Introduction

Alcohol abuse is a significant risk factor for the development of hepatic cirrhosis, which can lead to upper gastrointestinal bleeding. In non-cirrhotic patients, alcohol has been studied as a risk factor for non-variceal upper gastrointestinal bleeding (NVUGI), particularly in cases of peptic ulcer bleeding (1). However, the clinical impact of alcohol abuse on outcomes remains unclear. Only one retrospective study has analyzed this, finding an increased risk of rebleeding and non-significant increased mortality among alcohol consumers (2). Nevertheless, this study included cirrhotic patients, who accounted for most of the mortality. There is currently no available data on the impact of alcohol on NVUGI outcomes in non-cirrhotic patients.

Aims & Methods

This study aims to determine the impact of alcohol consumption on clinical outcomes in NVUGI.
We conducted a retrospective analysis at a Spanish tertiary hospital, encompassing NVUGI cases from 2013 to 2022. Alcohol abuse was defined as daily alcohol intake exceeding 20g. Key clinical outcomes included the need for intervention (transfusion, endoscopic, radiological, or surgical) and in-hospital mortality. In addition, we compared baseline characteristics and assessed both acute and delayed 6 months outcomes, including rebleeding and delayed cardiovascular events. Statistical analysis was performed using SPSS.

Results

A total of 892 cases were included. The alcohol abuse group had a higher proportion of men (95.6% vs. 64.1%, p < 0.001) and were younger (median age of 56 years vs. 66 years, p < 0.001). Non-alcohol consumers had more comorbidities and a higher ASA comorbidity risk score (58% had ASA 3 or 4 vs. 46% in the other group, p = 0.015). Additionally, the MAP(ASH) score was higher in the first group (>2 in 54.5% vs. 46.3%, p = 0.030). We did not find any other differences between groups, neither in key outcomes nor in the remaining comparisons for the acute episode. However, delayed mortality (8,2% in group 1 vs 3,1% in group 2, p=0,046) and six months cardiovascular events (8,9% vs 2,3%, p=0,011) were more frequent in the non-alcohol group. In multivariate analysis, only ASA 3-4 (OR: 4.17, CI: 1.49-11.68, p= 0.006) and MAP(ASH) (OR: 7.61, CI: 2.54-22.8, p < 0.001) were found to be independent risk factors for acute mortality.

Conclusion

Alcohol abuse is more common among younger individuals with fewer comorbidities. This consumption does not worsen clinical outcomes in non-cirrhotic NVUGI patients, with similar rates of need for intervention or mortality. Our results indicate that only comorbidities and bleeding severity (summarized as high ASA score and MAP(ASH)) score influence the outcomes. In summary, while alcohol consumption may increase the risk of NVUGI incidence, it does not impact acute outcomes.

References

1. Kelly JP, Kaufman DW, Koff RS, Laszlo A, Wiholm BE, Shapiro S. Alcohol consumption and the risk of major upper gastrointestinal bleeding. Am J Gastroenterol. 1995 Jul;90(7):1058-64.
2. Kärkkäinen JM, Miilunpohja S, Rantanen T, Koskela JM, Jyrkkä J, Hartikainen J, Paajanen H. Alcohol Abuse Increases Rebleeding Risk and Mortality in Patients with Non-variceal Upper Gastrointestinal Bleeding. Dig Dis Sci. 2015 Dec;60(12):3707-15

Introduction

Copeptin is a stable surrogate biomarker for the activation of the arginine vasopressin (AVP) system [1] as occurs in patients with cirrhosis and clinically significant portal hypertension (CSPH). Specifically, CSPH-induced haemodynamic alterations characterized by reduced peripheral vascular resistance and splanchnic hyperemia cause subsequent AVP system activation [2]. We aimed to evaluate serum copeptin levels (i) in different stages of cirrhosis and (ii) their prognostic value for clinical events in a cohort of stable outpatients with cirrhosis.

Aims & Methods

Stable outpatients with cirrhosis undergoing hepatic venous pressure gradient (HVPG) measurements and available copeptin levels were included; while patients with liver transplantation, malignacy, vascular liver disease, transjugular intrahepatic portosystemic shunt, heart failure and infection were excluded. Patients were stratified into 6 subgroups (S0-S5) for their clinical stage of cirrhosis, with S0-S2 representing compensated cirrhosis (S0: subclinical portal hypertension (PH) with an HVPG of 6-9 mmHg, S1: CSPH without varices, S2: CSPH with varices) and S3-S5 decompensated cirrhosis (S3: history of variceal bleeding, S4: non-bleeding decompensation, S5: further decompensation). Competing risk regression models were used to evaluate the association between copeptin levels and the risk of acute on chronic liver failure (ACLF) and liver-related death (LRD). Liver transplantation was considered as a competing event. Our previously established serum copeptin cut-off at >11.4 pmol/L [3] was used to stratify the patients into a high vs. low AVP system activation group.

Results

In total, 475 patients (S0: n=49, S1: n=53, S2: n=75, S3: n=22, S4: n=156, S5: n=120) with male predominance (72.6%; median age: 57.1 years) were included. Median follow-up time was 26.4 months. Median copeptin levels significantly increased throughout the substages of ACLD (from S0: 7.5 pmol/L to S5: 14.3 pmol/L; p<0.001). Patients with ascites had significantly higher copeptin levels (11.3 pmol/L vs. 7.2 pmol/L in non-ascites patients; p=<0.001).
Serum copeptin correlated significantly with C-reactive protein (ρ=0.281; p<0.001) and interleukin-6 levels (ρ=0.416; p<0.001) in patients with decompensated cirrhosis.
AVP system activation (i.e., Copeptin high >11.4 pmol/L) was found in n=194/475 (40.8%) patients. Patients with high-Copeptin had a significantly higher median MELD-Na (15 vs. low-Copeptin: 12; p<0.001) as well as significantly lower median mean arterial pressure (97 mmHg vs. low-Copeptin: 101 mmHg; p=0.027). The cumulative incidence of ACLF and LRD was significantly higher in patients with high-Copeptin at 1 year (ACLF: 24.1% vs. 4.0%; LRD: 21.9% vs. 4.0%), 2 years (ACLF: 32.0% vs. 7.2%; LRD: 26.7% vs. 6.3%) and 3 years (ACLF: 34.4% vs. 11.6%; LRD: 29.9% vs. 11.2%) of follow-up (p<0.001 for ACLF and LRD).
In competing risk regression adjusted for age, Child Turcotte Pugh score, creatinine, sodium and HVPG, higher levels of copeptin were independently predictive of ACLF (adjusted subdistribution hazard ratio [asHR] per pmol/L: 1.01; 95% confidence interval [95%CI]: 1.00-1.01; p=0.014), as well as LRD (asHR: 1.01; 95%CI: 1.00-1.01; p=0.024).

Conclusion

In ACLD, copeptin levels are upregulated with increasing disease severity suggesting progressive AVP system activation, associated with hemodynamic dysregulation and systemic inflammation. High-Copeptin represents an independent risk factor for ACLF and LRD development.

References

1. Abudeif A, Hashim MS, Ahmed NM, Ahmed AO. Serum copeptin is associated with major complications of liver cirrhosis and spontaneous bacterial peritonitis. Clin Exp Hepatol. 2023;9(1):71-8.

2. Kerbert AJ, Weil D, Verspaget HW, Moréno JP, van Hoek B, Cervoni JP, et al. Copeptin is an independent prognostic factor for transplant-free survival in cirrhosis. Liver Int. 2016;36(4):530-7.

3. Hartl L, Jachs M, Desbalmes C, Schaufler D, Simbrunner B, Paternostro R, et al. The differential activation of cardiovascular hormones across distinct stages of portal hypertension predicts clinical outcomes. Hepatol Int. 2021;15(5):1160-73.

Introduction

Malnutrition, sarcopenia, and frailty constitute the three vertices of a nutrition-status-determined physio-pathological triangle constantly featuring and dramatically burdening the prognosis of advanced chronic liver disease (ACLD) patients.
Dysgeusia is defined by a distortion of the sense of taste whose prevalence, relationship with the progression of the disease, and the direct contribution to malnutrition (and consequently, sarcopenia-frailty) in ACLD have never been systematically explored.

Aims & Methods

This observational study aimed to explore the prevalence of dysgeusia in a cohort of ACLD patients and evaluate the impact of this disorder on appetite levels and nutritional status (malnutrition, sarcopenia, and frailty), as well as to prospectively estimate the repercussions of dysgeusia-induced impaired nutritional status on liver-related events (LREs) occurrence. For this purpose, 40 controls, 50 chronic-liver disease-affected individuals staging initial-mild fibrosis (<F3), and 150 ACLD patients of various etiologies were enrolled. Anthropometrical, biochemical, clinical, and nutritional [European Prospective Investigation into Cancer and Nutrition (EPIC) questionnaire] data were collected. The opportunely modified Chemotherapy-induced Taste Alteration Scale (CITAS) questionnaire was used to assess the dysgeusia. Child-Pugh (CP) and Liver Frailty Index (LFI) calculations, Liver Stiffness Measurement (LSM), and Bioelectrical Impedance Analysis (BIA) were performed. Skeletal Muscle Mass (SMM) index (SMMI) (SMM/height²) < 7 kg/m² (male) and < 5.7 kg/m² (female) defined sarcopenia. ACLD patients were 3 years followed up semiannually and LREs (including ascites, hepatic encephalopathy, and bleeding) were collected.

Results

The prevalence of dysgeusia was significantly higher in ACLD (68%) in comparison to <F3 (8%) individuals and controls (5%) and in decompensated ACLD (dACLD) than compensated (cACLD) (54% vs 6%) patients (all p<0.0001). In line, CITAS-dysgeusia severity positively correlated with CP (R:0.81), as well as with the levels of appetite impairment (R:0.93) (both p<0.0001). Logistic regression analysis, appropriately weighted for factors notoriously impacting food intake in ACLD patients (low-sodic diet, drugs/supplements taken, physical activity frequency, occurrence of encephalopathy and ascites episodes in the previous 2 weeks), revealed the level of impairment of the appetite as a factor significantly associated with dysgeusia [HR: 2.12; p:0.02]. Compared to no-dysgeusia-affected dACLD (p:0.03), dysgeusia-affected dACLD patients (dys-dACLD) showed a decreased daily protein intake, reduced Free Fat Mass % (p<0.0001), and SMMI (p<0.0001: p:0.04), in contrast with increased LFI (p<0.0001). Consistently, dys-dACLD patients showed a higher prevalence (59% vs 39%) of sarcopenia (p:0.0002). The Kaplan-Meier Log-Rank Test analysis on LREs occurrence showed HR:3.53 [95% C.I: 1.58-4.92] for dys-dACLD individuals.

Conclusion

The prevalence of dysgeusia, increasing in parallel to the worsening of liver disease, promoted sarcopenia-frailty pictures, negatively influencing ACLD patients' outcomes.

References

1. Jafari A, Alaee A, Ghods K. The etiologies and considerations of dysgeusia: A review of literature. Journal of oral biosciences. 2021;63(4):319-26.
2. Sieber CC. Malnutrition and sarcopenia. Aging clinical and experimental research. 2019;31(6):793-8.
3. Tandon P, Montano-Loza AJ, Lai JC, Dasarathy S, Merli M. Sarcopenia and frailty in decompensated cirrhosis. Journal of hepatology. 2021;75 Suppl 1(Suppl 1):S147-s62.