Primary Biliary Cholangitis: personalizing second-line therapies.

Primary biliary cholangitis (PBC) is an enigmatic, autoimmune disease targeting the small intralobular bile ducts resulting in cholestasis and potentially progression to biliary cirrhosis. Primarily affecting middle-aged women, the diagnosis of PBC is typically straightforward, with most patients presenting with cholestatic liver tests and the highly specific antimitochondrial antibody. For decades, the foundational treatment of PBC has been ursodeoxycholic acid, which delays disease progression in most patients but has no impact on PBC symptoms.

Clinicopathologic Features of a Rare and Underrecognized Variant of Early-stage Primary Biliary Cholangitis With Ductopenia.

Primary biliary cholangitis (PBC) with early cholestasis and extensive bile duct loss but no significant fibrosis or cirrhosis is rare and underrecognized. We aimed to clarify the clinicopathology features and prognosis of these variants of patients with early-stage PBC with ductopenia. From January 2009 to January 2023, we retrospectively collected the laboratory and pathologic data of patients with early-stage PBC and recorded their liver-related events with a median follow-up of 4.

PPAR agonists for the treatment of cholestatic liver diseases: Over a decade of clinical progress.

Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are characterized by the destruction of the small bile ducts and the formation of multifocal biliary strictures, respectively, impairing bile flow. This leads to the hepatic accumulation of bile acids, causing liver injury and the risk of progression to cirrhosis and liver failure. First-line therapy for PBC is ursodeoxycholic acid, although up to 40% of treated individuals are incomplete responders, and there is no effective therapy for PSC, highlighting the need for better therapeutic options in these diseases.

Impact of Clinical Characteristics and Treatment on Cholangiocarcinoma Prognosis in Southern Thailand.

Background: Cholangiocarcinoma (CCA) is most commonly seen in Northeastern Thailand and other parts of Asia where liver flukes are prevalent. However, it is unknown whether CCA patients in low and high liver fluke prevalence areas are similar. This study aimed to analyze the clinical characteristics and outcomes of CCA patients in Southern Thailand.

[Progress in the diagnosis and treatment of acute pancreatitis complicated by biliary tract diseases].

Acute pancreatitis is a common surgical emergency characterized by severe local or systemic complications during its progression. Diseases of the biliary system are among the serious local complications of acute pancreatitis, primarily including acute acalculous cholecystitis (AAC) and biliary stricture. AAC often occurs in the later stages of acute pancreatitis, exacerbating systemic inflammation and leading to organ failure and life-threatening conditions in severe cases.

Cytoskeleton Remodeling-Related Proteins Represent a Specific Salivary Signature in PSC Patients.

Primary sclerosing cholangitis (PSC) and Primary biliary cholangitis (PBC) are chronic inflammatory biliary diseases characterized by progressive damage of the bile ducts, resulting in hepatobiliary fibrosis and cirrhosis. Currently, specific biomarkers that allow to distinguish between PSC and PBC do not exist. In this study, we examined the salivary proteome by carrying out a comprehensive and non-invasive screening aimed at highlighting possible quali-quantitative protein deregulations that could be the starting point for the identification of effective biomarkers in future.

Molecular Mechanisms of Fibrosis in Cholestatic Liver Diseases and Regenerative Medicine-Based Therapies.

The aim of this review is to explore the potential of new regenerative medicine approaches in the treatment of cholestatic liver fibrosis. Cholestatic liver diseases, such as primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and biliary atresia (BA), due to the accumulation of bile, often progress to liver fibrosis, cirrhosis, and liver failure. When the disease becomes severe enough to require liver transplantation.

Unexplained Chronically Elevated Aminotransferases: Liver Biopsy Gives Major Information with Therapeutic Implication in One Patient Out of Seven.

Background & Aims: Liver biopsy contribution in patients with unexplained elevation of transaminases is not clearly established. The aim was to study liver biopsy contribution in patients with unexplained elevated transaminases strictly defined according to the current guidelines, reflecting the present clinical practice.

Methods: In a retrospective study, we identified all the liver biopsies performed in patients with elevated transaminases for at least six months.

Liver Failure in Autoimmune Hepatitis Overlap Syndrome With Primary Biliary Cholangitis: A Case Report.

Autoimmune hepatitis (AIH) is a complex and long-term liver condition, primarily affecting women, and is marked by high levels of serum gamma globulins, the presence of circulating autoantibodies, and a genetic association. The disease can manifest in a variety of ways, ranging from mild or no symptoms to severe acute liver inflammation. AIH is often associated with other autoimmune disorders, such as primary biliary cholangitis (PBC) and autoimmune thyroiditis.

Quantitative fibrosis identifies biliary tract involvement and is associated with outcomes in pediatric autoimmune liver disease.

Background: Children with autoimmune liver disease (AILD) may develop fibrosis-related complications necessitating a liver transplant. We hypothesize that tissue-based analysis of liver fibrosis by second harmonic generation (SHG) microscopy with artificial intelligence analysis can yield prognostic biomarkers in AILD.

Methods: Patients from single-center studies with unstained slides from clinically obtained liver biopsies at AILD diagnosis were identified.

Global Epidemiology of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and a significant global health challenge due to its high mortality rate. The epidemiology of HCC is closely linked to the prevalence of chronic liver diseases, the predominant etiology being hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, alcohol consumption, and metabolic disorders such as metabolic dysfunction-associated steatotic liver disease (MASLD). HCC incidence varies widely globally, with the highest rates observed in East Asia and sub-Saharan Africa.

Comparison of target concentration of propofol during three phases of live donor liver transplant surgery using a target-controlled infusion of propofol total intravenous anaesthesia - A prospective, observational pilot study.

Background And Aims: Three phases (dissection, anhepatic, and neohepatic) exist for propofol pharmacokinetics during liver transplantation (LT), resulting in varying cardiac output, volume of distribution, and drug metabolism. The primary objective was to compare the mean target concentration of propofol required to maintain the bispectral index (BIS) between 40 and 60 during three phases of LT by using a target-controlled infusion of total intravenous anaesthesia (TCI-TIVA).

Methods: In this prospective, observational study, 20 adult patients diagnosed with chronic liver disease scheduled for live-donor LT were included.

Immune checkpoint inhibitors and the liver: balancing therapeutic benefit and adverse events.

Immune checkpoint inhibitors (ICI) have led to breakthrough improvements in the management of malignancy including hepatocellular (HCC) and biliary tract cancer, improving decades-old standards of care and increasing patient survival. In both liver tumour types, which commonly arise in the context of liver inflammation and underlying functional impairment, the lack of validated predictors of response underscores the need to balance predicted gains in survival with risk of treatment-related hepatoxicity and decompensation of underlying chronic liver disease.In addition, the liver is implicated in the toxicity associated with ICI therapy for non-liver cancers, which exhibits a high degree of variability in presentation and severity.

Hierarchically Positioning Laparoscopic Microwave Ablation in the Therapeutic Span of Early Hepatocellular Carcinoma: A Real-Life Comparative Analysis.

Background: Laparoscopic microwave ablation (LMWA) has yet to gain a specific place in treatment guidelines for early hepatocellular carcinoma (HCC). This study compared the outcomes of LMWA and trans-arterial chemoembolization (TACE) for early non-resectable patients with HCC, taking percutaneous radiofrequency ablation (PRFA) as the reference treatment.

Methods: A retrospective multicenter observational study was conducted, enrolling non-transplantable, non-resectable patients who had early HCC treated with LMWA (n = 658) from Padua and Milan centers, and with PRFA (n = 844), and TACE (n = 425) from the ITA.

Stard1 promotes cholestatic liver injury and disease progression by sensitizing to bile acid hepatotoxicity.

Background And Aims: Cholestatic liver diseases (CLD) are often accompanied by hepatocellular injury, fibrosis, and cirrhosis due to the intracellular accumulation of solutes that cannot be excreted into bile, including bile acids (BAs). These are synthesized in hepatocytes from cholesterol mainly via the classic pathway and in a lower proportion through the mitochondrial acidic pathway. The latter requires STARD1-dependent cholesterol transport to the mitochondrial inner membrane for metabolism, whose contribution to BA-induced hepatotoxicity and CLD is unknown.

Modulation of gut microbiota by probiotics to improve the efficacy of immunotherapy in hepatocellular carcinoma.

Hepatocellular carcinoma, a common malignancy of the digestive system, typically progresses through a sequence of hepatitis, liver fibrosis, cirrhosis and ultimately, tumor. The interaction between gut microbiota, the portal venous system and the biliary tract, referred to as the gut-liver axis, is crucial in understanding the mechanisms that contribute to the progression of hepatocellular carcinoma. Mechanisms implicated include gut dysbiosis, alterations in microbial metabolites and increased intestinal barrier permeability.

Safety and Effectiveness of Naltrexone in the Management of Alcohol Use Disorder in Patients With Alcohol-associated Cirrhosis: First Clinical Observation From Indian Cohort.

Background And Aims: Naltrexone is a promising drug to treat alcohol use disorder with limited evidence of safety in liver diseases. An observational study was performed to study the safety, effectiveness, and tolerability of Naltrexone in the management of alcohol use disorder in patients with alcohol-associated cirrhosis.

Methods: Naltrexone was started in patients with alcohol-related liver disease for the management of alcohol use disorder in 86 patients who were followed up for 4 weeks.

Expression of activin A in liver tissue and the outcome of patients with biliary atresia.

Biliary atresia (BA) is a rare disease of unknown etiology which leads to cirrhosis and death if left untreated. The standard of care is an early hepatoportoenterostomy (HPE). Long-term follow-up is mandatory, during which most patients will require a liver transplant.

Racial Disparities in Inpatient Hospital Outcomes of Primary Sclerosing Cholangitis in United States: Nationwide Analysis.

Primary sclerosing cholangitis (PSC) is an idiopathic cholestatic liver disease that may lead to biliary strictures and destruction. It is associated with p-ANCA positivity and inflammatory bowel disease, typically ulcerative colitis. The aim of this study is to investigate the trends of inpatient healthcare utilization and mortality from 2008 to 2017 in the United States.

Preoperative prediction of post hepatectomy liver failure after surgery for hepatocellular carcinoma on CT-scan by machine learning and radiomics analyses.

Introduction: No instruments are available to predict preoperatively the risk of posthepatectomy liver failure (PHLF) in HCC patients. The aim was to predict the occurrence of PHLF preoperatively by radiomics and clinical data through machine-learning algorithms.

Materials And Methods: Clinical data and 3-phases CT scans were retrospectively collected among 13 Italian centres between 2008 and 2022.

Evaluation of Liver Fibrosis Using Shear Wave Elastography after Surgery for Congenital Biliary Dilatation.

Purpose: Liver fibrosis is not thought to occur in patients with no adverse events after surgery for congenital biliary dilatation (CBD). However, this speculation is not supported by any reports. Real-time shear wave elastography (SWE) is a noninvasive, ultrasound-based technique to evaluate liver stiffness.

Precisely Controlling the Activation of an Iron-Locked Drug Generator in the Liver Sinusoid to Enhance Barrier Penetration and Reduction of Liver Fibrosis.

Complex physical barriers and the nanomaterial's clearance mechanism in the liver greatly hinder the feasibility of using a conventional liver-targeting nanoplatform to deliver antifibrotic drugs to pathological sites for the treatment of liver fibrosis. Here, a novel drug delivery strategy was designed to overcome drug penetration barriers in a fibrotic liver and cooperated with oral nattokinase (NKase)-mediated antifibrosis therapy as a proof of concept, which relies on the coadministration of a nanosized iron-locked drug generator (named Pro-HAase) and orally absorbed iron chelator deferasirox (DFX). Such a strategy starts from the rapid accumulation of intravenously injected Pro-HAase in the microcapillaries of the fibrotic liver followed by disrupting the polyphenol-iron coordination inside Pro-HAase by DFX, liberating antifibrotic components, including procyanidine (PA) and hyaluronidase (HAase).