Host regulatory immune response is involved in the hepatic inflammatory process caused by the hepatitis C virus (HCV). We aimed to determine if HCV clearance with direct-acting antivirals (DAAs) changes the hepatic fibrosis stage, biochemical parameters of liver injury, and inflammatory/immune responses. Sample: 329 chronic hepatitis C (CHC) patients, 134 of them treated with DAAs. Liver fibrosis was evaluated by transient elastography (FibroScan), biochemical and cellular parameters were determined by standard methods, cytokine concentration by enzyme-linked immunoabsorbent assay (ELISA), and genetic polymorphisms by polymerase chain reaction—restriction fragment length polymorphism (PCR-RFLP) or endpoint genotyping. Before DAA treatment, severe fibrosis or cirrhosis (F3/4) was associated with higher values of tumor necrosis factor-alpha (TNF-α) and genotypes transforming growth factor-beta-509 C/T_CC (TGF-β-509 C/T_CC), interleukine-10-1082 T/C_CC (IL-10-1082 T/C_CC), and IL-10-592 G/T_GT. After DAA treatment, fewer F3/4 patients and lower values of TNF-α were found. Patients with TNF-α-308 G/A_GG and IL-10-592 G/T_GT were at risk for F3/4. Lack of improvement of liver fibrosis was associated with lower baseline values of platelet count for genotypes TNF-α-308 G/A_GG and haplotype TT/GG of IL-10-1082 T/C and IL-10-592 G/T. Our study showed decreased liver fibrosis/inflammation and normalization of liver injury biomarkers after DAA treatment. It also points to the importance of suppressing the pro-inflammatory response by DAAs in the resolution of hepatitis C, contributing to the improvement of liver damage evaluated by transient elastography.

Introduction: Chronic hepatitis C (CHC) is a clinical and pathological syndrome with various causes and is characterized by varying degrees of hepatocellular necrosis and inflammation. It is a significant cause of liver transplantation and liver-related death worldwide. The hepatic manifestations of CHC are typically characterized by slowly progressing liver fibrosis, which is a non-specific and often disproportionate response to tissue damage. A large majority of HCV patients have extrahepatic manifestations with varying degrees of severity. HCV infection is a risk factor for cardiovascular disease and diabetes mellitus, which increases insulin resistance, oxidative stress, and iron overload and causes chronic systemic inflammation. HCV infection is treated using direct-acting antivirals (DAAs) with cure rates of over 95 percent, minimal side effects, and shorter therapeutic courses. Despite the effective elimination of the virus, it seemed pertinent to understand to what extent HCV clearance eliminates or attenuates all the systemic alterations already induced by the virus during infection and chronicity. Objectives: Our study aimed to determine whether eliminating HCV with DAAs alters the severity of liver disease (liver stiffness and liver fibrosis stage by TE) and the metabolic/cellular profile of patients with CHC. Materials and methods: A group of 329 CHC patients from a Gastroenterology and Hepatology outpatient department were prospectively studied. Of these, 134 were also studied with DAAs. The liver fibrosis stage was evaluated by transient elastography (TE) using a FibroScan^® device, and two groups were established for the analysis of liver stiffness (LS): mild and moderate stiffness (fibrosis F1 and F2; F1/2) and severe stiffness (fibrosis and cirrhosis F3 and F4; F3/4). Metabolic/cellular parameters were evaluated before and after antiviral treatment using standard methods: alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl-transpeptidase (γ-GT), haptoglobin (Hp), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG), free iron (Fe), transferrin saturation (TS), total iron binding capacity (TIBC), ferritin (Ft), glycemia, insulin, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and platelets count. The results were statistically analyzed using SPSS 24.0 for Windows. Results: Comparing the fibrosis stage before and after DAAs treatment, we verify a reduction in LS in 85.7% of patients and an improvement in liver fibrosis stage in 22.2% of them after DAAs treatment. Before DAAs treatment, patients showed a 2.410 risk for higher fibrosis stages (F3/4). Comparing metabolic/cellular parameters before and after DAAs treatment, patients showed lower ALP, AST, ALT, γGT, TG, Fe, TIBC, and Ft values and higher TC, LDL, and Hp values after treatment. As such, HCV elimination reduces iron overload and insulin resistance. On the other hand, it caused dyslipidemia, raising total cholesterol and LDL to levels outside the reference values. The improvement in the liver fibrosis stage by TE was mainly associated with higher baseline platelet count and HDL values and lower insulin resistance. Conclusions: With this study, we were able to contribute to the knowledge of the effects of HCV elimination with DAAs on liver disease and metabolic profile to improve the quality of treatment and follow-up of these patients after HCV elimination.

Human papillomavirus (HPV) infection is a necessary but not sufficient factor for the development of invasive cervical cancer (ICC) and high-grade intraepithelial lesion (HSIL). Oxidative stress is known to play a crucial role in HPV infection and carcinogenesis. In this study, we comprehensively investigate the modulation of HPV infection, HSIL and ICC, and ICC through an exploration of oxidative stress-related genes: CβS, MTHFR, NOS3, ACE1, CYBA, HAP, ACP1, GSTT1, GSTM1, and CYP1A1. Notably, the ACE1 gene emerges as a prominent factor with the presence of the I allele offering protection against HPV infection. The association of NOS3 with HPV infection is perceived with the 4a allele showing a protective effect. The presence of the GSTT1 null mutant correlates with increased susceptibility to HPV infection, HSIL and ICC, and ICC. This study also uncovers intriguing epistatic interactions among some of the genes that further accentuate their roles in disease modulation. Indeed, the epistatic interactions between the BB genotype (ACP1) and DD genotype (ECA1) were shown to increase the risk of HPV infection, and the interaction between BB (ACP1) and 0.0 (GSTT1) was associated with HPV infection and cervical lesions. These findings underscore the pivotal role of four oxidative stress-related genes in HPV-associated cervical lesions and cancer development, enriching our clinical understanding of the genetic influences on disease manifestation. The awareness of these genetic variations holds potential clinical implications.

Environmental health is at the intersection between health and the environment. However, it still has a recent (and narrow) history as a scientific area, mainly addressing human biomonitoring and toxicological issues. Only recently additional environmental ‘layers’, other than the traditional chemical, biological and physical environmental determinants, have been considered. This broader perspective of environmental health also encompasses digital, psychosocial, political, socioeconomic and cultural determinants, all of them relevant when considering human health from a planetary health paradigm. This reflects the progressive adoption of a systemic perspective regarding the impact of gains for human health and well-being towards a sustainable environment. It also implies a multi-method and participatory approach to understand the intertwined relationship between environmental changes and human health. In this paper, the broader approach to environmental health is discussed in order to ‘set the stage’ for introducing the Institute of Environmental Health (ISAMB) of the Lisbon School of Medicine, Portugal. Each of the research groups and labs that compose ISAMB are presented, as well as their main lines of research. Present and planned contributions of ISAMB to advance knowledge on environmental health and for promoting human health gains in an environmentally sustainable way are also discussed.

Chronic hepatitis C (CHC) progression is highly variable and can be influenced by lipid metabolism. The ATP-binding cassette transporter A1 (ABCA1) is involved in lipid metabolism and mediates cholesterol efflux from liver cells. ABCA1 gene polymorphism rs2230808 (R1587K) modulates lipid levels as it is located in an ABCA1 protein domain, which is essential for cholesterol efflux. We aimed to analyze the role of ABCA1 polymorphism R1587K (rs2230808) in modulating the biochemical parameters of lipid metabolism and liver function and its association with liver disease severity, according to gender. A total of 161 CHC patients were clinically, histologically, and biochemically evaluated. Genotyping was performed by melting-curve analysis and statistical analysis by SPSS 24.0. There were significant differences between ABCA1_rs2230808 genotypes and total cholesterol, γGT (γ-glutamyl-transpeptidase), and HCV-RNA. Gender differences: in females, ABCA1_rs2230808 (GG or GA) was associated with higher HCV-RNA serum levels; in males, ABCA1_rs2230808 (GG or GA) was associated with higher γGT, lower total cholesterol, increased risk for γGT ≥ 38 UI/L, and total cholesterol < 4.92 mmol/L. Only in the case of males were higher γGT and lower total cholesterol associated with severe fibrosis and steatosis. Total cholesterol < 4.92 mmol/L also associates with severe necroinflammation. We conclude that ABCA1_rs2230808 is gender-specific. ABCA1_rs2230808 Allele G was associated with different clinical and biochemical parameters, which are related to more severe liver disease.

The gene TAS2R38 single nucleotide polymorphisms (SNPs-P49A, A262V and V296I) can condition bitter tasting by PAV (proline–alanine–valine) and non-bitter-tasting by AVI (alanine–valine–isoleucine) homozygosity. We evaluated this polymorphisms association with thyroid function, metabolism and anthropometry parameters determined by: Endpoint analysis (SNPs); DXA (fat mass-%, total fat mass—kg, lean mass—kg); Standard methods (lipid metabolism parameters, HbA1c-%, glycemia—mg/dL, insulinemia—µIU/mL, HOMA-IR, uricemia—mg/dL, calcemia—mg/dL and BMI—kg/m²); ELISA (leptinemia—ng/mL); Spectrophotometry (Angiotensin Converting Enzyme activity—UI/L). Statistics: SPSS program; OR [IC95%]; p < 0.05. Sample: 114 hypothyroid, 49 hyperthyroid, and 179 controls. An association between A262V-valine–valine and hypothyroidism/hyperthyroidism was verified (OR = 2.841; IC95% [1.726–4.676]), p < 0.001/OR = 8.915; IC95% [4.286–18.543]), p < 0.001). Protector effect from thyroid dysfunction: A262V-alanine–valine (OR = 0.467; IC95% [0.289–0.757], p = 0.002/OR = 0.132; IC95% [0.056–0.309], p < 0.001) and PAV (OR = 0.456; IC95% [0.282–0.737], p = 0.001/OR = 0.101; IC95% [0.041–0.250], p < 0.001). Higher parameter values associated with genotypes were: fat-mass-% (V296I-valine–isoleucine), lean-mass (P49A-proline–proline; PVI), leptin (AVI), HbA1c (A262V-alanine–valine) and lower values in lean-Mass (AVI; PVV), leptin (A262V-alanine–alanine), HbA1c (PVV), uricemia (V296I-valine–isoleucine), glycemia (A262V-alanine–alanine; AAV) and plasma triglycerides (PVV). In conclusion, TAS2R38 influences thyroid function, body composition and metabolism. Bitter taste perception (PAV) and the genotype A262V-alanine–valine can protect from thyroid dysfunction. AVV, PVV and genotype A262V-valine–valine may confer higher predisposition for thyroid dysfunction, particularly PVV for hyperthyroidism.