Evidence suggests that breastfeeding protects the mother-infant dyad against the development and progression of nonalcoholic fatty liver disease (NAFLD). In this context, we aim to provide insight into the most notable and representative epidemiological studies published in the literature. Furthermore, we will delve into the potential underlying pathomechanisms that might be involved in this relationship. The current definitions of breastfeeding, lactation, mother-infant dyad, and nonalcoholic fatty liver disease (NAFLD) are provided. Next, the epidemiological evidence supporting potential benefits for the (long-term) lactating mother in terms of protection from the development and progression of NAFLD is reviewed. The putative mechanisms underlying this protection are also analyzed. Similarly, clinical and epidemiological studies evaluating the benefits of breastfeeding for the offspring are examined, together with a discussion of the putative underlying mechanisms. In conclusion, our understanding of breastfeeding (for the offspring) and lactation (for the mother) as protective factors from NAFLD development and fibrotic progression will provide further insight into unprecedented disease mechanisms shared by the mother-infant dyad promising to interrupt the vicious cycle of NAFLD transmission across generations.

This commentary is primarily devoted to a recent observational study by Mantovani and colleagues (Aliment Pharmacol Ther. 2023; 57: 1093-102) examining the adverse effect of the patatin-like phospholipase domain-containing protein-3 (PNPLA3) rs738409 G allele on the kidney function in a cohort of 1,144 middle-aged Italian individuals with metabolic dysfunction. In this study, the authors found that the PNPLA3 rs738409 G allele was significantly associated with lower levels of estimated glomerular filtrate rate (eGFR), even after adjusting for not only common anthropometric and cardiometabolic risk factors but also ethnicity, serum liver enzymes, use of drugs against dyslipidemia and chronic kidney disease polygenic risk score. Additionally, in a subgroup of 144 patients followed for a median of 17 months, the authors also found that the PNPLA3 rs738409 G allele was independently associated with a faster eGFR decline. Commenting on the cohort study by Mantovani et al., we also summarized the rapidly expanding evidence linking the PNPLA3 rs738409 variant with the risk of kidney disease. Furthermore, we discussed the potential research implications of these findings.

Hepatic steatosis is caused by exaggerated hepatic lipid accumulation and is a common histological and radiological finding. Non-alcoholic fatty liver disease (NAFLD), or metabolic dysfunction associated steatotic liver disease (MASLD), is highly associated with metabolic syndrome and represents the most common cause of hepatic steatosis. However, since several comorbidities, lifestyle factors, and drugs can cause hepatic steatosis, MASLD is, to some extent, a diagnosis of exclusion. Nevertheless, initiatives have been taken to encompass positive (instead of negative) criteria for diagnosis - such as the presence of cardiometabolic risk factors together with hepatic steatosis. Nonetheless, before confirming a patient with MASLD, it is essential to map and evaluate other causes of fatty liver disease or steatotic liver disease. Several causes of hepatic steatosis have been identified in studies; however, the study cohorts are scarce and often anecdotal. Additionally, many studies have shown correlation without proving causation, and many are retrospective without reporting relevant patient characteristics and comorbidities - making it difficult to draw conclusions regarding the underlying etiology or present comorbidity of hepatic steatosis. In this narrative review, we aimed to identify and summarize present studies evaluating the impact of the most common and often suggested causes of hepatic steatosis.

Acetaminophen (APAP) is the most widely used analgesic in the world. APAP overdose can cause severe hepatotoxicity and therefore is the most common cause of drug-induced liver injury. The only approved treatment for APAP overdose is N-acetyl-cysteine (NAC) supplementation. However, the narrow efficacy window of the drug severely limits its clinical use, prompting the search for other therapeutic options to counteract APAP toxicity. Recent research has pointed to fructose as a novel nutraceutical for APAP-induced liver injury. This review summarizes the current understanding of the molecular mechanisms underlying APAP-induced liver injury, introduces how fructose supplementation could prevent and treat APAP liver toxicity with a focus on the ChREBPα-FGF21 pathway, and proposes possible future directions of study.

Acute pancreatitis rarely occurs in pregnancy, with hypertriglyceridemia being the fourth leading cause during pregnancy. Hypertriglyceridemia, of which Familial Chylomicronemia Syndrome is the most severe form, ranks among the four principal causes of pancreatitis in pregnancy. Total Plasma exchange (TPE) has been found to be an effective and safe intervention both as a therapeutic and a prophylactic act. A 22-year-old female with FCS presented at the 21st week of gestation with acute hypertriglyceridemia pancreatitis. Despite medical management, she was then started on TPE at the two-week follow-up after serum triglyceride level was out of control. The triglyceride dropped from 55.0 % to 77.5 % during these sessions. Despite these interventions, pancreatitis recurred in week 34. An emergency C-section was carried out after a drop in the fetal heart rate. Postpartum triglycerides dropped by 57 % but remained above 1,000 mg/dl. FCS is difficult to manage during pregnancy, and it frequently fails to respond to various pharmacologic lines. TPE can help prolong a pregnancy, but it is not a definite treatment. Novel therapies for hypertriglyceridemia in pregnancy await additional safety testing.