Alcohol-related Cirrhosis Research Articles

Safety of naltrexone in patients with cirrhosis

Treatment of alcohol use disorder (AUD) improves survival in patients with alcohol-related cirrhosis. However, medications for alcohol use disorder (MAUD) are underutilized in this population, partially due to concerns regarding drug-induced liver injury (DILI). Our aim was to evaluate the safety of naltrexone in patients with cirrhosis. This was a retrospective study of patients with cirrhosis who were prescribed naltrexone using the VOCAL (Veterans Outcomes and Costs Associated with Liver Disease) database. Patients with new initiation of naltrexone after diagnosis of cirrhosis who had liver enzymes checked within a 3-month time frame were included. A chart review was performed on patients who developed alanine aminotransferase or alkaline phosphatase elevations to more than 2× or 5× the upper limit of normal, respectively. The RUCAM (Roussel Uclaf causality assessment method) was used to determine if DILI occurred. A total of 3,285 patients with cirrhosis were initiated on naltrexone, of whom 2,940 had laboratory testing during the high-risk DILI period. Only 2% of patients had liver enzyme elevations, and among those, 30 (48%) were classified as "DILI excluded" and 32 (52%) were classified as "DILI unlikely". No patients were classified as possible, probable, or highly probable DILI. No deaths or new decompensations were attributed to naltrexone. Naltrexone in patients with cirrhosis was not associated with development of DILI using RUCAM scoring. Naltrexone appears to be safe in patients with compensated and decompensated cirrhosis. Naltrexone is an effective medication for treating alcohol use disorder but is underutilized in patients with underlying liver disease due to historical concerns regarding hepatotoxicity. This retrospective study shows no drug-induced liver injury in a large cohort of patients with cirrhosis with new initiation of naltrexone. This study may encourage providers to prescribe naltrexone to patients with existing liver disease with ongoing alcohol use disorder.

Evaluation of D-dimer and prothrombin time in alcohol related liver cirrhosis with comparison of machine learning analyses

ObjectivesLiver cirrhosis (LC) can be caused by obesity, alcohol consumption, viral infection, and autoimmune disease. Early diagnosis and management of LC is important for patient quality of life. Non-invasive diagnostic methods are useful for predicting the current status and mortality risk of LC. The purpose of this study is to identify relevant diagnostic factors measured in routine laboratory test of alcohol-related liver cirrhosis (ALC) patients. MethodsThis study analyzed data from 127 patients with ALC, including their laboratory test results and clinical information, including coagulation parameters, hematologic parameters, and biochemical parameters. These data were used to compare the performance of the prediction models from three machine learning algorithms including K-nearest neighbor (KNN), support vector machine (SVM), and random forest (RF). ResultsHigher Model for End-stage Liver Disease (MELD) score were associated with prothrombin time (PT) and D-dimer. Logistic and multiple linear regression analyses revealed significant factors predicting mortality in the MELD group. Machine learning approaches were used to predict death in ALC patients using some laboratory parameters associated with mortality. The prediction model based on SVM exhibited better prediction performance than others. ConclusionPT and D-dimer were the factors that were most strongly associated with 90-day mortality, and machine learning methods can create prediction models with good predictive power.

Enfermedad hepática relacionada con el alcohol

Alcohol-related liver disease (ALD) is one of the leading causes of chronic liver disease worldwide. It encompasses a variety of disorders that result from alcohol consumption, including simple steatosis, alcohol-related hepatic steatosis, alcoholic hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. In addition, some individuals with established disease and high alcohol intake may develop alcoholic hepatitis, a disease with a high mortality rate. There is no specific treatment for ALD. Its management is based on addressing the alcohol use disorder to achieve abstinence, which is the major prognostic factor along with the presence of fibrosis. Therefore, education, prevention, and early diagnosis strategies are essential for reducing the burden of ALD.

Hepatocellular Carcinoma among Patients with Chronic Liver Disease in a Tertiary Care Centre: A Descriptive Cross-sectional Study

Introduction: Hepatocellular carcinoma is the most common primary liver cancer. Viral hepatitis, alcohol abuse, and autoimmune hepatitis are the common causes of hepatocellular carcinoma. Usually patients present at advanced stages where curative treatment is no longer possible. This study aimed to find the prevalence of hepatocellular carcinoma among patients with chronic liver disease in a tertiary care centre. Methods: This is a descriptive cross-sectional study conducted in a single tertiary care centre from March 2020 to August 2022. The study was done among inpatients of the Department of Gastroenterology after ethical approval from the Institutional Review Committee. A total population sampling method was used and data were collected using predetermined proformas. Point estimate at 95% Confidence Interval was calculated. Results: Among 1440 patients, hepatocellular carcinoma was seen in 54 (3.75%) (2.77-4.73, 95% Confidence Interval). At the time of diagnosis, 48 (88.89%) were symptomatic. The presenting symptoms were weight loss seen in 35 (64.81%) being the most common. Out of them, 37 (68.52%) consumed alcohol and 40 (74.07%) smoked cigarettes. Conclusions: Hepatocellular carcinoma is a notable concern. Alcohol-related liver cirrhosis is the most frequent condition encountered in patients with hepatocellular carcinoma in our setting.

Increasing prevalence of cirrhosis among insured adults in the United States, 2012-2018.

Liver cirrhosis is a chronic disease that is known as a "silent killer" and its true prevalence is difficult to describe. It is imperative to accurately characterize the prevalence of cirrhosis because of its increasing healthcare burden. In this retrospective cohort study, trends in cirrhosis prevalence were evaluated using administrative data from one of the largest national health insurance providers in the US. (2011-2018). Enrolled adult (≥18-years-old) patients with cirrhosis defined by ICD-9 and ICD-10 were included in the study. The primary outcome measured in the study was the prevalence of cirrhosis 2011-2018. Among the 371,482 patients with cirrhosis, the mean age was 62.2 (±13.7) years; 53.3% had commercial insurance and 46.4% had Medicare Advantage. The most frequent cirrhosis etiologies were alcohol-related (26.0%), NASH (20.9%) and HCV (20.0%). Mean time of follow-up was 725 (±732.3) days. The observed cirrhosis prevalence was 0.71% in 2018, a 2-fold increase from 2012 (0.34%). The highest prevalence observed was among patients with Medicare Advantage insurance (1.67%) in 2018. Prevalence increased in each US. state, with Southern states having the most rapid rise (2.3-fold). The most significant increases were observed in patients with NASH (3.9-fold) and alcohol-related (2-fold) cirrhosis. Between 2012-2018, the prevalence of liver cirrhosis doubled among insured patients. Alcohol-related and NASH cirrhosis were the most significant contributors to this increase. Patients living in the South, and those insured by Medicare Advantage also have disproportionately higher prevalence of cirrhosis. Public health interventions are important to mitigate this concerning trajectory of strain to the health system.

Health disparities in time to diagnosis and survival post-diagnosis of cirrhosis in individuals with alcohol use disorder: A retrospective cohort study

ObjectiveThis study investigates the impact of race, gender, and ethnicity on the progression from diagnosis to cirrhosis and subsequent survival in patients with alcohol use disorder, with a specific focus on identifying potential disparities in health outcomes. MethodEmploying a STROBE-compliant, retrospective cohort design, we analyzed data from patients diagnosed with alcohol use disorder from January 2000 to December 2022, using the University of California Health Data Warehouse. We estimated survival functions using the Kaplan–Meier method and assessed demographic associations using both bivariate and multivariate Cox proportional hazards models. ResultsThe analysis highlighted a significant association between Hispanic ethnicity and an accelerated timeline for both the diagnosis of alcohol-related cirrhosis following diagnosis of alcohol use disorder and mortality post-cirrhosis diagnosis. The former was evident only in bivariate analysis, but the latter association persisted in multivariate analysis. Gender did not demonstrate a significant correlation with the time to these outcomes, though multiracial identification emerged as a protective factor. ConclusionsThe study reveals critical health disparities in the progression and outcomes of cirrhosis, particularly between Hispanic and non-Hispanic patients. These findings underscore the urgent need for targeted healthcare interventions and policies that address these disparities. Future research should delve deeper into the multifaceted factors influencing these outcomes, facilitating the development of more nuanced and effective prevention and treatment strategies for alcohol use disorder and its severe complications.

Human Neutrophil Alpha-Defensins Promote NETosis and Liver Injury in Alcohol-Related Liver Cirrhosis: Potential Therapeutic Agents.

Background: Neutrophils are thought to play a pivotal role in the pathogenesis of many inflammatory diseases, such as hepatitis, liver cirrhosis, etc. Activated human neutrophils release human neutrophil peptides (HNP1-3) or alpha-defensins that are antimicrobial peptides in azurophil granules. Furthermore, HNP1-3 build a scaffold of neutrophil extracellular traps (NETs) and promote the process of programmed cell death called NETosis. Our study aimed to investigate the role of alpha-defensins in the pathogenesis of alcohol-related liver cirrhosis (ALC). Methods: The concentrations of alpha-defensins in the plasma of 62 patients with ALC and 24 healthy subjects were measured by ELISA. The patients with ALC were prospectively recruited based on the severity of liver dysfunction according to the Child-Pugh and Model of End-Stage Liver Disease-Natrium (MELD-Na) scores, modified Maddrey's Discriminant Function (mDF), and the presence of ALC complications. Results: The concentrations of alpha-defensins in plasma were significantly higher in the ALC patients than in the controls. The plasma levels of HNP1-3 correlated with the MELD and mDF scores. ALC subgroups with MELD > 20 and mDF > 32 displayed significantly higher HNP1-3 concentrations. The plasma levels of HNP1-3 revealed a good predictive AUC for hepatic encephalopathy and ascites development (0.81 and 0.74, respectively) and for patient survival (0.87) in those over 40 years of age. Conclusion: These findings suggest that alpha-defensins play an important role in the assessment of ALC.

A95 INCIDENCE OF LUMINAL GASTROINTESTINAL CANCERS IN PATIENTS WITH CIRRHOSIS: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract Background The global incidence of cirrhosis is increasing, as is the incidence of luminal gastrointestinal cancers. It is unknown, however, if cirrhosis itself is a predisposing factor for luminal gastrointestinal cancer. Such an association would have significant clinical implications, particularly for cancer screening prior to liver transplantation. Aims To investigate the incidence of luminal gastrointestinal cancers in patients with underlying cirrhosis. Methods An electronic search was conducted to study the incidence of luminal gastrointestinal cancers in patients with cirrhosis. Study-specific standardized incidence ratios (SIR) along with their corresponding 95% confidence intervals for both overall cancer incidence and luminal cancer incidence were analyzed using a random-effects model. Statistical heterogeneity was assessed using the Cochran’s Q test and I2 statistic. Subgroup analysis was performed based on cirrhosis etiology and location of luminal malignancy. Results We identified 5054 articles; 4 studies were selected for data extraction. The overall incidence of all cancers was significantly higher in patients with cirrhosis, with a SIR of 2.79 (95% CI 2.18–3.57). When stratified by cirrhosis etiology, the incidence of all cancers remained significantly elevated for alcohol (SIR 3.13, 95% CI 2.24–4.39), PBC (SIR 1.40, 95% CI 1.10–1.79), and unspecified cirrhosis (SIR 3.52, 95% CI 1.87–6.65). Unspecified cirrhosis had the greatest overall cancer risk followed by alcohol, and PBC cirrhosis (p ampersand:003C 0.01). Alcohol related cirrhosis was significantly associated with an increased incidence of luminal cancers (SIR 4.39, 95% CI 2.84–6.78). Specifically, the highest incidence was observed for oral cavity and pharyngeal cancer (SIR 10.44, 95% CI 8.90–12.24), followed by esophageal cancer (SIR 7.85, 95% CI 4.98–12.36), and colorectal cancer (SIR 2.43, 95% CI 1.62–3.66) (p ampersand:003C 0.01). PBC cirrhosis was significantly associated with an increased incidence of luminal cancers (SIR 2.11, 95% CI 1.10–4.04). However, subgroup analysis did not reveal a significant association with the incidence of any subgroups. Unspecified cirrhosis was significantly associated with an increased incidence of luminal cancers (SIR 2.60, 95% CI 1.65–4.09). Risk of oral cavity and pharynx cancers (SIR 4.75, 95% CI 2.18–10.33) were greatest, followed by esophageal (SIR 4.52, 95% CI 1.57–12.99), stomach (SIR 2.12, 95% CI 1.31–3.42), and colorectal cancer (SIR 1.57, 95% CI 1.14–2.16) (p = 0.03). Conclusions The incidence of luminal gastrointestinal cancer is increased amongst patients with cirrhosis. Oral cavity, pharyngeal and esophageal cancer had increased incidence across all cirrhosis etiologies compared to gastric and colorectal cancer. Therefore, increased screening of luminal cancers should be considered in this population. Funding Agencies None

A159 MALIGNANT PERITONEAL MESOTHELIOMA: A CASE OF MISTAKEN IDENTITY

Abstract Background In the Western hemisphere, cirrhosis is the most common cause of ascites. One of the least common causes is malignant peritoneal mesothelioma (MPM), which occurs in one in one million cases. MPM can be a diagnostic challenge due to its rarity and features that mimic other causes of ascites. Aims To describe a complex case of MPM, highlighting the diagnostic dilemma stemming from the subtleties of presentation, confounders in ascites diagnostic criteria, and indeterminate testing. Methods We performed a detailed retrospective chart review of a patient who presented with ascites. He was initially given the diagnosis of decompensated cirrhosis and eventually was diagnosed with MPM. He provided his consent for this case report. Results A 37-year-old male presented with progressive ascites and peripheral edema. He had no known exposure to asbestos and consumed 6 standard drinks a day for 2 years; with a prior history of 10 standard drinks a week for over 3 years. His physical examination was unremarkable for cardiac, renal or liver disease. His transthoracic echocardiogram and urinalysis were normal. Abdominal ultrasound showed features of liver cirrhosis with large-volume ascites and a FIB-4 score of 0.34, excluding advanced fibrosis Laboratory investigations including liver tests were normal; with a platelet count of 568 x 109/L. Viral, metabolic and autoimmune liver disease were excluded. A diagnostic paracentesis demonstrated a serum albumin-ascites gradient (SAAG) of 1.3 g/dL. Due to his history of alcohol misuse, imaging findings and high SAAG, he was diagnosed with alcohol-related cirrhosis. His repeat abdominal ultrasound showed multiple liver nodules. Magnetic resonance imaging was done to investigate for hepatocellular carcinoma; revealing diffuse peritoneal carcinomatosis, cirrhosis and large-volume ascites. Investigations to identify the primary malignancy included a computed tomography chest, colonoscopy and EGD. His EGD was the only positive test; showing a 2cm submucosal gastric lesion with normal gastric mucosa pathology. An endoscopic ultrasound (EUS) with fine needle aspiration was then performed; the lesion appearance in keeping with a gastrointestinal stromal tumor (GIST). Pathology favored a diagnosis of poorly differentiated gastric carcinoma. Cytology was positive for malignancy, with the differential being mesothelioma or adenocarcinoma and a repeat SAAG was 1.0 g/dL. Given the discordances, an ultrasound-guided core biopsy was performed of the peritoneal lesions. Pathology revealed features of poorly differentiated epithelioid mesothelioma. A subsequent review of his gastric biopsies revealed similar cells in retrospect were in keeping with mesothelioma. Conclusions The presentation of MPM is not easily distinguishable from other causes of ascites. There must be a high degree of suspicion for malignant ascites in the face of inconsistent clinical and diagnostic findings. Funding Agencies None

A299 ACUTE TUMOUR RUPTURE POST-TRANSARTERIAL CHEMOEMBOLIZATION IN A PATIENT WITH HEPATOCELLULAR CARCINOMA

Abstract Background Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, with increasing worldwide incidence. Transarterial chemoembolization (TACE) is an interventional radiological (IR) therapy used largely in intermediate stage HCC, which can provide successful bridge or downstaging to liver transplantation and increased survival rates. Tumour rupture is a very rare complication of TACE, with an estimated incidence of 0.68%. Potential risk factors include tumour size ampersand:003E 10 cm, and location of lesions in the right lobe or near the liver capsule. However, the pathophysiology of post-TACE tumour rupture is still not fully understood. Aims We aim to describe a case of HCC tumour rupture that occurred in the first 30 hours post-TACE. We also aim to highlight the extent of multiorgan ischemia associated with this tumour-related arterial bleed. Methods A PubMed literature review was done to ensure that post-TACE tumour rupture was a rare and sparsely reported event. Subsequently, inpatient notes, laboratory and imaging data were obtained from the patient's medical record in an anonymized manner. Results A 66-year-old male with alcohol-related liver cirrhosis (MELDNa 7; Child-Pugh Class A) was diagnosed with a 3.3 cm HCC, spanning segments 5 and 8. Six months later, after multidisciplinary discussion, he underwent successful elective TACE of a segment 8 artery that was supplying the HCC, as a bridge to liver transplantation. The next day, he developed diffuse abdominal pain, emesis, tachycardia, and abdominal firmness and tenderness. Labs showed a 45 g/L drop in hemoglobin (121 g/L to 76 g/L), leukocytosis (27.0 x109/L), and an elevated lactate (4.4 mmol/L). Computed tomography (CT) scan confirmed tumour rupture, with moderate-to-large hemoperitoneum with active bleeding from the embolized region of the HCC, and associated gas. Emergent IR-guided embolization was performed to the bleeding segment 8 artery. CT scan two days later revealed interval ischemic infarction of the spleen, pancreatic tail, and stomach. This widespread ischemia was suspected to be due to hypovolemic hypoperfusion vs. post-TACE embolic phenomena. Aggressive supportive measures, antibiotics, and anticoagulation were implemented. Due to tumour rupture, the patient was deemed no longer a suitable candidate for liver transplantation. Futility of definitive management was discussed, and the patient opted for medical care without resuscitation. After optimization of nutritional and physical functioning parameters, he was discharged home with medical management for pain and ascites. Conclusions Post-TACE tumour rupture is a rare occurrence for which the pathophysiology is not fully understood. This case provides an important reminder of this potential adverse event. Early detection and management are imperative to facilitating a favourable outcome in this life-threatening condition. Funding Agencies None

Analysis and prediction of disease burden of cirrhosis and other chronic liver diseases due to alcohol use in China from 1990 to 2030

Objective: To comprehensively understand the disease burden of liver cirrhosis and other chronic liver diseases caused by alcohol use in China from 1990 to 2019, as well as to predict the trends in disease burden from 2020 to 2030. Methods: The analysis utilized data from the Global Burden of Disease study in 2019 (GBD2019). Key indicators such as incidence rate, mortality rate, disability-adjusted life years (DALY), years of life lost due to premature mortality, and years lived with disability were selected to describe the disease burden of alcohol-related liver cirrhosis and other chronic liver diseases in China from 1990 to 2019. The estimated annual percentage change (EAPC) was used to depict the temporal trends in disease burden. Furthermore, a Bayesian age-period-cohort (BAPC) model was constructed using R software to predict the age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) of alcohol-related liver cirrhosis and other chronic liver diseases in China from 2020 to 2030. Results: From 1990 to 2019, the incidence of alcohol-related liver cirrhosis and other chronic liver diseases in China showed an upward trend, with an EAPC of 0.31% (95%CI: 0.10%-0.52%). However, the DALY declined, with an EAPC of -2.81% (95%CI: -2.92% - -2.70%). The ASMR showed a downward trend, with an EAPC of -2.55% (95%CI: -2.66% - -2.45%). The highest incidence of cirrhosis of liver caused by alcohol and other chronic liver diseases was reported in the age group of 35-49 years, while the ASMR increased gradually with age, with a significant rise after the age of 30. The age-standardized DALY rate peaked between the ages of 55 and 64. The disease burden indicators for males were consistently higher than those for females during the same period. According to the predictions of the BAPC model, from 2020 to 2030, the ASIR for cirrhosis of liver caused by alcohol and other chronic liver diseases in the entire population of China was projected to increase from 3.45/100 000 in 2020 to 3.78/100 000 in 2030, a growth of 9.57%. Conversely, the ASMR was expected to decrease from 1.45/100 000 in 2020 to 1.24/100 000 in 2030, a reduction of 14.48%. Conclusions: The disease burden of cirrhosis of liver caused by alcohol and other chronic liver diseases remained serious in China, especially in men and the middle-aged to elderly population. There is a pressing need to prioritize attention and resources towards these groups. Despite the projected decrease in ASMR, the ASIR continued to rise and is expected to persist in its upward trend until 2030.

Alcoholism and Socioeconomic Status among Patients with Hepatic Encephalopathy in Association with Increased Mortality.

Hepatic encephalopathy (HE) is a complex neuropsychiatric disorder indicated by a deterioration in the functioning of hepatocytes. Impaired brain function is observed in advanced alcoholic liver disease particularly manifesting as HE. The pathophysiology of alcohol-related HE remains unclear. Accordingly, this study aimed to assess alcoholism and socioeconomic status of patients with liver disease compared with stages of HE. This cross-sectional study was conducted on 62 alcoholic patients who have been consuming alcohol for more than 14 years. Patients were recruited based on the assessment of clinical symptoms and diagnosed according to the MELD and Child-Pugh scoring systems. Descriptive statistics including demographic details and clinical features of patients were classified based on alcoholism and socioeconomic status. Patients belonging to the lower- and middle-income classes were more in number with a mean age of 46.66±10.21 and 47.14±6.36 years, respectively compared to upper-middle- and upper-income classes. The amount of alcohol intake was 116.59±45.60 in the middle class and 110.0±62.45 in the upper class. Increased progression of HE leads to a rise in the mortality rate due to higher consumption of alcohol. HE is a severe complication in alcohol-related liver cirrhosis that contributes to impaired cognitive function in patients.

A Comparison of the Effects of Alcohol Abstinence and Drinking Habit on the Survival of Patients with Alcohol-related Cirrhosis: A Retrospective Observational Study.

Objective Abstaining from alcohol improves the outcome of alcohol-related cirrhosis. This study evaluated the effect of alcohol abstinence on the outcomes of patients with alcohol-related cirrhosis recruited from a core hospital in Boso Peninsula, Japan. Methods This single-center retrospective study recruited 116 patients with alcohol-related cirrhosis who were admitted to our department between April 2014 and October 2022. Taking the day of discharge as day 0, the patients were divided into two groups based on their subsequent behavior (abstinence/non-abstinence from alcohol). The study analysis included 98 patients after excluding 13 who died during hospitalization and 5 for whom follow-up at our hospital ended after discharge. We evaluated differences in the patient survival between the abstaining and drinking groups. Results The abstaining and drinking groups comprised 57 and 41 patients, respectively. We excluded from the analysis 10 and 6 patients with viable hepatocellular carcinoma in the abstaining and drinking groups, respectively. The findings revealed that the survival rate plateaued in the abstaining group from the third year onward, whereas the survival rate in the drinking group gradually decreased with time. Conclusion Our findings suggest that at least two years of alcohol abstinence is required to sustain the survival of patients with alcohol-related cirrhosis. The data collected by our hospital retrospectively demonstrated the importance of abstinence on a timescale of years of sustained abstinence.

Changing spectrum and mortality disparities of etiology of liver cirrhosis in Beijing, China.

Liver cirrhosis remains a major health concern globally, but its epidemiology and etiology evolve with time. However, the changing pattern in etiology and cause of liver-related mortality for patients with cirrhosis are not fully elucidated. Herein, our aim was to characterize the temporal trend of the etiological spectrum and evaluate the impact of etiology on liver-related death among patients with compensated cirrhosis (CC) in Beijing, China. Clinical profiles of patients with CC discharged between January 2008 and December 2015 were retrieved from the Beijing hospital discharge database. The mortalities of different etiologies of cirrhosis were calculated. The risks of readmission and liver-related death associated with etiologies were evaluated by the Cox regression model. A total of 23 978 cirrhotic patients were included. The predominant cause was hepatitis B virus (HBV) (58.93%), followed by alcohol (21.35%), autoimmune (14.85%), miscellaneous etiologies (3.55%), and hepatitis C virus (HCV) (1.32%). From 2008 to 2015, the proportion of HBV-related cirrhosis decreased to 28.11%. Meanwhile, the proportions of autoimmune- and miscellaneous-related cirrhosis increased to 28.54% and 13.11%. The risk of liver-related death ranked the highest in patients with miscellaneous cirrhosis, followed by HBV-related cirrhosis, alcohol-related cirrhosis, autoimmune-related cirrhosis, and HCV-related cirrhosis. The 5-year rates of liver-related death were 22.56%, 18.99%, 18.77%, 16.01%, and 10.76%, respectively. HBV-related cirrhosis caused the highest risk of hepatocellular carcinoma (HCC)-related death, whereas alcohol- and miscellaneous-related cirrhosis caused higher risks of decompensation (DC)-related death than HBV-related cirrhosis, with hazard ratios of 1.35 (95% confidence interval [CI]: 1.24-1.48) and 1.20 (95% CI: 1.03-1.40), respectively. HBV remained a common cause of liver cirrhosis but gradually decreased. Mortality disparities existed in etiologies, with higher risks of HCC-related death in HBV-related cirrhosis, and DC-related death in alcohol- and miscellaneous-related cirrhosis.

Acute Variceal Hemorrhage in Germany-A Nationwide Study of 65,357 Hospitalized Cases: Variceal Hemorrhage in Germany.

Background: Acute variceal hemorrhage (AVH) is a frequent cause of upper gastrointestinal bleeding (UGIB) in liver cirrhosis. Most cases require urgent endoscopic intervention due to potentially life-threatening courses. Different endoscopic hemostasis techniques can be used, in particular endoscopic variceal ligation (EVL) and endoscopic sclerotherapy (EST), depending on the bleeding side (esophageal, fundal, and gastric) as well as radiological interventions (e.g., embolization and transjugular intrahepatic portosystemic shunt [TIPS]). This study aimed to investigate trends in incidence, treatment modalities, and outcome parameters, such as in-hospital mortality and adverse events in Germany. Methods: We evaluated the current epidemiological trends, therapeutic strategies, and in-hospital mortality of AVH in Germany based on the standardized hospital discharge data provided by the German Federal Statistical Office from 2010 to 2019. Results: A total of 65,357 AVH cases, predominately males (68.3%), were included in the analysis. The annual incidence rate (hospitalization cases per 100,000 persons) was 8.9. The in-hospital mortality was 18.6%. The most common underlying disease was alcohol-related liver cirrhosis (60.6%). The most common clinical complication was bleeding anemia (60.1%), whereas hypovolemic shock (12.8%) was the less frequent. In esophageal variceal hemorrhage (EVH), EVL was the most frequently performed endoscopic therapy, while in gastric variceal hemorrhage (GVH), EST and fibrin glue injection were the most commonly performed therapies. EVL showed the lowest in-hospital mortality (12.3%) in EVH, while EST showed favorable results (14% in-hospital mortality) in GVH. Combination therapies overall showed a higher in-hospital mortality and were more frequent in GVH. The presence of hypovolemic shock, AKI, sepsis, artificial ventilation, ARDS, bleeding anemia, hepatic encephalopathy, and male sex was associated with a significantly worse outcome. Conclusion: Our study provides detailed insight into the incidence, patient-related risk factors, endoscopic treatment, and in-hospital mortality in a sizeable AVH collective in Germany. These data might help improve risk stratification and treatment strategies for AVH patients in the future.

Bleeding from Varices: Still a Heavy Burden in Patients with Cirrhosis

Introduction: Bleeding from varices is a severe complication in patients with cirrhosis. Despite its treatment has been well established in the last three decades the mortality can be still high. This study compares the epidemiological features and the bleeding-related outcomes of a group of patients published about ten years ago with a more recent group of 168 consecutive patients. Methods: The diagnosis, the treatment, and the main outcomes (5-day failure, 5-day and 6-week rebleeding, 5-day and 6-week mortality) of variceal bleeding were evaluated according to the current guidelines. Results: The number of patients with cirrhosis admitted for variceal bleeding every year has progressively decreased in the last ten years. The age sex and severity of liver disease, evaluated with Child Pugh and MELD scores, were comparable in the two series. In the more recent series, there were significantly fewer patients with HCV infection and more patients with alcohol-related cirrhosis. The main outcomes of bleeding were comparable too. Overall, at 6 weeks 36.4% of patients did not overcome the bleeding episode. Conclusion: The decreasing incidence of bleeding from varices is likely attributable to antiviral treatment of HCV and HBV and the larger diffusion of beta-blockers in primary prophylaxis. Despite the larger application of the gold standard therapy, the mortality of variceal bleeding remains high in patients with cirrhosis.

Patient Portal Use and Risk of Readmissions in Decompensated Cirrhosis: Retrospective Study.

Patient portals are a common electronic medical record tool that allow for the asynchronous exchange of health information between patients and their health care teams. Patients can leverage patient portals to perform tasks such as viewing test results, reviewing clinical notes, and messaging their health care team. The impact of patient portal use on clinical outcomes in cirrhosis is unknown. In this study, we evaluated the relationship between patient portal use patterns and readmissions in cirrhosis. We identified 131 patients with decompensated cirrhosis with an index cirrhosis-related admission between May 1, 2018, and May 1, 2019. We then examined patient portal enrollment and use data during the 6-month period preceding the study period. Portal functions evaluated included sending a message, reading a message, and reading a test result. Use was categorized as active (sending a message) and passive (reading a message or test result) and was further stratified as no, moderate, or frequent use based on the frequency of portal function use compared to the mean. The primary outcomes were 90-day and overall readmissions, adjusted for age, model for end-stage liver disease-sodium, alcohol-related cirrhosis etiology, ascites, and hepatic encephalopathy. Portal functions assessed included sending a message, reading a message, and reading a result; the total number of times a portal function was performed was divided by the number of months the patient was enrolled in the patient portal during the 6-month period. The study population was 50.4% (66/131) female, with a mean age of 58 years. Enrollment in the patient portal was 63.4% (83/131), and there was no significant difference in enrollment based on clinical or demographic characteristics. For the entire cohort, 14.5% (19/131) and 22.1% (29/131) of patients were moderate and frequent active users, respectively. Of those enrolled in the patient portal, 97.6% (81/83) of patients were moderate or frequent passive users for both reading a message and reading a test result. Moderate active users had less 90-day readmissions (odds ratio 0.77, 95% CI 0.60-1.00) and overall readmissions (subdistribution hazard ratio 0.42, 95% CI 0.21-0.84), compared to nonactive users. There was no relationship between readmissions and passive use. Passive use of the patient portal is very high but is not associated with the risk of readmissions in people with decompensated cirrhosis. However, moderately active use of the patient portal is associated with a reduced risk of readmissions. Further work is needed to identify possible confounders and refine key use behaviors that may be protective with regard to the risk of readmission in this population.

Binge-pattern alcohol consumption and genetic risk as determinants of alcohol-related liver disease

Alcohol-related liver disease (ARLD) represents a major public health burden. Identification of high-risk individuals would allow efficient targeting of public health interventions. Here, we show significant interactions between pattern of drinking, genetic predisposition (polygenic risk score, PRS) and diabetes mellitus, and risk of incident ARLD, in 312,599 actively drinking adults in UK Biobank. Binge and heavy binge drinking significantly increase the risk of alcohol-related cirrhosis (ARC), with higher genetic predisposition further amplifying the risk. Further, we demonstrate a pronounced interaction between heavy binge drinking and high PRS, resulting in a relative excess risk due to interaction (RERI) of 6.07. Diabetes consistently elevates ARC risk across all drinking and PRS categories, and showed significant interaction with both binge patterns and genetic risk. Overall, we demonstrate synergistic effects of binge drinking, genetics, and diabetes on ARC, with potential to identify high-risk individuals for targeted interventions.

Inpatient Screening, Brief Intervention, and Referral to Treatment for Alcohol Use Disorder in Patients Admitted with Alcohol-associated Liver Disease Is Not Universally Implemented in Practice, But Can Reduce Readmissions for Alcohol-associated Hepatitis.

The management of alcohol-related liver disease requires a multidisciplinary approach to treat alcohol use disorder. We aimed to determine the proportion of actively drinking patients admitted for alcohol-associated hepatitis (AAH) or decompensated alcohol-related cirrhosis (DARLC) who were offered or underwent screening, brief intervention, and referral to treatment (SBIRT) for alcohol use disorder during admission and if inpatient SBIRT is associated with reduced readmissions for alcohol-related liver disease. We conducted a retrospective cohort study of actively drinking patients admitted to our institution from January 2017 to December 2021 with AAH or DARLC. Logistic regression was used to identify factors, such as conducting SBIRT, that were associated with 30-day and 90-day readmissions for recurrent AAH or DARLC. There were 120 AAH admissions (mean age 47.7 ± 13.6 years), and 177 DARLC admissions (mean age 58.2 ± 9.5 years). SBIRT was conducted in only 51.7% of AAH admissions, and 23.7% of DARLC admissions. For AAH, conducting SBIRT was associated with significantly reduced 30-day (OR 0.098, P = 0.001, 95% CI 0.024-0.408) and 90-day (OR 0.166, P = 0.003, 95% CI 0.052-0.534) readmissions. For DARLC, there was no association between conducting SBIRT and 30-day or 90-day readmissions. SBIRT was conducted with actively drinking patients in only 51.7% of AAH admissions and 23.7% of DARLC admissions. Patients admitted for AAH who received inpatient SBIRT had decreased 30-day and 90-day readmission rates for AAH or DARLC.

Low sphingolipid levels predict poor survival in patients with alcohol-related liver disease

Alcohol-related hepatitis (AH) and alcohol-related cirrhosis are grave conditions with poor prognoses. Altered hepatic lipid metabolism can impact disease development and varies between different alcohol-related liver diseases. Therefore, we aimed to investigate lipidomics and metabolomics at various stages of alcohol-related liver diseases and their correlation with survival. Patients with newly diagnosed alcohol-related cirrhosis, who currently used alcohol (ALC-A), stable outpatients with decompensated alcohol-related cirrhosis with at least 8 weeks of alcohol abstinence (ALC), and patients with AH, were compared with each other and with healthy controls (HC). Circulating lipids and metabolites were analysed using HPLC and mass spectrometry. Forty patients with ALC, 95 with ALC-A, 30 with AH, and 42 HC provided plasma. Lipid levels changed according to disease severity, with generally lower levels in AH and cirrhosis than in the HC group; this was most pronounced for AH, followed by ALC-A. Nine out of 10 free fatty acids differed between cirrhosis groups by relative increases of 0.12-0.66 in ALC compared with the ALC-A group (p <0.0005). For metabolomics, total bile acids increased by 19.7, 31.3, and 80.4 in the ALC, ALC-A, and AH groups, respectively, compared with HC (all p <0.0001). Low sphingolipid ([d42:1] and [d41:1]) levels could not predict 180-day mortality (AUC= 0.73, p= 0.95 and AUC= 0.73, p= 0.95) more accurately than the model for end-stage liver disease score (AUC= 0.71), but did predict 90-day mortality (AUC d42:1= 0.922, AUC d41:1= 0.893; pd42:1= 0.005, pd41:1= 0.007) more accurately than the MELD score AUCMELD= 0.70, pMELD= 0.19). Alcohol-related severe liver disease is characterised by low lipid levels progressing with severity of liver disease, especially low sphingomyelins, which also associate to poor prognoses. Lipidomics has the potential to diagnose and risk stratify patients with liver diseases. Lipidomics differed between patients with alcohol-related hepatitis and alcohol-related cirrhosis with and without recent alcohol use. Furthermore, lipidomics could predict short-term mortality and might be suitable as a prognostic tool in the future. Scientific Ethics Committee of the Capital Region of Denmark, journal no. H-21013476.