Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease, affecting a quarter of the world’s population. The spectrum of NAFLD ranges from simple steatosis, non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and ultimately to hepatocellular carcinoma (HCC). Multiple factors are involved in the pathogenesis and progression of NAFLD, wherein genetic, epigenetic, environmental, gut-microbiome, and dietary factors play a substantial role. Robust genome-wide association studies (GWAS) have recently identified several genetic alterations contributing to NAFLD progression to liver cancer. This review describes the most critical genetic variations identified in various genes that modulate NAFLD pathogenesis. As expected, NAFLD shows gene variations that regulate or influence hepatocyte lipid metabolism. In addition to polymorphisms in genes that regulate insulin signaling, fibrosis, inflammation, and oxidative stress, cytokine/chemokine-expressing genes also participate in NAFLD pathogenesis. GWAS helped us distinguish genetic polymorphisms that modulate steatosis, fibrosis, or both in NAFLD patients. Identifying genetic factors predisposing an individual to NAFLD helps stratify people at high risk and aids in imparting preventive strategies early in life. Such studies should also help in adopting prevention strategies and targeted treatment regimes. Full article

This study aimed to evaluate the effect of coconut oil (CO) on steatosis and oxidative stress in rats fed a high-fat diet. Three groups of male Wistar rats were used: the control group (CG, n = 10) received a standard diet for 50 days, the hyperlipidic group (HL, n = 10) received a high-fat diet with 50% lard for 50 days, and the hyperlipidic-CO group (HL+CO, n = 10) received a high-fat diet with 50% lard for 30 days followed by 25% lard and 25% CO for 20 days. Then, the animals were euthanized, and their blood, liver, and adipose tissue were collected for biochemical analyses. The groups that received a high-fat diet had pronounced liver steatosis. Compared to the CG and HL groups, the HL+CO group had less weight gain, but liver fat and triglycerides were increased, with a significant reduction in liver cholesterol. Glutathione increased significantly and vitamin E decreased in the livers of the experimental groups compared to the control. Lipid peroxidation in the serum and liver was less in the HL+CO group compared to that in the HL group, but it was higher than that in the control group. CO caused significant accumulation of hepatic fat, triglycerides, and fat content, despite decreasing the hepatic cholesterol levels. There was a better hepatic antioxidant response in the CO group, especially compared with the HL group. CO was not able to prevent or improve liver fat levels, but the HL+CO group had a better antioxidant profile. Additional clinical studies are necessary to verify the efficacy and safety of different CO doses on both hepatic and lipid metabolism. Full article

The liver maintains important homeostatic functions such as metabolism and detoxification. Failure to remove toxic intermediates can cause hepatic damage, liver fibrosis, and even cancer development. This review focuses on acetaldehyde dehydrogenases (ALDHs), a group of key enzymes within the ALDH superfamily with the ability to convert highly reactive aldehyde substrates to the corresponding carboxylic acids in NAD(P)-dependent manners. These enzymes participate in a diverse array of biological processes such as detoxification, biosynthesis, antioxidant, and regulatory functions. ALDH dysfunction can disrupt homeostasis, leading to toxic buildup, tissue damage, and cancer. Here, we examine the expression patterns of hepatic ALDHs in adult normal human livers and two types of liver cancers—hepatocellular carcinoma and cholangiocarcinoma. We also investigated their distributions related to liver zonation. These observations provide deep insights into previously unrecognized spatial and temporal regulation of ALDHs in liver zonation. Full article

Hepatocellular carcinoma (HCC) is one of the most lethal and widespread cancers in the human race. Despite its fatal attributes, there is only a limited understanding of the factors contributing to its pathogenesis at the cellular and molecular levels. Consequently, unraveling new facets involved in HCC progression is elemental for establishing novel targets and biomarkers for this disease. Over the last few years, emerging evidence signifies the role of RNA-induced silencing complex in mediating gene silencing and contributing to HCC. Recent studies also highlight the importance of human telomerase holoenzyme and its complex accessory proteins in the development of HCC. The current review encompasses the multifaceted roles of RNA-induced silencing complex and telomerase activity as well as their synergistic function in HCC. Full article

Liver damage in cholestasis is multifactorial, yet bile acid-mediated hepatotoxicity is pivotal. Honey consumption has many physiological effects; it influences detoxification process (phase I, II and III), has antioxidant, anti-inflammatory, immune-stimulant, anti-ulcer, wound/burn healing effects and others. The bile acid ursodeoxycholic acid (UDCA) is currently used off-label to treat neonatal cholestasis. This study aimed to assess the effectiveness of spore-free natural honey to treat neonatal nonobstructive cholestasis. Thirty infants with cholestasis received spore-free natural honey. Their progression was compared to a control group with cholestasis (28 infants) and a historical group (31 infants) on UDCA. The mean ± standard deviation (SD) follow-up duration was 29.68 ± 18.68 months. At presentation, the total bilirubin concentrations were 9.5 ± 5.9 mg/dL, 10.9 ± 7 mg/dL and 14 ± 9 mg/dL in the honey, control and UDCA groups, respectively (p = 0.064), and their direct bilirubin concentrations were 6 ± 4 mg/dL, 6.7 ± 4 mg/dL and 8.4 ± 6.9 mg/dL, respectively (p = 0.169). The final total bilirubin concentrations were 1.2 ± 1.7 mg/dL, 4.6 ± 8.2 mg/dL and 7.3 ± 8.9 mg/dL, (p = 0.006), and their final direct bilirubin concentrations were 0.8 ± 1 mg/dL, 2.77 ± 5.2 mg/dL and 5.1 ± 7.2 mg/dL (p = 0.008), with cure achievement in 25, 16 and 16 (p = 0.023), improvement in 3, 5 and 3 (p = 0.565), failure in 2, 3 and 10 (p = 0.016), and death in 0, 4 and 2, respectively (p = 0.095). None suffered from botulism or flaccid paralysis. Spore-free honey is effective in clearing cholestasis in neonates and infants. UDCA use in cholestasis in pediatric age should be abandoned as it is less effective and is associated with a worse outcome. Full article

Growing scientific evidence has suggested the disrupted regulation of host cell cycle proteins in hepatitis C virus (HCV)-associated liver disease. Since the regulation of cell cycle proteins is closely associated with the control of the proliferation and survival of hepatocytes, any alteration in the regulation of these proteins would significantly contribute to the progression of the HCV disease and development of hepatocellular carcinoma (HCC). This mini-review aims to provide an overview of available information on hepatic cell cycle modulations during chronic HCV infection. Full article

The liver contributes substantially to the metabolic transformation and transport of lipids and lipoproteins. These bioactive substances represent a heterogeneous group of molecules with pivotal roles in diverse pathological processes as well as disease progression, the advent of complications, and the response to specific treatments in the context of cirrhosis. The present mini-review aims to summarize the underlying mechanisms regarding lipid changes across divergent circumstances. Recent evidence suggests the prognostic value of lipids/lipoproteins and their close relationship to an increased risk for morbidity and mortality among cirrhotic patients. However, more research regarding the development of risk stratification and therapeutic strategies based on altered lipid profiles in patients with cirrhosis is warranted. Full article

Primary biliary cholangitis (PBC) is an organ-specific chronic autoimmune disease characterized by T-lymphocyte mediated destruction of intrahepatic biliary epithelial cells due to a combination of genetic and possible environmental factors. PBC progresses to hepatic fibrosis and cirrhosis, with the potential of developing hepatocellular carcinoma (HCC) if left untreated. PBC is more common in middle-aged women. It is diagnosed in patients with elevated liver enzymes and the serological hallmark of antimitochondrial antibody (AMA). Early diagnosis and treatment are crucial in improving survival and preventing long-term complications of liver disease. Ursodeoxycholic acid (UDCA) is first-line treatment for PBC. Obeticholic acid (OCA) and fibrates, in combination with UDCA or as monotherapy, may be given to PBC patients with partial or no UDCA response. Liver transplantation has thus been indicated in patients with decompensated cirrhosis or unresectable HCC. Full article

Today, medicinal plants and phytobiotics that contain flavonoids, alkaloids, and essential oils are widely used in animal feed. These additives have many benefits, including increasing liver function and preventing certain diseases. The liver is one of the organs that plays a key role in insulin-mediated regulation of metabolism as well as in glucose, whole-body, and lipid homeostasis. The aim of this study was to investigate the effect of fennel (Foeniculum vulgare) seed powder consumption on insulin-like growth factor 1 (IGF1) gene expression in the liver tissue of growing lambs. Three groups (including 0, 10, and 20 g/kg dry matter of fennel) of animals, with 10 animals in each group, were studied. The Pfaffl method was applied to assess the real-time polymerase chain reaction (qPCR) output. Mixing fennel into the feed of lambs increased the weights of their testis and gallbladder and decreased the weight of their liver in comparison to feed without fennel. It was also found that by increasing the fennel level in the feed, the expression level of IGF1 in the liver increased significantly (p < 0.05). Fennel had a useful effect on the expression of IGF1 in the liver tissue of sheep and may be applied to their diet to attain better liver function. Full article