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Chronic liver disease (CLD), including non-alcoholic fatty liver disease (NAFLD) and its advanced form, non-alcoholic steatohepatitis (NASH), affects a significant portion of the population worldwide. NAFLD is characterised by fat accumulation in the liver, while NASH is associated with inflammation and liver damage. Osteosarcopenia, which combines muscle and bone mass loss, is an emerging clinical problem in chronic liver disease that is often underappreciated. The reductions in muscle and bone mass share several common pathophysiological pathways; insulin resistance and chronic systemic inflammation are the most crucial predisposing factors and are related to the presence and gravity of NAFLD and to the worsening of the outcome of liver disease. This article explores the relationship between osteosarcopenia and NAFLD/MAFLD, focusing on the diagnosis, prevention and treatment of this condition in patients with CLD.
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Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Fígado/metabolismo , Cirrose Hepática/patologia , Inflamação/metabolismoRESUMO
INTRODUCTION: Liraglutide 3.0 mg, a glucagon-like peptide-1 (GLP-1) analogue, is a medication approved for obesity treatment. This study aimed to investigate the relationship between psychiatric symptoms, including depression, anxiety, and binge eating, and their impact on therapy adherence. METHODS: A clinical audit was carried out on a cohort of 54 adults with obesity treated with liraglutide 3.0 mg. We retrospectively analyzed the connection between psychiatric symptoms assessed through the State-Trait Anxiety Inventory (STAI), Beck Depression Inventory (BDI), and Binge Eating Scale (BES). Adherence to therapy was assessed by the maximum dosage (MD) and treatment duration (TD). RESULTS: Notably, a discontinuation rate of 59% was encountered. However, among those who continued the treatment, we observed a negative association between anxiety symptoms (STAI score) and MD, depression symptoms (BDI score) and TD, and a higher likelihood of binge eating (BES score > 17) and TD. Moreover, presence of psychiatric symptoms did not compromise drug's effectiveness in achieving weight loss, which was 4.43% (± 5.5 SD) in the whole sample and 5.3% (± 6.3 SD) in the subgroup evaluated at 12 weeks. CONCLUSION: We observed a high discontinuation rate in real-life clinical setting, where Liraglutide 3.0 therapy is paid out-of-pocket. While psychiatric symptoms might play a role in diminishing adherence to therapy, they do not prevent drug's effectiveness to promote weight loss. This finding underscores the potential advantages of liraglutide 3.0 mg therapy for individuals contending with obesity while simultaneously managing mental health challenges. LEVEL OF EVIDENCE: Level V, descriptive studies.
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Bulimia , Saúde Mental , Adulto , Humanos , Liraglutida/uso terapêutico , Estudos Retrospectivos , Auditoria Clínica , Obesidade/tratamento farmacológico , Redução de PesoRESUMO
On March 14, 2024, after more than 25 years of intense research and a long series of failures, the Food and Drug Administration approved resmetirom as first drug for the treatment of non-alcoholic steatohepatitis (NASH) with fibrosis (now Metabolic-Associated Steatotic Liver Disease - MASLD). The present review covers this difficult process, finally providing a drug to complement lifestyle intervention, that has long been the sole approved therapeutic intervention. However, the availability of a drug shown to reduce disease progression in advanced stages of diseases opens a series of questions that deserve even more intense research. How to continue ongoing trials? How to generate an appropriate use of resmetirom in the community, limiting treatment according to predefined criteria and according to individual risk assessment? How to guarantee that both hepatic and non-hepatic comorbidities are appropriately targeted? How to define cost-effective strategies that might prevent the generation of unacceptable differences within the population, given the high costs of novel drugs and the extremely high numbers of candidates to treatment? Only a close surveillance of drug use in the real world, generated by insurance databases and national healthcare system registries, might provide adequate answers to these compelling questions.
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Background & Aims: Sarcopenia is associated with increased morbidity and mortality in patients with cirrhosis, but its definition in current literature is very heterogeneous. We performed a systematic review and meta-analysis to assess the association between mortality and sarcopenia evaluated by computed tomography (CT) in patients with cirrhosis, both overall and stratified for the criteria used to define sarcopenia. Methods: Medline, Embase, Scopus, and Cochrane Library were searched up to January 2023. We included studies assessing sarcopenia presence with CT scans and providing data on the risk of mortality. Adjusted hazard ratios (HRs) and 95% CIs were pooled using a random-effects model. Results: Thirty-nine studies comprising 12,827 patients were included in the meta-analysis. The summary prevalence of sarcopenia was 44% (95% CI 38-50%). The presence of sarcopenia (any definition) was an independent predictor of mortality with an adjusted HR of 2.07 (95% CI 1.81-2.36), and the result was consistent in all subgroup analyses. The prognostic role of the EASL/AASLD criteria was confirmed for the first time with an HR of 1.86 (95% CI 1.53-2.26) (n = 14 studies). The cut-offs used to define sarcopenia based on psoas muscle parameters varied among studies, thus, a subgroup analysis was not feasible. There was no substantial heterogeneity for the main estimates and no significant risk of publication bias. Conclusions: Sarcopenia on CT is associated with a 2-fold higher risk of mortality in patients with cirrhosis. The cut-offs proposed by EASL/AASLD are prognostically relevant and should be the recommended criteria used to define sarcopenia in clinical practice. Impact and implications: Sarcopenia assessed by the reference standard (computed tomography scan) is an independent predictor of mortality in patients with cirrhosis, with a 2-fold increase in the risk of death in all sensitivity analyses. This finding is particularly valid in patients from Europe and North America, and in transplant candidates. Stratifying for the parameters and cut-offs used, we confirmed for the first time the prognostic impact of the definition proposed by EASL/AASLD, supporting their use in clinical practice. Psoas muscle assessment is promising, but data are still limited and too heterogeneous to recommend its routine use at present.
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Metformin is a highly effective medication for managing type 2 diabetes mellitus. Recent studies have shown that it has significant therapeutic benefits in various organ systems, particularly the liver. Although the effects of metformin on metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatohepatitis are still being debated, it has positive effects on cirrhosis and anti-tumoral properties, which can help prevent the development of hepatocellular carcinoma. Furthermore, it has been proven to improve insulin resistance and dyslipidaemia, commonly associated with liver diseases. While more studies are needed to fully determine the safety and effectiveness of metformin use in liver diseases, the results are highly promising. Indeed, metformin has a terrific potential for extending its full therapeutic properties beyond its traditional use in managing diabetes.
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RATIONALE: To investigate the association between malnutrition and patient outcome following hospitalisation for Corona Virus Disease 2019 (COVID-19). METHODS: In April 2020, 268 adult patients (235 included in the follow-up) hospitalised for COVID-19 infection were evaluated for malnutrition risk and diagnosis using modified Nutritional Risk Screening 2002 and modified Global Leadership Initiative on Malnutrition criteria (GLIM), respectively. An 18-month follow-up was carried out to assess the incidence and the associated risk factors for death and re-hospitalization. RESULTS: The outcome was unknown for 33patients. Death occurred in 39% of the 235 patients included in the follow-up. The risk of death was independently associated with malnutrition risk or diagnosis of malnutrition, whereas the male sex showed a protective association. The Kaplan-Meier survival curves showed that patients with diagnosis of malnutrition had lower survival rate. The re-hospitalization rate was 31% and was negatively associated with BMI≥25, and positively associated with length of hospitalisation for COVID-19 and with cancer comorbidity. CONCLUSIONS: In hospitalized patients for SARS-CoV-2 disease, both malnutrition risk (p =0.050) and diagnosis of malnutrition (p=0.047 with modified GLIM and C-reactive protein > 0.5 mg/dL ; p=0.024 with modified GLIM and C-reactive protein > 5 mg/dL) were predictive risk factors for mortality, whereas male sex was associated with lower risk of death. Overweight at time of hospitalization and the length of hospitalisation were respectively protective and risk factor for re-hospitalization after discharge.
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BACKGROUND: The Covid pandemic seems to have had several detrimental effects on managing patients affected by inherited metabolic diseases (IMD), although published data about the impact of COVID-19 on patients suffering from IMD are very scarce. The scope of our work was to evaluate adherence to the vaccination plan, the side effects experienced by our adult IMD patients, and the symptoms of the SARS-CoV-2 infection. RESULTS: Sixty-seven patients agreed to respond to a phone interview. The mean age was 36.5 (± 11.6 SD). Regarding the vaccination campaign, fifty-five patients (82%) joined it, of whom ten had received two doses and the remaining forty-five, three. Forty-two patients (76%) reported adverse events following vaccination, the most frequent being local reaction, fever, and asthenia, which lasted an average of two days and resolved without sequelae. Regarding SARS-CoV-2 infection, twenty-seven out of sixty-seven patients (40%) tested positive for the virus; seven of them were not vaccinated at the time of infection; on the other hand, twenty had already had at least two doses. Regarding the prevalence of long-Covid, as many as 12 patients (44%) reported symptoms that persisted after the nasopharyngeal swab tested negative and lasted an average of 81 (± 74 SD) days. There were no statistically significant differences in BMI of patients who contracted the infection and patients who did not (25.15 vs. 25.20, p = .861), between those who had adverse reactions to the vaccine and those who did not (24.40 vs. 25.75, p = .223), between those who had long-Covid and those who did not (25.9 vs. 27.7, p = .183). No relation was observed between metabolic inherited disease, SARS-CoV-2 infection symptoms and adverse vaccine reactions. CONCLUSIONS: The data indicate that IMD patients adhered to the vaccination campaign comparably to the general Italian population. Adverse events to the vaccine were negligible. SARS-CoV-2 infection, which occurred in most cases after receiving at least two doses of the vaccine, did not cause serious symptoms and never required hospitalisation. A non-negligible share of patients suffered from long-Covid symptoms.