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Introduction:Although quarantine measures have been effective in preventing the spread of SARS-COV2 infection, they have limited physical activity and changed dietary habits, factors known to predispose the progression of nonalcoholic fatty liver disease (NAFLD). A role of PNPLA3 in weight gain has been recently reported. Aim: to evaluate changes on metabolic and hepatic profile in NAFLD patients during COVID-19 pandemic and to investigate the impact of PNPLA3 on the effect of lifestyle. Matherials and Methods and Results: 357 NAFLD patients who had a medical checkup no more than 6 months before COVID-19 blockade were included. Anthropometric, clinical and laboratory data and ultrasound grading of steatosis were collected before and after the blockade. Adherence to the Mediterranean Diet (MD) and physical activity (PA) was assessed at each visit. Genotyping for PNPLA3 was available in 188.After lockdown 48% patients gained weight and 16% worsened steatosis grade. Weight gain was associated with bad adherence to MD (p=0.005) and PA (p=0.03) and to PNPLA3 GG genotype (p=0.04). Interestingly, at multivariate analysis adjusted for sex, age, PA, MD and PNPLA3 GG, only PNPLA3 GG remained associated with weight gain (p=0.04). A higher glycemia (112±32 vs 106±25, p=0.002) and prevalence of increased transaminases (ALT 30% vs 21%, p= 0.02) were observed after lockdown only in patients who gained weight. Analyzing patients who gained weight according to age (i.e < or >67 ys), both older and younger patients showed less adherence to MD, but only younger patients had a significantly reduced PA during lockdown (23% vs 40%, p=0.002). Conclusions: During lockdown nearly half of NAFLD patients gained weight with consequent worsening of metabolic and liver features, highlighting, independently of the pandemic, the beneficial role of correct lifestyle.More interestingly, PNPLA3 GG genotype emerged as an independent risk factor for weight gain, opening new perspectives in NAFLD patients care.
ABSTRACT
Background : Several thrombotic manifestations have been reported with SARS-Cov-2 infection including liver vascular involvement. Aims : We present a dramatic case of acute liver necrosis in a 36-year-old SARS-Cov-2 positive Italian woman with no respiratory symptoms and triple positive antiphospholipid syndrome (APS). Methods : The patient was referred to our University Hospital for acute hypertransaminasemia and liver failure (Figure). She had systemic lupus erythematosus (positivity for: ANA, anti-dsDNA, complement activation, Coombs;thrombocytopenia, previous arthritis). Anti-phopspholipid antibodies (aPL) were detected for the first time in 2015 during routine pregnancy screening and chronically treated with aspirin. Apparently, no venous/arterial nor obstetric events were recorded up to the recent hospitalization. FIGURE 1 Results : At arrival, US-Doppler and CT-scan were consistent with signs of chronic liver disease and occlusion of the three hepatic veins defining a Budd-Chiari syndrome. We opted for a stepwise approach considering anticoagulation (clexane 100 UI/Kg b.i.d) the first line of therapy before any invasive intervention. Dexamethasone 6 mg/ day b.i.d., 6 sessions of plasma-exchange, i.v.-immunoglobulin were sequentially planned to revert the liver damage sustained by aPL. After 5-days, two hepatic-veins resulted recanalized in association with amelioration of liver-enzyme/function and aPL quantification. Then we performed hepatic vein catheterization and transjugular liver biopsy. The histology showed multiple areas of necrosis associated with liver cirrhosis. Unexpectedly, no signs of acute Budd-Chiari were observed (e.g. intraparenchymal hemorrhages, centrilobular congestion, sinusoidal dilation). Other etiologies were also excluded and we hypothesized the involvement of small arteries of the liver in a triple positive APS in a patients with SLE. We finally addressed the patient to a liver transplant program and a tight multispecialistic follow-up. Conclusions : Thrombosis of arterial/venous vessels or microcirculation causes liver damage in some patients with aPL. Our report suggests that SARS-Cov-2 can exacerbate this prothrombotic condition determining a life-threatening complication such as acute liver failure.
ABSTRACT
Background: Quarantine measures during Corona Virus Disease 2019 (COVID-19) pandemic changed lifestyle habits. In Nonalcoholic fatty liver disease (NAFLD) weight gain and unhealthy diet, along with PNPLA3 gene, impact on metabolic and hepatic disease. Aim: to evaluate prevalence and predictors of weight gain and steatosis progression in NAFLD outpatients during COVID-19 lockdown. Methods: 357 NAFLD outpatients were evaluated before COVID-19 lockdown and 6 months apart. Anthropometric, metabolic (i.e. presence and therapy of type 2 diabetes-T2DM, hypertension, dyslipidemia), laboratory data (glycemia, lipids, transaminases) as well as ultrasound (US) grading of steatosis were collected pre and post lockdown. Worsening of metabolic alterations was assessed post lockdown as newonset comorbidity or introduction of new therapies. Patients were questioned about diet and physical activity at each visit. In 222 patients genotyping for PNPLA3 was available. Results: Mean age was 61 ±12 ys, with 67% male. After lockdown 28% of the cohort worsened US steatosis grade from mild to moderate or severe. Patients who worsened steatosis had a higher prevalence of T2DM (34% vs 12%, p=0.006) and higher BMI (28.6 ±3.9 vs 26.8 ±3.6 kg/m2, p=0.01) pre lockdown compared to those who did not. No impact of diet or physical activity was observed on steatosis progression. An increase in body weight was registered in 170 (48%) patients with a mean increase of 3.2 ±2.4 Kg. As expected, patients with weight gain compared to those without it had a significantly lower adherence to diet (45% vs 61%, p=0.005) and decreased physical activity (28% vs 45%, p=0.001) at post lockdown visit. However, deterioration of lifestyle was not significant in subjects with PNPLA3 homozygosity for the risk allele. In addition, no impact on weight gain of pre lockdown lifestyle (diet adhesion 60% vs 52%, p=0.15;physical activity 48% vs 40%, p=0.16) or metabolic comorbidities was found. In patients who gained weight a worse glycemic control was observed (7% vs 2%, p=0.04) with increase in glycemia (106 ± 25 vs 111 ± 30 mg/dl p<0.001) compared to pre lockdown. Conclusion: Lockdown led to a dramatic change in lifestyle with consequent weight gain in almost half of our cohort of NAFLD patients. Indeed, genetic factors seem to modulate this impact. Therefore, during pandemic emergencies should be highly important to monitor patients' lifestyle at home, possibly by new technologies such as telemedicine.
ABSTRACT
Background: SARS-COV2 is a threatful viral disease which can evolve into respiratory failure but identification of risk factors for progression towards severe forms is still ongoing During infection impairment of liver function tests has been frequently reported and evidence of the negative impact of metabolic alterations on the clinical course are emerging, mainly evaluated in Asiatic populations Aim: to define the prognostic role of metabolic disease and liver damage on SARS-COV2 severity in a cohort of Italian patients Methods: All patients with confirmed COVID-19 infection admitted to low-intensity care COVID Units between March and April 2020 were enrolled Severe SARS-COV2 infection was defined according to International consensus requiring intensive respiratory support (CPAP/orotracheal intubation) All data were collected at admission Results: 382 patients were enrolled, mean age was 65±17 ys and 60% were male Mean BMI was 27±5 kg/m2 (61% overweight and 25% obese), prevalence of T2DM 17%, hypertension 44%, dyslipidemia 29% At admission 39% and 40% of patients had increased ALT and GGT levels, respectively Median hospitalization stay was 14 days (IQR 8-24), with 30% of patients experiencing severe SARS-COV2 infection and mortality in 14% of overall cases Subjects with severe infection presented higher prevalence of male sex (68% vs 56%, p=0 03), T2DM (25% vs 14%, p=0 01), dyslipidemia (36% vs 26%, p=0 05) and increased ALT (53% vs 32%, p<0 001) and GGT (53% vs 34%, p=0 01) levels at admission In multivariate analysis (adjusted for age, sex, T2DM, dyslipidemia, increased ALT and GGT at admission and SARS-COV2 therapy), T2DM (OR 3 1, 95%CI 1 6-6 0;p=0 001), dyslipidemia (OR 1 9, 95%CI 1 1-3 3;p=0 03), and increased ALT (OR 4 7, 95%CI 2 5- 9 0;p<0 001) and GGT (OR 2 0, 95%CI 1 2-3-3;p=0 009), resulted associated with high risk of more severe SARSCOV2 disease Interestingly, in patients with both T2DM and dyslipidemia, this risk was further increased (OR 5 2, 95%CI 2 1-12 6;p<0 001) Conclusion: We confirm that liver involvement is common during SARS-COV2 infection and it is a negative prognostic factor although it is not clear whether it precedes or follows, the severity of clinical course In addition, the risk of severe form of respiratory distress is increased by metabolic alterations, and the more numerous the alterations, the higher the risk.