A global research priority agenda to advance public health responses to fatty liver disease

BACKGROUND & AIMS: An estimated 38% of adults worldwide have non-alcoholic fatty liver disease (NAFLD). From individual impacts to widespread public health and economic consequences, the implications of this disease are profound. This study aimed to develop an aligned, prioritised fatty liver disease research agenda for the global health community. METHODS: Nine co-chairs drafted initial research priorities, subsequently reviewed by 40 core authors and debated during a three-day in-person meeting. Following a Delphi methodology, over two rounds, a large panel (R1 n = 344, R2 n = 288) reviewed the priorities, via Qualtrics XM, indicating agreement using a four-point Likert-scale and providing written feedback. The core group revised the draft priorities between rounds. In R2, panellists also ranked the priorities within six domains: epidemiology, models of care, treatment and care, education and awareness, patient and community perspectives, and leadership and public health policy. RESULTS: The consensus-built fatty liver disease research agenda encompasses 28 priorities. The mean percentage of 'agree' responses increased from 78.3 in R1 to 81.1 in R2. Five priorities received unanimous combined agreement ('agree' + 'somewhat agree'); the remaining 23 priorities had >90% combined agreement. While all but one of the priorities exhibited at least a super-majority of agreement (>66.7% 'agree'), 13 priorities had 90% combined agreement. CONCLUSIONS: Adopting this multidisciplinary consensus-built research priorities agenda can deliver a step-change in addressing fatty liver disease, mitigating against its individual and societal harms and proactively altering its natural history through prevention, identification, treatment, and care. This agenda should catalyse the global health community's efforts to advance and accelerate responses to this widespread and fast-growing public health threat. IMPACT AND IMPLICATIONS: An estimated 38% of adults and 13% of children and adolescents worldwide have fatty liver disease, making it the most prevalent liver disease in history. Despite substantial scientific progress in the past three decades, the burden continues to grow, with an urgent need to advance understanding of how to prevent, manage, and treat the disease. Through a global consensus process, a multidisciplinary group agreed on 28 research priorities covering a broad range of themes, from disease burden, treatment, and health system responses to awareness and policy. The findings have relevance for clinical and non-clinical researchers as well as funders working on fatty liver disease and non-communicable diseases more broadly, setting out a prioritised, ranked research agenda for turning the tide on this fast-growing public health threat

A global action agenda for turning the tide on fatty liver disease

BACKGROUND AND AIMS: Fatty liver disease is a major public health threat due to its very high prevalence and related morbidity and mortality. Focused and dedicated interventions are urgently needed to target disease prevention, treatment, and care. APPROACH AND RESULTS: We developed an aligned, prioritized action agenda for the global fatty liver disease community of practice. Following a Delphi methodology over 2 rounds, a large panel (R1 n = 344, R2 n = 288) reviewed the action priorities using Qualtrics XM, indicating agreement using a 4-point Likert-scale and providing written feedback. Priorities were revised between rounds, and in R2, panelists also ranked the priorities within 6 domains: epidemiology, treatment and care, models of care, education and awareness, patient and community perspectives, and leadership and public health policy. The consensus fatty liver disease action agenda encompasses 29 priorities. In R2, the mean percentage of "agree" responses was 82.4%, with all individual priorities having at least a super-majority of agreement (> 66.7% "agree"). The highest-ranked action priorities included collaboration between liver specialists and primary care doctors on early diagnosis, action to address the needs of people living with multiple morbidities, and the incorporation of fatty liver disease into relevant non-communicable disease strategies and guidance. CONCLUSIONS: This consensus-driven multidisciplinary fatty liver disease action agenda developed by care providers, clinical researchers, and public health and policy experts provides a path to reduce fatty liver disease prevalence and improve health outcomes. To implement this agenda, concerted efforts will be needed at the global, regional, and national levels

Consenso Mexicano para el Tratamiento de la Hepatitis C

El objetivo del Consenso Mexicano para el Tratamiento de la Hepatitis C fue el de desarrollar un documento como guía en la práctica clínica con aplicabilidad en México. Se tomó en cuenta la opinión de expertos en el tema con especialidad en: gastroenterología, infectología y hepatología. Se realizó una revisión de la bibliografía en MEDLINE, EMBASE y CENTRAL mediante palabras claves referentes al tratamiento de la hepatitis C. Posteriormente se evaluó la calidad de la evidencia mediante el sistema GRADE y se redactaron enunciados, los cuales fueron sometidos a voto mediante un sistema modificado Delphi, y posteriormente se realizó revisión y corrección de los enunciados por un panel de 34 votantes. Finalmente se clasificó el nivel de acuerdo para cada oración. Esta guía busca dar recomendaciones con énfasis en los nuevos antivirales de acción directa y de esta manera facilitar su uso en la práctica clínica. Cada caso debe ser individualizado según sus comorbilidades y el manejo de estos pacientes siempre debe ser multidisciplinario. Abstract The aim of the Mexican Consensus on the Treatment of Hepatitis C was to develop clinical practice guidelines applicable to Mexico. The expert opinion of specialists in the following areas was taken into account: gastroenterology, infectious diseases, and hepatology. A search of the medical literature was carried out on the MEDLINE, EMBASE, and CENTRAL databases through keywords related to hepatitis C treatment. The quality of evidence was subsequently evaluated using the GRADE system and the consensus statements were formulated. The statements were then voted upon, using the modified Delphi system, and reviewed and corrected by a panel of 34 voting participants. Finally, the level of agreement was classified for each statement. The present guidelines provide recommendations with an emphasis on the new direct-acting antivirals, to facilitate their use in clinical practice. Each case must be individualized according to the comorbidities involved and patient management must always be multidisciplinary

The impact of different infectious complications on mortality of hospitalized patients with liver cirrhosis

Introduction and objectives: Bacterial infections are common complications in patients with cirrhosis and are associated with poor prognosis. There are no studies that analyze the impact of different infectious complications in the mortality of these patients, so we aimed to perform this evaluation. Materials and methods: We performed a case-control study in adult patients with cirrhosis with a follow-up period of one year. We recorded demographic data, prognostic scales, infectious complications and mortality at 30, 90 and 365 days. For the survival analysis, Kaplan–Meyer survival curve was performed and hazard ratios were calculated with 95% confidence intervals by Cox-regression in univariate and multivariate models. For the comparison between groups the Chi squared test, Fisher's exact test and Mann–Whitney U test were performed. Results: We included 500 patients. Median age was 58 years, predominant sex was woman (52%) and the most common infections were urinary tract infections (35%), pneumonia (28.2%) and spontaneous bacterial peritonitis (SBP) (18%). From the patients, 40.4% were CTP score C and median MELD score was 15. In the univariate analysis, infections in general, SBP, pneumonia and central nervous system (CNS) infections had an increased mortality at the three follow up periods, however in the multivariate analysis with the prognostic scales, only pneumonia (HR 2.03, CI 95%[1.06–3.86]) and CNS infections (HR 4.84, CI 95%[1.38–16.93]) remained with increased mortality. Conclusions: Some infectious complications, as pneumonia and CNS infections, increase mortality in hospitalized patients with cirrhosis, regardless of the severity of liver disease

An Integrated Review of the Hepatorenal Syndrome

Among the complications of cirrhosis, hepatorenal syndrome (HRS) is characterized by having the worst survival rate. HRS is a disorder that involves the deterioration of kidney function caused primarily by a systemic circulatory dysfunction, but in recent years, systemic inflammation and cirrhotic cardiomyopathy have been discovered to also play an important role. The diagnosis of HRS requires to meet the new International Club of Ascites-Acute Kidney Injury (ICA-AKI) and Hepatorenal Syndrome-Acute Kidney Injury (HRS-AKI) criteria after ruling out other causes of kidney injury. At the time of diagnosis, it is important to start the medical treatment as soon as possible where three types of vasoconstrictors have been recognized: vasopressin analogs (ornipressin and terlipressin), alpha-adrenergic agonists (norepinephrine and midodrine) and somatostatin analogues (octreotide); all should be combined with albumin infusion. Among them, terlipressin and albumin are the first lines of treatment in most cases, although terlipressin should be monitor closely due to its adverse events. The best treatment of choice is a liver transplant, because it is the only definitive treatment for this disease

NRF-2 and nonalcoholic fatty liver disease

Currently, chronic liver diseases have conditioned morbidity and mortality, many of these with a metabolic, toxicologic, immunologic, viral, or other etiology. Thus, a transcription factor that has been of huge importance for biomedical research is NRF-2. The latter is considered a principal component of the antioxidant mechanism, and it has been acknowledged that it impairs the function of NRF-2 in many liver diseases and that it forms an essential part of the pathologic changes that occur in the liver to contain inflammation and damage. Within the investigations and experiments carried out, there are isolated drugs, many of them related to plants and natural extracts that possess antioxidant properties through the NRF-2 signaling pathway, or even involving the stimulation of the transcription target proteins of NRF-2. Notwithstanding all of these experimental findings, to date there is not sufficient clinical evidence to justify the use of NRF-2 in medical practice

Association of liver steatosis and fibrosis with clinical outcomes in patients with SARS-CoV-2 infection (COVID-19)

Introduction and Objectives: Liver function tests (LFT) abnormalities are reported in up to 50% of COVID-19 patients, and metabolic comorbidities are associated with poorer outcomes. The aim of the study was to determine the prevalence of liver steatosis and fibrosis in patients with COVID-19 and their association with clinical outcomes. Material and methods: Retrospective study in hospitalized COVID-19 patients was conducted. The risk for liver steatosis was estimated by HSI > 36, and risk for advanced liver fibrosis with APRI > 1.0, NAFLD FS > 0.675 and/or FIB-4 > 3.25. Clinical outcomes were admission to Intensive Care Unit (ICU) and mortality. Results: Of 155 patients, 71.6% were male (n = 111), and 28.4% (n = 44) were obese. Abnormal LFT were present in 96.8% (n = 150), prevalence of steatosis was 42.6% (n = 66) and of significative liver fibrosis was 44.5% (n = 69). Liver fibrosis by FIB-4 was associated with risk of ICU admission (OR 1.74 [95%CI 1.74–2.68; p = 0.023]) and mortality (OR 6.45 [95%CI 2.01−20.83, p = 0.002]); no independent associations were found. Conclusions: The prevalence of steatosis and significant liver fibrosis was high in COVID-19 patients but was not associated with clinical outcomes