MAFLD and CKD: An Updated Narrative Review

Accumulating evidence now indicates that non-alcoholic fatty liver disease (NAFLD), which is the most common chronic liver disease observed in clinical practice worldwide, is independently associated with an increased risk of incident chronic kidney disease (CKD). Given that NAFLD is linked to insulin resistance, obesity and type 2 diabetes mellitus, an international panel of experts have recently proposed a name change from NAFLD to metabolic associated fatty liver disease (MAFLD). Since the diagnostic criteria for NAFLD and MAFLD are different, observational studies assessing the potential concordance (or even superiority) of MAFLD, compared with NAFLD, in detecting patients at increased risk of hepatic and extra-hepatic complications (including CKD) are required. Hence, in the last two years, some observational studies have investigated the potential relationship between MAFLD and CKD. The result is that, at present, evidence regarding the concordance or even superiority of MAFLD, compared with NAFLD, in detecting patients at higher risk of CKD is still preliminary, although some data indicate that MAFLD identifies patients with CKD as accurately as NAFLD. In this narrative review, we will discuss: (a) the epidemiological evidence assessing the association between NAFLD and risk of incident CKD, (b) the epidemiological data investigating the association between MAFLD and risk of CKD and (c) the biological mechanisms underlying the association between NAFLD/MAFLD and CKD

Prevalence of portal vein thrombosis in non-alcoholic fatty liver disease: a meta-analysis of observational studies

Portal vein thrombosis (PVT) is a common complication of cirrhosis as a result of portal hypertension and modification in the hemostatic balance. Accumulating evidence now suggests that patients with non-alcoholic fatty liver disease (NAFLD), especially those with advanced forms, have an increased risk of PVT. Hence, we performed a meta-analysis of observational studies to estimate the overall prevalence of PVT in patients with NAFLD and its advanced forms compared with patients with advanced liver diseases from other etiologies. We systematically searched PubMed, Scopus and Web of Science databases from the inception date to December 30th 2022, using predefined keywords, to identify observational studies. Meta-analysis was performed using random-effects modeling. We included five observational studies for a total of 225,571 patients. Of these, 26,840 (11.9%) patients had NAFLD, whereas the PVT prevalence was 8.5% (n = 2,280). When compared with patients with advanced liver diseases from other etiologies, patients with NAFLD and its advanced forms had a higher risk of prevalent PVT (OR 1.34, 100% CI 1.07-1.67 p < 0,01). The between-study heterogeneity was substantial (I-2 = 88%). This meta-analysis suggests that compared with patients with advanced liver diseases from other etiologies, patient with NAFLD and its advanced forms had a higher risk of prevalent PVT. Further research is required to understand the complex link between NAFLD/NASH and PVT development

Plasma bile acid profile in patients with and without Type 2 Diabetes

A paucity of information currently exists on plasma bile acid (BA) profiles in patients with and without type 2 diabetes mellitus (T2DM). We assayed 14 plasma BA species in 224 patients with T2DM and in 102 nondiabetic individuals with metabolic syndrome. Plasma BA levels were measured with ultra-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) technique. Multivariable linear regression analyses were undertaken to assess associations between measured plasma BA species and T2DM status after adjustment for confounding factors. The presence of T2DM was significantly associated with higher plasma concentrations of both primary BAs (adjusted-standardized beta coefficient: 0.279, p = 0.005) and secondary BAs (standardized beta coefficient: 0.508, p < 0.001) after adjustment for age, sex, adiposity measures, serum alanine aminotransferase and use of statins or metformin. More specifically, the presence of T2DM was significantly associated with higher levels of plasma taurochenodeoxycholic acid, taurodeoxycholic acid, glycochenodeoxycholic acid, hyodeoxycholic acid, glycodeoxycholic acid, glycolithocholic acid, deoxycholic acid, taurochenodeoxycholic acid, taurodeoxycholic acid, glycochenodeoxycholic acid and glycodeoxycholic acid (adjusted-standardized beta coefficients ranging from 0.315 to 0.600; p < 0.01 or less), as well as with lower plasma levels of cholic acid (adjusted-standardized beta coefficient: -0.250, p = 0.013) and taurocholic acid (adjusted-standardized beta coefficient: -0.309, p = 0.001). This study shows that there are marked differences in plasma BA profiles between patients with and without T2DM. Further research will be needed to better understand how these differences in plasma BA profiles may interplay with the pathophysiology of T2DM

Glomerular Hyperfiltration: A Marker of Fibrosis Severity in Metabolic Associated Steatotic Liver Disease in an Adult Population

Glomerular hyperfiltration (GH) is an increase in the glomerular filtration rate, possibly progressing to chronic kidney disease (CKD). Metabolic-associated steatotic liver disease (MASLD) is linked to an increased risk of CKD, especially if fibrosis is present; however, the association between GH and MASLD has not been explored. To evaluate GH prevalence in MASLD and its possible correlation with liver fibrosis. 772 consecutive patients with ultrasound MASLD (mean age 47.3 ± 8.9 years, 67.1% males) were enrolled. GH was defined as estimated glomerular filtration rate (eGFR) greater than the upper quartile of values in the cohort. Liver stiffness measurement (LSM) by FibroScan ≥ 7.2 kPa suggested liver fibrosis. GH was present in 20% of patients, liver fibrosis in 30%. In total, 53.4% of the cohort was obese, 40.9% hypertensive, 36.3% diabetic and 70.8% dyslipidaemic. GH patients compared to non-GH were significantly younger (38.4 ± 8.3 vs. 49.5 ± 7.7, p < 0.001), with higher prevalence of LSM > 7.2 kPa (35.5% vs. 29%, p < 0.001), without any difference in metabolic comorbidities. In multivariate analysis, age (OR 0.85, CI 95% 0.82–0.87) and significant fibrosis (OR 1.83; CI 95%1.10–3.03) remained independently associated with GH, regardless of the presence of metabolic alterations and nephrotoxic drugs. GH, an early marker of renal damage, is highly prevalent in MASLD and is associated with hepatic fibrosis. GH may be considered an early marker of both liver and renal disease and its recognition could prompt the management of risk factors aimed at preventing the progression of both hepatic and renal disease

Performance of non-invasive respiratory function indices in predicting clinical outcomes in patients hospitalized for COVID-19 pneumonia in medical and sub-intensive wards: a retrospective cohort study

Coronavirus disease 2019 (COVID-19) is a newly recognized infectious disease which can lead to acute respiratory distress syndrome requiring ventilatory support and intensive care unit admission. The aim of our study is to evaluate the performance of two non-invasive respiratory function indices (the ROX index and the SatO2/FiO2 ratio), as compared to the traditional PaO2/FiO2 ratio, in predicting a clinically relevant composite outcome (death or intubation) in hospitalized patients for COVID-19 pneumonia. Four hospital centers in Northern Italy conducted an observational retrospective cohort study during the first wave of COVID-19 pandemic. Four hundred and fifty-six patients with COVID-19 pneumonia admitted to medical or sub-intensive wards were enrolled. Clinical, laboratory, and respiratory parameters, for the calculation of different indices, were measured at hospital admission. In medical wards (Verona and Padua) the PaO2/FiO2 ratio, ROX index and SatO2/FiO2 ratio were able to predict intubation or death with good accuracy (AUROC for the PaO2/FiO2 ratio, ROX index and SatO2/FiO2 ratio of 75%, 75% and 74%, respectively). Regarding sub-intensive wards (Milan and Mantua), none of the three respiratory function indices was significantly associated with the composite outcome. In patients admitted to medical wards for COVID-19 pneumonia, the ROX index and the SatO2/FiO2 ratio demonstrated not only good performance in predicting intubation or death, but their accuracy was comparable to that of the PaO2/FiO2 ratio. In this setting, where repeated arterial blood gas tests are not always feasible, they could be considered a reliable alternative to the invasive PaO2/FiO2 ratio

The role of red blood cell distribution width (RDW) in cardiovascular risk assessment: useful or hype?

Red blood cell distribution width (RDW) reflects erythrocyte size distribution, thus representing a reliable index of anisocytosis, widely used for the differential diagnosis of micro- and normocytic anaemias. Along with the large use in diagnostic hematology, RI)W has been associated with presence and complications of a vast array of human pathologies during the last decades, including cardiovascular (CV) diseases. This article is hence aimed to provide an overview of important studies and systematic reviews with meta-analysis, in which RDW has been associated with CV events and mortality, in the attempt of establishing whether enough evidence exists for supporting its routine use in clinical practice. According to available data it seems reasonable to conclude that although the diagnostic specificity is low, and this measure is still plagued by important lack of standardization, RDW can be regarded as an index of enhanced patient fragility and higher vulnerability to adverse outcomes. Abnormal RDW values shall hence persuade physicians to broaden the diagnostic reasoning over anaemias, especially those due to malnutrition or malabsorption, encompassing a comprehensive assessment of traditional and non-traditional CV risk factors

Unusual presentation of primary aldosteronism with advanced target organ damage: A case report

: Patients with primary aldosteronism have greater cardiovascular morbidity and mortality than patients with primary hypertension and a comparable cardiovascular risk profile. Herein we present the case of a patient who developed multiple end-organ damage due to unrecognized and uncontrolled hypertension caused by an aldosterone-producing adrenal adenoma. Clinical and radiological evaluation revealed hypertensive encephalopathy, cardiomyopathy, retinopathy and nephropathy which required hemodialysis. Blood pressure control before surgery was difficult due to renal impairment that precluded the administration of anti-aldosterone drugs. Primary aldosteronism was cured by laparoscopic adrenalectomy and all antihypertensive drugs were suspended. A remarkable aspect of this case is the discordant results at screening test for primary aldosteronism: even though aldosterone-to-renin ratio is the most reliable method to identify possible cases of primary aldosteronism it can be misleading especially in case of multiple comorbidities and concomitant antihypertensive treatment. Furthermore, anti-aldosterone drugs are worrisome to use when renal damage is advanced but can be reconsidered when hemodialysis begins

Unusual presentation of primary aldosteronism with advanced target organ damage: A case report

Patients with primary aldosteronism have greater cardiovascular morbidity and mortality than patients with primary hypertension and a comparable cardiovascular risk profile. Herein we present the case of a patient who developed multiple end-organ damage due to unrecognized and uncontrolled hypertension caused by an aldosterone-producing adrenal adenoma. Clinical and radiological evaluation revealed hypertensive encephalopathy, cardiomyopathy, retinopathy and nephropathy which required hemodialysis. Blood pressure control before surgery was difficult due to renal impairment that precluded the administration of anti-aldosterone drugs. Primary aldosteronism was cured by laparoscopic adrenalectomy and all antihypertensive drugs were suspended.A remarkable aspect of this case is the discordant results at screening test for primary aldosteronism: even though aldosterone-to-renin ratio is the most reliable method to identify possible cases of primary aldosteronism it can be misleading especially in case of multiple comorbidities and concomitant antihypertensive treatment. Furthermore, anti-aldosterone drugs are worrisome to use when renal damage is advanced but can be reconsidered when hemodialysis begins. Keywords: Primary aldosteronism, Hypertension, Advanced target organ damage, End stage renal disease, Case repor

Author's Reply: “Bacterial infections predispose to the development of portal vein thrombosis in patients with decompensated cirrhosis”

We read with great interest the letter, by Zanetto and colleagues [ 1 ], which has validated and expanded upon our recent results [ 2 ] concerning the association between bacterial infections and portal vein thrombosis (PVT) development in cirrhotic patients. They enrolled 128 patients, followed-up for up to one year. As reported, 14% developed PVT, and, as in our study, bacterial infections were more common in patients who developed PVT (56% vs 24%, p = 0.005), and were an independent risk factor for PVT occurrence in two models of multivariate analysis (Model 1: HR 2.99, p = 0.02; Model 2: HR 3.60, p = 0.007)