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Insulin resistance is the main mechanism in a whole series of pathological conditions, which are not only of metabolic interest but also of a systemic type. This phenomenon means that the body’s cells become less sensitive to the hormone insulin, leading to higher levels of insulin in the blood. Insulin resistance is a phenomenon that can be found in both men and women and in particular, in the latter, it is found mainly after menopause. Premenopause, hormonal fluctuations during the menstrual cycle, and the presence of estrogen can affect insulin sensitivity. Androgens, such as testosterone, are typically higher in men and can contribute to insulin resistance. In both sexes, different human body types affect the distribution and location of body fat, also influencing the development of diabetes and cardiovascular disease. Insulin resistance is also associated with some neurological and neurogenerative disorders, polycystic ovary syndrome, atherosclerosis, and some of the main neoplastic pathologies. A healthy lifestyle, including regular physical activity, a balanced diet, and self-maintenance, can help to prevent the onset of insulin resistance, regardless of gender, although the different habits between men and women greatly affect the implementation of preventative guidelines that help in fighting the manifestations of this metabolic disorder. This review may help to shed light on gender differences in metabolic diseases by placing a necessary focus on personalized medical management and by inspiring differentiated therapeutic approaches.

Barrett’s esophagus (BE) is an acquired pre-malignant condition that results from chronic gastroesophageal reflux. The malignant transformation occurred in 0.5% of patients/year and was independent of medical and endoscopic conservative treatments. Fatty acid synthase (FAS) is a multifunctional enzyme that catalyzes the synthesis of long-chain fatty acids from acetyl-coenzyme A, malonyl-coenzyme A, a reduced form of nicotinamide adenine dinucleotide phosphate (NADPH), and adenosine triphosphate. Activation of FAS is closely linked to malignant transformation. The aim of the present study was to evaluate the variation of FAS, p53, and Ki67 expressions in two groups of 21 BE patients each, after one year of continuous (group A) or discontinuous (group B) treatment with esomeprazole 40 mg/day in comparison to the initial expression. In both the two groups of BE patients, biopsies were taken from pathologic sites of the mucosa for histological and immuno-histochemical detection of FAS, Ki67, and p53 at entry and after one year of Esomeprazole 40 mg treatment. FAS expression was positive when a strong granular cytoplasmic staining was observed in esophageal cells. Ki67 and p53 were defined as positive when nuclear staining was clearly detected at ×10 magnification. FAS expression was reduced in 43% of patients treated with Esomeprazole continuously in comparison to the 10% of patients treated with Esomeprazole on demand (p = 0.002). Ki67 expression was reduced in 28% of continuously treated patients in comparison to 5% of patients treated on demand (p = 0.001). The p53 expression decreased in 19% of continuously treated patients in comparison to an increase in 2 patients (9%) treated on demand (p = 0.05). Continuously Esomeprazole treatment could help in the diminution of metabolic and proliferative activities in the esophageal columnar epithelium and in part it can help prevent the oxidative damage against cellular DNA, resulting in a diminution in p53 expression.

From the data in our possession derived from the literature, it has been shown that men have a high risk and appear to have a specific higher risk of suffering from thromboembolism than women, regardless of age group. Furthermore, at present, this difference between the two sexes has not yet been justified by scientific evidence. Taking this evidence into account, this review was designed to find information in the literature that could be potentially useful and that is crucial to knowledge about the differences between men and women in the genesis of thromboembolic disease. The role of the constitutional and physical factors underlying the difference between the two sexes, the different habitual lifestyles, the role of sex hormones, and what happens in situations such as venous thromboembolism in the course of a neoplastic disease or in the case of pregnancy. We have also focused our efforts on correlating the gender differences between men and women in thromboembolic disease with the dysregulation of the metabolism and the activation of the inflammatory response that often underlies this pathology.

Background: Traumatic brain injury (TBI) in the elderly is a noteworthy pathology due to the exponential increase in population age, and the effects of antiplatelet and anticoagulation on patients’ outcomes are still a matter of dispute. The aim of the present study was to evaluate the impact of various antithrombotic agents on patients with mild TBI, focusing on the risk of intracranial bleeding (ICH) and length of hospitalization (LOS). Methods: A retrospective analysis was conducted, including patients with a diagnosis of TBI admitted to the Emergency Department between 2021 and 2022. Patients were classified according to the concurrent antithrombotic therapy as aspirin (ASA), antiplatelets, direct oral anticoagulants (DOACs), and low-molecular-weight heparin (LMWH). The primary outcome was the ICH occurrence, while the secondary outcome was the LOS. The statistical analysis was performed via logistic regression models in R and STATA 13.1 software. Fisher’s exact test was used for the statistical significance. Results: 267 patients with mild TBI were included; 148 were not on antithrombotic agents, 43 were on aspirin, 33 on DOACs, 5 on LMWH, 22 on antiplatelets, and 16 on VKA. Out of the total, 9 patients experienced ICH, none of which were on DOACs, LMWH, or VKA, but 4—out of 65—were on antiplatelets, and 5—out of 148—were not on antithrombotic therapies. Patients not on antithrombotic therapy had the shortest LOS at 0.46 days, while those on VKA had the longest LOS at 1.19 days; similar trends were observed for patients on DOAC and LMWH. Conclusions: The results reveal that TBI patients on anticoagulants/antiplatelets had longer hospital stays compared with those on aspirin alone. Notably, VKA was the strongest predictor for an extended LOS. Regarding ICH, patients taking only aspirin were twice as likely to experience bleeding compared with those on anticoagulants/antiplatelets. However, to achieve statistically significant evidence, further research with a larger cohort of patients is needed.

The therapeutic management of atherosclerosis focuses almost exclusively on the reduction of plasma cholesterol levels. An important role in the genesis and evolution of atherosclerosis is played by chronic inflammation in promoting thrombosis phenomena after atheroma rupture. This review aims to take stock of the knowledge so far accumulated on the role of endemic HP infection in atherosclerosis. The studies produced so far have demonstrated a causal relationship between Helicobacter pylori (HP) and CVD. In a previous study, we demonstrated in HP-positive patients that thrombin and plasma fragment 1 + 2 production was proportionally related to tumor necrosis factor-alpha levels and that eradication of the infection resulted in a reduction of inflammation. At the end of our review, we can state that HP slightly affects the risk of CVD, particularly if the infection is associated with cytotoxic damage, and HP screening could have a clinically significant role in patients with a high risk of CVD. Considering the high prevalence of HP infection, an infection screening could be of great clinical utility in patients at high risk of CVD.

With the progressive lengthening of the average age of the population, especially in some countries such as Italy, vaccination of the elderly is a fixed point on which most of the public health efforts are concentrating as epidemic infectious diseases, especially those of the winter, have a major impact on the progression of severe disease, hospitalization, and death. The protection of the elderly against acute infectious diseases should not only limit mortality but also have a positive impact on the fragility of these people in terms of less disability and fewer care needs. However, vaccination of the elderly population differs in efficacy and safety compared to that of other population categories since aging and the consequent loss of efficiency of the immune system lead to a reduction in the immunogenicity of vaccines without achieving a lasting antibody coverage. There are various strategies to avoid the failure of immunization by vaccines such as resorting to supplementary doses with adjuvant vaccines, increasing the dosage of the antigen used, or choosing to inoculate the serum relying on various routes of administration of the vaccine. Vaccination in the elderly is also an important factor in light of growing antibiotic resistance because it can indirectly contribute to combating antibiotic resistance, reducing theoretically the use of those agents. Furthermore, vaccination in old age reduces mortality from infectious diseases preventable with vaccines and reduces the same rate of resistance to antibiotics. Given the importance and complexity of the topic, in this review, we will deal with the main aspects of vaccination in the elderly and how it can influence mortality and healthcare costs, especially in those countries where population aging is more evident. Therefore, we conducted a systematic literature search in PubMed to identify all types of studies published up to 31 May 2023 that examined the association between vaccination and the elderly. Data extraction and quality assessment were conducted by two reviewers (PC and TC) who independently extracted the following data and assessed the quality of each study.

This narrative review aims to shed light on the role of gender differences, on the biological and molecular functions in the main pathological mechanisms that recognize the role of vitamin D. Vitamin D deficiency is widespread worldwide, but it is still very controversial whether the amount of vitamin D taken daily is actually the only problem related to its biological functions. Currently, the plasma concentration of 25-hydroxyvitamin D represents the only indicator of the circulating blood quota. The concept is that the biological function of vitamin D is not only linked to its circulating levels, but it is hypothesized that its biological functions depend, above all, on its total bioavailability. In particular, vitamin D circulates for the most part linked to albumin and vitamin D binding protein (DBP), which depend on various pathological conditions and physiologically, above all, the function of the latter is regulated by estrogens, glucocorticoids, and inflammatory cytokines. During her life, women undergo various changes in the hormonal and sexual sphere concerning menarche, possible pregnancies, and breastfeeding but also the use of contraceptives and, finally, the transition from the period of fertility to menopause. Each of these phases presents specific needs and, consequently, sometimes also specific criticalities. Studies on young women have shown that vitamin D deficiency is present in 58 to 91% of cases. Obesity, metabolic disorders, and variation in estrogen contraction may affect vitamin D deficiency due to the decreased bioavailability from dietary sources due to deposition in body fat compartments.

The global prevalence of overweight and obesity has dramatically increased in the last few decades, with a significant socioeconomic burden. In this narrative review, we include clinical studies aiming to provide the necessary knowledge on the role of the gut microbiota in the development of diabetic pathology and glucose-metabolism-related disorders. In particular, the role of a certain microbial composition of the fermentative type seems to emerge without a specific link to the development in certain subjects of obesity and the chronic inflammation of the adipose tissues, which underlies the pathological development of all the diseases related to glucose metabolism and metabolic syndrome. The gut microbiota plays an important role in glucose tolerance. Conclusion. New knowledge and new information is presented on the development of individualized therapies for patients affected by all the conditions related to reduced glucose tolerance and insulin resistance.

Cerebral sinus venous thrombosis (CSVT) is a relatively rare acute disorder of cerebral circulation, but it can potentially be associated with serious sequelae and a poor prognosis. The neurological manifestations associated with it are often not adequately taken into consideration given the extreme variability and nuances of its clinical presentation and given the need for radiological methods suitable for this type of diagnosis. CSVT is usually more common in women, but so far there are little data available in the literature on sex-specific characteristics regarding this pathology. CSVT is the result of multiple conditions and is therefore to be considered a multifactorial disease where at least one risk factor is present in over 80% of cases. From the literature, we learn that congenital or acquired prothrombotic states are to be considered extremely associated with the occurrence of an acute episode of CSVT and its recurrences. It is, therefore, necessary to fully know the origins and natural history of CSVT, in order to implement the diagnostic and therapeutic pathways of these neurological manifestations. In this report, we summarize the main causes of CSVT considering the possible influence of gender, bearing in mind that most of the causes listed above are pathological conditions closely linked to the female sex.

Older age is a major risk factor for adverse outcomes of COVID-19, potentially due to immunosenescence and chronic low-grade inflammation, both characteristics of older adults which synergistically contribute to their vulnerability. Furthermore, older age is also associated with decreased kidney function and is consequently associated with an increased risk of cardiovascular disease. All of this in the course of COVID-19 infection can worsen and promote the progression of chronic kidney damage and all its sequelae. Frailty is a condition characterized by the decline in function of several homeostatic systems, leading to increased vulnerability to stressors and risk of adverse health outcomes. Thus, it is very likely that frailty, together with comorbidities, may have contributed to the high vulnerability to severe clinical manifestations and deaths from COVID-19 among older people. The combination of viral infection and chronic inflammation in the elderly could cause multiple unforeseen harmful consequences, affecting overall disability and mortality rates. In post-COVID-19 patients, inflammation has been implicated in sarcopenia progression, functional activity decline, and dementia. After the pandemic, it is imperative to shine a spotlight on these sequelae so that we can be prepared for the future outcomes of the ongoing pandemic. Here, we discuss the potential long-term consequences of SARS-CoV-2 infection and its possibility of causing permanent damage to the precarious balance existing in the frail elderly with multiple pathologies.

The endothelium plays a fundamental role in the biological processes that ensure physiological vessel integrity, synthesizing numerous substances that are capable of modulating the tone of vessels, inflammation and the immune system, and platelet function. Endothelial dysfunction refers to an anomaly that develops at the level of the tunica that lines the internal surface of arterial and venous vessels, or, more precisely, an alteration to normal endothelial function, which involves the loss of some structural and/or functional characteristics. Studies on sex differences in endothelial function are conflicting, with some showing an earlier decline in endothelial function in men compared to women, while others show a similar age of onset between the sexes. Since increased cardiovascular risk coincides with menopause, female hormones, particularly estrogen, are generally believed to be cardioprotective. Furthermore, it is often proposed that androgens are harmful. In truth, these relationships are more complex than one might think and are not just dependent on fluctuations in circulating hormones. An increase in serum uric acid is widely regarded as a possible risk factor for cardiovascular disease; however, its role in the occurrence of endothelial dysfunction has not yet been elucidated. Several studies in the literature have evaluated sex-related differences in the association between elevated uric acid levels and cardiovascular events, with conflicting results. The association between uric acid and cardiovascular disease is still controversial, and it is not yet clear how gender differences affect the serum concentration of these substances. This review was primarily aimed at clarifying the effects of uric acid at the level of the vascular endothelium and describing how it could theoretically cause damage to endothelial integrity. The second aim was to determine if there are gender differences in uric acid metabolism and how these differences interact with the vascular endothelium.

Acute kidney injury (AKI) is a major clinical problem associated with increased morbidity and mortality. Despite intensive research, the clinical outcome remains poor, and apart from supportive therapy, no other specific therapy exists. Furthermore, acute kidney injury increases the risk of developing chronic kidney disease (CKD) and end-stage renal disease. Acute tubular injury accounts for the most common intrinsic cause of AKI. The main site of injury is the proximal tubule due to its high workload and energy demand. Upon injury, an intratubular subpopulation of proximal epithelial cells proliferates and restores the tubular integrity. Nevertheless, despite its strong regenerative capacity, the kidney does not always achieve its former integrity and function and incomplete recovery leads to persistent and progressive CKD. Clinical and experimental data demonstrate sexual differences in renal anatomy, physiology, and susceptibility to renal diseases including but not limited to ischemia-reperfusion injury. Some data suggest the protective role of female sex hormones, whereas others highlight the detrimental effect of male hormones in renal ischemia-reperfusion injury. Although the important role of sex hormones is evident, the exact underlying mechanisms remain to be elucidated. This review focuses on collecting the current knowledge about sexual dimorphism in renal injury and opportunities for therapeutic manipulation, with a focus on resident renal progenitor stem cells as potential novel therapeutic strategies.

In medicine, there is growing evidence that gender differences are important and lead to variations in the pathophysiology and treatment of many diseases with traits that appear to be particularly relevant in influencing the outcomes of many morbid forms. Today, the inclusion of gender in biomedical research, to improve the scientific quality and scientific relevance of knowledge, of technology is an increasingly present element precisely due to the practical implications that derive from it. Gender differences describe the biological variability between women and men, which is, in turn, related to differences in the information contained in sex chromosomes, the specific gene expression of autosomes linked to sex, the different number and quality of sex hormones, and their different effects on systems and organs, without neglecting the fact that each of the sexes has different target organs on which these hormones act. Additionally, both genders undergo metabolic changes throughout their lives, and this is especially true for women who show more dramatic changes due to their role in reproduction. Gender differences are not only the result of our genetic makeup but are also mixed with socio-cultural habits, behaviors, and lifestyles, differences between women and men, exposure to specific environmental influences, different food and lifestyle styles or stress, or different attitude in compliance with treatments and disease prevention campaigns. Gender differences also affect behavior throughout life, and physical changes can have implications for lifestyle, social roles, and mental health. Therefore, determinism and therapeutic outcome in chronic diseases are influenced by a complex combination of biological and environmental factors, not forgetting that there are many interactions of social and biological factors in women and men. This review will address the role of gender differences in the management of various forms of diabetes and its complications considering the different biological functions of hormones, the difference in body composition, physiological differences in glucose and fat metabolism, also considering the role of the microbiota. intestinal, as well as the description of gestational diabetes linked to possible pathophysiological events typical of reproduction.

(1) Background: In our previous study, acute ischemic stroke (AIS) patients showed increased levels of circulating miRNAs (-195-5p and -451a) involved in vascular endothelial growth factor A (VEGF-A) regulation. Here, we evaluated, for the first time, both circulating miRNAs in acute intracerebral hemorrhagic (ICH) patients. (2) Methods: Circulating miRNAs and serum VEGF-A were assessed by real-time PCR and ELISA in 20 acute ICH, 21 AIS patients, and 21 controls. These were evaluated at hospital admission (T0) and after 96 h (T96) from admission. (3) Results: At T0, circulating miRNAs were five-times up-regulated in AIS patients, tending to decrease at T96. By contrast, in the acute ICH group, circulating miRNAs were significantly increased at both T0 and T96. Moreover, a significant decrease was observed in serum VEGF-A levels at T0 in AIS patients, tending to increase at T96. Conversely, in acute ICH patients, the levels of VEGF-A were significantly decreased at both T0 and T96. (4) Conclusions: The absence of a reduction in circulating miRNAs (195-5p and -451a), reported in acute ICH subjects after 96 h from hospital admission, together with the absence of increment of serum VEGF-A, may represent useful biomarkers indicating the severe brain damage status that characterizes acute ICH patients.

The region of Lombardy was the epicenter of the COVID-19 outbreak in Italy. Emergency Hospital 19 (EH19) was built in the Milan metropolitan area during the pandemic’s second wave as a facility of Humanitas Clinical and Research Center (HCRC). The present study aimed to assess whether the implementation of EH19 was effective in improving the quality of care of COVID-19 patients during the second wave compared with the first one. The demographics, mortality rate, and in-hospital length of stay (LOS) of two groups of patients were compared: the study group involved patients admitted at HCRC and managed in EH19 during the second pandemic wave, while the control group included patients managed exclusively at HCRC throughout the first wave. The study and control group included 903 (56.7%) and 690 (43.3%) patients, respectively. The study group was six years older on average and had more pre-existing comorbidities. EH19 was associated with a decrease in the intensive care unit admission rate (16.9% vs. 8.75%, p < 0.001), and an equal decrease in invasive oxygen therapy (3.8% vs. 0.23%, p < 0.001). Crude mortality was similar but overlap propensity score weighting revealed a trend toward a potential small decrease. The adjusted difference in LOS was not significant. The implementation of an additional COVID-19 hospital facility was effective in improving the overall quality of care of COVID-19 patients during the first wave of the pandemic when compared with the second. Further studies are necessary to validate the suggested approach.

The Lean method entails a set of standardized processes intending to optimize resources, reduce waste, and improve results. Lean has been proposed as an operative model for the COVID-19 outbreak. Herein, we summarized data resulted from the Lean model adoption in an Emergency Department of the Lombardy region, the Italian epicenter of the pandemic, to critically appraise its effectiveness and feasibility. The Lean algorithm was applied in the Humanitas Clinical and Research Hospital, Milan, north of Italy. At admission, patients underwent outdoor pre-triage for fever, respiratory, and gastrointestinal symptoms, with a focus on SpO2. Based on these data, they were directed to the most appropriate area for the COVID-19 first-level screening. High-risk patients were assisted by trained staff for second-level screening and planning of treatment. Out of 7.778 patients, 21.9% were suspected of SARS-CoV-2 infection. Mortality was 21.9% and the infection rate in health workers was 4.8%. The lean model has proved to be effective in optimizing the overall management of COVID-19 patients in an emergency setting. It allowed for screening of a large volume of patients, while also limiting the health workers’ infection rate. Further studies are necessary to validate the suggested approach.

Background: Cardiomyopathies are a heterogeneous group of pathologies characterized by structural and functional alterations of the heart. Aims: The purpose of this narrative review is to focus on the most important cardiomyopathies and their epidemiology, diagnosis, and management. Methods: Clinical trials were identified by Pubmed until 30 March 2021. The search keywords were “cardiomyopathies, sudden cardiac arrest, dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy, arrhythmogenic cardiomyopathy (ARCV), takotsubo syndrome”. Results: Hypertrophic cardiomyopathy (HCM) is the most common primary cardiomyopathy, with a prevalence of 1:500 persons. Dilated cardiomyopathy (DCM) has a prevalence of 1:2500 and is the leading indication for heart transplantation. Restrictive cardiomyopathy (RCM) is the least common of the major cardiomyopathies, representing 2% to 5% of cases. Arrhythmogenic cardiomyopathy (ARCV) is a pathology characterized by the substitution of the myocardium by fibrofatty tissue. Takotsubo cardiomyopathy is defined as an abrupt onset of left ventricular dysfunction in response to severe emotional or physiologic stress. Conclusion: In particular, it has been reported that HCM is the most important cause of sudden death on the athletic field in the United States. It is needless to say how important it is to know which changes in the heart due to physical activity are normal, and when they are pathological.

Background: The global active prevalence of migraines is approximately 14.7%. Oxygen therapy may reduce the use of non-steroidal anti-inflammatory drugs (NSAIDs) which often have various negative side effects. The purpose of this systematic review is to analyze the literature on the efficacy of high flow oxygen for the management of headache disorders, compared to placebo treatment. Methods: Studies were identified by PubMed, Web of Science and Scopus database from 1980 to the 30 October 2020. The search included the following terms: “oxygen therapy” and “headache” and “migraine”. Studies were included if high flow oxygen was used in the treatment of headache disorders. All selected studies were qualitatively analyzed. Results: Our literature search identified 71 studies, of which 65 were discarded and 6 were included in the meta-analysis. The random effect model did not show a pooled significant resolution of headache disorders (OR 2.08 (95% CI 0.92–4.70), p < 0.0001) in the oxygen therapy group compared to the placebo group. Conclusion: In our systematic review of six studies, there were no significant differences between high flow oxygen and placebo treatment groups.

Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS) are two different entities sharing common clinical and physio-pathological features, with insulin resistance (IR) as the most relevant. Large evidence leads to consider it as a risk factor for cardiovascular disease, regardless of age, sex, smoking habit, cholesterolemia, and other elements of MS. Therapeutic strategies remain still unclear, but lifestyle modifications (diet, physical exercise, and weight loss) determine an improvement in IR, MS, and both clinical and histologic liver picture. NAFLD and IR are bidirectionally correlated and, consequently, the development of pre-diabetes and diabetes is the most direct consequence at the extrahepatic level. In turn, type 2 diabetes is a well-known risk factor for multiorgan damage, including an involvement of cardiovascular system, kidney and peripheral nervous system. The increased MS incidence worldwide, above all due to changes in diet and lifestyle, is associated with an equally significant increase in NAFLD, with a subsequent rise in both morbidity and mortality due to both metabolic, hepatic and cardiovascular diseases. Therefore, the slowdown in the increase of the “bad company” constituted by MS and NAFLD, with all the consequent direct and indirect costs, represents one of the main challenges for the National Health Systems.

(1) Background: Circulating micro-RNAs (miRNAs) modulate the expression of molecules in diabetes. We evaluated the expression of serum miRNA-195-5p and -451a in diabetic patients with ischemic stroke and correlated them with two markers of brain tissue integrity. (2) Methods: Seventy-eight subjects with acute ischemic stroke (AIS) or transient ischemic attack (TIA) (40 with diabetes) were enrolled. Serum miRNA levels, brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor A (VEGF-A) were assessed at admission and 24 and 72 h after a post-ischemic stroke, and were compared to 20 controls. (3) Results: Both circulating miRNAs were two-fold up-regulated in diabetic AIS and TIA patients compared to non-diabetics. Their levels progressively decreased at 24 and 72 h in both AIS and TIA patients. Interestingly, in the non-diabetic TIA group, both circulating miRNAs, although higher than the controls, tended to achieve a complete decay after 72 h. Furthermore, miRNA-195-5p and miRNA-451a levels inversely correlated with both BDNF and VEGF-A serum levels. (4) Conclusions: These data show a different profile of both micro-RNAs in diabetic versus non-diabetic patients after acute ischemic stroke, suggesting their pivotal role in cerebrovascular ischemic attack.

The aim of this paper is to review and up to date the prevalence of hepatitis C virus (HCV)-associated non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) and their significance in both accelerating progression of HCV-related liver disease and development of HCV-associated extrahepatic diseases. The reported mean prevalence of HCV-related NAFLD was 55%, whereas NASH was reported in 4%–10% of cases. HCV genotype 3 directly induces fatty liver deposition, namely “viral steatosis” and it is associated with the highest prevalence and degree of severity, whereas, HCV non-3 genotype infection showed lower prevalence of steatosis, which is associated with metabolic factors and insulin resistance. The host’s genetic background predisposes him or her to the development of steatosis. HCV’s impairment of lipid and glucose metabolism causes fatty liver accumulation; this seems to be a viral strategy to optimize its life cycle. Irrespective of insulin resistance, HCV-associated NAFLD, in a degree-dependent manner, contributes towards accelerating the liver fibrosis progression and development of hepatocellular carcinoma by inducing liver inflammation and oxidative stress. Furthermore, NAFLD is associated with the presence of metabolic syndrome, type 2 diabetes, and atherosclerosis. In addition, HCV-related “metabolic steatosis” impairs the response rate to interferon-based treatment, whereas it seems that “viral steatosis” may harm the response rate to new oral direct antiviral agents. In conclusion, a high prevalence of NAFLD occurs in HCV infections, which is, at least in part, induced by the virus, and that NAFLD significantly impacts progression of the liver disease, therapeutic response, and some extrahepatic diseases.