Introduction

Liver cirrhosis, the end stage of chronic liver diseases, is associated with high morbidity, mortality, and medical costs worldwide(1). The progression of liver cirrhosis from compensated to decompensated cirrhosis, portal hypertension (PHT) with complications is developed(2). Transjugular intrahepatic portosystemic shunt (TIPS) is an effective procedure for treating PHT. Whereas complications of post-TIPS, especially hepatic encephalopathy and stent dysfunction, limit the application of TIPS as a first-line treatment for liver cirrhosis.
Osteoarthritis (OA) and rheumatoid arthritis (RA) are characterized by chronic polyarticular inflammation which may cause irreversible joint damage. The conventional agent of modifying antirheumatic drugs and corticosteroids are associated with hepatotoxicity and are contraindicated in chronic hepatitis (3,4). Treatment of liver cirrhosis combined OA/RA should be carefully considered.
Systemic inflammation is tightly associated with the progression of liver cirrhosis and RA/OA. Selective COX-2 inhibitor is one of the most well-investigated anti-inflammation drugs with antifibrotic effects (5,6,7). However, there are no relevant studies about the anti-inflammatory concept of cirrhotic patients with RA or OA after TIPS.

Aims & Methods

Aim：To assess the effects and safety of anti-inflammatory therapy of selective cyclooxygenase-2 (COX-2) inhibitors in patients with decompensated liver cirrhosis undergone transjugular intrahepatic portosystemic shunt (TIPS) accompanied with rheumatoid arthritis (RA) or osteoarthritis (OA).
Methods：Clinic data from patients with liver cirrhosis underwent TIPS were collected from January 2017 to October 2022 for a retrospective analysis. According to whether receiving selective COX-2 inhibitors orally for arthritis, patients were divided into the TIPS and TIPS+COX-2-I group. Occurrences of clinic adverse events were examined.

Results

Eligible patients in the TIPS (n=95) and TIPS+COX-2-I group (n=51) were analyzed. Clinic events containing variceal rebleeding, hepatic encephalopathy, ascites (>grade 2), hepatocellular carcinoma (HCC) and stent dysfunction in the TIPS+COX-2-I group was less than the TIPS group (5.88% vs. 27.37%, p=0.002). Among those patients in the TIPS+COX-2-I group, 1.96% (1/51) patient experienced esophageal and gastric variceal bleeding (EGVB) again. No patients occurred HE with only 1 patient experienced ascites relapse, and 1 patient finally progressed to HCC. However, in the TIPS group, the rates of clinic adverse events including EGVB, HE, ascites, HCC and stents dysfunction were all higher, which were 10.53%, 4.21%, 4.21%, 2.11%, 6.32% respectively. No concerned side effects related to selective COX-2 inhibitors mainly including cardiovascular events and gastrointestinal hemorrhage occurred during follow-up periods.
Table 1. Clinic advers events between two groups

Conclusion

Anti-inflammatory therapy of selective COX-2 inhibitors for post-TIPS patients with RA or OA, not only can reduce the occurrence of adverse clinic events, but also safe in those patients, which is a completely effective and safe therapy.

References

1. Smith A, Baumgartner K, Bositis C. Cirrhosis: diagnosis and management.Am Fam Physician. 2019; 100:759–770.
2. 2.Ginès P, Krag A, Abraldes JG, Solà E, Fabrellas N, Kamath PS. Liver cirrhosis. Lancet. 2021; 398:1359-1376.
3. Olsson-White DA, Olynyk JK, Ayonrinde OT, Paramalingam S, Keen HI. Assessment of liver fibrosis markers in people with rheumatoid arthritis on methotrexate. Intern Med J. 2022;52(4):566-573.
4. Kim PS, Ho GY, Prete PE, Furst DE. Safety and efficacy of abatacept in eight rheumatoid arthritis patients with chronic hepatitis B. Arthritis Care Res (Hoboken). 2012;64(8):1265-8.
5. Su W, Tai Y, Tang SH, Ye YT, Zhao C, Gao JH, et al. Celecoxib attenuates hepatocyte apoptosis by inhibiting endoplasmic reticulum stress in thioacetamide-induced cirrhotic rats. World J Gastroenterol. 2020; 26:4094-4107.
6. Tai Y, Zhao C, Zhang L, Tang S, Jia X, Tong H, et al. Celecoxib reduces hepatic vascular resistance in portal hypertension by amelioration of endothelial oxidative stress. J Cell Mol Med. 2021 Nov;25(22):10389-10402.
7. Gao JH, Wen SL, Yang WJ, Lu YY, Tong H, Huang ZY, et al. Celecoxib ameliorates portal hypertension of the cirrhotic rats through the dual inhibitory effects on the intrahepatic fibrosis and angiogenesis. PLoS One. 2013; 8: e69309.
   

Disclosure

There is no conflict of interest.

Introduction

Alcoholic liver cirrhosis (ALC) is a complex condition marked by numerous complications, often leading to a poor prognosis and high mortality rates^​. This study evaluates the clinical characteristics, causes of hospitalization, and factors associated with prolonged hospital stay and in-hospital mortality among patients with alcoholic liver cirrhosis.

Aims & Methods

A retrospective study was conducted on 357 patients diagnosed with alcoholic liver cirrhosis in a tertiary gastroenterology department. The mean age was 57.8 ± 9.8 years, and 85% were male. Data on causes of hospital admission, length of stay, and clinical complications were analyzed. Associations with prolonged hospitalization (defined as >3 days) and in-hospital mortality were assessed using univariate and multivariate statistical analyses.

Results

The overall in-hospital mortality rate was 21.5%. The most common causes of admission included urinary tract infections (57.7%), hepato-renal syndrome (28.2%), digestive hemorrhage (22.6%), acute alcoholic hepatitis (19.3%), spontaneous bacterial peritonitis (8.4%), and pulmonary infections (5.6%). The median hospital stay was 6.6 days.
Variables significantly associated with prolonged hospitalization in univariate analysis included ascites (p<0.0001), spontaneous bacterial peritonitis (p=0.01), hepatic encephalopathy (p<0.0001), urinary tract infections (p<0.0001), and hepato-renal syndrome (p=0.09). In multivariate analysis, only urinary tract infection was independently associated with prolonged hospital stay.
Regarding in-hospital mortality, significant associations in univariate analysis were found with spontaneous bacterial peritonitis (p<0.0001), acute alcoholic hepatitis (p<0.0001), digestive hemorrhage (p<0.0001), and hepato-renal syndrome (p<0.0001). In multivariate analysis, only hepato-renal syndrome remained independently associated with mortality (p<0.0001).

Conclusion

Urinary tract infection is an independent predictor of prolonged hospitalization in patients with alcoholic liver cirrhosis, while hepato-renal syndrome is the only independent predictor of in-hospital mortality. These findings highlight the importance of early recognition and management of infections and renal complications in this high-risk population.

Introduction

Transjugular intrahepatic portosystemic shunt (TIPS) is now an effective and standard procedure to prevent variceal bleeding and recurrent ascites in decompensated cirrhosis (1). Moreover, there is increasing evidence (2, 3) showing that TIPS is feasible in patients with partial or occlusive portal vein thrombosis (PVT). However, thrombosis may develop at intrahepatic branches of the portal vein after TIPS, even in patients without PVT before the procedure. Our retrospective study showed that warfarin could prevent portal branch PVT and might improve liver function among cirrhosis patients receiving TIPS (4). Thus, to obtain clinical evidence with higher quality, a prospective study on post-TIPS de novo PVT regarding the incidence, risk factors, and impact on liver function is necessary.

Aims & Methods

Aim: We aimed to assess the incidence and risk factors for thrombosis developed at branches of the portal vein after TIPS in cirrhosis patients without preexisting PVT. In addition, we aimed to evaluate the influence of post-TIPS PVT on liver function and cirrhosis-related events.
Methods: A total of 70 decompensated cirrhosis patients who received TIPS without PVT were included. Routine laboratory and radiological examinations and assessment of cirrhosis-related complications proceed at 1, 3, 6 and 12 months after TIPS. For the primary outcome, the presence of post-TIPS PVT was assessed by doppler ultrasound showing that the blood flow signal partially or completely disappeared or by contrast-enhanced computed tomography showing filling defects or occlusion in the portal vein branches. For the liver function and complications comparison within 1 year after TIPS (secondary outcome), a 1:1 match using propensity score matching (PSM) based on age, sex and preoperative Child‒Pugh score was conducted between patients with and without post-TIPS PVT.

Results

Among 70 patients, 34 (48.6%) were Child‒Pugh class A, and the median Child‒Pugh score was 7 (5-8). The most common indication for TIPS was variceal bleeding (76.8%), followed by refractory ascites (21.4%). During the follow-up, 25 (35.7%) patients developed post-TIPS PVT, with incidences of 8.0%, 16.0% and 26.8% at 1, 2 and 3 months after TIPS, respectively. Univariate analysis showed that lower serum albumin (p = 0.023), Child‒Pugh B/C class (p = 0.029) and stenting at the left branch of the portal vein (p = 0.020) were significantly associated with post-TIPS PVT. Multivariate analysis showed that lower serum albumin (OR 0.87, p = 0.022) and stenting at the left branch of the portal vein (OR 6.56, p = 0.020) were independent risk factors. Twenty four of 25 patients with post-TIPS PVT were matched with 24 of 45 patients without post-TIPS PVT. Preoperative clinical characteristics of the matched patients were compared, and no significant differences were shown between the two groups. However, the Child‒Pugh score was significantly higher in the PVT group at 1 year after TIPS compared with non-PVT group [7 (6-8) vs 8 (7-9), p = 0.044]. In addition, the incidence of overt hepatic encephalopathy (50.0% vs 20.8%, p = 0.035) and the presence of ascites (54.2% vs 25.0%, p = 0.039) at 1 year after TIPS were significantly higher in the PVT group.

Conclusion

PVT may develop at intrahepatic branches of the portal vein early in the post-TIPS period in cirrhosis, leading to further liver damage and cirrhosis-related complications. Lower serum albumin levels and stenting at the left branch of the portal vein were independent risk factors for de novo PVT within 1 year after TIPS.

References

1.de Franchis R, Bosch J, Garcia-Tsao G, Reiberger T, Ripoll C; Baveno VII Faculty. Baveno VII - Renewing consensus in portal hypertension. J Hepatol. 2022 Apr;76(4):959-974.
2.Lv Y, Bai W, Li K, Wang Z, Guo W, Luo B, Wang J, Wang Q, Wang E, Xia D, Li X, Yuan J, Han N, Niu J, Yin Z, Fan D, Han G. Anticoagulation and Transjugular Intrahepatic Portosystemic Shunt for the Management of Portal Vein Thrombosis in Cirrhosis: A Prospective Observational Study. Am J Gastroenterol. 2021 Jul 1;116(7):1447-1464.
3.Guo DF, Fan LW, Le Q, Huang CB. Transjugular intrahepatic portosystemic shunt for the prevention of rebleeding in patients with cirrhosis and portal vein thrombosis: Systematic review and meta-analysis. Front Pharmacol. 2022 Aug 16;13:968988.
4.Zhang L, Huan H, Tong H, Wei B, Wang Z, Liu C, Wu H. Warfarin prevented de novo portal vein thrombosis after transjugular intrahepatic portosystemic shunt: A retrospective study. Medicine (Baltimore). 2020 Jan;99(2):e18737.

Introduction

Transjugular intrahepatic portosystemic shunt (TIPS) reduces the portal vein blood flow into the liver while declining portal venous pressure, resulting in liver ischemia injury and even liver failure.

Aims & Methods

This study aimed to verify the impact of the post-TIPS early liver injury on survival through large sample retrospective analysis and explore the risk factors of post-TIPS liver injury. The data of patients undergoing TIPS in West China Hospital from November 2009 to March 2021 were collected. We analysed the predictive ability of end-stage liver disease model score (MELD) on the 90-day, 1-year and 3-year survival rates after TIPS and screened out the independent predictive factors of post-TIPS liver injury by regression analysis.

Results

A total of 1108 patients were included. The post-TIPS MELD score was superior to other scoring systems, with a better predictive effect on the 90-day survival rate and 1-year survival rate. The 90-day survival rate (98.3% vs. 87.2%, HR 15.9, 95% CI 7.9-31.9, P < 0.001), 1-year survival rate (95.1% vs. 79.2%, HR 8.3, 95% CI 5.0-13.7, P < 0.001) and 3-year survival rate (86.5% vs. 68.8%, HR 4.0, 95% CI 2.8-5.7, P < 0.001) were significantly higher in patients with a post-MELD score less than 15. Preoperative total bilirubin, serum creatinine, INR and change of portosystemic pressure gradient were independent predictors of early liver injury after TIPS.

Conclusion

Baseline liver function and pressure reduction contribute to the occurrence of early liver injury after TIPS. Post-TIPS MELD score can accurately predict short-term and long-term survival.

Introduction

Patients with liver cirrhosis, particularly those with decompensated cirrhosis, are at significant risk of morbidity from viral and bacterial infections, which can also affect the progression of liver disease. Therefore, international guidelines recommend full vaccination coverage of these patients against a range of pathogens, irrespective of age.

Aims & Methods

The aim of our study was to evaluate vaccination coverage in a group of inpatients with cirrhosis. We retrospectively analysed patients with liver cirrhosis who were admitted after presenting to the emergency department and were hospitalised between 2019 and 2022 in the First Propaedeutic Department of Internal Medicine of Aristotle University of Thessaloniki. The patients were evaluated with regard to their vaccination status and the presence of antibodies against hepatitis A and hepatitis B. Active vaccination against influenza was defined as vaccination during the latest vaccination period. Only the vaccinations administered prior to hospitalisation were included, and not those that were recommended afterwards. Patients who were diagnosed with cirrhosis during hospitalisation were excluded from the study.

Results

182 patients were recorded, with a mean age of 65.4 ± 13.1. The patients were predominantly male (67%). Alcohol-related liver disease (47.8%), metabolic-associated steatohepatitis (18.1%) and chronic hepatitis B (11%) were the most common causes of cirrhosis. The majority of patients were classified as Child-Pugh stage B (51.6%), followed by stage C (31.9%) and A (16.5%). Most patients (79.7%) had decompensated cirrhosis. Regarding exposure to hepatitis B, 86 out of 157 patients (54.8%) required vaccination, of whom 25.6% (22/86) were already vaccinated. Concerning hepatitis A, 89 of the 108 (83.5%) patients who were checked tested positive for antibodies without being vaccinated, while only two of the remaining 19 (10.5%) had been vaccinated. As for influenza vaccination, 41.2% received the vaccine during the last vaccination season. Additionally, 21.4% of the patients had undergone vaccination against pneumococcus. The only correlation observed about vaccination coverage was the increased rates of pneumococcal vaccination in patients of Child-Pugh B cirrhosis compared to patients with Child-Pugh A or C (p=0.042).

Conclusion

Our study underlines the low vaccination coverage of patients with cirrhosis. Thus, the need to intensify vaccination efforts is highlighted, as infectious complications could be critical for patients with cirrhosis, not only due to their immediate morbidity but also because of their potential impact on the progression of liver disease.

Introduction

Proton Pump Inhibitors (PPIs) are commonly prescribed for gastrointestinal disorders. Several studies have reported an overprescription of PPIs in patients with liver cirrhosis^1,2, yet their use in these patients increases the risk of spontaneous bacterial peritonitis and mortality rates. HAS-BLED score is a tool used to evaluate bleeding risk in individuals on chronic anticoagulation therapy, and cardiologists use it to prescribe PPIs in patients on anticoagulants, to reduce the risk of gastrointestinal bleeding³.

Aims & Methods

This study aimed to assess the appropriateness of PPI prescriptions in patients with liver cirrhosis and anticoagulant treatment. A secondary objective was to investigate whether the guidelines for administering PPIs based on a patient's HAS-BLED score align with the indications for PPI prescription recommended in established gastroenterological guidelines.
This study was retrospective. From January 2022 to December 2023, we included consecutive cirrhotic patients who had anticoagulant treatment for various indications (atrial fibrillation, deep vein thrombosis, pulmonary embolism). All patients were counted only once, even if hospitalized multiple times. To establish the validity of PPI prescription, we used the current guidelines^4–7. Anticoagulant treatment alone, is not a valid indication for PPI prescription in patients with liver cirrhosis, in the absence of concomitant antiplatelet treatment⁴. HAS-BLED scores were calculated⁸, and patients with a score ≥ 4 were considered at high risk for bleeding. We looked for an association between high HAS-BLED score and PPI prescription, and whether these prescriptions were aligned with the current gastroenterological guidelines.

Results

We found 577 hospitalizations for cirrhosis, among these, 61 patients (mean age 71.3 years old ± 8,88, 46 males) were under chronic anticoagulant treatment. We identified 32 patients on PPIs during the hospital stay. Fourteen (43.7%) had no valid indication, but 5 had a high HAS-BLED score. The remaining patients (n=18) were prescribed PPIs for the following reasons: gastritis (n=10), antiplatelet with high risks (n=3), NSAID and corticosteroid (n=2), peptic ulcer disease (n=2), gastroesophageal reflux disease (n=1). In our cohort, 27 (44.3%) patients had a high HAS-BLED score. Among these patients, 18 were on PPI. In the patients with low HAS-BLED (n=34), 14 were on PPIs, and 9 of them didn’t have a valid indication based on current gastroenterological guidelines. We computed the Chi2 statistic to assess the association between PPI prescription and a high HAS-BLED score: the chi-square statistic yielded 3.921 (p=0.048). A similar association was observed at discharge: the chi-square statistic was 3.994 (p=0.046). No association was observed between HAS-BLED score and inappropriate PPI prescription (Chi2 = 0.147, p = 0.7).

Conclusion

In our cohort of patients with liver cirrhosis, over 50% were prescribed PPIs during their hospital stay, with 43.7% lacking a valid indication. An association was observed between the HAS-BLED score and the prescription of PPIs; however, only a portion of the non-valid indications can be attributed to the high HAS-BLED score.

References

1. Gamelas Vet al. Prescription Pattern of Proton Pump Inhibitors at Hospital Admission and Discharge. GE Port J Gastroenterol. 2019;26(2):114-120. doi:10.1159/000488506
2. Ct C, et al. Inappropriate use of proton pump inhibitors in a local setting. Singapore Med J. 2014;55(7). doi:10.11622/smedj.2014087
3. Pisters R, et al. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest. 2010;138(5):1093-1100. doi:10.1378/chest.10-0134
4. Scarpignato C et al. Italian Society of Pharmacology, and the Italian Association of Hospital Gastroenterologists. Effective and safe proton pump inhibitor therapy in acid-related diseases - A position paper addressing benefits and potential harms of acid suppression. BMC Med. 2016;14(1):179. doi:10.1186/s12916-016-0718-z
5. http://www.ncbi.nlm.nih.gov/books/NBK552570/
6. Lanza FL, et al, Practice Parameters Committee of the American College of Gastroenterology. Guidelines for prevention of NSAID-related ulcer complications. Am J Gastroenterol. 2009;104(3):728-738. doi:10.1038/ajg.2009.115
7. Freedberg et al. The Risks and Benefits of Long-term Use of Proton Pump Inhibitors: Expert Review and Best Practice Advice From the American Gastroenterological Association. Gastroenterology. 2017;152(4):706-715. doi:10.1053/j.gastro.2017.01.031
8. Gallego P et al. Relation of the HAS-BLED bleeding risk score to major bleeding, cardiovascular events, and mortality in anticoagulated patients with atrial fibrillation. Circ Arrhythm Electrophysiol. 2012;5(2):312-318. doi:10.1161/CIRCEP.111.967000