Persons with metabolic dysfunction-associated steatotic liver disease are at increased risk of severe depression.

BACKGROUND AND AIM: 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.

Spontaneous remission of Cronkhite-Canada syndrome without immunosuppressive medication in the context of decompensated cirrhosis: A case report.

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.

Elevated neutrophil-to-hemoglobin ratio as an indicator of poor survival in hepatitis B virus-related decompensated cirrhosis.

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].

Transjugular intrahepatic portosystemic shunt for recompensating decompensated cirrhosis?

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.

Reduced risk of overt hepatic encephalopathy and death after transjugular intrahepatic portosystemic shunt in patients with hepatic venovenous communications.

PURPOSE: 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). METHOD: 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.

Integrated policy of medical expense subsidies and clinical registry for patients with liver cancer and decompensated cirrhosis in Japan.

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.

Cardiac dysfunction in patients with cirrhosis and acute decompensation.

The prevalence of cirrhotic cardiomyopathy (CCM) has been reported as high as 60%-70% in patients with liver cirrhosis and is associated with various negative outcomes. There has been a growing understanding of CCM over recent years. Indeed, the development of imaging techniques has enabled new diagnostic criteria to be proposed by the Cirrhotic Cardiomyopathy Consortium. However, important unanswered questions remain over pathophysiological mechanisms, optimal diagnostic modalities and potential treatment options. While there has been an increasing volume of literature evaluating CCM, there is a lack of clarity on its implications in acute decompensation, acute-on-chronic liver failure and following interventions such as transjugular intrahepatic portosystemic shunt insertion and liver transplantation. This review aims to summarise the literature in these challenging domains and suggest where future research should focus. We conclude that systemic inflammation and structural myocardial changes are likely to be crucial in the pathophysiology of the disease, but the relative contribution of different components remains elusive. Furthermore, future studies need to use standardised diagnostic criteria for CCM as well as incorporate newer imaging techniques assessing both myocardial structure and function. Finally, while specific treatments are currently lacking, therapeutics targeting systemic inflammation, microbial dysbiosis and bacterial translocation are promising targets and warrant further research.

Efficacy of long-term albumin therapy in the treatment of decompensated cirrhosis.

BACKGROUND AND AIMS: Decompensated liver cirrhosis has a poor prognosis, with a median overall survival of two to four years, which is worse than for many oncological disorders. These patients are highly susceptible to infections due to increased systemic inflammation leading to kidney failure and death. The aim was to study the efficacy of albumin in reducing episodes of decompensation, preventing bacterial infection, kidney dysfunction and mortality. METHOD: Study involved patients with Child B or C cirrhosis with an albumin level below 3.0 g/dL, who were administered 20% human albumin weekly with standard medical treatment (SMT) for three months or till serum albumin levels were 4.0 g/dL (whichever is earlier) and compared with age and sex-matched controls who received only SMT. The primary end-point was six-month mortality and the secondary end-points were reduction in infections, kidney dysfunction, ascites recurrence, hepatic encephalopathy (HE), gastrointestinal (GI) bleed and complications of cirrhosis. RESULTS: From September 2021 to January 2023, 88 cases and 86 controls were taken and followed up for six months. Overall, six-month survival was not statistically significant between groups (95.1% vs. 91.9%; p = 0·330). The incidence of recurrence of ascites (34.09% vs. 59.3%, p < 0.001), kidney dysfunction (6.8% vs. 24.4%, p < 0.001), HE (15.9% vs, 37.2%, p = 0.015), spontaneous bacterial peritonitis (SBP) (3.4% vs 17.4%, p = 0.002) and non-SBP infections (7.9% vs. 18.6%, p = 0.038) were significantly less in cases as compared with controls; however, GI bleed (14.8% vs. 17.4%, p = 0.632) was not statistically significant. CONCLUSION: Long-term human albumin acts as a disease-modifying treatment in patients with decompensated cirrhosis.

Novel approaches in the medical management of compensated cirrhosis.

INTRODUCTION: Classically, clinical practice guidelines and expert recommendations have focused on the management of decompensated cirrhotic patients, so we focused this review on improving care for compensated cirrhotic patients who are followed up in outpatient clinics. AREAS COVERED: We reviewed the current methods for establishing liver function, the diagnosis and management of advanced chronic liver disease and clinically significant portal hypertension as well as the prevention of its complications, with special attention to covert hepatic encephalopathy, we also paid attention to the extrahepatic complications of cirrhosis and the palliative care. All this from the perspective of evidence-based medicine and trying to empower precision medicine. The literature search was undertaken by PubMed with 'cirrhosis,' 'advanced chronic liver disease,' 'liver function,' 'portal hypertension,' 'covert hepatic encephalopathy,' 'minimal hepatic encephalopathy,' 'palliative care' as MeSH terms. EXPERT OPINION: We must offer compensated cirrhotic patients specific care and measures to prevent the progression of the disease and the appearance of its complications beyond the calculation of liver function and imaging screening for hepatocellular carcinoma that we perform every six months. Entities that have typically received little attention, such as covert hepatic encephalopathy, extrahepatic complications and symptoms of cirrhosis, and palliative care, must come to the spotlight.

Triglyceride-Glucose Index is an Independent Risk Factor for Hepatocellular Carcinoma Development in Patients with HBV-Related Liver Cirrhosis.

Aim: This study aimed to explore the effects of the triglyceride-glucose (TyG) index on hepatocellular carcinoma (HCC) development in patients with hepatitis B virus (HBV)-related liver cirrhosis (LC). Methods: A total of 242 patients with HBV-related LC were enrolled and followed-up. Logistic regression analysis was performed to investigate risk factors for HCC. Results: The median follow-up time was 37 months (range: 6-123 months). At the end of the follow-up, 11 (11.3%) patients with compensated cirrhosis (CC) and 45 (31.0%) with decompensated cirrhosis (DC) developed HCC. The TyG index was higher in the HCC group than in the non-HCC group (P=0.05). Univariate analysis showed that age (P<0.01), DC (P<0.01), TyG index (P=0.08), albumin (ALB) level (P=0.05), platelet (PLT) count (P<0.01), and HBV DNA positivity (P<0.01) were associated with HCC development. Multivariate analysis revealed that age, DC, TyG index, PLT count, and HBV DNA positivity were independent risk factors for HCC development (P=0.01, 0.01, <0.01, 0.05, and <0.01, respectively). For patients with DC, multivariate logistic regression analysis revealed that age, TyG index, and HBV DNA positivity were independent risk factors for HCC development (all P<0.05). A new model encompassing age, DC, TyG, PLT, and positive HBV DNA had optimal predictive accuracy in patients with DC or CC, with a cutoff value of 0.197. The areas under the receiver operating characteristic curves (AUROCs) of the model for predicting HCC development in patients with LC, DC, and CC were 0.778, 0.721, and 0.783, respectively. Conclusion: TyG index was identified as an independent risk factor for HCC development in patients with LC.

Reduced bone mineral density is associated to post-TIPS survival of female patients with decompensated cirrhosis.

BACKGROUND: Malnutrition is common in patients with cirrhosis, eventually leading to sarcopenia and loss of bone mass. AIMS: The aims of this study was the assessment of body composition (BC) and bone mineral density (BMD) in patients with decompensated cirrhosis and the prognostic impact on survival after transjugular intrahepatic portosystemic shunt (TIPS) implantation. METHODS: BMD and BC of 107 patients with cirrhosis undergoing TIPS implantation were prospectively analyzed by dual-energy X-ray absorptiometry. The prevalence and predisposing risk factors for reduced BMD and sarcopenia were assessed. Impact on 12-month survival after TIPS implantation was evaluated. RESULTS: Sarcopenia was diagnosed in 48.6 % of the patients with a predominance of male patients (58.7% vs. 25.0 %, p = 0.001). 67.2 % had reduced BMD. Low BMI was independently associated with sarcopenia (OR 0.751 (95 % CI: 0.662;0.852), p < 0.001) and reduced BMD (OR 0.851 (0.773;0.937), p = 0.001). Patients with reduced BMD, but not sarcopenia, had impaired 12-month survival after TIPS-implantation (61.2% vs. 82.9 %, p = 0.030). Subgroup analysis showed that this was especially valid for female patients. CONCLUSIONS: Sarcopenia and reduced BMD are frequently observed in patients with decompensated cirrhosis. Reduced BMD negatively affects post-TIPS survival. Since malnutrition is a leading cause, assessment of nutritional status and specific treatment should be included in clinical practice.

Influence of further decompensation on survival across clinical stages of decompensated cirrhosis: The role of portal hypertension and HVPG changes.

BACKGROUND AND AIMS: Decompensated-cirrhosis encompasses several stages with different prognosis, such as bleeding, ascites and bleeding-plus-ascites. Development of further-decompensation worsens survival, while non-selective ß-blockers (NSBBs) can modify the risk. However, how this applies to each stage is uncertain. We aimed to investigate, in each stage of decompensated-cirrhosis, the influence of further-decompensation on mortality and whether changes in portal-pressure (HVPG) under NSBBs influence these outcomes. METHODS: Patients with variceal bleeding were consecutively included differentiating those with bleeding-alone from those who also had ascites. Patients with ascites and high-risk varices referred for primary-prophylaxis were also investigated. A baseline haemodynamic study was performed and was repeated after 1-3-months under NSBBs. Outcomes were investigated by competing-risk. RESULTS: Totally 103 patients had bleeding-alone, 186 bleeding-plus-ascites and 187 ascites-alone. Mean follow-up was 32-months (IQR, 12-60). Patients with bleeding-plus-ascites had higher HVPG and were more hyperdynamic than patients with ascites-alone and these than those with bleeding-alone. At each stage, the mortality risk was more than twice in patients developing further-decompensation vs. those without (p < .001). In each stage, HVPG-decrease under NSBBs showed better discrimination to predict further-decompensation than the baseline MELD, Child-Pugh or HVPG, by time-dependent ROC-curves (c-statistic >70%). At each stage, patients without HVPG-decreases, either ≥10% or ≥20% from the baseline, had higher risk of further-decompensation (sHR from 2.43 to 6.73, p < .01) and worse survival. CONCLUSIONS: In each stage of decompensated cirrhosis, mortality risk significantly and very markedly increase with further-decompensation. HVPG-non-response to NSBBs may adequately stratify the risk of further decompensation and death, in each stage. This suggests potential benefit with pre-emptive therapies in HVPG-non-responders at each-stage.

D-dimer-to-platelet count ratio as a novel indicator for predicting prognosis in HBV-related decompensated cirrhosis.

Background: Hepatitis B virus-related decompensated cirrhosis (HBV-DC) is a critical illness with a low survival rate. Timely identification of prognostic indicators is crucial for risk stratification and personalized management of patients. The present study aimed to investigate the potential of the D-dimer-to-platelet count ratio (DPR) as a prognostic indicator for HBV-DC. Methods: A retrospective review of medical records was conducted for 164 patients diagnosed with HBV-DC. Baseline clinical and laboratory characteristics were extracted for analysis. The endpoint was 30-day mortality. Disease severity was assessed by the Model for End-stage Liver Disease (MELD) score. A multivariate logistic regression model and receiver operating characteristic curve analysis (ROC) were used to evaluate the predictive value of DPR for mortality. Results: During the 30-day follow-up period, 30 (18.3%) patients died. Non-survivors exhibited significantly higher DPR values than survivors, and a high DPR had a strong association with increased mortality. Importantly, DPR was identified as an independent risk factor for mortality in HBV-DC patients after adjustments for confounding factors (Odds ratio = 1.017; 95% Confidence interval, 1.006-1.029; p = 0.003). The cut-off value of DPR as a predictor of mortality was>57.6 (sensitivity = 57%, specificity = 86%, p < 0.001). The area under ROC curve for DPR for 30-day mortality was 0.762, comparable to the MELD score (p = 0.100). Furthermore, the combined use of DPR and MELD score further increased the area under the ROC curve to 0.897. Conclusion: Elevated DPR was demonstrated to have a correlation with unfavorable outcomes in HBV-DC patients, suggesting its potential utility as an effective biomarker for assessment of prognosis in these patients.

Hospital-Level Care at Home for Patients with Cirrhosis.

BACKGROUND: Patients with cirrhosis have a 30-day readmission rate of over 30%. Novel care delivery models are needed to reduce healthcare costs and utilization associated with cirrhosis care. One such model is Home Hospital (HH), which provides inpatient-level care at home. Limited evidence currently exists supporting HH for cirrhosis patients. AIMS: The aims of this study were to characterize patients with cirrhosis who received hospital-level care at home in a two-site clinical trial and to describe the care they received. Secondary aims included describing their outcomes, including adverse events, readmissions and mortality. METHODS: We identified all patients with cirrhosis who enrolled in HH as part of a two-site clinical trial between 2017 and 2022. HH services include daily clinician visits, intravenous and oral medications, continuous vital sign monitoring, and telehealth specialist consultation. We collected sociodemographic data and analyzed HH stays, including interventions, outcomes, adverse events, and follow-up. RESULTS: 22 patients with cirrhosis (45% Hispanic; 50% limited English proficiency, median MELD-Na 12) enrolled in HH during the study period. Interventions included lab chemistries (82%), intravenous medications (77%), specialist consultation (23%), and advanced diagnostics/procedures (23%). The median length of stay was 7 days (IQR 4-12); 186 bed-days were saved. Two patients (9%) experienced adverse events (AKI). No patients required escalation of care; 9% were readmitted within 30 days. CONCLUSIONS: In this two-site study, HH was feasible for patients with cirrhosis, holding promise as a hepatology delivery model. Future randomized trials are needed to further evaluate the efficacy of HH for patients with cirrhosis.

Preventing Readmissions of Hepatic Encephalopathy: Strategies in the Acute Inpatient, Immediate Postdischarge, and Longitudinal Outpatient Setting.

Hepatic encephalopathy (HE) is a strong predictor of early hospital readmission in patients with cirrhosis. Early hospital readmission increases health care costs and is associated with worse survival. Herein we provide an overview of strategies to prevent hospital readmissions in patients with HE, divided into 3 contexts: (a) acute inpatient, (b) immediate postdischarge, and (c) longitudinal outpatient setting.

The challenges and potential of microRNA-based therapy for patients with liver failure syndromes and hepatocellular carcinoma.

INTRODUCTION: Morbidity and mortality from liver disease continues to rise worldwide. There are currently limited curative treatments for patients with liver failure syndromes, encompassing acute liver failure and decompensated cirrhosis states, outside of transplantation. Whilst there have been improvements in therapeutic options for patients with hepatocellular carcinoma (HCC), there remain challenges necessitating novel therapeutic agents. microRNA have long been seen as potential therapeutic targets but there has been limited clinical translation. AREAS COVERED: We will discuss the limitations of conventional non-transplant management of patients with liver failure syndromes and HCC. We will provide an overview of microRNA and the challenges in developing and delivering microRNA-based therapeutic agents. We will finally provide an overview of microRNA-based therapeutic agents which have progressed to clinical trials. EXPERT OPINION: microRNA have great potential to be developed into therapeutic agents due to their association with critical biological processes which govern health and disease. Utilizing microRNA sponges to target multiple microRNA associated with specific biological processes may improve their therapeutic efficacy. However, there needs to be significant improvements in delivery systems to ensure the safe delivery of microRNA to target sites and minimize systemic distribution. This currently significantly impacts the clinical translation of microRNA-based therapeutic agents.

Severe hepatitis E virus genotype 3b in a patient with alcohol­associated liver disease: A case report.

Hepatitis E virus (HEV) infection occasionally causes acute-on-chronic liver failure in patients with alcohol-associated cirrhosis. These reports have been published mainly from highly HEV genotype 1-endemic countries. The present study describes the case of a patient with severe HEV genotype 3b infection and alcohol-associated liver disease. A male patient in his 70s who consumed alcohol, and who had begun consuming alcohol at the age of 12, had high levels of alanine aminotransferase (ALT) and total bilirubin. The peak levels of ALT and total bilirubin were 1,067 IU/l and 26.3 mg/dl, respectively. A computed tomography scan revealed an atrophic liver. Upon admission, both anti-HEV immunoglobulin A and HEV RNA were positive, and his HEV was genotype 3b. He also had chronic kidney disease, as his estimated glomerular filtration rate was <45 ml/min/1.73 m2, and ribavirin could not be used. The abnormal levels of the liver function parameters of the patient gradually improved due to conservative treatment, and he was discharged on day 43. On the whole, the present study demonstrates that careful attention should be paid to patients with viral hepatitis, including hepatitis E, when alcohol-associated liver disease is present. Novel anti-HEV drugs need to be developed for severe HEV infections with chronic kidney disease.

Efficacy of fresh frozen plasma transfusion in decompensated cirrhosis patients with coagulopathy admitted to ICU: a retrospective cohort study from MIMIC-IV database.

We aimed to explore the association between FFP transfusion and outcomes of DC patients with significant coagulopathy. A total of 693 DC patients with significant coagulopathy were analyzed with 233 patients per group after propensity score matching (PSM). Patients who received FFP transfusion were matched with those receiving conventional therapy via PSM. Regression analysis showed FFP transfusion had no benefit in 30-day (HR: 1.08, 95% CI 0.83-1.4), 90-day (HR: 1.03, 95% CI 0.80-1.31) and in-hospital(HR: 1.30, 95% CI 0.90-1.89) mortality, associated with increased risk of liver failure (OR: 3.00, 95% CI 1.78-5.07), kidney failure (OR: 1.90, 95% CI 1.13-3.18), coagulation failure (OR: 2.55, 95% CI 1.52-4.27), respiratory failure (OR: 1.76, 95% CI 1.15-2.69), and circulatory failure (OR: 2.15, 95% CI 1.27-3.64), and even associated with prolonged the LOS ICU (ß: 2.61, 95% CI 1.59-3.62) and LOS hospital (ß: 6.59, 95% CI 2.62-10.57). In sensitivity analysis, multivariate analysis (HR: 1.09, 95%CI 0.86, 1.38), IPTW (HR: 1.11, 95%CI 0.95-1.29) and CAPS (HR: 1.09, 95% CI 0.86-1.38) showed FFP transfusion had no beneficial effect on the 30-day mortality. Smooth curve fitting demonstrated the risk of liver failure, kidney failure and circulatory failure increased by 3%, 2% and 2% respectively, for each 1 ml/kg increase in FFP transfusion. We found there was no significant difference of CLIF-SOFA and MELD score between the two group on day 0, 3, 7, 14. Compared with the conventional group, INR, APTT, and TBIL in the FFP transfusion group significantly increased, while PaO2/FiO2 significantly decreased within 14 days. In conclusion, FFP transfusion had no beneficial effect on the 30-day, 90-day, in-hospital mortality, was associated with prolonged the LOS ICU and LOS hospital, and the increased risk of liver failure, kidney failure, coagulation failure, respiratory failure and circulatory failure events. However, large, multi-center, randomized controlled trials, prospective cohort studies and external validation are still needed to verify the efficacy of FFP transfusion in the future.