Background: Metabolic dysfunction-associated steatohepatitis (MASH), formerly nonalcoholic steatohepatitis (NASH), is a progressive liver disease and a leading cause of cirrhosis and liver-related mortality worldwide, affecting approximately 3%–5% of the global adult population and up to 30%–40% of individuals with type 2 diabetes mellitus (T2DM) or those attending dedicated diabetes and endocrine centers. For decades, treatment was limited to lifestyle interventions. The years 2024 and 2025 marked a paradigm shift with the first-ever FDA approvals of pharmacologic agents for MASH. Scope: This comprehensive narrative review synthesizes the evidence for newly approved and emerging pharmacotherapies for MASH, addressing the mechanisms of action, pivotal clinical trial data, efficacy, safety profiles, and place in therapy for resmetirom and semaglutide. It also discusses key agents including pioglitazone, saroglitazar, and vitamin E, and evaluates the non-invasive testing (NIT) toolkit—including FIB-4, VCTE, shear wave elastography, MRE, and ELF—in the context of a structured, risk-stratified clinical algorithm. Findings: Resmetirom (Rezdiffra), a THR-β agonist, achieved MASH resolution in 26%–30% versus 10% placebo and fibrosis improvement in 24%–26% versus 14% placebo at 52 weeks in the MAESTRO-NASH trial. Semaglutide 2.4 mg (Wegovy) demonstrated a 28.7% delta over placebo in MASH resolution in the ESSENCE trial. Pioglitazone has additional evidence for reducing the FIB-4 index in real-world studies. Saroglitazar, a PPAR-α/γ dual agonist approved in India, has shown significant reductions in ALT, liver fat, and metabolic parameters in Phase 2 studies and is advancing to Phase 2b. Shear wave elastography is a clinically important alternative to VCTE for fibrosis staging, particularly in patients with obesity, and offers value in resolving discordant FIB-4/VCTE results. Conclusion: The approval of resmetirom and semaglutide marks a new era in MASH management. A risk-stratified algorithmic approach using NITs guides patient selection, with liver biopsy reserved for specific clinical scenarios. The therapeutic landscape is rapidly evolving, with saroglitazar and combination approaches representing key frontiers.

Hepatobiliary disorders during pregnancy represent a significant cause of maternal and fetal morbidity, requiring careful differentiation between physiological adaptations of pregnancy and true hepatic pathology. This narrative review provides a comprehensive overview of three major hepatobiliary conditions encountered during pregnancy: gallstone disease, intrahepatic cholestasis of pregnancy (ICP), and viral hepatitis (HAV, HBV, HCV, HDV, and HEV). Pregnancy-induced hormonal and immunological changes influence disease pathogenesis, clinical presentation, diagnostic interpretation, and therapeutic decision-making. Gallstone disease remains the most common non-obstetric surgical condition in pregnancy, with contemporary evidence supporting timely laparoscopic intervention when indicated. ICP is characterized by pruritus and elevated serum bile acids and is associated with increased risks of preterm birth, fetal distress, and stillbirth, necessitating close surveillance and individualized delivery planning. Viral hepatitis poses unique challenges because of the potential for vertical transmission, maternal complications, and adverse neonatal outcomes. Universal antenatal screening for hepatitis B and C is increasingly recognized as a cornerstone of care. For HBV, maternal antiviral prophylaxis combined with neonatal immunoprophylaxis has reduced mother-to-child transmission to below 1%, whereas the role of direct-acting antivirals for HCV during pregnancy continues to evolve. HEV remains the most severe viral hepatitis in pregnancy, carrying disproportionately high maternal mortality in endemic regions. Across all conditions, multidisciplinary management involving hepatologists, gastroenterologists, obstetricians, maternal–fetal medicine specialists, surgeons, and neonatologists is essential to optimize outcomes. This review synthesizes current evidence, highlights pregnancy-specific diagnostic and therapeutic considerations, and identifies emerging areas of research that may further improve maternal and neonatal outcomes.

Background: Cocaine is the second most widely used illicit substance worldwide and exerts potent sympathomimetic effects by inhibiting the reuptake of norepinephrine, dopamine, and serotonin. While cardiovascular and neurological complications are well recognized, gastrointestinal (GI) manifestations are increasingly reported. These arise from multifactorial mechanisms including vasospasm, endothelial dysfunction, thrombosis, ischemia, and direct mucosal toxicity, often with severe clinical consequences. Objective: This narrative review summarizes the mechanisms, pharmacokinetics, pharmacodynamics, routes of use, and spectrum of GI complications associated with cocaine exposure, with emphasis on ischemic, ulcerative, hemorrhagic, inflammatory, fibrotic, hepatobiliary, and pancreatic sequelae; provides a differential-diagnosis and diagnostic algorithm; and critically appraises the strength of the supporting evidence and its principal confounders. Methods: PubMed/MEDLINE, Embase, and Scopus were searched from January 1, 1987 through July 17, 2026, using the Boolean strings detailed in the Methods section. Case reports, case series, retrospective cohort/case-control studies, and systematic reviews published in English were eligible; both abstract and, where accessible, full text were screened. Reference lists of retrieved articles were hand-searched (snowballing) for additional citations. Results: Cocaine induces GI injury through vasoconstriction, pro-thrombotic effects, microvascular dysfunction, and direct cytotoxicity. Reported complications span ischemic/vascular disease (mesenteric ischemia/infarction, colonic ischemia, ischemic/hemorrhagic colitis, vascular thrombosis), ulcerative/perforative disease (peptic ulcer disease; gastric, duodenal, small-, and large-bowel perforation), inflammatory/fibrotic disease (enteritis, enterocolitis, strictures, retroperitoneal fibrosis), hepatobiliary and pancreatic injury, splenic infarction/hematoma/rupture, and other presentations including gastric antral vascular ectasia, an inflammatory bowel disease (IBD)-mimicking phenotype, and, rarely, acalculous cholecystitis. A systematic review of 53 studies (69 patients) found broadly similar mortality and surgical rates across routes of cocaine use, and two hybrid cohort/case-control studies of cocaine-associated ischemic colitis reported substantially higher mortality and surgical intervention rates than non-cocaine-related ischemic colitis. Polysubstance use — particularly concurrent alcohol (via the metabolite cocaethylene) and tobacco — and pre-existing vascular disease are common but incompletely characterized confounders. Notably, the evidence base underlying nearly every complication described here remains dominated by single case reports and small case series rather than comparative studies, a limitation that should temper the strength of any causal inference drawn from it. Conclusion: Cocaine use is a significant and under-recognized contributor to severe GI morbidity and mortality, with complications spanning ischemia and perforation to hepatopancreatic injury. The evidentiary foundation remains overwhelmingly derived from case reports and small series; only three comparative or aggregated studies provide quantitative risk data, two limited to ischemic colitis and one examining route of use across the wider intestinal-ischemia literature. Clinicians should maintain a high index of suspicion for cocaine-related GI disease in young patients presenting with abdominal pain or ischemic features, use the differential-diagnosis framework and algorithm proposed here to avoid diagnostic delay, and account for polysubstance use when interpreting presentations. Future research should prioritize registry-based or multicenter comparative studies to better quantify risk, outcomes, and the independent contribution of confounders.

Neurofibromas are rare benign tumors of the peripheral nerve sheath, predominantly associated with neurofibromatosis type 1 (NF1). Isolated colorectal neurofibromas that arise in patients without clinical manifestations of NF1 are extremely rare and are frequently identified inadvertently during endoscopic examinations. The rarity of these conditions complicates diagnosis, necessitating histopathologic and immunohistochemical validation. We report a case of an incidental rectal submucosal neurofibroma found during a colonoscopy performed to evaluate chronic constipation in a patient with no previous diagnosis of neurofibromatosis.