Introduction

Acute variceal hemorrhage (AVH) is a dreaded complication of liver cirrhosis and continues to be associated with high mortality despite significant medical knowledge and advances in recent years. In addition, the severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) pandemic has led to a temporary reduction in the diagnosis, surveillance and treatment of chronic liver diseases and their complications due to the necessary protective measures.

Aims & Methods

This study aimed to analyze the impact of the SARS-COV-2 pandemic on the course of disease in patients with AVH. In this retrospective multi-center study of patients with AVH due to cirrhosis disease courses during to two different time periods (01.03.2016-28.02.2020, and 01.03.2020-28.02.2022, termed COVID period) were compared regarding patients baseline characteristics, management, post-bleeding infections, rebleeding and mortality.

Results

For the COVID and pre-COVID period 96 and 151 patients were analyzed, respectively. During the COVID period the amount of alcohol-associated liver disease or active alcohol consumption did not differ between cohorts (58.2% vs. 47.9%; p=0.147 and 44.2% vs 39.1%; p= 0.496). There was a trend towards a higher median Model for End-Stage Liver Disease (MELD) (16 vs. 19; p=0.06) while the Child-Pugh Score was comparable (10 vs. 10; p=0.304). Intubation rates during endoscopy (16.1% vs. 16.0%; p= 1.000) as well as active bleeding rates (59.6% vs. 50.0%; p=0.150) did not differ but transjugular intrahepatic portosystemic shunt placement (11.3% vs. 23.2%; p=0.019) was performed more frequently during the pandemic. Additionally, during the pandemic there was a trend to a higher incidence of post-bleeding infections in patients without present infection at the time of AVH, who received antibiotic prophylaxis (21.6% vs. 35.4%; p=0.068). A Coronavirus-infection was present in only one patient. The 6-week recurrent bleeding and mortality rates did not differ between groups (22.3% vs. 22.8%; p=1.000 and 30.1% vs. 32.2%; p=0.767).

Conclusion

Despite an observed trend to a higher incidence of post-bleeding infections and a lower MELD score mortality in patients with AVH was not increased during the SARS-COV-2 pandemic.

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with a variety of complications, including liver damage. However, its impact on chronic liver disease (CLD) and its association with cholestasis remains unclear. This retrospective cohort study aimed to investigate the incidence of cholestasis and its impact in patients with CLD after SARS-CoV-2 infection.

Aims & Methods

We retrospectively analyzed medical records of 428 patients followed in a tertiary center Liver Unit who were diagnosed with SARS-CoV-2 infection between March 2020 and September 2022. Patients were stratified as having no CLD, non-advanced CLD (NACLD) or advanced CLD (ACLD). Liver chemistries before and several times after SARS-CoV-2 infection were registered. The incidence of cholestasis and its associated risk factors were analyzed using multivariate logistic regression.

Results

A total of 428 patients were included, 357 (66.1% males) with CLD (NACLD in 198 and ACLD in 159 patients). Alcohol-associated liver disease (ALD) was the main etiology (30.8%), closely followed by metabolic-associated fatty liver disease (MAFLD) (24.6%). SARS-CoV-2 infection-related cholestasis was higher in patients with ACLD than in patients with NACLD (39.6% vs. 5.6%, p<0.001). No patient without CLD developed cholestasis. The incidence of decompensation episodes, such as ascites, hepatic encephalopathy and variceal bleeding was significantly higher in patients with cholestasis (32.4%, 32.4% and 17.6% vs. 0.3%, 0.3% and 0%, respectively; p<0.001). Additionally, patients with cholestasis had a longer hospital stay (median/IQR 17/12 vs. 10.5/9 days, p=0.483) and a significantly higher mortality rate (23.0% vs. 0.6%, p<0.001) than those without cholestasis. Patients with ACLD (vs. NACLD) presented higher global mortality (10.7% vs. 0%, p<0.001) and liver-related mortality (10.1% vs. 0%, p<0.001). Multivariate logistic regression analysis showed that ACLD and decompensated disease were independent risk factors for cholestasis in patients with SARS-CoV-2 infection (p=0.031 and p<0.001, respectively).

Conclusion

Our study suggests that SARS-CoV-2 infection is a risk factor for cholestasis in patients with CLD, especially in those with ACLD or decompensated disease. Clinicians should be aware of the potential for cholestasis in these patients with underlying liver disease and closely monitor liver function tests. Further studies are needed to investigate the underlying mechanisms of SARS-CoV-2-induced cholestasis and develop appropriate management strategies for these patients.

Introduction

Patients with chronic liver disease (CLD), particularly those with cirrhosis, exhibit increased risk of developing severe illness when infected with SARS-CoV-2, primarily due to their underlying immune dysfunction and coexisting conditions. As such, vaccination plays a crucial role in safeguarding this population. Here, to fully assess the efficacy COVID-19 vaccination in patients with CLD, we thoroughly characterized the overall and SARS-CoV-2-specific cellular immune response of these patients.

Aims & Methods

Blood samples were systematically collected from patients with CLD (n=22) and healthy volunteers (n=12) at various intervals spanning one year after the initial administration of the BNT162b2 vaccine. Peripheral blood mononuclear cells (PBMCs) were isolated and stained with a panel of 22 surface markers and a viability dye, allowing for the detection of 28 immune cell subsets. In parallel, we analysed the presence of cells specific against SARS-CoV-2 peptide tetramers. Samples were analysed by flow cytometry with acquisition on a four-laser Cytek Aurora® spectral analyzer.

Results

Prior to vaccination, patients with CLD patients were already displaying fewer T cells and an increased number of B cells, comparing to healthy subjects. Within the T cell subsets, differences were significant for CD4+ T cells and the Naïve and Central Memory CD4+ subsets. At both 6-months and 1- year after vaccination, variances between groups were no longer observed. Rather, at 1-year postvaccination, T, CD8+ and CD4+ cells, as well as monocytes were found increased in both groups, suggesting that the vaccination is critical for inducing a strong cellular immune response. Analysis of SARS-CoV-2 epitope-specific cells demonstrated significantly lower frequencies of monocytes, CD4+ and CD8+ T cells, B cells, NK T cells, and NK cells including the regulatory and cytotoxic subsets recognizing the peptide tetramers in CLD patients, in comparison with healthy controls.

Conclusion

Together, these results indicate that CLD patients are capable of mounting a satisfactory immune cellular response following COVID-19 vaccination. However, the SARS-CoV-2-specific response is significantly weaker in CLD patients comparing with healthy individuals. These results reinforce the need for prioritization and/or booster vaccination for CLD patients. (Supported by 2022.08837.PTDC, FCT).

Introduction

Acute variceal bleeding (AVB) is a medical emergency that requires urgent evaluation. It is a complication of portal hypertension and, despite the improvements in the management of these patients, mortality is still high. According to the best available data, all patients should be risk stratified according to the validated clinical scores MELD and Child-Pugh.

Aims & Methods

To access the predictive capacity of PALBI and CLIF-C AD scores and to compare them with the currently recommended MELD and Child-Pugh scores for the following outcomes: in-hospital mortality, mortality at 6 weeks and rebleeding.
Retrospective review of all cirrhotic patients admitted for AVB between January 2016 and December 2022 in a Gastroenterology department in Portugal. The area under the receiver operating characteristics curve (AUROC) was calculated for all scores and compared with DeLong test.

Results

100 patients included, average age 61.87±14.68years, 77% male. Alcohol was the most frequent aetiology (n=56).
All patients were hemodynamically resuscitated and more than 90% underwent endoscopic evalutation within 12hours from admission. 30% of patients had active bleeding at the time of upper GI endoscopy. 90% of patients had esophageal varices (GOV-1) bleeding treated with endoscopic band ligation. 10% of patients had acute gastric (cardiofundal) variceal (GOV2, IGV1) bleeding treated with cyanoacrylate injection. 5% of patients had persistent bleeding and thus a Sengstaken-Blakemore tube was placed. Rebleeding occurred in 11% of patients.
Median time of admission was 6 days (1-30 days). In-hospital mortality was 28% and mortality at 6 weeks was 19%.
The average scores were MELD: 15.98 ± 6.89 points; Child-Pugh 8.65 ± 2.10 points; PALBI -1.71 ± 0.47 points; CLIF-C AD 58.48 ± 11.42 points.
The AUROC of PALBI for in-hospital mortality (AUROC=0.742) and for mortality at 6 weeks (AUROC=0.616) was similar to the traditional scores MELD (AUROC=0.747 and AUROC=0.698) and Child-Pugh (AUROC=0.794 and AUROC=0.673). PALBI was also a good predictor for rebleeding (AUROC=0.795), superior to MELD (AUROC=0.726) and inferior to Child-Pugh (AUROC=0.801). Comparison of the AUROCs of the three scores showed no statistically significant differences.
Regarding CLIF-C AD, it was a good predictor for in-hospital mortality (AUROC=0.708) and mortality at 6 weeks (AUROC=0.706), with no statistically significant differences compared to MELD and Child-Pugh scores. The predictive capacity for CLIF-C AD for rebleeding was not satisfactory (AUROC=0.552).

Conclusion

In addition to liver-specific scores, the predictive performance and clinical utility of PALBI and CLIF-AD C scores for identifying patients with AVB at higher risk for in-hospital mortality, mortality at 6 weeks and rebleeding is very good.
PALBI score deserves recognition, not only because of it is very good predictive capacity for all outcomes, but also because it does not take into account variables whose evaluation has some degree of subjectivity, like hepatic encephalopathy and ascites.

Introduction

Upper gastrointestinal bleeding (UGIB) is associated with an unfavorable prognosis in cancer patients. In biliary tract cancers (BTCs), little is known about the occurrence of UGIB and its prognostic relevance for the course of the disease.

Aims & Methods

The aim of this study was to analyze the prevalence of UGIB in BTC patients, compare therapeutic approaches for efficacy, and identify parameters associated with survival and recurrence rates. This retrospective observational study included all patients with BTCs and UGIB, that were treated in our tertiary care hospital between 2010 and 2023.

Results

A total of 1033 patients with BTC were analyzed. 41 (4.0%) of these patients had a total of 60 bleeding events. At the time of the bleeding event, 30.8% of patients displayed symptoms of shock, and 67.5% received red blood cell transfusions. The most common causes of bleeding were tumor infiltration (24.4%), variceal bleeding (19.5%), or ulcer bleeding (14.6%). At the time of presentation, 56.4% of patients had stage IV cancer. Most patients had perihilar (39.0%) or intrahepatic (34.1%) cholangiocarcinoma. At index bleeding, endoscopic treatment was performed in 41,5% of cases, while conservative measures (53,7%) or interventional radiological procedures (4.9%) were used in the remaining cases. In cases of bleeding caused by tumor infiltration, endoscopic hemostasis was usually performed using hemostatic powder (18.8%) or clip application (12.5%). Admission to an intermediate or intensive care unit (odds ratio 6.7; 95% CI 1.5 – 33.9) as well as symptoms of shock at the time of the bleeding event (odds ratio 2.6; 95% CI 0.5 – 15.6) were risk factors of rebleeding within 14 days. In patients with UGIB due to tumor infiltration, bleeding recurred after endoscopic therapy in 33.3% of cases. With conservative therapy, the recurrence rate was 28.6%. Survival of Patients with UGIB due to tumor infiltration was significantly shorter compared with patients having non-tumor-associated UGIB (median survival 0.93 vs. 6.5 months, log-rank test p = 0.018).

Conclusion

UGIB is a rare but serious complication in patients with BTC. Patients with major bleeding episodes should be closely monitored for short-term rebleeding. The occurrence of UGIB due to tumor infiltration is associated with adverse outcomes and significantly shortened survival time.

Introduction

Acute esophageal variceal bleeding (EVB) typically requires initial treatment involving pharmacotherapy and endoscopy, particularly endoscopic variceal ligation (EVL). In cases of rebleeding, transjugular intrahepatic portosystemic shunt (TIPS) is recommended, but in regions with limited TIPS access, repeated endoscopic therapy is common. This study evaluates the outcomes of EVL in managing rebleeding and mortality in resource-constrained settings.

Aims & Methods

Patients experiencing acute EVB and undergoing EVL were followed for up to five years or until death. Treatment involved vasoactive drugs and EVL until variceal eradication was achieved. Primary endpoints included bleeding control effectiveness and the need for a second EVL session to manage rebleeding. Rebleeding and mortality rates at 6 weeks and 5 years were analyzed. Logistic regression analysis identified risk factors associated with rebleeding and mortality.

Results

Among 118 patients with acute EVB undergoing EVL, no treatment failures occurred within five days. Eighty-three percent were successfully controlled with one EVL session, while 17% required at least two sessions for recurrent bleeding. In the rebleeding group, no patients rebled within five days after the first EVL, but 75% rebled within 6 weeks. Second EVL was performed for these patients, with a failure rate of 25%. Recurrent EVBs were ultimately controlled by other endoscopic therapy. There was no significant difference in 6-week mortality between rebleeding (15%) and non-rebleeding (18%) groups (p=0.72). Factors associated with 6-week mortality included age, hepatocellular carcinoma, post-bleeding beta-blocker use, creatinine, bilirubin, albumin, Child-Pugh class, and MELD score (Table). Beta-blocker use was associated with preventing recurrent EVB within six months (OR 0.053, 95% CI: 0.004-0.687, p = 0.025). Over five years, the rebleeding group showed a higher mortality trend (90%) compared to the non-rebleeding group (68.8%), though not statistically significant (p=0.06).

Conclusion

In resource-limited settings, multiple attempts of EVL demonstrate success in controlling rebleeding. Long-term trends indicate higher mortality in rebleeding cases, although not statistically significant.

Disclosure

The authors declare that they have no conflict of interest.