Pre-emptive TIPS in high-risk acute variceal bleeding. An updated and revised individual patient data meta-analysis.

BACKGROUND AND AIMS: A previous individual patient data meta-analysis (IPD-MA) showed that compared with drugs+endoscopy, the placement of transjugular portosystemic shunt within 72 hours of admission (pre-emptive transjugular intrahepatic portosystemic shunt: p-TIPS) increases the survival of high-risk patients (Child-Pugh B+ active bleeding and Child-Pugh C<14 points) with cirrhosis and acute variceal bleeding. However, the previous IPD-MA was not a two-stage meta-analysis, did not consider the potential risk of selection bias of observational studies, and did not include the most recent randomized clinical trial. We performed an updated and revised IPD-MA to reassess the efficacy of p-TIPS, addressing all previous issues. APPROACH AND RESULTS: We included all studies from the previous IPD-MA and searched for other possible eligible publications until September 2022. We performed a two-stage IPD-MA of data from 8 studies (4 randomized clinical trials and 4 observational). In addition, we performed a sensitivity analysis excluding those patients dying up to the first 72 hours after admission in the Drugs+Endoscopy arms of the 4 observational studies. The primary end point was the effects of p-TIPS versus Drugs+Endoscopy on 1-year survival.We identified 1389 patients (342 p-TIPS and 1047 Drugs+Endoscopy). The two-stage IPD-MA showed that p-TIPS significantly reduced the mortality in the overall population (HR=0·43, 95% CI: 0.32-0.60, p <0.001. This effect was observed in both subgroups of patients with Child-Pugh. The sensitivity analysis confirmed the survival benefit of p-TIPS. CONCLUSIONS: The updated two-stage IPD-MA confirms the significant survival advantage of p-TIPS in high-risk patients with cirrhosis and acute variceal bleeding. As a result, we recommend p-TIPS as the preferred first-choice treatment for these patients.

Enhanced diagnosis and prognosis of severe alcoholic hepatitis using novel metabolomic biomarkers.

AIM: Differentiating alcoholic hepatitis (AH) from acute decompensation of alcoholic cirrhosis (DC) is challenging, as the presentation and biochemistry are similar. We aimed to identify potential metabolomic biomarkers to differentiate between AH and DC, and to predict short-term mortality. METHODS: We included consecutive biopsy proven AH and DC patients, which were managed according to current guidelines and followed up until the end of the study. Untargeted metabolomics was assessed in all patients at baseline. Specific analyses were successively performed to identify potential biomarkers, which were further semi-quantitatively analysed against relevant clinical endpoints. RESULTS: Thirty-four patients with AH and 37 with DC were included. UHPLC-MS analysis identified 83 molecules potentially differentiating between AH and DC. C16-Sphinganine-1P (S1P) was the most increased, whereas Prostaglandin E2 (PGE2) was the most decreased. The PGE2/S1P ratio < 1.03 excellently discriminates between AH and DC: AUC 0.965 (p < 0.001), Se 90%, Sp 100%, PPV 0.91, NPV 1, and diagnostic accuracy 95%. This ratio is not influenced by the presence of infection (AUC 0.967 vs. 0.962), correlates with the Lille score at 7 days (r = -0.60; P = 0.022) and tends to be lower in corticosteroid non-responders as compared with patients who responded [0.85(±0.02) vs. 0.89(±0.05), P = 0.069]. Additionally, decreased ursodeoxycholic acid levels are correlated with MELD and Maddrey scores and predict mortality with a 77.27% accuracy (NPV = 100%). CONCLUSION: This study suggests the PGE2 (decreased)/S1P (increased) ratio as a biomarker to differentiate AH from DC. The study also finds that low levels of ursodeoxycholic acid could predict increased mortality in AH.

Liver Transplantation for Porto-sinusoidal Vascular Liver Disorder: Long-term Outcome.

BACKGROUND: Porto-sinusoidal vascular liver disorder (PSVD) is a rare disease that occasionally requires liver transplantation (LT), despite usually presenting preserved liver function. There remains a paucity of data pertaining to LT in PSVD. The aim was to identify features associated with post-LT outcomes in PSVD. METHODS: Retrospective multicentre study of 79 patients who received LT for PSVD. RESULTS: Median post-LT follow-up was 37 (range 1-261) mo. Refractory ascites 24 (30%), hepatic encephalopathy 16 (20%), and hepatopulmonary syndrome 13 (16.3%) were the most frequent indications for LT. Hepatocellular carcinoma was the indication in only 2 patients. Twenty-four patients died, 7 due to liver and 17 to non-liver related causes. Post-LT survival was 82.2%, 80.7%, and 68.6% at 1, 2, and 5 y, respectively. Post-LT survival was significantly better in patients without (n = 58) than in those with a persistent severe PSVD-associated condition (n = 21). Pre-LT hyperbilirubinemia levels and creatinine >100 µmol/L were also independently associated with poor survival. Six patients (7.6%) required a second LT. Recurrence of PSVD was confirmed by liver biopsy in only 1 patient and in 3 further patients it was likely. CONCLUSIONS: LT in PSVD is associated with an acceptable outcome in the absence of associated severe conditions. However, persistence of a severe associated condition, pre-LT high bilirubin levels, or creatinine >100 µmol/L impact outcome, and these are features that should be considered when evaluating PSVD patients for LT. PSVD recurrence is possible after LT and needs to be explored, at least, in cases of posttransplant portal hypertension.

Diagnostic challenges in non-cirrhotic portal hypertension - porto sinusoidal vascular disease.

Non-cirrhotic portal hypertension consists of a group of diseases characterized by signs and complications of portal hypertension, which differ from cirrhosis through histological alterations, hemodynamic characterization and, clinical outcome. Because of the similarities in clinical presentation and imaging signs, frequently these patients, and particularly those with porto-sinusoidal vascular disease (PSVD), are misdiagnosed as having liver cirrhosis and thus raising difficulties in their diagnosis. The most challenging differentiation to be considered is between PSVD and cirrhosis and, although not pathognomonic, liver biopsy is still the standard of diagnosis. Although they still require extended validation before being broadly used, new non-invasive methods for the diagnosis of porto-sinusoidal vascular disease, like transient elastography, contrast-enhanced ultrasound or metabolomic profiling, have shown promising results. Another issue is the differentiation between PSVD and chronic extrahepatic portal vein obstruction, especially now when it is known that 40% of patients suffering from PSVD develop portal vein thrombosis. In this particular case, once the portal vein thrombosis occurred, the diagnosis of PSVD is impossible according to the current guidelines. Moreover, so far, the differentiation between PSVD and sinusoidal obstruction syndrome has not been clear so far in particular circumstances. In this review we highlighted the diagnostic challenges regarding the PSVD, as well as the current techniques used in the evaluation of these patients.

Are presepsin and resistin better markers for bacterial infection in patients with decompensated liver cirrhosis?

BACKGROUND: Bacterial infections impair prognosis in patients with cirrhosis. Presepsin and, more recently, resistin are promising markers of infection and sepsis in patients without cirrhosis. AIMS: The aim of our study was to assess the performance of presepsin and resistin as early markers of infection compared with C reactive protein (CRP) and procalcitonin (PCT), and their prognostic relevance in patients with decompensated cirrhosis. METHODS: One hundred and fourteen consecutive patients with decompensated cirrhosis were enrolled and followed-up for 28 days. Diagnostic performances of CRP, PCT, presepsin and resistin were assessed. RESULTS: Fifty-three (46.5%) patients had bacterial infections of which 30 (56%) had sepsis. Presepsin and resistin had similar performance as CRP and PCT for the diagnosis of infection (best cut-off of 1444 pg/ml and 20 ng/ml, respectively) and sepsis. Presepsin (HR = 5.5; 95%CI: 2.36-13.21, p < 0.0001) and the ≥500 pg/ml increase of presepsin at 48 h (HR = 9.24; 95%CI: 3.66-23.27, p < 0.008) were independently associated with 28-day mortality. CONCLUSIONS: Presepsin and resistin have similar diagnostic performances to CRP and PCT for bacterial infection in decompensated cirrhosis. Presepsin and Δ presepsin ≥500 pg/ml have also a prognostic relevance for 28-day mortality.