Timing of endoscopy in patients with cirrhosis and acute variceal bleeding: a single-center retrospective study.

BACKGROUND: The optimal timing of endoscopy in liver cirrhosis with acute variceal bleeding (AVB) remains controversial in current guidelines and studies. METHODS: Consecutive patients with liver cirrhosis and AVB were screened. The timing of endoscopy was calculated from the last presentation of AVB or the admission to endoscopy. Early endoscopy was defined as the interval < 12 h, < 24 h, or < 48 h. A 1:1 propensity score matching (PSM) analysis was performed. Five-day failure to control bleeding and in-hospital mortality were evaluated. RESULTS: Overall, 534 patients were included. When the timing of endoscopy was calculated from the last presentation of AVB, PSM analysis demonstrated that the rate of 5-day failure to control bleeding was significantly higher in early endoscopy group defined as < 48 h (9.7% versus 2.4%, P = 0.009), but not < 12 h (8.7% versus 6.5%, P = 1.000) or < 24 h (13.4% versus 6.2%, P = 0.091), and that the in-hospital mortality was not significantly different between early and delayed endoscopy groups (< 12 h: 6.5% versus 4.3%, P = 1.000; <24 h: 4.1% versus 3.1%, P = 1.000; <48 h: 3.0% versus 2.4%, P = 1.000). When the timing of endoscopy was calculated from the admission, PSM analyses did not demonstrate any significant difference in the rate of 5-day failure to control bleeding (< 12 h: 4.8% versus 12.7%, P = 0.205; <24 h: 5.2% versus 7.7%, P = 0.355; <48 h: 4.5% versus 6.0%, P = 0.501) or in-hospital mortality (< 12 h: 4.8% versus 4.8%, P = 1.000; <24 h: 3.9% versus 2.6%, P = 0.750; <48 h: 2.0% versus 2.5%, P = 1.000) between early and delayed endoscopy groups. CONCLUSION: Our study could not support any significant association of timing of endoscopy with cirrhotic patients with AVB.

Beyond the scope and the glue: update on evaluation and management of gastric varices.

Gastric varices are encountered less frequently than esophageal varices. Nonetheless, gastric variceal bleeding is more severe and associated with worse outcomes. Conventionally, gastric varices have been described based on the location and extent and endoscopic treatments offered based on these descriptions. With improved understanding of portal hypertension and the dynamic physiology of collateral circulation, gastric variceal classification has been refined to include inflow and outflow based hemodynamic pathways. These have led to an improvement in the management of gastric variceal disease through newer modalities of treatment such as endoscopic ultrasound-guided glue-coiling combination therapy and the emergence of highly effective endovascular treatments such as shunt and variceal complex embolization with or without transjugular intrahepatic portosystemic shunt (TIPS) placement in patients who are deemed 'difficult' to manage the traditional way. Furthermore, the decisions regarding TIPS and additional endovascular procedures in patients with gastric variceal bleeding have changed after the emergence of 'portal hypertension theories' of proximity, throughput, and recruitment. The hemodynamic classification, grounded on novel theories and its cognizance, can help in identifying patients at baseline, in whom conventional treatment could fail. In this exhaustive review, we discuss the conventional and hemodynamic diagnosis of gastric varices concerning new classifications; explore and illustrate new 'portal hypertension theories' of gastric variceal disease and corresponding management and shed light on current evidence-based treatments through a 'new' algorithmic approach, established on hemodynamic physiology of gastric varices.

Partial splenic artery embolization for severe hepatic myelopathy in cirrhosis.

Hepatic myelopathy (HM) is a devastating but rare complication of cirrhosis and portal hypertension that profoundly affects quality of life and improves only with liver transplantation. We present a case where progressive severe spastic paraparesis due to HM was substantially reversed with partial splenic artery emobilization (PSAE). (Hepatology 2018;67:1169-1171).

A comprehensive review on the hepatotoxicity of herbs used in the Indian (Ayush) systems of alternative medicine.

Complementary and alternative medicine-related liver injuries are increasing globally. Alternative medicine, as an inclusive healthcare practice, is widely accepted in developing and underdeveloped countries. In this context, the traditional systems of medicine in India have been at the forefront, catering to the preventive and therapeutic spectrum in the absence of conclusive evidence for benefits and lack of data on safety. Contrary to popular belief, it is evident that apart from adverse events caused by contamination and adulteration of alternative medicines, certain commonly used herbal components have inherent hepatotoxicity. This narrative review updates our current understanding and increasing publications on the liver toxicity potential of commonly used herbs in traditional Indian systems of medicine (Ayush), such as Tinospora cordifolia (Willd.) Hook.f. & Thomson (Giloy/Guduchi), Withania somnifera (L.) Dunal (Ashwagandha), Curcuma longa L. (Turmeric), and Psoralea corylifolia L. (Bakuchi/Babchi). This review also highlights the importance of the upcoming liver toxicity profiles associated with other traditional herbs used as dietary supplements, such as Centella asiatica (L.) Urb., Garcinia cambogia Desr., Cassia angustifolia Vahl (Indian senna), and Morinda citrofolia L. (Noni fruit). Fortunately, most reported liver injuries due to these herbs are self-limiting, but can lead to progressive liver dysfunction, leading to acute liver failure or acute chronic liver failure with a high mortality rate. This review also aims to provide adequate knowledge regarding herbalism in traditional practices, pertinent for medical doctors to diagnose, treat, and prevent avoidable liver disease burdens within communities, and improve public health and education.

Citizens protein project: A self-funded, transparent, and concerning report on analysis of popular protein supplements sold in the Indian market.

Protein powders, including those containing herbal and dietary supplements such as vitamins, minerals, and other natural or synthetic ingredients, can be associated with hepatotoxicity. Protein supplements are often mislabeled and deceptive in their contents. In this self-funded transparent study, we extensively analyzed popular protein supplements in India to identify potential hepatotoxic substances based on industrial standards. All products underwent extensive analysis, including total protein content, fungal aflatoxin detection, pesticide residue estimation, heavy metal quantification, steroid detection, and complete organic and inorganic profiling, according to industry standards. Most protein supplements did not meet the labeled and advertised protein content, while certain brands surpassed the stated levels, raising concerns about potential "protein/amino-spiking." In addition, the major brands contained detectable fungal toxins and pesticide residues. Furthermore, many major formulations contained harmful heavy metals such as lead and arsenic, and some featured hepatoxic herbal extracts, particularly green tea extract, turmeric, Garcinia cambogia, and Ashwagandha. Indian-made products were inferior to those manufactured by multinational companies. The presence of various potentially toxic compounds, such as cycloheptatriene, benzene derivatives, toluene, and isopropyl alcohol, within a nonstandardized and unregulated diverse ingredient mix added to the overall concern. We demonstrate that the protein-based herbal and dietary supplement industry requires stringent scrutiny, regulation, and basic safety studies before being marketed. Manufacturers must consider reducing "ingredient complexities" of their protein powders to prevent adverse interactions between herbal and nonherbal components in consumers. Manufacturers must avoid using known toxic ingredients to reduce the avoidable disease burden within the public community.

Complementary and alternative medicines and liver disease.

Complementary and alternative medicines (CAM) include conventional medical treatments. Patients worldwide use CAM at alarming rates; thus, reports of CAM-related DILI have been on the rise. The clinical presentations include asymptomatic liver test abnormalities, acute hepatitis with or without jaundice, acute cholestatic liver disease (bland or with hepatitis), acute liver failure, severe hepatitis with features of portal hypertension, and acute decompensation of known or unknown cirrhosis that can lead to acute-on-chronic liver failure. Acute hepatitis with or without necrosis, hepatocellular and canalicular cholestasis, herb-induced or CAM-triggered autoimmune hepatitis, granulomatous hepatitis, severe steatohepatitis, and vanishing bile duct syndrome are common liver biopsy findings in CAM-DILI. The presence of preexisting liver disease predicts severe liver injury, risk of progression to liver failure, and decreased transplant-free survival in patients with CAM-DILI. This review discusses global epidemiology and trends in CAM-DILI, clinical presentation, assessment and outcomes, commonly emerging threats in the context of hepatotoxic herbs, pragmatic assessment of "liver beneficial" herbs and health care myths, patient communication, regulatory framework, and future directions on research in CAM.

A Short Review on Obeticholic Acid: An Effective Modulator of Farnesoid X Receptor.

Farnesoid X receptor (FXR) was identified as an orphan nuclear receptor resembling the steroid receptor in the late '90s. Activation of FXR is a crucial step in many physiological functions of the liver. A vital role of FXR is impacting the amount of bile acids in the hepatocytes, which it performs by reducing bile acid synthesis, stimulating the bile salt export pump, and inhibiting its enterohepatic circulation, thus protecting the hepatocytes against the toxic accumulation of bile acids. Furthermore, FXR mediates bile acid biotransformation in the intestine, liver regeneration, glucose hemostasis, and lipid metabolism. In this review, we first discuss the mechanisms of the disparate pleiotropic actions of FXR agonists. We then delve into the pharmacokinetics of Obeticholic acid (OCA), the first-in-class selective, potent FXR agonist. We additionally discuss the clinical journey of OCA in humans, its current evidence in various human diseases, and its plausible roles in the future.

Development and validation of modified Liaoning score for predicting the prognosis of liver cirrhosis: a retrospective, international multicenter, observational study.

BACKGROUND: Liaoning score has been developed and validated to predict the risk of esophageal varices in liver cirrhosis. This study aimed to further modify the Liaoning score by combining clinical and laboratory parameters to predict the long-term outcome of cirrhotic patients. METHODS: First, 474 cirrhotic patients were retrospectively enrolled from Shenyang, China as the training cohort. Independent predictors for death were identified by competing risk analyses, and then a new prognostic model, called as modified Liaoning score, was developed. Its performance was externally validated at three centers from Fuzhou, China (n = 1944), Jinan, China (n = 485), and São Paulo, Brazil (n = 221). RESULTS: Age, total bilirubin (TBIL), albumin (ALB), serum creatinine (SCr), and Liaoning score were independently associated with death in the training cohort. Modified Liaoning score = 0.159×Liaoning score + 0.010×TBIL(µmol/L)+0.029×age(years)+0.011×SCr(µmol/L)-0.037×ALB(g/L). The area under curve of modified Liaoning score was 0.714 (95%CI = 0.655-0.773), which was higher than that of Child-Pugh score (0.707, 95%CI = 0.645-0.770), MELD score (0.687, 95%CI = 0.623-0.751), and Liaoning score (0.583, 95%CI = 0.513-0.654). A modified Liaoning score of ≥ 1.296 suggested a higher cumulative incidence of death in liver cirrhosis (p < 0.001). Modified Liaoning score still had the highest prognostic performance in Chinese and Brazilian validation cohorts. CONCLUSIONS: Modified Liaoning score can be considered for predicting the long-term outcome of cirrhotic patients.

Investigating the correlation between COVID-19 and the progression of chronic liver disease.

INTRODUCTION: The novel coronavirus disease 2019 has thrown light on various heterogeneous afflictions of newly emerging viruses on the human body. Early reports demonstrated direct effect of novel coronavirus on the liver, but subsequently, this did not stand up to validation. The SARS-CoV-2 virus affects the liver differentially; in healthy compared to those with preexisting liver disease. AREAS COVERED: This exhaustive paper reviews the current, literature on mechanisms by which COVID-19 affects the healthy liver and those with preexisting liver disease such as alcohol-related and nonalcoholic fatty liver, autoimmune liver disease, chronic liver disease and cirrhosis, hepatocellular carcinoma, viral hepatitis, and liver transplant recipients, with special mention on drug-and herb-induced liver injury with COVID-19 therapies. Search methodology: the review (Dec. 2022 - Jan. 2023) is based on PubMed (NLM) search using the keyword 'COVID' with supplementary searches using 'fibrosis;' 'liver;' 'cirrhosis;' 'CLD;' 'NAFLD;' 'NASH;' 'hepatocellular carcinoma;' 'hepatitis;' 'fatty liver;' 'alcohol;' 'viral;' 'transplant;' and 'liver failure.' EXPERT OPINION: Direct liver tropism of SARS-CoV-2 does not cause liver damage. Adverse events following infection depend on the severity of liver disease, the severity of COVID-19, and other risk factors such as metabolic syndrome and older age. Alcohol-related liver disease independently predicts adverse outcomes.