Serum metabolomic analysis in cirrhotic alcohol-associated liver disease patients identified differentially altered microbial metabolites and novel potential biomarkers for disease severity.

BACKGROUND: Alcohol-Associated Liver Disease (ALD) is a leading cause of liver mortality. Mechanisms responsible for severe ALD and the roles of gut microbiota are not fully understood. Multi-omics tools have enabled a better understanding of metabolic alterations and can aid in identifying metabolites as biomarkers for severe ALD. AIMS: Examine differences between cirrhotic and non-cirrhotic ALD, investigate microbial contributions to such changes, and identify potential diagnostic and prognostic metabolites for severe ALD. METHODS: Untargeted metabolomics were performed on the serum of 11 non-cirrhotic and 11 cirrhotic ALD patients. Data were analyzed using MetOrigin and Metaboanalyst to identify enriched pathways. RESULTS: Increased methylated nucleotides, gamma-glutamyl amino acids, bile acids, and specific metabolites kynurenine and campesterol were increased in ALD cirrhosis, whereas branched-chain amino acids, serotonin, and xanthurenate were decreased. Microbial contributions included increases in the short-chain fatty acid indolebutyrate and methionine sulfoxide in ALD cirrhosis. The analysis also identified the potential for serum levels of 3-ureidopropionate, cis-3,3-methyleneheptanoylglycine, retinol, and valine to be used as biomarkers for clinical assessment of alcohol-associated cirrhosis. CONCLUSION: We have identified a set of metabolites that are differentially altered in cirrhotic compared to non-cirrhotic ALD that can potentially be used as biomarkers for the severity of the disease.

Practical considerations when treating chronic hepatitis E in solid organ transplant recipients.

Hepatitis E virus (HEV) can lead to chronic infections in immunosuppressed patients. The use of ribavirin to treat chronic HEV has been well-established in case reports and guidelines. However, practical approaches to the use of this antiviral treatment in a post-transplant patient, including drug interactions, dosing adjustments, and monitoring parameters, are lacking. Thus, we present our real-world approach to the use of ribavirin to treat chronic HEV in a solid organ transplant recipient.

Validity of an automated algorithm using diagnosis and procedure codes to identify decompensated cirrhosis using electronic health records.

Viral hepatitis-induced cirrhosis can progress to decompensated cirrhosis. Clinical decompensation represents a milestone event for the patient with cirrhosis, yet there remains uncertainty regarding precisely how to define this important phenomenon. With the development of broader treatment options for cirrhotic hepatitis patients, efficient identification of liver status before evolving to decompensated cirrhosis could be life-saving, but research on the topic has been limited by inconsistencies across studies, populations, and case-confirmation methods. We sought to determine whether diagnosis/procedure codes drawn from electronic health records (EHRs) could be used to identify patients with decompensated cirrhosis. In our first step, chart review was used to determine liver status (compensated cirrhosis, decompensated cirrhosis, non-cirrhotic) in patients from the Chronic Hepatitis Cohort Study. Next, a hybrid approach between Least Absolute Shrinkage and Selection Operator regression and Classification Regression Trees models was used to optimize EHR-based identification of decompensated cirrhosis, based on 41 diagnosis and procedure codes. These models were validated using tenfold cross-validation; method accuracy was evaluated by positive predictive values (PPVs) and area under receiver operating characteristic (AUROC) curves. Among 296 patients (23 with hepatitis B, 268 with hepatitis C, and 5 co-infected) with a 2:1 ratio of biopsy-confirmed cirrhosis to noncirrhosis, chart review identified 127 cases of decompensated cirrhosis (Kappa=0.88). The algorithm of five liver-related conditions-liver transplant, hepatocellular carcinoma, esophageal varices complications/procedures, ascites, and cirrhosis-yielded a PPV of 85% and an AUROC of 92%. A hierarchical subset of three conditions (hepatocellular carcinoma, ascites, and esophageal varices) demonstrated a PPV of 81% and an AUROC of 86%. Given the excellent predictive ability of our model, this EHR-based automated algorithm may be used to successfully identify patients with decompensated cirrhosis. This algorithm may contribute to timely identification and treatment of viral hepatitis patients who have progressed to decompensated cirrhosis.

Hepatitis B Reactivation in a Patient Receiving Chemotherapy for Breast Cancer: A Case Report.

Hepatitis B virus (HBV) reactivation is a known complication of immunosuppressive therapy. While patients who are undergoing treatment with anti-CD20 agents or stem cell transplantation are commonly screened for chronic HBV infection prior to treatment, there are no consensus guidelines regarding HBV screening for patients undergoing chemotherapy for solid tumors. We present a rare case of fulminant liver failure due to HBV reactivation in a patient receiving chemotherapy for breast cancer. Our case highlights the importance of developing definitive guidelines regarding HBV screening in patients receiving chemotherapy for solid tumors and raises the question of the need for universal screening.

Adefovir dipivoxil in chronic hepatitis B: history and current uses.

INTRODUCTION: The nucleotide analogue adefovir dipivoxil (ADV) was approved in 2002 for the treatment of chronic infection with hepatitis B virus (HBV), in both hepatitis B e antigen (HBeAg)-positive and -negative patients. ADV 10 mg daily has been associated with improved liver histology, decreased levels of HBV DNA and alanine aminotransferase (ALT), and seroconversion of HBeAg. AREAS COVERED: This paper reviews the use of ADV as a first-line treatment for chronic hepatitis B and as an add-on therapy in chronic HBV-infected patients with lamivudine resistance. In the years since its launch, clinical resistance to ADV has emerged, and tenofovir and entecavir have shown greater efficacy in reducing viral load. EXPERT OPINION: Many patients who started antiviral therapy with ADV (either as monotherapy or in combination with lamivudine) remain on this agent because they have undetectable viremia, but its future use will probably diminish because of the availability of more potent drugs. ADV is generally well tolerated, though the 10 mg dose is associated with low risk of nephrotoxicity.