Liver Injury and Elevated FIB-4 Define a High-Risk Group in Patients with COVID-19

Liver involvement in Coronavirus Disease 2019 (COVID-19) has been widely documented. However, data regarding liver-related prognosis are scarce and heterogeneous. The current study aims to evaluate the role of abnormal liver tests and incidental elevations of non-invasive fibrosis estimators on the prognosis of hospitalized COVID-19 patients. We conducted a retrospective cohort study to investigate the impact of elevated liver tests, non-invasive fibrosis estimators (the Fibrosis-4 (FIB-4), Forns, APRI scores, and aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio), and the presence of computed tomography (CT)-documented liver steatosis on mortality in patients with moderate and severe COVID-19, with no prior liver disease history. A total of 370 consecutive patients were included, of which 289 patients (72.9%) had abnormal liver biochemistry on admission. Non-survivors had significantly higher FIB-4, Forns, APRI scores, and a higher AST/ALT ratio. On multivariate analysis, severe FIB-4 (exceeding 3.25) and elevated AST were independently associated with mortality. Severe FIB-4 had an area under the receiver operating characteristic (AUROC) of 0.73 for predicting survival. The presence of steatosis was not associated with a worse outcome. Patients with abnormal liver biochemistry on arrival might be susceptible to a worse disease outcome. An FIB-4 score above the threshold of 3.25, suggestive of the presence of fibrosis, is associated with higher mortality in hospitalized COVID-19 patients.

Gastric adenocarcinoma with enteroblastic differentiation: an unexpected cause of upper gastrointestinal bleeding

A 78-year-old male with previous medical history of hypertension, dyslipidemia, benign prostatic hyperplasia and colectomy for colon adenocarcinoma 16 years earlier presented to emergency department with melena for approximately 2 weeks. He denied hematemesis or hematochezia. He also denied other symptoms including abdominal pain, nausea, vomiting, fever, anorexia or weight loss. Usual medications included silodosin, simvastatin, losartan, hydrochlorothiazide, pantoprazole and midazolam. He denied recent intake of iron supplements or non-steroidal anti-inflammatory drugs. Physical examination was unremarkable except for pale skin. Laboratory studies revealed the presence of anemia (hemoglobin level: 7.1 g/dL). Leukocyte and platelet counts, liver tests, renal function, electrolyte levels, C-reactive protein and coagulation studies were all normal. Upper digestive endoscopy revealed red blood and blood clots in gastric lumen and a polypoid lesion with a diameter of approximately 20 mm located at the greater curvature of the proximal body with active oozing hemorrhage (Figure 1). Bleeding was successfully controlled with injection of diluted epinephrine at the base of the polyp and the patient was admitted in intermediate care unit for close monitoring. During the following days,

Abnormal Liver Tests during Hospitalization Predict Mortality in Patients with COVID-19: A Multicenter Study from South America

Background. The role of liver function tests (LFT) as prognostic factors in patients admitted with COVID-19 has not been fully investigated, particularly outside resource-rich countries. We aimed at evaluating the prognostic value of abnormal LFT on admission and during hospitalization of patients with COVID-19. Methods. We performed a retrospective study that included 298 adult patients hospitalized for COVID-19, between 05/2020 and 02/2021, in 6 hospitals from 5 countries in South America. We analyzed demographic and comorbid variables and laboratory tests on admission and during hospitalization. LFT over twice the upper limit of normal (ALEx2) were also evaluated in relation to a variety of factors on admission and during hospitalization. De novo-ALEx2 was defined as the presence of ALEx2 at one week of hospitalization in patients without ALEx2 on admission. Patients were followed until hospital discharge or death. Multivariable analysis was used to evaluate the association between ALEx2 on admission and during hospitalization and mortality. Results. Of the total of 298 patients, 60% were male, with a mean age of 60 years, and 74% of patients had at least one comorbidity. Of those, 137 (46%) patients were transferred to the intensive care unit and 66 (22.1%) patients died during hospitalization. ALEx2 on admission was present in 87 (29.2%) patients and was found to be independently associated with 1-week mortality (odds ratio (OR) = 3.55; 95% confidence interval (95%CI) 1.05–12.05). Moreover, 84 (39.8%) out of 211 patients without ALEx2 at admission developed de novo-ALEx2, which was independently associated with mortality during second week of hospitalization (OR = 6.09; 95%CI 1.28–29) and overall mortality (OR = 2.93, 95%CI 1.05–8.19). Conclusions. A moderate elevation of LFT during admission was associated with a poor short-term prognosis in patients hospitalized with COVID-19. In addition, moderate elevation of LFT at one week of hospitalization was an independent risk factor for overall mortality in these patients.

Elevated markers of liver function are associated with poorer outcomes in HFREF: an analysis of DAPA-HF

Background Abnormalities of liver tests in patients with heart failure with reduced ejection fraction (HFrEF) is a well-recognised phenomenon. We examined the prognostic value of measures of liver function in a large contemporary cohort of patients with HFrEF enrolled in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial Methods In this post-hoc analysis of the DAPA-HF trial we studied 4625 patients with liver function tests available at baseline. Cox proportional hazards models were used to assess the association between liver tests (total bilirubin, alkaline phosphatase [ALP], alanine transaminase [ALT], aspartate transaminase [AST]) and the Model for End-stage Liver Disease excluding INR (MELD-XI) score (calculated as 5.11 Ln [total bilirubin as mg/dL] + 11.76 Ln [creatinine as mg/dL] + 9.44), and the risk of the primary composite endpoint (hospitalisation or urgent visit for heart failure or cardiovascular death). Models were adjusted for age, sex, race, region, systolic blood pressure, heart rate, LVEF, eGFR, log-transformed NT-proBNP, NYHA class, history of hypertension, stroke, myocardial infarction, atrial fibrillation, heart failure aetiology and randomized treatment to dapagliflozin and stratified by diabetic status at baseline. An interaction term between each measure and the effect of treatment on the primary composite outcome was tested as a fractional polynomial. Results Total bilirubin, ALP, and MELD-XI score were associated with a higher risk of all the primary outcome (Figure 1) but not ALT or AST. These relationships persisted after adjustment: total bilirubin per log unit increase (HR=1.46; 95% CI 1.28 – 1.67, p<0.001), ALP per log unit increase (HR=1.39; 95% CI 1.15 – 1.66, p<0.001), MELD-XI per 1 SD increase (HR 1.27; 95% CI 1.13 – 1.42, p<0.001). The effect of dapagliflozin on the primary outcome was not modified by the baseline levels of either total bilirubin, ALP or MELD-XI score (Figure 2) Conclusions Higher total bilirubin, ALP and MELD-XI score were independently associated with a higher risk of cardiovascular death or worsening HF and may be useful routinely available biomarkers to assess prognosis. The efficacy of dapagliflozin was the not modified by baseline levels of any of these markers. FUNDunding Acknowledgement Type of funding sources: None. Figure 2

COMPARISON OF BIOCHEMICAL PARAMETERS OF PATIENTS WITH LIVER CIRRHOSIS WITH AND WITHOUT COVID-19

There have been many published studies on how COVID-19 can affect the liver and how the severity of liver damage can influence the clinical course of COVID-19. The article describes the features of the biochemical parameters of the liver in different age groups developing with a new coronavirus infection using the example of observations in the department of gastroenterology. In patients under 60 years of age with liver cirrhosis in combination with Covid-19, along with deeper changes in liver tests, a decrease in hemoglobin, leukopenia and thrombocytopenia was observed.

More than a decade of real-world experience of pegvisomant for acromegaly: ACROSTUDY

Objective: To report the final long-term safety and efficacy analyses of patients with acromegaly treated with pegvisomant from the ACROSTUDY. Design: Global (15 countries), multicentre, non-interventional study (2004-2017). Methods: The complete ACROSTUDY cohort comprised patients with acromegaly, who were being treated with pegvisomant (PEGV) prior to the study or at enrolment. Main endpoints were long-term safety (comorbidities, adverse events [AEs], pituitary tumour volumes, liver tests) and efficacy (IGF-1 changes). Results: Patients (n = 2221) were treated with PEGV for a median of 9.3 years (range, 0-20.8 years) and followed up for a median of 7.4 years (range, 0-13.9 years). Before PEGV, 96.3% had received other acromegaly treatments (surgery/radiotherapy/medications). Before PEGV treatment, 87.2% of patients reported comorbidities. During ACROSTUDY, 5567 AEs were reported in 56.5% of patients and of these 613 were considered treatment-related (in 16.5% of patients) and led to drug withdrawal in 1.3%. Pituitary imaging showed a tumour size increase in 7.1% of patients; the majority (71.1%) reported no changes. Abnormal AST or ALT liver tests occurred in 3.2% of patients. IGF-1 normalization rate improved over time, increasing from 11.4% at PEGV start to 53.7% at year 1, and reaching 75.4% at year 10 with use of ≥30 mg PEGV/day in an increasing proportion of patients. Conclusion: This comprehensive review of the complete cohort in ACROSTUDY confirmed the overall favourable benefit-to-risk profile and high efficacy of PEGV as mono- and combination therapy in patients with an aggressive course/uncontrolled/active acromegaly requiring long-term medical therapy for control.