Effectiveness Of Reactive Oxygen Species In An Oil-Based Medication For Healing Burn Wounds: A Case Series.

Oxygen is considered a key element in the complex tissue repair process. O3-Oil antiseptics are obtained from the chemical reaction between ozone and unsaturated fatty acids of vegetable oils. The purpose of this study was to assess the effectiveness of a commercially available O3-Oil in the management of recalcitrant burn wounds. This study involved 20 patients with mid-deep and deep burn wounds (average TBSA approximately 23%, range 7-35%). Patient average age was 47 years (range 26-74 years), 8 were male. The presence of exudate, pain and delayed re-epithelialization, absence of tissue necrosis and/or sepsis were the inclusion criteria for the topical use of O3-Oil. In each patient two clinically similar areas were identified and treated every 48 hours with O3-Oil (Group 1) and conventional medication (Group 2). All the patients had positive bacterial culture results before treatment. A quicker reduction of exudates and pain and a progressive and faster bacterial load reduction was observed in Group 1. Negative cultures were obtained after 4 days on average in Group 1 (range 1-7 days) and 8 days in Group 2 (range 5-11 days). The present study demonstrated that Novox® provides a significant antibacterial effect, while stimulating reparative processes. According to our experience, the use of gel or pad is useful for re-epithelializing lesions, while the impregnated gauzes, which tend to adhere to the wound, are better used on lesions with granulation tissue.

L'oxygène est un élément- clé du processus complexe de réparation tissulaire. Les antiseptique O3-huile sont obtenus par réaction chimique entre l'ozone et des acides gras polyinsaturés d'origine végétale. Cette étude avait pour but d'évaluer l'efficacité d'un tel produit sur les brûlures d'évolution torpide. Elle a concerné 20 patients (dont 8 hommes) de 47 ans d'âge moyen (26- 74) ayant des brûlures intermédiaires à profondes sur 23% de SCT (7 à 35). Les indications de mise sous O3- huile pouvaient être la persistance d'exsudation, la douleur, l'absence d'épithélialisation, l'absence de séparation de l'escarre, l'infection (tous les patients ayant d'ailleurs une bactériologie cutanée positive avant le début du traitement). Chez chaque patient, deux zones similaires recevaient toutes les 48 h soit de l'huile ozonée (groupe 1) soit un traitement conventionnel (groupe 2). La réduction des exsudats, de la douleur et de la charge bactérienne était plus rapide dans le groupe 1, les cultures se négativant à J4 (1 à 7) dans ce groupe contre J8 (5 à 11) dans le groupe 2. Cette étude montre que le Novox® a un effet antibactérien significatif et stimule la cicatrisation. Dans notre expérience, l'utilisation de gel ou de plaques imprégnées sont plus efficaces pour promouvoir l'épithélialisation quand les compresses saturées, qui adhèrent à la plaie, sont préférables sur des tissus hyperbourgeonnants.

Non-Healing Burn Wound Treatment With A Sterile Silicone Gel.

Treatment of burn wounds can be complicated due to fluid and electrolyte loss and the increased chance of infectious complications. Silicone-based products have become increasingly used for non-healing wound treatment, but no study has specifically addressed its potential on burn patients. The purpose of this study was to compare the use of sterile silicone gel with conventional medication in improving the healing of burn wounds. Between November 2019 and March 2020, 12 patients with mid-deep and deep burn wounds were included in the present study (average TBSA approximately 29%, range 13-51%). Patient average age was 49 years (range 29-67 years), 7 were male. In each patient two clinically similar areas were identified and treated every 48 hours with topical application of silicone gel in the form of Stratamed® (Group 1) and conventional medication (Group 2). All the cases healed without requiring skin grafting. No secondary wound infection nor allergic reactions were found. The mean days from commencing the treatment to 95% re-epithelialization in Groups 1 and 2 were 5.4 and 12.5, respectively. Culture samples were negative for common pathogens. Silicone gel has shown to be particularly effective in speeding up the re-epithelialization process. The protective film formed by the silicone helps to reduce possible infectious complications. Finally, silicone gel is easy to apply and associated with greater pain control during medication.

La cicatrisation des brûlures peut être obérée par les pertes hydro- électrolytiques et les infections. Les produits à base de silicone sont de plus en plus utilisées dans le traitement des brûlures d'évolution torpide mais n'ont pas été évalués. Cette étude compare un gel de silicone stérile à un traitement conventionnel dans cette indication. Douze patients avec des brûlures intermédiaires et profondes ont été inclus dans cette étude, qui s'est déroulée entre novembre 2019 et mars 2020. Ils étaient brûlés sur 29% SCT (13 à 51%), avaient 49 ans et 7 étaient des hommes. Deux zones comparables étaient traité l'une par silicone (Statamed®, groupe 1), l'autre par traitement conventionnel (groupe 2), changés toutes les 48 h. Une cicatrisation spontanée a été obtenue chez tous les patients, il n'a été observé ni infection (clinique comme bactériologique) ni allergie. Cette cicatrisation sur 95% de la surface traitée était observée à J5,4 dans le groupe 1 et J12,5 dans le groupe 2. La silicone semble être particulièrement efficace pour accélérer l'épithélialisation et le film formé permet de prévenir les infections. Il est facile à mettre en place et permet une meilleure analgésie.

Association between non-alcoholic fatty liver disease and decreased lung function in adults: A systematic review and meta-analysis.

AIM: Recent observational studies assessed the association between non-alcoholic fatty liver disease (NAFLD) and lung function in adults, but the magnitude of this association remains uncertain. We estimated the magnitude of the association between NAFLD and lung function on spirometry (predicted forced expiratory volume in 1 s [FEV1] and forced vital capacity [FVC]). METHODS: We searched publication databases using predefined keywords to identify studies (published up to October 4, 2018), in which NAFLD was diagnosed by imaging or biochemistry (no studies with biopsy-proven NAFLD were available). Data from selected studies were extracted, and meta-analysis was performed using random-effects modelling. RESULTS: Six observational studies (5 cross-sectional and 1 longitudinal) with aggregate data on 133,707 individuals (27.8% with NAFLD) of predominantly Asian ethnicity (74.6%) were included in the final analysis. There were significant differences in predicted FEV1 (n = 5 studies; pooled weighted mean difference [WMD]: -2.43%, 95% CI: -3.28 to -1.58; I2 = 69.7%) and predicted FVC (pooled WMD: -2.96%, 95% CI: -4.75 to -1.17; I2 = 91.7%) between individuals with and without NAFLD. Decreased FEV1 and FVC at baseline were also independently associated with a ∼ 15% increased risk of incident NAFLD (n = 1 study in Korean individuals). Subgroup analyses did not materially modify these findings. CONCLUSIONS: NAFLD is associated with significant reductions of both FEV1 and FVC in Asian and United States adults, and such small, but significant, reductions of lung volumes at baseline may be also associated with increased NAFLD incidence in Asian individuals. Further research is needed to better elucidate the link between NAFLD and impaired lung volumes.

Effectiveness of topical α-Tocopherol Acetate in burn infection treatment.

Infection following burn injury is critical, especially for patients with large total body surface area burns and in skin graft donor sites. Although various aspects of α-tocopherol acetate (α-TA) beneficial effects on wound healing have been validated, it appears that no study has specifically addressed its antimicrobial potential. The purpose of this study was to explore the therapeutic efficacy of topical application of α-TA in terms of bacterial load reduction. Between January 2018 and June 2018, 20 patients with mid-deep and deep burn wounds were included in the present study (average TBSA approximately 42%, range 25-67%). Patient average age was 47.75 years (range 25-72 years), 8 were male. In each patient two clinically similar areas were identified and treated every 24 hours with topical application of α-TA in the form of Filme Olio® (Group 1) and conventional medication (Group 2). All the patients had positive results for bacterial cultures before treatment. Despite the presence of initial bacterial infection, a quicker reduction of exudates and pain and a progressive and faster bacterial load reduction was observed in Group 1. Negative cultures were obtained after 3 days on average in Group 1 (range 1-6 days) and 8 days in Group 2 (range 5-9 days). This study clearly shows the importance of the therapeutic targeting of infection in the treatment of burns. α-TA may represent a safe, simple and inexpensive method for improving the healing of difficult wounds with local infection.

Les infections sont une complication majeure des brûlures, en particulier chez les patients largement atteints et au niveau des sites donneurs. Alors que ATA a été évalué, et considéré bénéfique, dans de nombreux aspects de la cicatrisation, aucune étude ne s'est penchée sur son potentiel antimicrobien. Cette étude a exploré l'effet de ATA topique sur la réduction de l'inoculum bactérien. Vingt patients dont 12 femmes, ayant des brûlures intermédiaires et profondes, ont été inclus dans cette étude, qui s'est déroulée entre janvier et juin 2018. Leur âge était en moyenne de 47,75 ans (25- 72), la surface brûlée de 42% (25- 67%). Chez tous les patients, deux zones similaires, à la culture bactérienne positive, étaient traitées par ATA (groupe 1) ou traitement conventionnel (groupe 2). La diminution des l'exsudation, de la douleur et de la charge bactérienne était plus rapide dans le groupe 1. Les cultures se négativaient en 3 jours (1- 6) dans le groupe 1 contre 8 (5- 9) dans le groupe 2. Cette étude montre l'intérêt du traitement local des infections de zones brûlées, ATA apparaissant dans ce cadre comme un traitement simple, sûr et peu onéreux.

Enzymatic escharolysis with nexobrid® on partial thickness burn wounds: pre- and post-debridement histological assessment.

Enzymatic escharolysis is an innovative, non-surgical treatment method for severe burn patients as it allows very early, nontraumatic removal of necrotic tissue even on patients whose overall clinical conditions would mandate delaying traditional surgical escharectomy. The aim of this work was to examine aspects related to the "quality" of enzymatic debridement, which is inherently different from surgical debridement. To this end, biopsies harvested from partial thickness burn wounds, before and after enzymatic treatment, were histologically assessed. As is well known, surgical escharectomy removes the necrosis as well as some of its neighbouring healthy tissue, sharply and radically, leaving a perfectly clean and viable wound bed. On the other hand, enzymatic escharolysis is more selective, as it completely wipes out the necrotic portion while sparing unharmed and partially damaged tissue. In this study, only mid-deep partial thickness wounds were examined, and it was observed that partially damaged dermis was always spared by the lytic action. This dermis, however, showed some "homogenization" characteristics, had few vital skin annexes in it, and therefore looked very similar to the scaffold of dermal matrices currently available on the market. This scaffold should be safeguarded with a view to possibly achieving a more complete and functional spontaneous tissue regeneration. Conversely, if this dermal portion is mismanaged, it could desiccate, thus leading to the formation of a neo-eschar with unpredictable clinical evolution. Understanding how escharolysis actually works allowed us to extrapolate fruitful usage suggestions to optimize the procedure and fully exploit its potential.

La détersion enzymatique est une technique innovante non chirurgicale permettant l'ablation très précoce et non traumatique des tissus nécrosés même chez des patients dont l'état général nécessiterait de repousser une excision chirurgicale. Le but de ce travail était d'évaluer la « qualité ¼ du débridement enzymatique, par essence différent du traitement chirurgical. À cette fin, nous avons examiné histologiquement des biopsies réalisées avant et après détersion. Il est bien connu que la chirurgie emporte totalement et radicalement la nécrose et une partie du tissu environnant, laissant en place un tissu parfaitement propre et viable. Le débridement enzymatique est plus sélectif, emportant tout le tissu nécrosé sans affecter les tissus sains ou viables. Cette étude ne s'est intéressée qu'aux brûlures intermédiaires et nous avons observé que les régions saines étaient toujours préservées. Ce derme restant apparaît toutefois homogénéisé, avec peu d'annexes viables ce qui fait penser aux matrices des dermes artificiels actuellement commercialisés. Il doit être préservé afin de promouvoir une régénération tissulaire complète et fonctionnelle. Ainsi, si ce derme restant n'est pas correctement pris en charge, il peut se dessécher et aboutir à la formation d'un nouvel escarre, d'évolution imprévisible. Le compréhension du mécanisme exact de la lyse de la brûlure permet de développer des protocoles d'optimisation de la technique de lyse enzymatique.

Nonalcoholic fatty liver disease and decreased bone mineral density: is there a link?

PURPOSE: Liver diseases are associated with decreased bone mineral density (BMD) and evidence suggests that nonalcoholic fatty liver disease (NAFLD) affects several extra-hepatic organs, interacting with the regulation of multiple endocrine and metabolic pathways. This review focuses on the rapidly expanding body of evidence that supports a strong association between NAFLD and the risk of decreased BMD, expression of low bone mass (osteoporosis), or reduced mineralization (osteomalacia). METHODS: We identified studies by searching PubMed for original articles published in English through March 2015 using the keywords "nonalcoholic fatty liver disease" or "fatty liver" combined with "bone mineral density", "osteoporosis", or "osteomalacia". RESULTS: Recent cross-sectional and case-control studies involving both adults and children have consistently shown that patients with NAFLD exhibit a greater prevalence of decreased BMD compared with age-, sex-, and body mass index-matched healthy controls. Accumulating clinical and experimental evidence suggests that NAFLD may contribute to the pathophysiology of low BMD, possibly through the direct contribution of NAFLD to whole-body and hepatic insulin resistance and/or the systemic release of multiple pro-inflammatory, pro-coagulant, and pro-fibrogenic mediators. CONCLUSIONS: Although more research is needed before firm conclusions can be drawn, it appears that there is a non-chance, statistical association between NAFLD and low BMD. This finding argues for more careful monitoring and evaluation of BMD among patients with NAFLD. The potential contribution of NAFLD itself to the development and progression of decreased BMD warrants further study.

Cardiovascular risk, lipidemic phenotype and steatosis. A comparative analysis of cirrhotic and non-cirrhotic liver disease due to varying etiology.

BACKGROUND: Liver regulates lipid metabolism in health and disease states. Nevertheless, the entity of cardiovascular risk (CVR) resulting from dysregulation of lipid metabolism secondary to liver disease is poorly characterized. AIM AND METHODS: To review, based on a PubMed literature search, the features and the determinants of serum lipid phenotype and its correlation with hepatic steatosis, insulin resistance (IR) and CVR across the wide spectrum of the most common chronic liver diseases due to different etiologies. RESULTS: Alcoholic liver disease (ALD) is associated with steatosis, IR and a typical lipid profile. The relationship between alcohol intake, incident type 2 diabetes (T2D) and CVR describes a J-shaped curve. Non-alcoholic fatty liver disease (NAFLD), and probably nonalcoholic steatohepatitis (NASH) in particular, is associated with IR, atherogenic dyslipidemia and increased CVR independent of traditional risk factors. Moreover, NASH-cirrhosis and T2D contribute to increasing CVR in liver transplant recipients. HBV infection is generally free from IR, steatosis and CVR. HCV-associated dysmetabolic syndrome, featuring steatosis, hypocholesterolemia and IR, appears to be associated with substantially increased CVR. Hyperlipidemia is an almost universal finding in primary biliary cirrhosis, a condition typically spared from steatosis and associated with neither subclinical atherosclerosis nor excess CVR. Finally, little is known on CVR in patients with hepatocellular carcinoma. CONCLUSIONS: CVR is increased in ALD, NAFLD and chronic HCV infection, all conditions featuring IR and steatosis. Therefore, irrespective of serum lipid phenotype, hepatic steatosis and IR may be major shared determinants in amplifying CVR in common liver disease due to varying etiology.

Practice guidelines for the diagnosis and management of nonalcoholic fatty liver disease. A decalogue from the Italian Association for the Study of the Liver (AISF) Expert Committee.

We report the evidence-based Italian Association for the Study of Liver guidelines for the appropriate diagnosis and management of patients with nonalcoholic fatty liver disease in clinical practice and its related research agenda. The prevalence of nonalcoholic fatty liver disease varies according to age, gender and ethnicity. In the general population, the prevalence of nonalcoholic fatty liver disease is about 25% and the incidence is of two new cases/100 people/year. 2-3% of individuals in the general population will suffer from nonalcoholic steatohepatitis. Uncomplicated steatosis will usually follow a benign course. Individuals with nonalcoholic steatohepatitis, however, have a reduced life expectancy, mainly owing to vascular diseases and liver-related causes. Moreover, steatosis has deleterious effects on the natural history of HCV infection. Nonalcoholic fatty liver disease is usually diagnosed in asymptomatic patients prompted by the occasional discovery of increased liver enzymes and/or of ultrasonographic steatosis. Medical history, complete physical examination, etiologic screening of liver injury, liver biochemistry tests, serum lipids and insulin sensitivity tests should be performed in every patient. Occult alcohol abuse should be ruled out. Ultrasonography is the first-line imaging technique. Liver biopsy, the gold standard in diagnosis and prognosis of nonalcoholic fatty liver disease, is an invasive procedure and its results will not influence treatment in most cases but will provide prognostic information. Assessment of fibrosis by composite scores, specific laboratory parameters and transient elastography might reduce the number of nonalcoholic fatty liver disease patients requiring liver biopsy. Dieting and physical training reinforced by behavioural therapy are associated with improved nonalcoholic fatty liver disease. Diabetes and the metabolic syndrome should be ruled out at timed intervals in nonalcoholic fatty liver disease. Nonalcoholic steatohepatitis patients should undergo periodic evaluation of cardiovascular risk and of advancement of their liver disease; those with nonalcoholic steatohepatitis-cirrhosis should be evaluated for early diagnosis of hepatocellular carcinoma.

Genetic polymorphisms in non-alcoholic fatty liver disease: interleukin-6-174G/C polymorphism is associated with non-alcoholic steatohepatitis.

BACKGROUND: Environmental and genetic factors play a role in the pathogenesis and natural history of non-alcoholic fatty liver disease (NAFLD). METHODS: In 114 subjects with NAFLD we report the prevalence and correlation with clinical parameters of three polymorphisms: interleukin-6 (-174G/C), plasma cell differentiation antigen (K121Q) and microsomal transfer protein (-493G/T). In 59 biopsied patients with NAFLD the polymorphisms were also related to histological features. RESULTS: IL-6 -174C variant was more prevalent (p<0.01) in NAFLD compared to controls. In the NAFLD group, C carriers had higher HOMA-IR and fasting insulin than G carriers (p<0.05). The prevalence of IL-6/C variant was higher (83%) in biopsied than in not biopsied subjects (66%) (p<0.05). In biopsied subjects, C carriers had higher HOMA and fasting insulin (p<0.05) compared than those with G allele. The prevalence of IL-6 -174G/C polymorphism was significantly higher in NASH than in NAFLD (p=0.048). At logistic regression analysis IL-6 -174C was an independent predictor of both NAFLD (OR 4.116, C.I. 1.126-15.048) and NASH (OR 7.035, C.I. 1.167-42.394). Conversely, the distribution of PC-1 and MTP polymorphisms was not significantly different compared to the control group, nor associated with clinical or histological characteristics. CONCLUSIONS: Our data suggest that IL-6 -174C genetic polymorphisms, involved in inflammation and insulin resistance, are associated with NASH. These data may contribute to the understanding of the genetic susceptibility to NAFLD.

HCV and diabetes. A two-question-based reappraisal.

We used available studies to answer two clinically relevant questions, i.e. whether those with type 2 diabetes should undergo hepatitis C virus screening and whether hepatitis C virus positive individuals should be screened for diabetes. Four reasons argue against the hypothesis of screening diabetics for hepatitis C virus. First, although it induces insulin resistance, hepatitis C virus is not directly diabetogenic. Second, the clinical phenotype of hepatitis C virus-associated type 2 diabetes might be a clue to target the specific diabetic population to be screened. Third, diabetic patients are expected to be poor responders to antivirals and evidence that this might result in recovery from type 2 diabetes is insufficient. Fourth, no econometric data are available in the specific subset of those with type 2 diabetes. Case finding of type 2 diabetes in those with hepatitis C virus infection, in contrast, might be considered in those patients with type 2 diabetes who have cirrhosis, in whom--due to increased prevalence and severity of hepatic encephalopathy--diabetes is associated with increased mortality. Preliminary evidence suggests that the prognosis of cirrhosis might benefit from improved glycemic control and thus from earlier diagnosis of type 2 diabetes. Finally, studies are needed to ascertain the most cost-effective strategy of case-finding type 2 diabetes among those who are hepatitis C virus-infected. In conclusion, available data enabled us to answer the two questions. Hepatitis C virus screening should best be restricted to those (lean) diabetic patients with (advanced) liver disease. Glucose tolerance testing should best be performed in those with hepatitis C virus-related cirrhosis. However, additional studies are needed to support the cost-effectiveness of our conclusions.

Non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease: an open question.

AIMS: To review available data concerning the basic science and epidemiological-clinical evidence for an association of NAFLD and cardiovascular disease. DATA SYNTHESIS: Non-alcoholic fatty liver disease (NAFLD) defines alcohol-like hepatic histological lesions seen in the non-alcoholic, insulin resistant patient representing the hepatic counterpart of the metabolic syndrome. Along with insulin resistance, additional genetic, endocrine and vascular changes together with environmental stimuli--which are also involved in the pathogenesis of atherosclerosis--play a prominent role in the development and progression of NAFLD. Clinical and epidemiological studies seem to indicate that NAFLD is associated with an increased risk for cardiovascular disease but further studies are needed to confirm the available data. The mainstay of NAFLD treatment is based on the correction of the same metabolic changes that predispose to atherosclerosis. CONCLUSIONS: Non-invasive evaluation of risk for cardiovascular events is recommended in all individuals presenting with NAFLD and conversely, the presence of NAFLD should always be looked for in subjects with features belonging to the metabolic syndrome. Further studies are needed on the mechanisms linking fatty liver and vascular diseases.

Analysis of body fluid mixtures by mtDNA sequencing: An inter-laboratory study of the GEP-ISFG working group.

The mitochondrial DNA (mtDNA) working group of the GEP-ISFG (Spanish and Portuguese Group of the International Society for Forensic Genetics) carried out an inter-laboratory exercise consisting of the analysis of mtDNA sequencing patterns in mixed stains (saliva/semen and blood/semen). Mixtures were prepared with saliva or blood from a female donor and three different semen dilutions (pure, 1:10 and 1:20) in order to simulate forensic casework. All labs extracted the DNA by preferential lysis and amplified and sequenced the first mtDNA hypervariable region (HVS-I). Autosomal and Y-STR markers were also analysed in order to compare nuclear and mitochondrial results from the same DNA extracts. A mixed stain prepared using semen from a vasectomized individual was also analysed. The results were reasonably consistent among labs for the first fractions but not for the second ones, for which some laboratories reported contamination problems. In the first fractions, both the female and male haplotypes were generally detected in those samples prepared with undiluted semen. In contrast, most of the mixtures prepared with diluted semen only yielded the female haplotype, suggesting that the mtDNA copy number per cell is smaller in semen than in saliva or blood. Although the detection level of the male component decreased in accordance with the degree of semen dilution, it was found that the loss of signal was not consistently uniform throughout each electropherogram. Moreover, differences between mixtures prepared from different donors and different body fluids were also observed. We conclude that the particular characteristics of each mixed stain can deeply influence the interpretation of the mtDNA evidence in forensic mixtures (leading in some cases to false exclusions). In this sense, the implementation of preliminary tests with the aim of identifying the fluids involved in the mixture is an essential tool. In addition, in order to prevent incorrect conclusions in the interpretation of electropherograms we strongly recommend: (i) the use of additional sequencing primers to confirm the sequencing results and (ii) interpreting the results to the light of the phylogenetic perspective.

Is cholangiocarcinoma another complication of insulin resistance: a report of three cases.

BACKGROUND: Cholangiocarcinoma is the second most common primary liver cancer, and the number of cases of intrahepatic cholangiocarcinoma (ICC) have been steadily increasing worldwide. Although the reasons for this surge are unknown, insulin resistance (IR) could be a risk factor, similar to what has been reported for other cancers. CASE REPORT: We report on 3 cases of ICC arising in subjects sharing IR as an underlying risk factor. Case 1 was an obese and dyslipidemic patient with NAFLD. The second and the third patients were affected by type 2 diabetes. CONCLUSIONS: Evidence for a link between IR and onset of cholangiocarcinoma in our patients rests on three lines of evidence: epidemiological, biological, and exclusion of others risk factors. Studies are needed to confirm our hypothesis that IR is a risk factor for the development of ICC.

Hepatitis C and steatosis: a reappraisal.

The overall prevalence of steatosis in patients with Hepatitis C virus (HCV) chronic infection is 55.5% (range 34.8-81.2%). This is a two to threefold increase compared with the prevalence of steatosis in chronic hepatitides because of other aetiologies and of the figures expected on the grounds of a steatosis-HCV chance association. HCV genotype 3 (HCV-3) has specific epidemiological features; furthermore, as compared with HCV-non-3 genotypes, it is associated with a higher prevalence (74.1%vs 47.9%, P < 0.01) and with more severe grades of steatosis (prevalence of grade 3 steatosis 29.6 vs 5.5 P < 0.01). Host and viral factors play a role, although to a variable extent, in the pathogenesis of HCV-3 and non-3 steatosis. HCV load and body mass index are associated with steatosis in HCV-3 and in HCV-non-3 patients respectively. Serum cholesterol levels and liver steatosis at baseline follow an inverse relationship in HCV infection. As hypocholesterolaemia corrects only in those sustained responders to antiviral treatment both in genotype 3 and in non-3 genotypes, the occurrence of a virally induced, acquired and reversible hypobetalipoproteinaemia seems plausible. Steatosis affects the natural course of HCV infection: it is associated with fibrosis, a possible mediator of increased risk to develop type 2 diabetes, it impairs the response to antiviral treatment in HCV-3 patients and might constitute a risk factor for the development of hepatocellular carcinoma. These observations indicate the need to evaluate the efficacy of combined antiviral and 'metabolic' approaches vs standard antiviral regimes in patients with steatosis and HCV chronic infection.

Review article: the metabolic syndrome and non-alcoholic fatty liver disease.

Metabolic syndrome represents a common risk factor for premature cardiovascular disease and cancer whose core cluster includes diabetes, hypertension, dyslipidaemia and obesity. The liver is a target organ in metabolic syndrome patients in which it manifests itself with non-alcoholic fatty liver disease spanning steatosis through hepatocellular carcinoma via steatohepatitis and cirrhosis. Given that metabolic syndrome and non-alcoholic fatty liver disease affect the same insulin-resistant patients, not unexpectedly, there are amazing similarities between metabolic syndrome and non-alcoholic fatty liver disease in terms of prevalence, pathogenesis, clinical features and outcome. The available drug weaponry for metabolic syndrome includes aspirin, metformin, peroxisome proliferator-activated receptor agonists, statins, ACE (angiotensin I-converting enzyme) inhibitors and sartans, which are potentially or clinically useful also to the non-alcoholic fatty liver disease patient. Studies are needed to highlight the grey areas in this topic. Issues to be addressed include: diagnostic criteria for metabolic syndrome; nomenclature of non-alcoholic fatty liver disease; enlargement of the clinical spectrum and characterization of the prognosis of insulin resistance-related diseases; evaluation of the most specific clinical predictors of metabolic syndrome/non-alcoholic fatty liver disease and assessment of their variability over the time; characterization of the importance of new risk factors for metabolic syndrome with regard to the development and progression of non-alcoholic fatty liver disease.

Review article: hepatic steatosis and insulin resistance.

Hepatic steatosis may be both an adaptive phenomenon and an example of lipotoxicity. Its prevalence ranks in the same order of magnitude of insulin resistance in the general population. Studies support the finding that hepatic steatosis is secondary to insulin resistance and not vice versa. A steatotic liver will further contribute to the development of insulin resistance through impaired clearance of insulin from the portal blood, creating a vicious cycle. Insulin resistance is the leading force in the pathogenesis and natural history of non-alcoholic fatty liver disease. Dysfunction of energetic homeostasis and the interaction of adiponectin, leptin and tumour necrosis factor-alpha are key events in the pathogenesis of steatosis and insulin resistance. Insulin resistance represents the frame within which hepatic and extrahepatic non-alcoholic fatty liver disease-related clinical manifestations are to be anticipated and interpreted.