Imaging of Alcohol-Associated Liver Disease.

Alcohol-associated liver disease (ALD) continues to be a global health concern, responsible for a significant number of deaths worldwide. Although most individuals who consume alcohol do not develop ALD, heavy drinkers and binge drinkers are at increased risk. Unfortunately, ALD is often undetected until it reaches advanced stages, frequently associated with portal hypertension and hepatocellular carcinoma (HCC). ALD is now the leading indication for liver transplant. The incidence of alcohol-associated hepatitis (AH) surged during the COVID-19 pandemic. Early diagnosis of ALD is therefore important in patient management and determination of prognosis, as abstinence can halt disease progression. The spectrum of ALD includes steatosis, steatohepatitis, and cirrhosis, with steatosis the most common manifestation. Diagnostic techniques including ultrasound, CT, and MRI provide useful information for identifying ALD and excluding other causes of liver dysfunction. Heterogeneous steatosis and transient perfusion changes on CT and MRI in the clinical setting of alcohol-use disorder are diagnostic of severe AH. Elastography techniques are useful for assessing fibrosis and monitoring treatment response. These various imaging modalities are also useful in HCC surveillance and diagnosis. This review discusses the imaging modalities currently used in the evaluation of ALD, highlighting their strengths, limitations, and clinical applications.

Outcomes of idiopathic versus secondary nodular regenerative hyperplasia of the liver: A longitudinal study of 167 cases.

BACKGROUND: Nodular regenerative hyperplasia (NRH) is a rare condition characterized clinically by the development of non-cirrhotic portal hypertension. NRH is the histopathological result in the liver of various systemic disease processes including autoimmune disorders, haematological malignancies and medications. However, natural history of this condition has been limited to small case series while patient outcomes pertaining to different aetiologies of NRH are largely unknown. METHODS: A retrospective cohort of consecutive patients diagnosed with pathology-confirmed NRH at Mayo Clinic between 2002 and 2017 was identified. The histological diagnosis of NRH was determined by expert liver pathologists. Patients with metastatic liver disease, history of liver transplantation or younger than 18 were excluded. Potential aetiologies of NRH were classified as haematological, rheumatological, drug-associated, miscellaneous or idiopathic. Long-term mortality was analysed using Kaplan-Meier estimation and Cox regression models. RESULTS: One hundred and sixty-seven consecutive patients with pathology-confirmed NRH were analysed over a 15-year period and followed for a median time of 50 months (1-306 months). The mean age at diagnosis was 53 years. No aetiology or risk factor for NRH was identified in the majority of patients (94, 56.3%), whereas an associated, possibly causal, condition was found in 73 patients (secondary NRH). The most common presenting feature was elevated liver tests (80%), but no significant differences in laboratory tests were seen based on aetiology of NRH. Compared to idiopathic NRH, those with an identified cause had a higher rate of splenomegaly at presentation (54% vs. 27%, p = 0.002). Portal hypertension-related complications at diagnosis were common, with ascites present in one-third of patients. Overall transplant-free survival was 63% at 5 years. Median survival in idiopathic NRH was 9.4 years compared to 7.3 years in secondary NRH. Age, renal function and volume status at presentation were significantly associated with survival; however, MELD score was not. CONCLUSIONS: The rates of liver-related complications and mortality in NRH are low, and only a small number of patients ultimately require liver transplantation. Most patients do not have an identified risk factor or aetiology for NRH, and liver-related outcomes do not appear to differ based on associated, possibly causal, conditions.

The Role of Therapeutic Endoscopy in Patients With Cirrhosis-Related Causes of Gastrointestinal Bleeding.

PURPOSE OF REVIEW: This article aims to review current therapeutic endoscopic treatments available for the management of gastrointestinal bleeding related to cirrhosis. RECENT FINDINGS: Endoscopic band ligation is an effective treatment for primary prophylaxis, acute bleeding, and secondary prophylaxis of esophageal varices as well as for acute bleeding and secondary prophylaxis of select gastric varices. Sclerotherapy is a treatment option for acute bleeding and secondary prophylaxis of esophageal varices when band ligation is technically difficult. Cyanoacrylate glue injection is an effective treatment for acute bleeding of gastric and ectopic varices. Argon plasma coagulation is first-line and radiofrequency ablation is second-line treatment for chronic bleeding secondary to gastric antral vascular ectasia. There are a variety of endoscopic treatment modalities for cirrhosis-related gastrointestinal bleeding, and the appropriate therapy depends on the location of the bleed, history or presence of acute bleeding, and risk factors for intervention-related adverse events.

Acute on Chronic Liver Failure in Patients with Alcohol-Associated Hepatitis: A Review.

Acute on chronic liver failure (ACLF) is a unique disease process associated with significant short-term mortality wherein patients with either chronic liver disease or cirrhosis suffer rapid decompensation in hepatic function accompanied by extrahepatic organ failures. Alcohol-associated hepatitis (AH) is a common precipitant of ACLF and has been shown to uniquely affect the pathophysiology of systemic and hepatic immune responses in patients with ACLF. Treatment of AH-associated ACLF includes supportive measures as well as treatment directed at AH; however, AH-directed therapies unfortunately remain limited and are of suboptimal efficacy.

Machine Learning Techniques Differentiate Alcohol-Associated Hepatitis From Acute Cholangitis in Patients With Systemic Inflammation and Elevated Liver Enzymes.

OBJECTIVE: To develop machine learning algorithms (MLAs) that can differentiate patients with acute cholangitis (AC) and alcohol-associated hepatitis (AH) using simple laboratory variables. METHODS: A study was conducted of 459 adult patients admitted to Mayo Clinic, Rochester, with AH (n=265) or AC (n=194) from January 1, 2010, to December 31, 2019. Ten laboratory variables (white blood cell count, hemoglobin, mean corpuscular volume, platelet count, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, direct bilirubin, albumin) were collected as input variables. Eight supervised MLAs (decision tree, naive Bayes, logistic regression, k-nearest neighbor, support vector machine, artificial neural networks, random forest, gradient boosting) were trained and tested for classification of AC vs AH. External validation was performed with patients with AC (n=213) and AH (n=92) from the MIMIC-III database. A feature selection strategy was used to choose the best 5-variable combination. There were 143 physicians who took an online quiz to distinguish AC from AH using the same 10 laboratory variables alone. RESULTS: The MLAs demonstrated excellent performances with accuracies up to 0.932 and area under the curve (AUC) up to 0.986. In external validation, the MLAs showed comparable accuracy up to 0.909 and AUC up to 0.970. Feature selection in terms of information-theoretic measures was effective, and the choice of the best 5-variable subset produced high performance with an AUC up to 0.994. Physicians did worse, with mean accuracy of 0.790. CONCLUSION: Using a few routine laboratory variables, MLAs can differentiate patients with AC and AH and may serve valuable adjunctive roles in cases of diagnostic uncertainty.

The Mortality Index for Alcohol-Associated Hepatitis: A Novel Prognostic Score.

OBJECTIVE: To develop a new scoring system that more accurately predicts 30-day mortality in patients with alcohol-associated hepatitis (AH). METHODS: A cohort of consecutive adults diagnosed with AH at a single academic center from January 1, 1998, to December 31, 2018, was identified for model derivation. Multivariate logistic regression was used to create a new scoring system to predict 30-day mortality. External validation of this score was performed on a multicenter retrospective cohort. RESULTS: In the derivation cohort of 266 patients, the 30-day mortality rate was 19.2%. The following variables were found to be significantly associated with mortality on multivariate analysis: age (P=.002), blood urea nitrogen (P=.003), albumin (P=.01), bilirubin (P=.02), and international normalized ratio (P=.001). A model incorporating these variables, entitled the Mortality Index for Alcohol-Associated Hepatitis (MIAAH), achieved a C statistic of 0.86. Comparison of the accuracy of the MIAAH to existing prognostic models, including the Model for End-Stage Liver Disease and Maddrey Discriminant Function, showed that the highest concordance was achieved by the MIAAH and that this difference was significant. In the validation cohort of 249 patients, the MIAAH C statistic decreased to 0.73 and was found to be significantly superior to the Maddrey Discriminant Function but not to the Model for End-Stage Liver Disease. CONCLUSION: The MIAAH competes with the current prognostication models and is at a minimum as accurate as these existing scores in identifying patients with AH at high risk of short-term mortality. Furthermore, the MIAAH demonstrates advantageous performance characteristics in its ability to increasingly accurately dichotomize patients into those at highest risk of death and those likely to survive.

Advances in Predictive Modeling Using Machine Learning in the Field of Hepatology.

Content available: Author Interview and Audio Recording.

Sex Differences in Alcohol Consumption and Alcohol-Associated Liver Disease.

Alcohol-associated liver disease is becoming increasingly prevalent throughout the United States. Previously alcohol-associated liver disease was known to affect men more often than women; however, this gap between the sexes is narrowing. Studies show that women develop liver disease with lesser alcohol exposure and suffer worse disease as compared with men. This review article explores the increasing prevalence of alcohol-associated liver disease in women, reasons for changing patterns in alcohol consumption and liver disease development including obesity and bariatric surgery, proposed mechanisms of sex-specific differences in alcohol metabolism that may account for this discrepancy between men and women, and sex differences in treatment enrollment and response. Studies were identified by performing a literature search of PubMed and Google Scholar and through review of the references in retrieved articles. Search terms included alcohol-associated liver disease, alcoholic hepatitis, alcoholic cirrhosis, sex, gender, female, epidemiology, bariatric surgery, obesity, treatment. Due to the paucity of literature on some of the relevant subject matter and inclusion of landmark studies, no date range was selected. Studies were included if their methods were sufficiently robust and they made a comparison between the sexes that is clinically relevant. Understanding of the changing epidemiology and mechanisms of liver disease development unique to women are paramount in creating appropriate and effective interventions for women who represent a rapidly growing subset of patients with alcohol-associated liver disease.

Risk Prediction of Nosocomial and Posthospital Discharge Infections in Alcohol-Associated Hepatitis.

Alcohol-associated hepatitis (AAH) is a severe form of liver injury with mortality as high as 30%-40% at 90 days. As a result of altered immune function in AAH, bacterial infections are common and are associated with poor outcomes. However, determining the risk and subsequent development of infection in patients with AAH remain challenging. We performed a retrospective study of consecutive patients admitted with a diagnosis of AAH at two independent tertiary centers from 1998 to 2018 (test cohort, n = 286) who developed infections following hospitalization. The diagnosis of AAH was confirmed by manual chart review according to the recent National Institute on Alcohol Abuse and Alcoholism definition. Infections were categorized by location and time of diagnosis as hospital-acquired infection (48 hours after admission until discharge) and posthospital infections (up to 6 months following discharge). The cohort was 66% men, and the median age was 48 (21-83) years. Corticosteroids were used in 32% of all patients with AAH. The overall infection rate was 24%. Of those with infections, 46% were hospital acquired and 54% were acquired after hospitalization. Variables found to be significant risk factors for bacterial infection included the presence of ascites on admission (hazard ratio [HR], 2.06), corticosteroid administration (HR, 1.70), Model for End-Stage Liver Disease (MELD) >23 (HR, 2.61), and white blood cell (WBC) count on admission per point (HR, 1.02). Conclusion: In this multicenter cohort study of patients hospitalized with AAH, MELD score, ascites, WBC count, and use of corticosteroids were identified as significant predictors of the development of bacterial infection. We created a novel predictive equation that may be used to aid in the identification of patients with AAH at high risk of infection.

Maternal iron nutriture modulates placental development in a rat model of fetal alcohol spectrum disorder.

Prenatal alcohol exposure (PAE) causes developmental abnormalities known as fetal alcohol spectrum disorder (FASD). Maternal iron status modulates the severity of these defects in the offspring. Because the placenta is central in supporting fetal development, we investigated whether maternal iron status similarly modulates alcohol's effects in the placenta. We hypothesized that PAE causes placental insufficiency by decreasing placental weight and efficiency, and we hypothesized that these are worsened by maternal iron deficiency (ID) and alleviated by dietary iron fortification (IF). We also determined whether altered placental iron flux and inflammatory balance contribute to placental insufficiency. Pregnant Long-Evans rats consumed an iron-deficient (ID; 2-6 ppm), iron-sufficient (IS; 100 ppm), or iron-fortified (IF; 500 ppm) diet. Alcohol (5 g/kg body weight) or isocaloric maltodextrin (MD) was gavaged daily from gestational day (GD) 13.5-19.5. Placental outcomes were evaluated on GD20.5. PAE reduced fetal weight (p < 0.0001), placental weight (p = 0.0324), and placental efficiency (p = 0.0043). PAE downregulated placental transferrin receptor (p = 0.0032); it also altered placental Il1b and Tnf expression and the Il6:Il10 ratio (p = 0.0337, 0.0300, and 0.0034, respectively) to generate a response favoring inflammation. ID-PAE further reduced fetal growth and placental efficiency and induced a heightened pro-inflammatory placental profile. IF did not rescue the alcohol-reduced fetal weight, but it normalized placental efficiency and decreased placental inflammation. These placental cytokines correlated with fetal and placental growth, and explained 45% of the variability in fetal weight and 20% of the variability in placental efficiency. In summary, alcohol induces placental insufficiency and is associated with a pro-inflammatory cytokine profile exacerbated by maternal ID and mitigated by maternal IF. Because the placenta is closely linked to intrauterine growth, the placental insufficiency reported here may correlate with the lower birth weights in a subgroup of individuals who experienced PAE.