Internal Medicine

Transjugular Intrahepatic Portosystemic Shunt (TIPS) in Portal Hypertension

Portal hypertension is the increased blood pressure within the portal venous system, which can lead to serious complications like variceal bleeding, refractory ascites, and hepatic hydrothorax. TIPS reduces portal hypertension by diverting a portion of the portal blood flow directly into the systemic circulation, thereby decreasing the pressure in the portal venous system

The key indications include recurrent variceal bleeding that is unresponsive to endoscopic or pharmacological treatments, refractory ascites that does not respond to diuretics or repeated paracentesis, and hepatic hydrothorax resistant to medical therapy. Additionally, TIPS may be used in managing Budd-Chiari syndrome, where thrombosis of the hepatic veins leads to increased portal pressure.

Caput Medusae

Caput medusae is a clinical sign characterized by the appearance of dilated, tortuous veins radiating from the umbilicus across the abdominal wall. This condition is named after Medusa, a figure from Greek mythology known for her hair of snakes, due to its resemblance to the radiating pattern of veins.

Caput medusae is a manifestation of severe portal hypertension, which is defined as an increase in the pressure gradient between the portal vein and inferior vena cava. This increased pressure leads to the development of portosystemic collaterals, including those around the umbilicus.

Metabolic Dysfunction–Associated Steatohepatitis (MASH) and Emerging Treatments

Overview:

Metabolic dysfunction–associated steatohepatitis (MASH), a prevalent liver disease worldwide, is primarily driven by obesity and currently lacks effective treatments. Glucagon-like peptide-1 (GLP-1) receptor agonists, emerging as promising anti-obesity treatments, may offer a potential therapeutic option for MASH. Recent studies explore the efficacy of these agents, particularly when combined with other incretin hormones or complementary pathway molecules.

Semaglutide Study:

A phase 2 trial investigated , a GLP-1 receptor agonist, in MASH patients. While semaglutide achieved steatohepatitis resolution in 40-59% of participants, it did not significantly reduce liver fibrosis, a crucial surrogate endpoint. Furthermore, it failed to improve histological outcomes in patients with cirrhosis.

Enhanced GLP-1 Receptor Agonist-Based Treatments:

A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis | New England Journal of Medicine (nejm.org)

1. 🎯 Aim: The trial evaluated resmetirom, an oral liver-directed thyroid hormone receptor beta–selective agonist, for treating nonalcoholic steatohepatitis (NASH) with liver fibrosis.

2. 🧪 Methodology: A phase 3 trial with 966 adults having biopsy-confirmed NASH and fibrosis. They were randomized to receive resmetirom (80 mg or 100 mg) or placebo.

3. 🔬 Primary Endpoints: NASH resolution without fibrosis worsening and fibrosis improvement without NAFLD (nonalcoholic fatty liver disease) activity score worsening at week 52.

4. ✅ Results: Significant NASH resolution in the resmetirom groups (25.9% at 80 mg, 29.9% at 100 mg) vs. placebo (9.7%).

5. 📈 Fibrosis Improvement: Significant improvement in the resmetirom groups (24.2% at 80 mg, 25.9% at 100 mg) vs. placebo (14.2%).

Next-Generation Multitarget Stool DNA Test for Colorectal Cancer Screening | NEJM

In a study comparing screening methods, the next-generation multitarget stool DNA test exhibited superior sensitivity for detecting colorectal cancer (93.9%) and advanced precancerous lesions (43.4%) compared to FIT. However, it demonstrated slightly lower specificity for advanced neoplasia at 90.6%. This indicates that the stool DNA test could significantly enhance early detection of colorectal cancer and precancerous conditions, offering a promising alternative to traditional fecal immunochemical test with improved performance characteristics, though at the expense of some specificity.

A Cell-free DNA Blood-Based Test for Colorectal Cancer Screening | NEJM

In the ECLIPSE trial, a cfDNA blood-based test for colorectal cancer screening demonstrated an 83.1% sensitivity in detecting colorectal cancer and 89.6% specificity for advanced neoplasia (cancer or advanced precancerous lesions) among 7,861 eligible individuals. The test showed an 87.5% sensitivity for early-stage (I-III) cancers and a lower sensitivity of 13.2% for advanced precancerous lesions. This suggests that the cfDNA test could significantly contribute to early cancer detection and potentially improve screening adherence, offering a promising alternative to traditional colonoscopy screening methods.