Decompensated liver cirrhosis (dLC) is associated with intestinal dysbiosis, however, underlying reasons and clinical consequences remain largely unexplored. We investigated bacterial and fungal microbiota, their relation with gut barrier integrity, inflammation, and cirrhosis-specific complications in dLC-patients. Competing-risk analyses were performed to investigate clinical outcomes within 90 days. Samples were prospectively collected from 95 dLC-patients between 2017 and 2022. Quantitative metagenomic analyses clustered patients into three groups (G1-G3) showing distinct microbial patterns. G1 (n = 39) displayed lowest diversity and highest Enterococcus abundance, G2 (n = 24) was dominated by Bifidobacteria, G3 (n = 29) was most diverse and clustered most closely with healthy controls (HC). Of note, bacterial concentrations were significantly lower in cirrhosis compared with HC, especially for G1 that also showed the lowest capacity to produce short chain fatty acids and secondary bile acids. Consequently, fungal overgrowth, dominated by Candida spp. (51.63%), was observed in G1. Moreover, G1-patients most frequently received antibiotics (n = 33; 86.8%), had highest plasma-levels of Zonulin (p = 0.044) and a proinflammatory cytokine profile along with numerically higher incidences of subsequent infections (p = 0.09). In conclusion, distinct bacterial clusters were observed at qualitative and quantitative levels and correlated with fungal abundances. Antibiotic treatment significantly contributed to dysbiosis, which translated into intestinal barrier impairment and systemic inflammation.

The presence of non-cirrhotic portal hypertension in pregnancy poses a challenging clinical scenario as it predisposes women to several life-threatening complications such as variceal haemorrhage, splenic artery aneurysm, pulmonary hypertension and bacterial peritonitis. The haemodynamic changes in pregnancy along with the demands of a growing fetus may worsen the severity of pre-existing non-cirrhotic portal hypertension. In this case series, we discuss four cases of non-cirrhotic portal hypertension in pregnancy in a low to middle income setting and review the literature related to this condition.

Portal hypertension resulting from non-cirrhotic extrahepatic portal vein obstruction (EHPVO) in children has been primarily managed with the Meso-Rex bypass, but only a few patients have a viable Rex recessus, required by surgery. This study reports a preliminary series of patients who underwent interventional radiology attempts at portal vein recanalization (PVR), with a focus on technical aspects and safety.

A retrospective review of consecutive patients with severe portal hypertension due to non-cirrhotic EHPVO at a single institution from 2022, who underwent percutaneous attempts at PVR, was performed. Technical and clinical data including fluoroscopy time, radiation exposure, technical and clinical success, complications and follow-up were recorded.

Eleven patients (6 males and 5 females; median age 7 years, range 1-14) underwent 15 percutaneous transhepatic (n = 1), transplenic (n = 11), or simultaneous transhepatic/transplenic (n = 3) procedures. Rex recessus was patent in 4/11 (36%). Fluoroscopy resulted in a high median total dose area product (DAP) of 123 Gycm2 (range 17-788 Gycm2) per procedure. PVR was achieved in 5/11 patients (45%), 3/5 with obliterated Rex recessus. Two adverse events of grade 2 and grade 3 occurred without sequelae. After angioplasty, 4/5 patients required stenting to obtain sustained patency, as demonstrated by colour-Doppler ultrasound in all PVR after a median follow-up of 6 months (range 6-14).

Our preliminary experience suggests that 45% of children with non-cirrhotic EHPVO can restore portal flow even with obliterated Rex recessus. In non-cirrhotic EHPVO, PVR may be an option, if a Meso-Rex bypass is not feasible, although the radiation exposure deserves attention.

Innovative percutaneous procedures may have the potential to be an alternative option to the traditional surgical approach in the management of non-cirrhotic EHPVO and its complications in children not eligible for Meso-Rex bypass surgery.

Non-cirrhotic portal hypertension in children has been traditionally managed by surgery with Meso-Rex bypass creation. Percutaneous PVR may restore the patency of the native portal system even when the Rex recessus is obliterated and surgery has been excluded. Interventional radiological techniques may offer a minimally invasive solution in complex cases of EHPVO in children when Meso-Rex bypass is not feasible.

The superior efficacy of non-selective beta-blockers (NSBB) compared with variceal band ligation (VBL) in the primary prevention of variceal bleeding is uncertain.

To compare carvedilol versus VBL for primary prevention of variceal bleeding.

CALIBRE was an investigator-initiated, multicentre, randomised, controlled, open-label trial. Participants were randomly assigned to 12.5 mg carvedilol once daily or VBL. Inclusion criteria were cirrhosis and medium to large oesophageal varices that had not bled. The primary outcome is any variceal bleeding within 1 year of randomisation. Secondary outcomes include survival, other complications of cirrhosis, quality of life, cost-effectiveness and adverse events. Recruitment closed early, mainly due to the impact of the pandemic.

265 participants (10% of the intended sample size) from 52 sites were randomised to carvedilol (n = 133) or VBL (n = 132) between 22 January 2019 and 31 August 2022. 5/133 participants (3.8%) in the carvedilol arm vs. 10/132 participants (7.6%) in the VBL arm experienced variceal bleeding (risk ratio 0.50 (95% confidence interval [CI]; 0.17-1.41); risk difference - 0.038 (95% CI; -0.094-0.017)). Serious adverse events occurred in one participant in each treatment arm, with no treatment-related deaths. Of the secondary outcomes, there were no statistically significant differences. Carvedilol was cheaper and resulted in slightly more quality-adjusted life years than VBL.

The early terminated and, thus, underpowered CALIBRE trial showed no difference between carvedilol and VBL in the primary prevention of variceal bleeding in patients with cirrhosis and medium-to large-sized oesophageal varices. No untoward safety concerns were noted.

ISRCTN73887615.

The course of BCR::ABL1-negative myeloproliferative neoplasms (MPN) is frequently complicated by thromboembolic events in the splanchnic venous system, resulting in portal hypertension (PH). Therefore, the introduction of spleen stiffness measurement (SSM) might improve the diagnosis of PH. The aim of this study was to evaluate the clinical utility of SSM (performed by using the 100 Hz probe) in non-invasive stratification of PH in these patients.

We performed a retrospective, monocentric, cross-sectional analysis including consecutive patients with BCR::ABL1-negative MPN attending the haematological outpatient clinic at the Medical University of Vienna with available liver stiffness (LSM)/SSM from 10/2023 to 09/2024. LSM/SSM were linked to signs and events of PH.

Fifty-five patients were included (mean age 57.9 ± 14.2 years, 69% females, polycythaemia vera as main entity). One fourth of patients had splanchnic vein thrombi. Nineteen patients (34.5%) had specific and 29 patients (52.7%) had unspecific signs of PH. Twelve patients (21.8%) experienced PH events prior to study inclusion. SSM correlated with disease severity (i.e., JAK2 V617F allele frequency). LSM/SSM adequately stratified patients with vs. without PH. While SSM was strongly linked with splenomegaly, it yielded independent information regarding PH on top of splenomegaly. The implementation of sequential LSM (< 5 & ≥ 15 kPa) and SSM (< 21 & ≥ 50 kPa) for ruling in and out PH reduced the grey zone (24%) with adequate sensitivity/specificity.

While SSM is strongly correlated with splenomegaly and disease severity, it is independently associated with PH in patients with BCR::ABL1-negative MPN. Implementation of LSM/SSM might improve patient management.

Splanchnic vein thrombosis (SVT) can be associated with liver cirrhosis or prothrombotic conditions, including myeloproliferative disorders, intra-abdominal inflammation, solid cancers or surgery. While anticoagulation therapy improves outcomes in noncirrhotic patients and reduces all-cause mortality in cirrhotic populations, its safety in patients with a history of portal hypertension (PH)-related bleeding is less clear. This systematic review examines the impact of anticoagulant therapy on rebleeding risk in SVT patients with a history of PH-related bleeding. A systematic review and meta-analysis were conducted according to PRISMA guidelines. A comprehensive search of PubMed, Web of Science and Scopus was performed for studies published up to September 2024. Studies were included if they compared SVT patients with a history of PH-related bleeding receiving anticoagulant therapy versus those not receiving anticoagulants. The primary outcome was the cumulative incidence of PH-related rebleedings. Of 2853 identified studies, five (186 participants) met the inclusion criteria: two randomised controlled trials (RCTs) and three observational studies. The cumulative incidence of PH-related rebleeding was significantly lower in the anticoagulant group at 17.10% [95% CI 17.02, 17.19] compared to the control group at 40.00% [95% CI 39.90, 40.09]. The overall odds ratio (OR) from observational studies was 0.15 [95% CI 0.04, 0.52], indicating a reduced bleeding risk, while the OR from RCTs was 0.84 [95% CI 0.31, 2.32], showing a nonsignificant trend. Anticoagulant therapy may reduce rebleeding risk in SVT patients with a history of PH-related bleeding, but further high-quality studies are needed.

Patients with cirrhosis develop multiple hemostatic alterations. Although fibrinolysis is also affected by liver disease, studies have produced conflicting results, highlighting the need for a reliable fibrinolysis assay. Assessing the kinetics of plasmin generation (PG) is a new method to study the fibrinolytic state of cirrhosis patients.

This study aimed to compare fibrinolysis between patients with cirrhosis and healthy subjects.

This single-center cohort study included cirrhosis patients from the Padova University Hospital. Fibrinolysis and hemostasis were assessed with PG, thrombin generation (TG), and clot lysis time. To quantify malalignment between TG and PG, ratios were calculated.

In total, 101 patients with cirrhosis (Child-Pugh A/B/C: 36/24/41) and 20 healthy subjects were included. Compared with healthy subjects, patients showed a significantly lower endogenous plasmin potential and plasmin peak. The PG capacity decreased with liver disease severity. The lag time to PG was prolonged in patients. No differences in endogenous thrombin potential and lag time were found when comparing TG profiles. Patients had a shorter clot lysis time. Increased TG/PG ratios for the endogenous plasmin potential and plasmin peak were found in patients compared with that in controls. TG/PG ratios increased with liver disease severity.

Patients with cirrhosis have a complex fibrinolytic profile, with a delayed and decreased capacity to generate plasmin and a more rapid clot lysis. A disbalance was found between coagulation and fibrinolysis, with a normal-to-increased TG capacity and a decreased PG capacity. These results support the theory that cirrhosis patients are in a prothrombotic state.

The transjugular intrahepatic portosystemic shunt procedure remains technically challenging in cases involving occlusion of the portal trunk. This study aimed to evaluate the feasibility, efficacy, and safety of utilizing the inferior vena cava-splenic vein shunt (IVCSS) as a new treatment option in cirrhotic patients with complete portal trunk occlusion and portal cavernoma.

The IVCSS procedure was performed on twelve patients, involving the creation of a shunt using a covered stent between the inferior vena cava and the proximal end of the splenic vein to reduce distal portal pressure.

Technical success was achieved in all patients, with a mean procedure duration of 71.7 ± 44.2 min. The portosystemic gradient was reduced by a mean of 11.0 ± 5.6 mmHg after the procedure. After a median follow-up of 6.7 [2.8-11.4] months, clinical symptoms improved in all patients. Stent dysfunction occurred in 1 patient, the recurrence rates for variceal bleeding and ascites were 8.3% and 16.7%, respectively. One patient (8.3%) experienced a procedure-related complication of retroperitoneal hemorrhage. Three patients (25%) had an episode of hepatic encephalopathy, which improved after conservative treatment.

IVCSS effectively reduced distal portal pressure, which contributed to an improvement of the patients' clinical symptoms with an acceptable procedure-related complication rate. IVCSS may serve as an alternative strategy to manage symptomatic portal hypertension for patients with complete portal trunk occlusion and portal cavernoma.

Question What is an alternative treatment for cirrhotic patients with symptomatic portal hypertension caused by chronic portal vein occlusion other than TIPS? Findings Inferior vena cava-splenic vein shunt (IVCSS) is feasible for reducing distal portal pressure and effectively improving clinical symptoms. Clinical relevance For cirrhotic patients with complete portal trunk occlusion and portal cavernoma, the IVCSS approach seemed to be a promising alternative treatment for symptomatic portal hypertension.

This study aimed to evaluate the feasibility, safety, and efficacy of the transjugular mesenteric-caval shunt (TMCS) as a treatment for the cavernous transformation of the portal vein (CTPV) and recurrent variceal bleeding.

This retrospective case series was conducted with approval from the institutional review board. It involved seven patients diagnosed with CTPV and recurrent variceal bleeding who underwent the TMCS procedure. We analyzed the rate of procedural complications, incidents of rebleeding, stent stenosis, hepatic encephalopathy, and overall survival to assess treatment outcomes.

The TMCS was successfully performed in all seven patients without any life-threatening complications. Postoperatively, one patient developed a lung infection and pleural effusion, which resolved with appropriate treatment. Additionally, two patients experienced an increase in total bilirubin levels, but there was no further deterioration in liver function. The median portal pressure gradient significantly decreased from a preoperative value of 27 mmHg (range 20-36 mmHg) to a postoperative value of 6 mmHg (range 4-11 mmHg). A notable improvement was observed in one cirrhotic patient, with liver function progressing from Child-Pugh class B (score 9) to class A (score 6). Over a median follow-up period of 14 months (range 7-18 months), none of the patients encountered rebleeding, stent stenosis, hepatic encephalopathy, or mortality.

The TMCS appears to be a viable and effective alternative for managing CTPV with recurrent variceal bleeding. Its long-term outcome requires further evaluation.

TMCS provides a promising treatment for patients with life-threatening CTPV complications when occluded portal vein cannot be recanalized and portal vein recanalization TIPS is not an option.

Performing TIPS in patients with portal vein cavernoma is complex due to the requirement for recanalization of the occluded portal vein. Creating a mesenteric-caval shunt through a transjugular approach is a feasible technique. Establishing a TMCS provides a means to manage life-threatening complications arising from portal vein cavernoma.

Acute hemorrhage can be a life-threatening emergency that is complex in its management and affects many patient populations. The past 15 years has seen the introduction of comprehensive massive hemorrhage protocols, wider use of viscoelastic testing, new coagulation factor products, and the publication of robust randomized controlled trials in diverse bleeding patient populations. Although gaps continue to exist in the evidence base for several aspects of patient care, there is now sufficient evidence to allow for an individualized hemostatic response based on the type of bleeding and specific hemostatic defects. We present 3 clinical cases that highlight some of the challenges in acute hemorrhage management, focusing on the importance of interprofessional communication, rapid provision of hemostatic resuscitation, repeated measures of coagulation, immediate administration of tranexamic acid, and prioritization of surgical or radiologic control of hemorrhage. This article provides a framework for the clear and collaborative conversation between the bedside clinical team and the consulting hematologist to achieve prompt and targeted hemostatic resuscitation. In addition to providing consultations on the hemostatic management of individual patients, the hematology service must be involved in setting hospital policies for the prevention and management of patients with major hemorrhage.

Acute superior mesenteric vein thrombosis (ASMVT) is a rare but life-threatening condition associated with high morbidity and mortality. While anticoagulation remains the standard treatment, endovascular therapies such as thrombolysis, thrombectomy, and angioplasty are increasingly utilized in selected cases. However, evidence on their outcomes remains limited. This study retrospectively reports the clinical outcomes of ASMVT patients treated with endovascular combination therapies.

Between August 2019 and May 2024, 12 patients (males = 9; mean age, 52.33 ± 12.51 years) were diagnosed with ASMVT. The study collected comprehensive data on demographic details, presenting symptoms, etiology, treatment modalities, response to treatment, and follow-up outcomes. Computed Tomography (CT) was available from diagnosis, and an average of 6.3 CT scans with a median follow-up of 3 months (IQR: 2-20 months).

The average time from symptom onset to angiographic treatment initiation was 8.0 ± 4.71 days, preceded by anticoagulation with heparin from the time of diagnosis. Patients were treated with combination therapy involving endovascular thrombolysis, rheolytic thrombectomy, and balloon angioplasty via transjugular (n = 9, 75%) or percutaneous (n = 3, 25%) approaches. Thrombolysis was performed with an average recombinant tissue plasminogen activator (rt-PA) infusion duration of 2.75 ± 1.14 days and a total dose of 61.25 ± 18.48 mg rt-PA. Superior mesenteric vein (SMV) flow was initially restored almost completely in 58.3% and partially in 41.7% of patients. Complications observed were hepatic artery bleeding (n = 2, 16.7%), hepatic arteriovenous fistula (n = 1, 8.3%), hepatic parenchymal bleeding (n = 1, 8.3%), melena (n = 1, 8.3%), and nostril bleeding (n = 1, 8.3%). Two patients experienced worsening symptoms of post-intervention, leading to bowel resection revealing intestinal necrosis. SMV patency was almost complete in 25%, and partially in 25% of patients at follow-up.

Endovascular combination therapy with long-term thrombolysis and thrombectomy in patients with ASMVT demonstrated promising technical outcomes. In view of complications, individual indication for intervention needs to be confirmed in a multidisciplinary team.

Portal vein thrombosis (PVT) has been increasingly diagnosed in pediatric patients owing to the widespread use of non-invasive radiological techniques. Although the prevalence of PVT in adults with cirrhosis and intrahepatic non-cirrhotic portal hypertension ranges from 0.6 to 26 % and 13 to 46 %, respectively, no available data exist in the pediatric population. The prevalence of PVT in children with cirrhotic and intrahepatic non-cirrhotic portal hypertension was evaluated in this study.

This retrospective study included children with cirrhosis and intrahepatic non-cirrhotic portal hypertension, which consisted of congenital hepatic fibrosis (CHF) and idiopathic noncirrhotic portal hypertension (INCPH). Patients with extrahepatic portal venous obstruction were excluded from the study. The presence of PVT was evaluated using abdominal Doppler ultrasonography and/or CT. Etiological, clinical, and laboratory findings were compared between the groups.

One hundred and forty-two patients with cirrhosis (mean admission age: 64.6 months ± 66.4, mean follow-up duration: 46.8 months ± 45.6) and 41 patients with non-cirrhotic patients (CHF=16, INCPH = 25, mean admission age: 126 months ± 64.2) were enrolled in this study. The prevalence of PVT was not significantly different between cirrhotic (8.5 %) and non-cirrhotic (9.7 %) patients. The incidence of PVT was significantly higher in patients with biliary atresia than in those with other etiologies in the cirrhotic group (p = 0.022). The frequency of PVT was higher in patients who had Child-Pugh score ≥7 in the cirrhotic group, but the difference was not statistically significant (p = 0066). The PVT group required more liver transplantations than the non-PVT group (p = 0.038).

The prevalence of PVT was similar in pediatric patients with cirrhosis and intrahepatic non-cirrhotic portal hypertension in our cohort, which is compatible with adult studies. Biliary atresia is found to be an important risk factor for PVT in our pediatric population. It might be associated with rapid progression of the disease, ascending cholangitis, and embryological abnormalities. These patients should be routinely evaluated to identify portal vein complications and early warning signs during follow-up.

Portal vein (PV) thrombosis may represent a relative contraindication to liver transplantation (LT). Transjugular intrahepatic portosystemic shunt (TIPS) used in portal hypertension complications, may allow portal vein recanalization (PVR).

We reported PVR-TIPS in patients who were candidates for LT for clinical conditions but deemed contraindicated because of PV anatomy. We included consecutive patients undergoing PVR-TIPS at our center from February 2014 to May 2024.

We identified 25 patients (19 males [76 %], mean age 56 years [IQR 51-62]) in which PVR-TIPS was offered because foreseen high complex PV anastomosis. Twelve (48 %) patients showed main PV thrombosis, 8 (32 %) had cavernoma and 5 (20 %) had PV with very small diameter. PVR-TIPS was successfully achieved in all but one patient. All patients were listed after PVR-TIPS, with a listing MELD-Na score higher than pre-PVR-TIPS values (19 [IQR 15-23] vs. 16 [IQR 13-18], p < 0.018). Overall, 3 patients (13 %) were delisted for clinical improvement, 2 (8 %) died on the waiting-list and 16 (66 %) underwent LT. LT was technically feasible in all patients, without immediate major vascular complication.

PVR-TIPS may be a strategy to enable LT in patients otherwise excluded due to PV anatomy. This needs high technical expertise and often at the expense of a worsening in liver function.

In phase 2 trials involving patients with stage 2 or 3 fibrosis caused by metabolic dysfunction-associated steatohepatitis (MASH), efruxifermin, a bivalent fibroblast growth factor 21 (FGF21) analogue, reduced fibrosis and resolved MASH. Data are needed on the efficacy and safety of efruxifermin in patients with compensated cirrhosis (stage 4 fibrosis) caused by MASH.

In this phase 2b, randomized, placebo-controlled, double-blind trial, we assigned patients with MASH who had biopsy-confirmed compensated cirrhosis (stage 4 fibrosis) to receive subcutaneous efruxifermin (at a dose of 28 mg or 50 mg once daily) or placebo. The primary outcome was a reduction of at least one stage of fibrosis without worsening of MASH at week 36. Secondary outcomes included the same criterion at week 96.

A total of 181 patients underwent randomization and received at least one dose of efruxifermin or placebo. Of these patients, liver biopsy was performed in 154 patients at 36 weeks and in 134 patients at 96 weeks. At 36 weeks, a reduction in fibrosis without worsening of MASH occurred in 8 of 61 patients (13%) in the placebo group, in 10 of 57 patients (18%) in the 28-mg efruxifermin group (difference from placebo after adjustment for stratification factors, 3 percentage points; 95% confidence interval [CI], -11 to 17; P = 0.62), and in 12 of 63 patients (19%) in the 50-mg efruxifermin group (difference from placebo, 4 percentage points; 95% CI, -10 to 18; P = 0.52). At week 96, a reduction in fibrosis without worsening of MASH occurred in 7 of 61 patients (11%) in the placebo group, in 12 of 57 patients (21%) in the 28-mg efruxifermin group (difference from placebo, 10 percentage points; 95% CI, -4 to 24), and in 18 of 63 patients (29%) in the 50-mg efruxifermin group (difference from placebo, 16 percentage points; 95% CI, 2 to 30). Gastrointestinal adverse events were more common with efruxifermin; most events were mild or moderate.

In patients with compensated cirrhosis caused by MASH, efruxifermin did not significantly reduce fibrosis at 36 weeks. (Funded by Akero Therapeutics; SYMMETRY ClinicalTrials.gov number, NCT05039450.).

The updated EASL Clinical Practice Guidelines on the management of hepatitis B virus (HBV) infection provide comprehensive, evidence-based recommendations for its management. Spanning ten thematic sections, the guidelines address diagnostics, treatment goals, treatment indications, therapeutic options, hepatocellular carcinoma surveillance, management of special populations, HBV reactivation prophylaxis, post-transplant care, HBV prevention strategies, and finally address open questions and future research directions. Chronic HBV remains a global health challenge, with over 250 million individuals affected and significant mortality due to cirrhosis and hepatocellular carcinoma. These guidelines emphasise the importance of early diagnosis, risk stratification based on viral and host factors, and tailored antiviral therapy. Attention is given to simplified algorithms, vaccination, and screening to support global HBV elimination targets. The guidelines also discuss emerging biomarkers and evolving definitions of functional and partial cure. Developed through literature review, expert consensus, and a Delphi process, the guidelines aim to equip healthcare providers across disciplines with practical tools to optimise HBV care and outcomes worldwide.

Extrahepatic surgery in patients with cirrhosis of the liver represents a growing clinical challenge due to the increasing prevalence of chronic liver disease and improved long-term survival of these patients. The presence of cirrhosis significantly increases the risk of perioperative morbidity and mortality following abdominal surgery. Advances in preoperative risk stratification, surgical techniques, and perioperative care have led to better outcomes, yet integration of these improvements into routine clinical practice is needed. These clinical practice guidelines provide comprehensive recommendations for the assessment and perioperative management of patients with cirrhosis undergoing extrahepatic surgery. An individualised patient-centred risk assessment by a multidisciplinary team including hepatologists, surgeons, anaesthesiologists, and other support teams is essential.

Autoimmune hepatitis (AIH) is a chronic liver disease of unknown aetiology which may affect any patient irrespective of age, sex, and ethnicity. At baseline, the clinical spectrum of the disease varies largely from asymptomatic cases to acute liver failure with massive hepatocyte necrosis. The aim of these EASL guidelines is to provide updated guidance on the diagnosis and management of AIH both in adults and children. Updated guidance on the management of patients with variants and specific forms of AIH is also provided, as is detailed guidance on the management of AIH-associated cirrhosis, including surveillance for portal hypertension and hepatocellular carcinoma, as well as liver transplantation in decompensated cirrhosis.

Esophageal variceal bleeding is affected by various risk factors. We hypothesized that increased exposure to gastric acid in patients with abnormal gastroesophageal flap valve (GEFV) might increase esophageal variceal bleeding. The aim of this study is to investigate the relationship between GEFV and esophageal variceal bleeding episodes.

In this cross-sectional study, 300 consecutive patients with esophageal varices and a documented GEFV during esophagogastroduodenoscopy were included. Patients were divided into two groups according to: the Hill's grade of flap valve (grade 1,2- normal and grade 3,4- abnormal), size of varices - large (>5 mm) and small (<5 mm) and the number of bleeding episodes into: Group A with ≤ 1 and Group B with ≥ 2 bleeding episodes. We compared GEFV and various other factors to the number of variceal bleeding episodes.

224 patients (74.60 %) had a normal and 76 (25.40 %) had an abnormal GEFV. Clinical variables were statistically significant in the abnormal GEFV group (P < 0.0.5). Propensity score matching was done to reduce the significant differences in the clinical background at baseline between the 2 groups. 152 patients (76 in each group) were analysed after propensity score matching. A significant difference between the two groups disappeared except for number of bleeding episodes. Binary logistic Cox regression analysis was applied using the clinical variables to assess their role in predicting recurrent variceal bleeding. On univariate analysis, abnormal GEFV and large varices were significantly associated with recurrent esophageal variceal bleed (P = 0.001). On Multivariate analysis, abnormal GEFV (OR 7.25, 95 % CI 3.27- 16.08, P = 0.001), History of EVL (OR 6.21, 95 % CI 1.98- 12.22, P = 0.03) and large varices (OR 5.70, 95 % CI 2.45- 13.20, P = 0.001) were independent predictors for recurrent esophageal variceal bleeding.

Abnormal GEFV, History of EVL and large varices are independent risk factors for recurrent esophageal variceal haemorrhage.

Background and Aim: Dental diseases are common in patients with cirrhosis. In these patients, reduced mastication might interfere with protein intake and contribute to malnutrition. We addressed the relationship between reduced mastication and dynapenia in patients with cirrhosis. Methods: This cross-sectional study involved patients with cirrhosis treated in a Brazilian center. Trained dentists performed oral examinations and tested the patients for nutritional parameters such as handgrip strength (HGS) and gait speed test (GST). Reduced mastication was presumed when a patient had molar edentulism (≥ 3 teeth), bad dental occlusion, or ill-fitting denture. Associations between mastication status and malnutrition were evaluated using multivariate linear regression analysis for continuous measures and adjusted prevalence ratio (PR (95% confidence interval)) for binary measures. Results: We included 149 patients with cirrhosis (60 ± 13 years old, 76% men, 64% Child A, 60% due to alcoholism only). Reduced mastication affected 107 patients (72%), low muscle strength (decreased HGS) occurred in 45 (30%), and decreased GST was observed in 58 (41%, among 143 patients able to walk). Thirty-one out of 143 (22%) presented decreased HGS and GST, characterizing dynapenia. Reduced mastication was associated either with decreased HGS [PR = 2.28 (1.08-4.81), p = 0.030; reduced mastication decreases the HGS mean by 12.5 kg for men (p < 0.001) and 8.1 kg for women (p = 0.065)] or with decreased GST [PR 1.97 (1.09-3.55), p = 0.024; reduced mastication increased the time of GST by 1.1 s on average (p = 0.005)], adjusting for age, alcoholic etiology, and Child-Pugh classification. Conclusions: Reduced mastication is associated with dynapenia markers in patients with cirrhosis. Further studies are needed to assess whether oral rehabilitation can change the curse of malnutrition in this population.

Large language models generate plausible text responses to medical questions, but inaccurate responses pose significant risks in medical decision-making. Grading LLM outputs to determine the best model or answer is time-consuming and impractical in clinical settings; therefore, we introduce EVAL (Expert-of-Experts Verification and Alignment) to streamline this process and enhance LLM safety for upper gastrointestinal bleeding (UGIB). We evaluated OpenAI's GPT-3.5/4/4o/o1-preview, Anthropic's Claude-3-Opus, Meta's LLaMA-2 (7B/13B/70B), and Mistral AI's Mixtral (7B) across 27 configurations, including zero-shot baseline, retrieval-augmented generation, and supervised fine-tuning. EVAL uses similarity-based ranking and a reward model trained on human-graded responses for rejection sampling. Among the employed similarity metrics, Fine-Tuned ColBERT achieved the highest alignment with human performance across three separate datasets (ρ = 0.81-0.91). The reward model replicated human grading with 87.9% of cases across temperature settings and significantly improved accuracy through rejection sampling by 8.36% overall. EVAL offers scalable potential to assess accuracy for high-stakes medical decision-making.

Over the last few years, the approach to clinical recognition and risk stratification of advanced liver disease has changed substantially, and liver cirrhosis has been increasingly conceptualized as a clinical rather than a histopathologic condition. In this Clinical Insight, we summarize the latest developments on recognition and management of 'clinically' advanced chronic liver disease.

Limited data exist on the role of systemic inflammation and gut barrier dysfunction in acute variceal bleed (AVB). We studied inflammatory markers and changes in the intestinal barrier in patients with AVB and assessed if these can be used to identify a higher risk subgroup with regard to outcomes.

In this prospective observational study, patients with cirrhosis and AVB presenting at a tertiary care center were stratified by whether or not they developed acute decompensation (AD) over 6 weeks follow-up. Utility of systemic inflammatory markers (interleukin-6 [IL-6], C-reactive protein), endotoxinemia (serum IgM/IgG anti-endotoxin antibodies), and duodenal epithelial tight junction proteins (TJPs) by immunohistochemistry (IHC) for tight-junction proteins (claudin-2,-4, zonula occludens-1(ZO-1), junctional adhesion molecule (JAM)) was assessed to predict the outcomes. These parameters were compared with a pre-existing cohort of patients with cirrhosis and no recent variceal bleed and with those without cirrhosis (dyspepsia with no endoscopic pathology). A nomogram was developed from multivariate model to predict 6-wk AD in patients with AVB.

Patients with AVB(n = 66) (age:46.4 ± 11.7 years; etiology: alcohol/NASH/HBV/HCV [48.5%/12.1%/12.1%/7.6%]) were included. Twenty-four (36.3%) patients developed 6-wk AD. Patients with 6-wk AD had higher serum IL-6 (median: 156.14 pg/ml [IQR: 136.12-170.52] vs 58.28 pg/ml [31.70-110.67]; P < 0.001) and Child score (median: 9 [6.75-10.25] vs 7 [6-9]; P = 0.042) at baseline. Serum endotoxinemia and duodenal epithelial TJP were similar. A nomogram combining CTP and IL-6 was generated that predicted 6-wk AD with optimism-corrected c-statistic of 0.87. Comparison with non-bleeder cirrhosis (n = 52) (7.57 [5.48-9.87]) and dyspepsia controls (n = 53) (5.72 [4.40-6.45]; P < 0.001) also identified significant elevation of serum IL-6, not entirely explainable by derangements in TJP and bacterial translocation markers.

6-wk AD rates in patients with cirrhosis and AVB can be predicted using combination of Child score and serum IL-6.

Non-selective beta-blockers (NSBBs) can lower the risk of first decompensation in patients with cirrhosis and clinically significant portal hypertension (CSPH) (identified by a hepatic venous pressure gradient ≥10 mm Hg) with active etiology. Our aim was to examine the effect of NSBBs on first decompensation occurrence in patients with cirrhosis and enduring CSPH after etiological treatment.

Patients with compensated cirrhosis and clinical evidence of CSPH (gastroesophageal varices [GEVs] and/or spontaneous portosystemic collaterals [SPSSs]) after 2 years from etiological treatment. The primary endpoint was first decompensation (occurrence of variceal bleeding, ascites, or hepatic encephalopathy) in patients on NSBBs vs off NSBBs.

The final cohort included 406 patients. Baseline characteristics of patients on NSBBs (n = 187) and off NSBBs (n = 219) were comparable, except for signs of portal hypertension that were more pronounced in the on-NSBBs group. During a mean follow-up of 32 months, 127 (31%) patients decompensated, with ascites being the most common (77%) decompensating event. Decompensation rates were lower in patients on NSBBs (16% vs 44%; P < .0001). The benefit of NSBBs on decompensation was maintained in patients with small GEVs (17% vs 43%; P < .0001), in those with spontaneous portosystemic shunt only (8% vs 43%; P = .003), and in each different etiology, including hepatitis C virus-cured cirrhosis (9% vs 32%; P < .0001). At Cox regression analysis, hemoglobin, Child-Pugh, Model for End-Stage Liver Disease-Sodium, diabetes at baseline, and previous bacterial infections were independent predictors of decompensation, while NSBBs use had a protective effect (hazard ratio, 0.32; 95% confidence interval, 0.20-0.49; P < .0001). NSBBs use significantly reduced bacterial infection rates (hazard ratio, 0.36; 95% confidence interval, 0.22-0.58; P < .0001).

NSBBs decrease the risk of first decompensation in patients with cirrhosis and enduring CSPH after etiological treatment.

The effectiveness of emergent endoscopy (EE), defined as endoscopy performed within six hours of admission, for improving outcomes in patients presenting with acute upper gastrointestinal bleeding (AUGIB) remains controversial. This study aimed to evaluate the impact of EE on 42-day rebleeding and mortality rates and identify subgroups of patients who benefit most from this approach.

We conducted a retrospective cohort study at a tertiary hospital with 24/7 endoscopy services. Eligible patients were aged ≥18 years, presented with AUGIB, and underwent endoscopy within 24 h of admission. The exclusion criteria included prior interventions at other facilities, in-hospital bleeding for unrelated reasons, or loss to follow-up. All patients were managed under a standardized AUGIB protocol. The primary outcomes were 42-day rebleeding and mortality. The data were analysed via multivariate logistic regression and interaction analyses.

There were 651 patients with a median age of 58.6 years (18-92). The median time from admission to endoscopy was 4.8 h (3.1-8.0). The 42-day rebleeding and mortality rates were 16.7 % and 11.8 %, respectively. EE was significantly associated with 42-day mortality but not rebleeding. Independent risk factors for mortality included hemodynamic instability, malignancy, NSAID use, and elevated serum creatinine. Interaction analysis revealed that EE was associated with reduced 42-day mortality in hemodynamically unstable patients (OR: 0.29, 95 % CI: 0.145-0.579), a benefit not observed in patients with other risk factors for mortality.

EE appears to be associated with reduced 42-day mortality in patients presenting with hemodynamically unstable AUGIB.

Accurate prediction of disease severity and prognosis are challenging in patients with cirrhosis. We evaluated whether the deep learning-based AI-Cirrhosis-ECG (ACE) score could detect hepatic decompensation and predict clinical outcomes in cirrhosis.

We analyzed 2,166 ECGs from 472 patients in a retrospective Mayo Clinic cohort, 420 patients in a prospective Mayo transplant cohort, and 341 patients in an external validation cohort from Hospital Clínic de Barcelona. The ACE score's performance was assessed using receiver-operating characteristic analysis for decompensation detection and competing risks Cox regression for outcome prediction.

The ACE score showed high accuracy in detecting hepatic decompensation (area under the curve 0.933, 95% CI: 0.923-0.942) with 88.0% sensitivity and 84.3% specificity at an optimal threshold of 0.25. In multivariable analysis, each 0.1-point increase in ACE score was independently associated with increased risk of liver-related death (hazard ratio [HR] 1.44, 95% CI 1.32-1.58, p <0.001). Adding ACE to model for end-stage liver disease-sodium significantly improved prediction of adverse outcomes across all cohorts (c-statistics: retrospective cohort 0.903 vs. 0.844; prospective cohort 0.779 vs. 0.735; external validation 0.744 vs. 0.732; all p <0.001).

The ACE score accurately identifies hepatic decompensation and independently predicts liver-related outcomes in cirrhosis. This non-invasive tool enhances current prognostic models and may improve risk stratification in cirrhosis management.

This study demonstrates the potential of artificial intelligence to enhance prognostication in liver disease, addressing the critical need for improved risk stratification in cirrhosis management. The AI-Cirrhosis-ECG (ACE) score, derived from widely available ECGs, shows promise as a non-invasive tool for detecting hepatic decompensation and predicting liver-related outcomes, which could significantly impact clinical decision-making and resource allocation in hepatology. These findings are particularly important for hepatologists, transplant surgeons, and patients with cirrhosis, as they offer a novel approach to complement existing prognostic models such as model for end-stage liver disease-sodium. In practical terms, the ACE score could be integrated into routine clinical assessments to provide more accurate risk predictions, potentially improving the timing of interventions, optimizing transplant listing decisions, and ultimately enhancing patient outcomes. However, further validation in diverse populations and integration with other established predictors is necessary before widespread clinical implementation.

Over the past several years, there has been a wealth of new data pertaining to the management of complications of cirrhosis, resulting in several important updates to best practices and consensus guidelines. Despite these advancements and numerous recent targeted quality initiatives, hospitalizations resulting from complications of cirrhosis remain frequent, costly and associated with poor patient outcomes. An emphasis on evidence-based management of hospitalized patients with decompensated cirrhosis has the potential to decrease readmission rates and length of stay while improving overall patient outcomes. Herein, we provide an updated, evidence-based overview of the optimal inpatient management of the most frequently encountered complications associated with cirrhosis.

The study sought to compare the efficacy of endoscopic injection sclerotherapy with cyanoacrylate glue (EIS-CYA) vs EIS-CYA plus a radiologic intervention (RI) (either transjugular intrahepatic portosystemic shunt or balloon-occluded retrograde transvenous obliteration) for secondary prophylaxis in patients with liver cirrhosis who presented with acute variceal bleeding from cardiofundal varices. Primary outcome measure was gastric varix (GV) rebleed rates at 1 year.

Consecutive cirrhosis patients with acute variceal bleeding from cardiofundal varices were randomized into 2 arms (45 in each) after primary hemostasis by EIS-CYA. In the endoscopic intervention (EI) arm, EIS-CYA was repeated at regular intervals (1, 3, 6, and 12 months), while in the RI arm, patients underwent transjugular intrahepatic portosystemic shunt or balloon-occluded retrograde transvenous obliteration followed by endoscopic surveillance.

GV rebleed rates at 1 year were higher in the EI arm compared with the RI arm: 11 (24.4%; 95% confidence interval [CI], 12.9%-39.5%) vs 1 (2.2%; 95% CI, 0.1%-11.8%) (P = .004; absolute risk difference: 22.2%; 95% CI, 8.4%-36.6%). GV rebleed-related mortality in the EI arm (8 [17.8%; 95% CI, 8.0%-32.1%]) was significantly higher than in the RI arm (1 [2.2%; 0.1%-11.8%]) (P = .030; absolute risk difference: 15.6; 95% CI, 2.9%-29.2%); however, there was no difference in all-cause mortality between the 2 groups (12 [26.7%; 95% CI, 14.6%-41.9%] vs 7 [15.6%; 95% CI, 6.5%-29.5%]). The number needed to treat to prevent 1 GV-related rebleed at 1 year was 4.5.

RI for secondary prophylaxis reduces rebleeding from GV and GV rebleeding-related mortality in patients with GV hemorrhage. (CTRI/2021/02/031396).

Prospective studies are needed to increase knowledge of fruit and vegetable consumption effects on hepatocellular carcinoma (HCC) risk. This study aimed to investigate the association between fruit and vegetable consumption and incident HCC in French patients with cirrhosis.

This study used data from a French prospective observational cohort nested in two national prospective cohorts of patients with histologically proven compensated alcohol-related or viral cirrhosis. Fruit and vegetable consumption was assessed by a trained dietitian using a semiquantitative food-frequency questionnaire validated in French and analyzed as binary exposure according to predefined thresholds (≥240 g/day for fruit or vegetables and ≥400 g/day for fruit and vegetables combined). Incident HCC was primary outcome. Propensity scores were used in Poisson regression models.

Among 179 patients analyzed, 20 HCC were diagnosed during follow-up (median 7.3 [Q1-Q3: 4.1-8.0] years). A significant association was observed between HCC incidence and vegetable consumption ≥240 g/day (adjusted relative risk [RR] 0.35, 95%CI [0.13; 0.98], p = 0.04), but not with consumption of fruit and vegetable ≥400 g/day (RR = 0.49, 95%CI [0.18; 1.32], p = 0.16), nor with fruit consumption ≥240 g/day (RR = 0.80, 95% CI [0.28; 2.31], p = 0.68).

This longitudinal study documented insufficient fruit and/or vegetable consumption in 42.5% of patients with cirrhosis and a 65% reduction of HCC incidence in those with vegetable consumption ≥240 g/day. Reproduction of results in a larger sample are necessary to explore the potential of fruit and vegetables as protective factors in HCC.

The association between fruit and vegetable consumption and the risk of hepatocellular carcinoma (HCC) is poorly documented in the population of patients with cirrhosis, while such knowledge is crucial for adapting HCC prevention messages. Our study shows 57.5% of patients with cirrhosis reported consuming fruit and/or vegetables at or above the French and WHO threshold of 400 g/day, with a higher proportion of patients consuming at least 240 g/day of vegetables compared with those consuming at least 240 g/day of fruit (47.5% vs. 38.6%). The results suggest that consuming at least 240 g/day of vegetables reduces the risk of HCC by 65% in patients with cirrhosis.

Systemic inflammation drives the progression of portal hypertension in patients with liver cirrhosis. Interleukin-6 is a key mediator of the cytokine network in acute inflammation that stimulates the production of many acute phase reactants. In this study, we investigated the association between serum interleukin-6 and acute phase reactant levels and the disease stage and prognosis of patients with liver cirrhosis.

A single-center retrospective cohort of 359 patients with liver cirrhosis was staged according to the symptomatic decompensation. Baseline serum C-reactive protein , interleukin-6, procalcitonin, and serum amyloid A protein levels were measured. The outcomes of further decompensation, hepatocellular carcinoma development, and mortality were identified during a 3.3-year median follow-up period.

Serum C-reactive protein , interleukin-6, and procalcitonin levels were significantly different across the stages. The multivariate Cox proportional hazards model identified serum interleukin-6 as an independent predictor of further decompensation in patients with compensated and the first single decompensated cirrhosis. Kaplan-Meier analyses showed that the probability of further decompensation was stratified by serum interleukin-6 level in a dose-dependent manner. In the entire cohort, serum interleukin-6 level also showed a significant association with liver-related and all-cause mortalities, but not with hepatocellular carcinoma development, independent of stage and liver disease severity indices.

Elevated levels of serum markers of systemic inflammation were associated with symptomatic decompensation, and serum interleukin-6 level is a predictor of further decompensation and mortality in patients with liver cirrhosis.

Liver biopsy remains the gold standard for fibrosis staging in patients with chronic hepatitis delta (CHD). Here, we comparatively evaluated the performance of transient elastography (TE) and biomarkers for the diagnosis of liver fibrosis in patients with CHD.

A total of 230 HDV-infected RNA-positive patients from various centers who underwent liver biopsy and liver stiffness measurements (LSMs) using Fibroscan, within a period of 6 months maximum, were investigated retrospectively. Area under the receiver operating characteristic curve and Youden index were used to establish cutoff values of LSM. TE was compared with other noninvasive tests: aspartate aminotransferase to platelet ratio index, Fibrosis-4, and Delta-4 fibrosis scores.

Histologic fibrosis stage distribution was: 20.4% for F0-F1; 27.0% for F2; 18.7% for F3; and 33.9% for F4. TE demonstrated good diagnostic performance for detecting cirrhosis and advanced fibrosis with an Area under the receiver operating characteristic curve of 0.88 and 0.86, which were significantly higher than those obtained with the other noninvasive tests (P = .004 and P < .001). With a cutoff value of >12 kPa for cirrhosis, the sensitivity was 70.5%, specificity was 86.2%, positive predictive value was 72.4%, negative predictive value was 85.1%, and accuracy was 80.9%. Using 10.4 kPa as the cutoff value for F3, the sensitivity was 70.2%, specificity was 83.5%, positive predictive value was 82.5%, negative predictive value was 71.7%, and accuracy was 76.5%. In 89% of patients with LSM ≤6.2 kPa, liver biopsy disclosed only absent or minimal fibrosis.

TE demonstrated good diagnostic performance for advanced fibrosis and cirrhosis in patients with CHD. Advanced fibrosis is highly probable for LSM values ≥10 kPa. LSM values <6 kPa almost totally exclude significant fibrosis. Between 6 and 10 kPa, liver biopsy should be discussed.

Spontaneous bacterial peritonitis (SBP) bacteriology has changed over time. Reappraisal of primary SBP prophylaxis showed an increased rate of resistance in patients on primary prophylaxis with resultant discontinuation of this prophylaxis throughout the Veterans Affairs (VA). We aimed to re-evaluate the risk-benefit ratio of secondary SBP prophylaxis (SecSBPPr).

Using validated International Classification of Diseases-9/10 codes, we used the VA Corporate Data Warehouse and the Non-VA National TriNetX database to identify patients in 2 different large US systems who survived their first SBP diagnosis (with chart review from 2 VA centers) between 2009 and 2019. We evaluated the prevalence of SecSBPPr and compared outcomes between those who started on SecSBPPr vs not.

We identified 4,673 veterans who survived their index SBP episode; 54.3% of whom were prescribed SecSBPPr. Multivariable analysis showed higher SBP recurrence risk in those on vs off SecSBPPr (hazards ratio 1.63 [1.40-1.91], P < 0.001). This was accompanied by higher fluoroquinolone resistance odds in SecSBPPr patients (odds ratio = 4.32 [1.36-15.83], P = 0.03). In TriNetX, we identified 6,708 patients who survived their index SBP episode; 48.6% were on SecSBPPr. Multivariable analysis similarly showed SecSBPPr increased SBP recurrence risk (hazards ratio 1.68 [1.33-1.80], P < 0.001). Both data sets showed higher SBP recurrence trends over time in SecSBPPr patients. Results remained consistent at 6-month and 2-year timepoints.

In 2 national data sets of >11,000 patients with SBP, we found that SecSBPPr was prescribed in roughly half of patients. When initiated, SecSBPPr, compared with no prophylaxis after SBP, increased the risk of SBP recurrence in multivariable analysis by 63%-68%, and this trend worsened over time. SecSBPPr should be reconsidered in cirrhosis.