Effectiveness of phototherapy with and without probiotics for the treatment of indirect hyperbilirubinaemia in preterm neonates: a randomised controlled trial.

INTRODUCTION: Raised serum bilirubin levels can cause kernicterus, and premature infants are at increased risk owing to metabolic immaturity. The standard treatment for neonatal jaundice is phototherapy, but probiotics alone can reduce the duration of phototherapy and hospitalisation. OBJECTIVES: To determine the effectiveness of phototherapy with and without probiotics for the treatment of indirect hyperbilirubinaemia in preterm neonates. PATIENTS AND METHODS: The open-labelled randomised controlled trial was conducted from January 2022 to January 2023 in the neonatal unit of the University of Lahore Teaching Hospital, Pakistan. A total of 76 preterm neonates who fulfilled the selection criteria were included and divided into two groups. Both groups received standard phototherapy. In Group B, a probiotic (Saccharomyces boulardii) 125 mg, twice daily, orally (in 5 cc of whichever milk the infant was receiving) was given until discharge from hospital. The primary outcome measurements were the duration of phototherapy and the length of hospitalisation. RESULTS: The mean (SD) duration of phototherapy was 36.55 (14.25) hours in Group A and 24.61 (9.25) hours in Group B (p <0.05). The mean (SD) duration of hospital stay was 47.36 (16.51) hours in Group A and 33.13 (8.93) hours in Group B (p <0.05). CONCLUSION: Oral probiotics (Saccharomyces boulardii) have a significant effect on the duration of phototherapy for neonatal hyperbilirubinaemia, and they decrease the chances of nosocomial infection. Exploration of clinical outcomes by investigating faecal flora and undertaking large randomised controlled trials of various probiotics are needed. ABBREVIATIONS: ABE: acute bilirubin encephalopathy; CNS: central nervous system; GA: gestational age; IVIG: intravenous immunoglobulin; KSD: kernicterus; NNU: neonatal unit; RCT: randomised controlled trial; S. boulardii: Saccharomyces boulardii.

NCCN Guidelines® Insights: Biliary Tract Cancers, Version 2.2023.

In 2023, the NCCN Guidelines for Hepatobiliary Cancers were divided into 2 separate guidelines: Hepatocellular Carcinoma and Biliary Tract Cancers. The NCCN Guidelines for Biliary Tract Cancers provide recommendations for the evaluation and comprehensive care of patients with gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma. The multidisciplinary panel of experts meets at least on an annual basis to review requests from internal and external entities as well as to evaluate new data on current and emerging therapies. These Guidelines Insights focus on some of the recent updates to the NCCN Guidelines for Biliary Tract Cancers as well as the newly published section on principles of molecular testing.

Incorporating fatty liver disease in multidisciplinary care and novel clinical trial designs for patients with metabolic diseases.

With the global epidemics of obesity and associated conditions, including type 2 diabetes, metabolic dysfunction-associated fatty liver disease, chronic kidney disease, hypertension, stroke, cardiovascular disease, osteoporosis, cancer, and cognitive changes, the prevalence of multimorbidity is rapidly increasing worldwide. In this Review, a panel of international experts from across the spectrum of metabolic diseases come together to identify the challenges and provide perspectives on building a framework for a virtual primary care-driven, patient-centred, multidisciplinary model to deliver holistic care for patients with metabolic dysfunction-associated fatty liver disease and associated metabolic diseases. We focus on clinical care and innovative trial design for metabolic dysfunction-associated fatty liver disease and associated metabolic diseases. This work represents a call to action to promote collaboration and partnerships between stakeholders for improving the lives of people with, or at risk of, metabolic dysfunction-associated fatty liver disease and associated metabolic diseases.

Kratom-Induced Cholestatic Liver Injury and Its Conservative Management.

Drug-induced liver injury (DILI) is a common cause of hepatotoxicity associated with prescription-based and over-the-counter exposure to medications and herbal supplements. Use of unapproved and inadequately tested herbal supplements can cause DILI. Therefore, thorough history-taking on exposure to herbal supplements must be an integral part of clinical evaluation of DILI. Kratom is an herbal supplement or remedy that has been known for its analgesic effects and has also been used for self-treatment of opiate withdrawals. A 52-year-old man was seen for evaluation of yellow discoloration of the eyes and skin. He reported taking kratom for right shoulder strain for at least a couple of months. On workup, his total bilirubin was noted to be 23.2 mg/dL, which peaked at 28.9 mg/dL. He was noted to have mild elevation of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase. Extensive laboratory tests were ordered and known causes of chronic liver disease ruled out. Magnetic resonance imaging of the abdomen was unremarkable without stigmata of portal hypertension or signs of chronic liver disease. He demonstrated no evidence of coagulopathy or hepatic encephalopathy during his illness. He underwent liver biopsy, which demonstrated histologic evidence of acute cholestatic hepatitis highly suspicious of DILI. He was advised to avoid kratom or other herbal supplements in future and prescribed ursodeoxycholic acid with significant improvement in his liver chemistries. Kratom is associated with significant liver enzymes derangements leading to DILI. Kratom is not approved for use in the United States and should be avoided.

The Role of Vitamin E in the Treatment of NAFLD.

There has been a growing interest in the role of vitamin E supplementation in the treatment and/or prevention of nonalcoholic fatty liver (NAFLD). We performed a systematic review of the medical literature from inception through 15 June 2018 by utilizing PubMed and searching for key terms such as NAFLD, vitamin E, alpha-tocopherol, and nonalcoholic steatohepatitis (NASH). Data from studies and medical literature focusing on the role of vitamin E therapy in patients with NAFLD and nonalcoholic steatohepatitis (NASH) were reviewed. Most studies assessing the impact of vitamin E in NAFLD were designed to evaluate patients with NASH with documented biochemical and histological abnormalities. These studies demonstrated improvement in biochemical profiles, with a decline in or normalization of liver enzymes. Furthermore, histological assessment showed favorable outcomes in lobular inflammation and hepatic steatosis following treatment with vitamin E. Current guidelines regarding the use of vitamin E in the setting of NAFLD recommend that vitamin E-based treatment be restricted to biopsy-proven nondiabetic patients with NASH only. However, some concerns have been raised regarding the use of vitamin E in patients with NASH due to its adverse effects profile and lack of significant improvement in hepatic fibrosis. In conclusion, the antioxidant, anti-inflammatory, and anti-apoptotic properties of vitamin E accompanied by ease-of-use and exceptional tolerability have made vitamin E a pragmatic therapeutic choice in non-diabetic patients with histologic evidence of NASH. Future clinical trials with study design to assess vitamin E in combination with other anti-fibrotic agents may yield an additive or synergistic therapeutic effect.

Potential Therapeutic Benefits of Herbs and Supplements in Patients with NAFLD.

Our aim is to review the efficacy of various herbs and supplements as a possible therapeutic option in the treatment and/or prevention of nonalcoholic fatty liver disease (NAFLD). We performed a systematic review of medical literature using the PubMed Database by searching the chemical names of many common herbs and supplements with "AND (NAFLD or NASH)". Studies and medical literature that discussed the roles and usage of herbs and supplements in NAFLD and nonalcoholic steatohepatitis (NASH) from inception until 20 June 2018 were reviewed. Many studies have claimed that the use of various herbs and supplements may improve disease endpoints and outcomes related to NAFLD and/or NASH. Improvement in liver function tests were noted. Amelioration or reduction of lobular inflammation, hepatic steatosis, and fibrosis were also noted. However, well-designed studies demonstrating improved clinical outcomes are lacking. Furthermore, experts remain concerned about the lack of regulation of herbs/supplements and the need for further research on potential adverse effects and herb⁻drug interactions. In conclusion, preliminary data on several herbs have demonstrated promising antioxidant, anti-inflammatory, anti-apoptotic, and anti-adipogenic properties that may help curtail the progression of NAFLD/NASH. Clinical trials testing the safety and efficacy must be completed before widespread can be recommended.

Tenofovir monotherapy and tenofovir plus entecavir combination as rescue therapy for entecavir partial responders.

BACKGROUND AND AIMS: Despite high potency, a significant proportion of patients treated with entecavir achieve only partial viral suppression. Our goal was to examine the complete viral suppression rate (undetectable HBV DNA PCR levels) with alternative therapies in such patients. METHODS: We retrospectively studied 42 consecutive patients with partial response to entecavir (detectable HBV DNA at ≥12 months of therapy) who were treated at three clinics with rescue therapies: entecavir + adefovir (n = 5), tenofovir (n = 6), and entecavir + tenofovir (n = 31). Antiviral resistance was excluded by negative mutation analysis and/or absence of virologic breakthrough (increase >1 log(10)IU/mL from nadir). RESULTS: All patients were Asian and 57 % were male with a median age of 36 (22-64) years. Only a few patients had prior exposure to lamivudine (7 %) or adefovir (7 %). Almost all patients (95 %) had positive HBeAg. Overall, the complete viral suppression rate was 79 %, and the alanine aminotransferase normalization rate was 83 % in entecavir partial responders after 6 months on rescue therapies. Cumulative complete viral suppression rates were significantly different (P = 0.0164) among the entecavir + adefovir, tenofovir, and entecavir + tenofovir treatment groups at 6 months (20 vs. 83 vs. 83 %, respectively) and 12 months (20 vs. 100 vs. 97 %). All three patients without complete viral suppression on entecavir + adefovir became aviremic 6 months after switching to entecavir + tenofovir. CONCLUSIONS: Virologic response to entecavir + tenofovir combination therapy and tenofovir monotherapy appeared to be similar in most patients, but not with the entecavir + adefovir combination.