Introduction

Adrenal dysfunction is known to occur in patients with liver cirrhosis during infection or acute decompensation and is associated with adverse outcomes, especially acute-on-chronic liver failure (ACLF) in these patients (1). However, little is known about pituitary-adrenal signaling in stable patients with ACLD.

Aims & Methods

We aimed to evaluate (i) the pituitary-adrenal axis and (ii) the prognostic value of total serum cortisol (t-Cort) in a cohort of outpatients with advanced chronic liver disease (ACLD).
Consecutive outpatients with ACLD and hepatic venous pressure gradient (HVPG) ≥6 mmHg within the prospective VICIS (NCT03267615) study were included. Exclusion criteria were intake of corticosteroids, a history of liver transplantation (LT), hepatocellular carcinoma, vascular liver disease, occlusive portal vein thrombosis and evidence of infection. According to d’Amico et al. (2) patients were stratified into 6 subgroups for their clinical stage of ACLD (S0: subclinical portal hypertension [PH], S1: clinically significant PH (CSPH) without varices, S2: CSPH with varices; S3: history of variceal bleeding, S4: non-bleeding decompensation S5: ACLD with further decompensation). Competing risk regression was conducted considering LT and death - or non-liver-related death, as appropriate - as competing.

Results

In total, 137 patients (compensated: S0: n=13, S1: n=12, S2: n=26; decompensated: S3: n=7, S4: n=46, S5: n=33) with male predominance (67.9%; median age: 58.1 years) were included. Median ACTH (from S0: 44.0pg/mL to S5: 20.0pg/mL; p=0.006), cortisol binding globulin (from S0: 49.3µg/mL to S5: 38.9µg/mL; p<0.001) and serum total cortisol (t-Cort; from S0: 13.9µg/dL to S5: 9.2µg/dL; p=0.091) levels decreased throughout the substages of ACLD, while serum free cortisol (f-Cort; from S0: 6.5ng/mL to S5: 5.7ng/mL; p=0.474) stayed unchanged.
Importantly, t-Cort showed a strong correlation with f-Cort and (Spearman’s ρ: 0.889). Lower levels of t-Cort were independently predictive of bacterial infections (adjusted subdistribution hazard ratio [asHR] per µg/dL: 1.11, 95% confidence interval [95%CI]: 1.04-1.19; p=0.002), (further) decompensation (asHR: 1.08; 95%CI: 1.02-1.12; p=0.008), ACLF (asHR: 1.11; 95%CI: 1.04-1.19; p=0.002), as well as liver-related death (asHR: 1.09; 95%CI: 1.01-1.18; p=0.045).
Youden’s index determined t-Cort level <12 µg/dL as ideal cutoff for the prediction of ACLF. Overall, n=87/137 (63.5%) patients exhibited t-Cort <12 µg/dL. The cumulative incidence of ACLF was more than 3 times higher in patients with t-Cort <12 µg/dL at 1 year (15.6% vs. 4.4%), 2 years (28.4% vs. 6.9%) and 3 years (34.4% vs. 11.0%) of follow-up (p=0.005).

Conclusion

Pituitary-adrenal signaling is impaired in cirrhosis. Lower levels of both t-Cort are independently linked to bacterial infections, (further) decompensation, ACLF and liver-related death, possibly due to impaired stress response. Moreover, t-Cort <12 µg/dL identifies stable patients with ACLD with a particularly high risk of ACLF.

References

1. Piano S, Favaretto E, Tonon M, Antonelli G, Brocca A, Sticca A, Mareso S, et al. Including Relative Adrenal Insufficiency in Definition and Classification of Acute-on-Chronic Liver Failure. Clin Gastroenterol Hepatol 2020;18:1188-1196.e1183.
2. D'Amico G, Morabito A, D'Amico M, Pasta L, Malizia G, Rebora P, Valsecchi MG. Clinical states of cirrhosis and competing risks. J Hepatol 2018;68:563-576.

Introduction

High-definition anorectal manometry (HD-ARM), balloon expulsion test (BET) and magnetic resonance defecography (MR-defecography) are important tools in studying constipation.

Aims & Methods

Evaluate the prevalence of functional defecation disorders and structural anorectal alterations in patients with constipation and compare the findings of HD-ARM and BET with MR-defecography.
Retrospective cohort study including patients with functional constipation (FC) or irritable bowel syndrome with constipation (IBS-C) submitted to HD-ARM, BET and MR-defecography. Patients were divided into three groups: 1) normal anorectal evacuation pattern in HD-ARM and BET; 2) abnormal anorectal evacuation pattern and BET; 3) normal anorectal evacuation pattern and abnormal BET, or abnormal anorectal evacuation pattern and normal BET.

Results

A total of 64 patients were included, 49 with FC (76.6%) and 15 with IBS-C (23.4%). There were 20 patients in group 1 (31.3%), 11 in group 2 (17.2%) and 33 in group 3 (51.5%). In MR-defecography, 47 patients had relevant structural anorectal alterations (73.4%) and 15 had an abnormal contraction of the puborectalis during the defecatory maneuver (23.4%).
Nineteen patients were diagnosed with dyssynergic defecation (29.7%). These patients had significantly higher residual anal pressure and lower percentage of anal relaxation during defecation (109.6±43.2 vs 85.8±29.7 mmHg, p=0.038 and 9% vs 24%, p=0.018, respectively), as well as a lower differential of rectoanal pressure (-32.2±31.4 vs 3.0±29.6 mmHg, p<0.001).
Patients with structural anorectal alterations had a significantly higher body mass index (BMI) (27.4±4.5 vs 23.5±3.3, p=0.002), and all obese patients had structural alterations.
Comparing the findings of HD-ARM and BET with MR-defecography: in group 1, 15 patients had structural alterations (75.0%); in group 2, 8 patients had structural alterations (72.7%); in group 3, 22 patients only had structural alterations (66.7%), 6 only had dyssynergic defecation (18.2%), 2 patients had both (6.0%) and 3 did not have any findings (9.1%). In 24.2% of patients with inconclusive findings in HD-ARM and BET, MR-defecography allowed the diagnosis of dyssynergic defecation.

Conclusion

Patients with structural anorectal alterations had a significantly higher BMI. Almost three quarters of patients with FC and IBS-C had relevant structural anorectal alterations and one third had dyssynergic defecation. Therefore, it is important to combine MR-defecography with HD-ARM and BET in the study of constipation.

Introduction

Malnutrition and sarcopenia are two very frequent complications in patients with liver cirrhosis (LC). These conditions are associated with increased morbidity and mortality, particularly in advanced stages and require early investigation. Despite their significant impact on the prognosis, they are often overlooked and underdiagnosed.

Aims & Methods

Aim: To provide a general overview regarding the nutritional status and dietary intake in patients with LC and highlight any disparities in nutritional parameters between outpatients and hospitalized LC patients.
Methods: In this prospective observational study, all consecutive LC patients attending the portal hypertension clinic and those admitted to the gastroenterology ward at Policlinico Umberto I from May 2023 to January 2024 underwent nutritional screening. Demographic information, clinical characteristics, SARC-F questionnaire, anthropometric measurements, liver frailty index (LFI) parameters, 24-hour diet recall, and food frequency questionnaire were included in the screening. Data was analyzed using Student’s t-test and chi-square test by Jamovi software version 2.3.28.

Results

Altogether 126 patients [male- 72.2%; age 63.7±10.7 years; etiology: Alcohol-53%, MASLD-19%, Viral-20%, Others-8%; MELD- 11.8±4.4; MELD Na- 13.6±5.5; 50% Child A] were enrolled. 36% of the patients were sarcopenic according to SARC-F questionnaire (score ≥ 4), with a mean LFI of 4.6±0.9. Although 65% of the patients consumed at least one protein source daily, only 15% achieved recommended daily protein intake, and 78% had lower energy intake than recommended. Of these 126 patients, 68.3% were outpatient and 31.7% were hospitalized, with comparable age and gender distribution. Hospitalized patients had a lower BMI (kg/m²) [24.7±4.1 vs 27.8±6.9; p=0.01], higher prevalence of frailty [5.1±1.1 vs 4.3±0.7; p=<0.001], lower TSF (mm) [12.4±6.8 vs 16.2±8.1; p=0.04], and lower MUAC (cm) [29.6±5.1 vs 32.2±5.6; p=0.02] than outpatients. Further, none of the hospitalized patients met adequate protein intake, contrasting with 22% of outpatients (p=0.01).

Table 1: Comparison between outpatient and hospitalized patients

Conclusion

​The impairment of nutritional status tend to increase in the more advanced stages of liver disease. There is a need for timely and routine assessment of nutritional status and implementation of targeted lifestyle interventions to optimize patient outcomes.