Increased Natural Killer Cells Are Associated with Alcohol Liver Fibrosis and with T Cell and Cytotoxic Subpopulations Change

Natural killer (NK) cells play a therapeutic role in liver fibrosis (LF). We aimed to analyze NK cells in heavy drinkers without cirrhosis or decompensated liver disease and establish correlations with other related subpopulations. Data on sociodemographic characteristics, alcohol consumption, laboratory parameters, and immunophenotyping of NK (CD16+/CD56+), T (CD3+), B (CD19+), NKT (CD16+/CD56+/CD3+), and cytotoxic (CD3-CD8+) cells were collected. Fibrosis-4 (FIB-4) scores were used to compare patients without (FIB-4 < 1.45) and with (FIB-4 > 3.25) advanced LF (ALF). We included 136 patients (76% male) with a mean age of 49 years who had a 15-year alcohol use disorder (AUD) and alcohol consumption of 164 g/day. Patients with ALF (n = 25) presented significantly lower absolute total lymphocyte, T cell, B cell, and NKT cell numbers than patients without LF (n = 50; p < 0.01). However, the NK cells count was similar (208 ± 109 cells/µL vs. 170 ± 105 cells/µL) in both groups. The T cells percentage was lower (80.3 ± 5.6% vs. 77 ± 7%; p = 0.03) and the NK cells percentage was higher (9.7 ± 5% vs. 13 ± 6%; p = 0.02) in patients with ALF than in those without LF. The percentages of NK cells and T cells were inversely correlated in patients without (r = –0.65, p < 0.01) and with ALF (r = −0.64; p < 0.01). Additionally, the NK cells and CD3-CD8+ cell percentages were positively correlated in patients without (r = 0.87, p < 0.01) and with (r = 0.92; p < 0.01) ALF. Conclusions: Heavy drinkers without decompensated liver disease showed an increase in NK cells related to T cells lymphopenia and an increase in cytotoxic populations. The interaction of NK cells with other subpopulations may modify alcohol-related liver disease progression.

Effect of COVID-19 on presentations of decompensated liver disease in Scotland

Background and aimsSARS-CoV-2 and consequent pandemic has presented unique challenges. Beyond the direct COVID-related mortality in those with liver disease, we sought to determine the effect of lockdown on people with liver disease in Scotland. The effect of lockdown on those with alcohol-related disease is of interest; and whether there were associated implications for a change in alcohol intake and consequent presentations with decompensated disease.MethodsWe performed a retrospective analysis of patients admitted to seven Scottish hospitals with a history of liver disease between 1 April and 30 April 2020 and compared across the same time in 2017, 2018 and 2019. We also repeated an intermediate assessment based on a single centre to examine for delayed effects between 1 April and 31 July 2020.ResultsWe found that results and outcomes for patients admitted in 2020 were similar to those in previous years in terms of morbidity, mortality, and length of stay. In the Scotland-wide cohort: admission MELD (Model for End-stage Liver Disease) (16 (12–22) vs 15 (12–19); p=0.141), inpatient mortality ((10.9% vs 8.6%); p=0.499) and length of stay (8 days (4–15) vs 7 days (4–13); p=0.140). In the Edinburgh cohort: admission MELD (17 (12–23) vs 17 (13–21); p=0.805), inpatient mortality ((13.7% vs 10.1%; p=0.373) and length of stay (7 days (4–14) vs 7 days (3.5–14); p=0.525)).ConclusionThis assessment of immediate and medium-term lockdown impacts on those with chronic liver disease suggested a minimal effect on the presentation of decompensated liver disease to secondary care.

Prophylaxis for venous thromboembolism in liver disease: a narrative literature review

Background: Patients with liver disease have traditionally been regarded as auto-anticoagulated against developing blood clots due to haemorrhage being regarded as the most significant haemostatic complication. More recently, there has been increasing recognition that hypercoagulability is a prominent aspect of cirrhosis, with an increasing number of patients developing thromboembolisms. When prescribing prophylactic low molecular weight heparin for prevention, clinicians are often concerned about the risk of bleeding, including gastrointestinal bleeding, specifically in those with decompensated liver disease and cirrhosis, due to the altered coagulopathy associated with these patients. Aim: The aim of this review was to assess if the use of prophylaxis in patients with liver disease is effective in the prevention of venous thromboembolism (VTE) and whether its use is related to an increase in bleeding episodes. Methods: A review of the literature was conducted to identify the incidence of VTE and bleeding in liver patients when given prophylactic VTE treatment. Results: The majority of evidence was inconclusive; however, the main emerging theme was that administering prophylaxis to patients with decompensated liver disease results in an increased risk of bleeding, while having little effect on reducing the risk of VTE development. Conclusion: The bleeding risk associated with VTE prophylaxis treatment and liver disease remains uncertain. Thus the ideal methods of medical prophylactic VTE prevention and monitoring in this patient population have not yet been determined. It is suggested that additional consideration should be given to serum albumin, platelet count and international normalised ratio, as well as renal function, in conjunction with risk assessment tools, when deciding whether to prescribe VTE prophylaxis or not.

Clinical Pharmacology of Hyperammonemia by Sodium Valproate and Carbamazepine in People Living with HIV

IntroductionHyperammonaemia (HA) is observed in decompensated liver disease. The picture of hyperammonemic encephalopathy in non-cirrhotic patients was reported mostly associated with valproic acid. There are few reports of hyperammonemia in people living with human immunodeficiency virus (PLHIV) and they are associated with other comorbidities and few with antiretrovirals (HAART), but not as adverse drug reactions associated with psychotropic drugs associated with the virus.ObjectiveReport of cases of PLHIV in HARRT with hyperammonemia, its clinical impact and ammonium levels.Materials and MethodsWe report 67 PLHIV in treatment with HAART, negative viral loads, psychopharmacological treatment with valproic acid (n=45) or carbamazepine (n=22). Exclusion criteria were = HCV, HBV and alcohol consumption disorder (current or recent history) and decompensated liver pathology. We apply scales to evaluate side effects (UKU), subjective adherence (DAI), daily life activities (Barthel Index), liver severity (Child-Pugh Classification) and degrees of hepatic encephalopathy (West Haven Scale). The ethical-legal requirements were met. Results: 26.86% presented hyperammonemia, among which 38.88% was symptomatic. The clinical presentation was heterogeneous with a higher prevalence of gastrointestinal and cognitive alterations; the most severe cases presented alterations of the sensorium and 1 case of convulsions. We recorded a greater symptomatic severity with carbamazepine (average ammonia =104.4 pmol/L), but a higher prevalence of non-symptomatic hyperammonemia with valproic acid (62.3 pmol/L). The time of onset of symptoms was lower with carbamazepine, but the time until its decrease was higher with valproic acid.ConclusionsWe observed a higher prevalence of hyperammonemia and associated symptomatology in PLHIV with HAART medicated with carbamazepine. The significant percentage of this adverse drug reaction suggests a biochemical, perhaps preventive, control.