fetus.Critical relevance statement Pregnancy-related liver diseases are the most important cause of liver dysfunction in pregnant patients and, in pregnancy, even common liver conditions can have an unexpected turn. Fear of radiations should never delay necessary imaging studies in pregnancy.Key points• Pregnancy-related liver diseases are the most frequent cause of liver dysfunction during gestation.• Fear of radiation should never delay necessary imaging studies.• Liver imaging is important to assess liver emergencies and for the diagnosis and follow-up of any other liver diseases.• Common liver conditions and lesions may take an unexpected turn during pregnancy.• Pregnancy-specific diseases such as pre-eclampsia and HELLP syndrome must be rapidly identified. However, imaging should never delay delivery when it is considered to be urgent for maternal-fetal survival.

BACKGROUND: Liver disorders are important adverse effects associated with antifungal drug treatment. However, the accuracy of Clinical International Classification of Diseases (ICD)-10 codes in identifying liver disorders for register based research is not well-established. This study aimed to determine the positive predictive value (PPV) of the ICD-10 codes for identifying patients with toxic liver disease, hepatic failure, and jaundice among patients with systemic antifungal treatment.
METHODS: Data from the Swedish Prescribed Drug Register and the National Patient Register were utilized to identify adult patients who received systemic azole antifungal drugs and had a recorded diagnosis of toxic liver disease (K71.0, K71.1, K71.2, K71.6, K71.8, K71.9), hepatic failure (K72.0, K72.9), or jaundice (R17) between 2005 and 2016. The medical records of all included patients were reviewed. Prespecified criteria were used to re-evaluate and confirm each diagnosis, serving as the gold standard to calculate PPVs with 95% confidence intervals (95% CI) for each diagnostic group.
RESULTS: Among the 115 included patients, 26 were diagnosed with toxic liver disease, 58 with hepatic failure, and 31 with jaundice. Toxic liver disease was confirmed in 14 out of 26 patients, yielding a PPV of 53.8% (95% CI 33.4-73.4%). Hepatic failure was confirmed in 26 out of 38 patients, resulting in a PPV of 62.1% (95% CI 48.4-74.5%). The highest PPV was found in jaundice, with 30 confirmed diagnoses out of 31, yielding a PPV of 96.8% (95% CI 83.3-99.9%).
CONCLUSIONS: Among patients who received azole antifungal treatment and were subsequently diagnosed with a liver disorder, the PPV for the diagnosis of jaundice was high, while the PPVs for toxic liver disease and hepatic failure were lower.

Endoplasmic reticulum (ER) is the site for synthesis and folding of secreted and transmembrane proteins. Disturbance in the functioning of ER leads to the accumulation of unfolded and misfolded proteins, which finally activate the unfolded protein response (UPR) signaling. The three branches of UPR-IRE1 (Inositol requiring enzyme 1), PERK (Protein kinase RNA-activated (PKR)-like ER kinase), and ATF6 (Activating transcription factor 6)-modulate the gene expression pattern through increased expression of chaperones and restore ER homeostasis by enhancing ER protein folding capacity. The liver is a central organ which performs a variety of functions which help in maintaining the overall well-being of our body. The liver plays many roles in cellular physiology, blood homeostasis, and detoxification, and is the main site at which protein synthesis occurs. Disturbance in ER homeostasis is triggered by calcium level imbalance, change in redox status, viral infection, and so on. ER dysfunction and subsequent UPR signaling participate in various hepatic disorders like metabolic (dysfunction) associated fatty liver disease, liver cancer, viral hepatitis, and cholestasis. The exact role of ER stress and UPR signaling in various liver diseases is not fully understood and needs further investigation. Targeting UPR signaling with drugs is the subject of intensive research for therapeutic use in liver diseases. The present review summarizes the role of UPR signaling in liver disorders and describes why UPR regulators are promising therapeutic targets.

Acid sphingomyelinase (ASMase) serves as one of the most remarkable enzymes in sphingolipid biology. ASMase facilitates the hydrolysis of sphingomyelin, yielding ceramide and phosphorylcholine via the phospholipase C signal transduction pathway. Owing to its prominent intervention in apoptosis, ASMase, and its product ceramide is now at the bleeding edge of lipid research due to the coalesced efforts of several research institutions over the past 40 years. ASMase-catalyzed ceramide synthesis profoundly alters the physiological properties of membrane structure in response to a broad range of stimulations, orchestrating signaling cascades for endoplasmic reticulum stress, autophagy, and lysosomal membrane permeabilization, which influences the development of hepatic disorders, such as steatohepatitis, hepatic fibrosis, drug-induced liver injury, and hepatocellular carcinoma. As a result, the potential to modulate the ASMase action with appropriate pharmaceutical antagonists has sparked a lot of curiosity. This article emphasizes the fundamental mechanisms of the systems that govern ASMase aberrations in various hepatic pathologies. Furthermore, we present an insight into the potential therapeutic agents used to mitigate ASMase irregularities and the paramountcy of such inhibitors in drug repurposing.

OBJECTIVE: Non-Alcoholic fatty liver disease is characterized by the accumulation of excess fat in the liver, chronic inflammation, and cell death, ranging from simple steatosis to fibrosis, and finally leads to cirrhosis and hepatocellular carcinoma. The effect of Fibroblast growth factor 2 on apoptosis and ER stress inhibition has been investigated in many studies. In this study, we aimed to investigate the effect of FGF2 on the NAFLD in-vitro model in the HepG2 cell line.
METHODS: The in-vitro NAFLD model was first induced on the HepG2 cell line using oleic acid and palmitic acid for 24 h and evaluated by ORO staining and Real-time PCR. The cell line was then treated with various concentrations of fibroblast growth factor 2 for 24 h, total RNA was extracted and cDNA was consequently synthesized. Real-time PCR and flow cytometry was applied to evaluate gene expression and apoptosis rate, respectively.
RESULTS: It was shown that fibroblast growth factor 2 ameliorated apoptosis in the NAFLD in-vitro model by reducing the expression of genes involved in the intrinsic apoptosis pathway, including caspase 3 and 9. Moreover, endoplasmic reticulum stress was decreased following upregulating the protective ER-stress genes, including SOD1 and PPARα.
CONCLUSIONS: FGF2 significantly reduced ER stress and intrinsic apoptosis pathway. Our data suggest that FGF2 treatment could be a potential therapeutic strategy for NAFLD.

The research work was commenced with an aim to document plant based drug recipes used by autochthonous practitioners against liver diseases in Multan region. The data was collected by interviews and semi-structured questionnaire from 43 traditional herbal practitioners. Recorded data was evaluated using the use value, relative frequency of citation (RFC), family importance value (FIV) and family use value (FUV). Total of 69 plant species belonging to 38 families were reported to be utilized to treat various liver disorders. The most important species regarding their use value were 3.0 for Polygonum bistorta, Citrus limon. It means that highly cited plants are more important in traditional medicines but this does not mean the plants low-citation plants by respondents are less medicinal important. It may be due to unavailability of plants in the area or lack of knowledge. Most of plant parts used were leaves due to ease of collection as compared to underground parts. One the basis family use value Asteraceae as the dominating or prominent family. These plants can be further investigated for allied pharmacological studies that will affect the socio-economical condition of the local community.

Liver disorders are one of the most common pathological problems worldwide. It affects more than 1.5 billion worldwide. Many types of hepatic cells have been reported to be involved in the initiation and propagation of both acute and chronic liver diseases, including hepatocytes, Kupffer cells, sinusoidal endothelial cells, and hepatic stellate cells (HSCs). In addition, oxidative stress, cytokines, fibrogenic factors, microRNAs, and autophagy are also involved. Understanding the molecular mechanisms of liver diseases leads to discovering new therapeutic interventions that can be used in clinics. Recently, antioxidant, anti-inflammatory, anti-HSCs therapy, gene therapy, cell therapy, gut microbiota, and nanoparticles have great potential for preventing and treating liver diseases. Here, we explored the recent possible molecular mechanisms involved in the pathogenesis of acute and chronic liver diseases. Besides, we overviewed the recent therapeutic interventions that targeted liver diseases and summarized the recent studies concerning liver disorders therapy.

Camel milk is known as the white gold of the desert because it contains within it a variety of nutrients which play a key role in the human diet. The health benefits of camel milk have been described for a variety of diseases such as diabetes, kidney disease, hepatitis, etc. including improved overall survival. A major health burden worldwide is liver diseases, and the ninth leading cause of death in Western countries is due to liver cirrhosis. Treatment is mostly ineffective for cirrhosis, fatty liver, and chronic hepatitis which are the most common diseases of the liver; furthermore current treatments carry the risk of side effects, and are often extremely expensive, particularly in the developing world. A systematic review of studies was performed to determine the association of consumption of camel milk on multiple diseases of the liver. The impact of camel milk on the laboratory tests related to the liver disorders, viral hepatitis, non-alcoholic fatty liver disease (NAFLD), cirrhosis, and hepatocellular carcinoma (HCC) were evaluated. The consumption of camel milk was accompanied by modulation of the values of serum gamma-glutamyl transferase, aspartate aminotransferase, and alanine aminotransferase in persons who are at risk of liver disease. In the patients with chronic liver disease, it was observed that they have low rates of mortality and low chances of progression to cirrhosis when they consume camel milk. Therefore, in patients with liver diseases, the addition of camel milk to their normal daily diet plan should be encouraged. In this review, camel milk\'s impact on the different kinds of liver diseases or any disorder associated with liver functioning was evaluated. Camel milk has a therapeutic as well as a preventive role in the maintenance and improving the metabolic regulations of the body.

UNASSIGNED: The present study aims to determine the health-related quality of life (HRQoL) among liver disorder patients being treated in tertiary care hospital in north India and exploration of factors affecting HRQoL.
UNASSIGNED: The HRQoL was assessed among 230 patients visiting either the outpatient department (OPD) or those admitted in high dependency unit (HDU) or liver intensive care unit (ICU) using direct measuring tools such as Euro QoL five-dimension questionnaire (EQ-5D) and EQ visual analog scale. Multivariate regression was used to explore the factors influencing HRQoL.
UNASSIGNED: Mean EQ-5D scores among chronic hepatitis and compensated cirrhosis patients were 0.639 ± 0.062 and 0.562 ± 0.048, respectively. Among those who were admitted in the ICU or HDU, mean EQ-5D score was 0.295 ± 0.031. At discharge, this score improved significantly to 0.445 ± 0.055 (P < 0.001). The multivariate results implied that HRQoL was significantly better among patients with lower literacy level (P = 0.018) and those treated in OPD settings (P < 0.001).
UNASSIGNED: HRQoL is impaired among patients suffering from liver disorders specifically those admitted in ICU. Further, there is a need to generate more evidence to explore the impact of determinants and treatment-associated costs on the HRQoL.