UNASSIGNED: Data on the association between proton pump inhibitor (PPI) use and hepatic encephalopathy (HE) are conflicting, and data from multicentre studies are scarce. The aim of this study was to dissect the potential association between PPI use and minimal (MHE) and overt HE (OHE).
UNASSIGNED: Data from patients with cirrhosis recruited at seven centres across Europe and the US were analysed. MHE was defined by the psychometric hepatic encephalopathy score (PHES). PPI use was recorded on the day of testing with PHES. Patients were followed for OHE development and death/liver transplantation.
UNASSIGNED: A total of 1,160 patients with a median MELD of 11 were included (Child-Pugh stages: A 49%/B 39%/C 11%). PPI use was noted in 58% of patients. Median follow-up time was 18.1 months, during which 230 (20%) developed an OHE episode, and 224 (19%) reached the composite endpoint of death/liver transplantation. In multivariable analyses, PPI use was neither associated with the presence of MHE at baseline nor OHE development during follow-up. These findings were consistent in subgroup analyses of patients with Child-Pugh A or B cirrhosis and after excluding patients with a history of OHE. PPI use was also not associated with a higher risk of OHE, neither in patients with an indication for treatment nor in patients without an indication.
UNASSIGNED: PPI use is not associated with a higher risk of HE in patients with cirrhosis. Based on these findings, at present, a prescription should not be prohibited in case of a generally accepted indication.
UNASSIGNED: Data on the association between proton pump inhibitor (PPI) use and hepatic encephalopathy (HE) are conflicting. In this study, PPI use was not associated with a higher risk of minimal HE at baseline or overt HE during follow-up in patients with cirrhosis. Based on these findings, prescription of a PPI for a generally accepted indication should not be prohibited in patients with cirrhosis.

UNASSIGNED: Hepatic recompensation may be achieved in patients with decompensated cirrhosis due to chronic hepatitis B (CHB) upon effective suppression of viral replication by nucleos(t)ide analogues (NAs). However, the optimal timing and predictors of recompensation and the subsequent clinical course of patients with CHB with vs. without recompensation are not well-defined.
UNASSIGNED: This study was a retrospective extension of a multi-centre prospective cohort, focusing on patients with CHB and decompensated cirrhosis treated with entecavir. We followed patients beyond treatment week 120 until a second decompensation event or June 2023. We identified the optimal timing and predictors of recompensation by week 120, evaluated durability of recompensation in patients fulfilling recompensation criteria by week 120 and examined late recompensation in those who did not fulfil it by week 120.
UNASSIGNED: At treatment week 24, serum albumin ≥34 g/L predicted recompensation by week 120. The Brec-PAS model offered good predictive ability for recompensation by week 120. Of the 283 patients who finished 120 weeks of therapy, 175 were followed beyond week 120 (median follow-up: 240 weeks). Among the 106 patients achieving recompensation by week 120, 92 (86.8%) maintained recompensation for another 120 (72-168) weeks. Among the 69 patients without recompensation by week 120, 40.6% attained late recompensation during the subsequent 120 (72-168) weeks. Additionally, hepatocellular carcinoma incidence was lower in the recompensated group (5.0% vs. 16.13%, p = 0.002).
UNASSIGNED: A serum albumin ≥34 g/L at treatment week 24 predicted recompensation by week 120. Recompensation achieved by week 120 of NA treatment is maintained in >80% of patients in the long term. Some patients may achieve recompensation only after >120 weeks of NA treatment. The incidence of hepatocellular carcinoma was reduced but not completely abolished after recompensation.
UNASSIGNED: Our research provides a meaningful contribution to understanding the long-term prognosis of recompensation in patients with chronic hepatitis B and decompensated cirrhosis, as well as to evaluating the predictive value of serum albumin levels, offering a comprehensive view of clinical outcomes after recompensation. The significance of early biomarkers in guiding therapeutic decisions is highlighted, shedding light on the continued benefits and possible risks after recompensation. This enhances the capability for more precise prognostic evaluations and informed therapeutic strategies. For healthcare providers, these insights afford a detailed perspective on patient monitoring and intervention planning, underscoring the need for ongoing assessment past the initial recompensation phase.

Alcohol-associated hepatitis (AH) is the most severe form of alcohol-related liver disease. The natural course of alcohol-related liver disease is influenced by heavy alcohol consumption and abstinence periods. Differentiating between AH and decompensated cirrhosis (DC) could be extremely challenging in clinical practice due to clinical and bioclinical similarities. The severity of AH is made on bioclinical grounds, the severe form necessitating corticotherapy treatment. Liver biopsy is still the standard of care for establishing the diagnosis in atypical presentations. The pathogenesis of AH is an interplay between gene expression, cytokine dysregulation, the immune system and the gut microbiota. Non-invasive tests are increasingly and widely used for the purpose of early diagnosis and reliable prognostication. The non-invasive tests are emerging in concordance with disease pathogenesis. In this review, we describe the non-invasive tools that can distinguish AH from DC. We outline the available cut-offs and their performance in diagnosis and prognosis, as well as in assessing the treatment response to corticotherapy. Promising circulating biomarkers like keratin 18, microRNAs and sphingolipids will be in the review.

OBJECTIVE: Impact of type 2 diabetes mellitus (T2DM) in patients with end-stage liver disease (ESLD) awaiting liver transplantation (LT) remains poorly defined. The objective of the present study is to evaluate the relationship between T2DM and clinical outcomes among patients with LT waitlist registrants. We hypothesize that the presence of T2DM will be associated with worse clinical outcomes.
METHODS: 593 patients adult (age 18 years or older) who were registered for LT between 1/2010 and 1/2017 were included in this retrospective analysis. The impact of T2DM on liver-associated clinical events (LACE), survival, hospitalizations, need for renal replacement therapy, and likelihood of receiving LT were evaluated over a 12-month period. LACE was defined as variceal hemorrhage, hepatic encephalopathy, and ascites. Kaplan-Meier and Cox regression analysis were used to determine the association between T2DM and clinical outcomes.
RESULTS: The baseline prevalence of T2DM was 32% (n = 191) and patients with T2DM were more likely to have esophageal varices (61% vs. 47%, p = 0.002) and history of variceal hemorrhage (23% vs. 16%, p = 0.03). The presence of T2DM was associated with increased risk of incident ascites (HR 1.91, 95% CI 1.11, 3.28, p = 0.019). Patients with T2DM were more likely to require hospitalizations (56% vs. 49%, p = 0.06), hospitalized with portal hypertension-related complications (22% vs. 14%; p = 0.026), and require renal replacement therapy during their hospitalization. Patients with T2DM were less likely to receive a LT (37% vs. 45%; p = 0.03). Regarding MELD labs, patients with T2DM had significantly lower bilirubin at each follow-up; however, no differences in INR and creatinine were noted.
CONCLUSIONS: Patients with T2DM are at increased risk of clinical outcomes. This risk is not captured in MELD score, which may potentially negatively affect their likelihood of receiving LT.

OBJECTIVE: Few population-based studies have investigated the association between metabolic dysfunction-associated steatotic liver disease (MASLD) and depression. Additionally, it remains unclear if depression affects progression to major adverse liver outcomes (MALO) in MASLD.
METHODS: All patients in Sweden with newly diagnosed MASLD between 2006 and 2020 were identified from the National Patient Register. Each patient was matched on age, sex, inclusion year, and municipality with up to 10 comparators from the general population. Cox regression was used to compare rates of severe depression in persons with MASLD to the comparators. In persons with MASLD, Cox regression was used to estimate rates of MALO using severe depression before baseline or diagnosed during follow-up as a time-varying exposure.
RESULTS: We included 11 301 persons with MASLD and 104 205 comparators who were followed for a median of 3.9 (IQR 1.5-7.6) and 4.9 years (IQR 2.3-8.7), respectively. The median age was 56 years and 5576 of 11 301 (49.3%) persons with MASLD were male. Incident severe depression developed in 228 of 11 301 (2.0%) persons with MASLD and 1160 of 104 205 (1.1%) comparators (fully adjusted hazard ratio [HR] = 1.8, 95% CI = 1.5-2.1). Of persons with MASLD, 25 of 1229 (2.0%) of those with severe depression before or after baseline progressed to MALO compared to 322 of 10 326 (3.1%) of those without severe depression (fully adjusted HR = 1.0, 95% CI = .6-1.5).
CONCLUSIONS: We confirm an association between MASLD and severe depression. However, no association between severe depression and incident MALO was found, but conclusions are limited by few observed outcomes.

Aim: Our goal was to explore the prognostic value of the neutrophil-to-hemoglobin ratio (NHR) in HBV-related decompensated cirrhosis (HBV-DC) patients. Methods: 172 HBV-DC patients were enrolled. Multivariate analyses were used to identify risk factors influencing 30-day mortality. Results: The 30-day mortality was 12.8% (22/172). nonsurvivors exhibited a higher NHR than survivors. On multivariate analysis, NHR and model for end-stage liver disease (MELD) score were the only independent predictors of mortality. Notably, the predictive capabilities of NHR were found to be comparable to those of the MELD score. Conclusion: High NHR was associated with poor prognosis in HBV-DC patients, and NHR can serve as an effective and readily available indicator for the prediction of mortality in these patients.
[Box: see text].

Chronic hepatitis B and C are among the most significant infectious diseases worldwide, and are major risk factors for liver cirrhosis and liver cancer. In Japan, comprehensive hepatitis measures are implemented for the testing and treatment of viral hepatitis, thus enabling the early diagnosis of liver cancer. Nevertheless, patients with decompensated cirrhosis and liver cancer often have unfavorable prognoses and require repetitive long-term treatment. In fiscal year 2018, an integrated policy of medical expense subsidies and research was established in Japan that aimed to alleviate patients\' financial burden and launch the clinical registry of advanced liver disease. Over time, updates to the eligibility for the subsidy increased access to patients and has led to an increased number of beneficiaries. Additionally, the accumulation of clinical data in the registry has revealed the treatment choices for these diseases. However, the disparities in efforts across prefectures have also become evident. Raising public awareness of the policy and tightening the multisector healthcare network are keys to success in supporting qualifying patients with advanced liver disease.

Transjugular intrahepatic portosystemic shunt (TIPS) is a medical procedure that has been used to manage variceal bleeding and ascites in patients with cirrhosis. It can prevent further decompensation and improve the survival of high-risk decompensated patients. Recent research indicates that TIPS could increase the possibility of recompensation of decompensated cirrhosis when it is combined with adequate suppression of the causative factor of liver disease. However, the results of the studies have been based on retrospective analysis, and further validation is required by conducting randomized controlled studies. In this context, we highlight the limitations of the current studies and emphasize the issues that must be addressed before TIPS can be recommended as a potential recompensating tool.

OBJECTIVE: Hepatic venovenous communications (HVVC) is detectable in more than one-third of cirrhotic patients, where portal hypertension (PHT) tends to present more severely. We aimed to explore the prognostic implications of HVVC in patients with sinusoidal PHT treated by transjugular intrahepatic portosystemic shunt (TIPS).
METHODS: The multicenter data of patients (2020-2022) undergoing balloon-occluded hepatic venography during TIPS were retrospectively analyzed. Pre-TIPS total bile acids (TBA) levels in portal, hepatic and peripheral veins were compared between groups. The primary endpoint was the development of overt hepatic encephalopathy (HE) within one year after TIPS.
RESULTS: 183 patients were eligible and classified by the presence (n = 69, 37.7 %) or absence (n = 114, 62.3 %) of HVVC. The agreement between wedged hepatic venous pressure and portal venous pressure was poor in HVVC group (intraclass correlation coefficients [ICC]: 0.141, difference: 13.4 mmHg, p < 0.001), but almost perfect in non-HVVC group (ICC: 0.877, difference: 0.4 mmHg, p = 0.152). At baseline, patients with HVVC had lower Model for end-stage liver disease scores (p < 0.001), blood ammonia levels (p < 0.001), TBA concentrations in the hepatic (p = 0.011) and peripheral veins (p = 0.049) rather than in the portal veins (p = 0.516), and a higher portosystemic pressure gradient (p = 0.035), suggesting more effective intrahepatic perfusion in this group. Within 1-year post-TIPS, HVVC group had a lower incidence of overt HE (11.7 % vs. 30.5 %, p = 0.004, HR: 0.34, 95 % CI: 0.16-0.74, absolute risk difference [ARD]: -17.4) and an improved liver transplantation-free survival rate (97.1 % vs. 86.8 %, p = 0.021, HR: 0.16, 95 % CI: 0.05-0.91, ARD: -10.3).
CONCLUSIONS: For patients with sinusoidal PHT treated by TIPS, the presence of HVVC was associated with a reduced risk of overt HE and a potential survival benefit.

We present a case of Cronkhite-Canada syndrome in a patient with decompensated cirrhosis who had successful induction of remission with nutritional supplementation alone. We propose that early institution of high-protein, high-energy enteral supplementation should be offered to all patients, especially those with compelling contraindications to immunosuppression.