International Journal of Molecular Medical Science, 2025, Vol.15, No.1, 33-41 http://medscipublisher.com/index.php/ijmms 35 Symptom severity in PLD correlates with cyst burden and total liver volume. Patients may develop symptoms such as early satiety, dyspnea, or back pain due to the compression of surrounding organs (Santos-Laso et al., 2017). Hormonal factors, particularly in women, accelerate cyst growth, likely explaining the higher prevalence and symptomatology among females (Chen et al., 2022; Mason, 2024). Disease progression in polycystic liver cysts can lead to a dramatic reduction in quality of life, necessitating careful management. 3.2 Diagnostic approaches The diagnosis of liver cysts relies heavily on imaging modalities, which allow for detailed visualization of the cystic architecture. Ultrasound is typically the first-line diagnostic tool due to its wide availability and cost-effectiveness. It can detect cysts larger than 1 cm and help distinguish simple cysts from complex ones. Advanced imaging techniques, such as Computed Tomography (CT) and Magnetic Resonance Imaging (MRI), are more sensitive and provide detailed information on cyst size, number, and impact on surrounding structures (Giuliani et al., 2015). MRI, in particular, is highly effective in assessing biliary tree involvement and communicating cysts, especially in polycystic liver diseases. Genetic testing complements imaging by identifying causative mutations, particularly in familial cases. Testing for mutations in PKD1, PKD2, and PRKCSHcan confirm diagnoses of ADPKD or isolated polycystic liver disease (PCLD) (Lee-Law et al., 2019). Additionally, biomarker studies exploring aquaporin-1 expression in cysts show potential for diagnostic stratification (Li et al., 2015). 3.3 Complications and comorbidities Liver cysts can lead to a range of complications, including cyst rupture, infection, intracystic hemorrhage, and compression of adjacent organs. These complications are more common in large cysts and PLD. Cyst rupture and hemorrhage may present with acute abdominal pain and hypotension, while infections are associated with fever, localized tenderness, and systemic symptoms (Kataoka et al., 2021). PLD is often accompanied by renal manifestations, particularly in ADPKD, where renal failure is a significant comorbidity. Other complications include portal hypertension, biliary obstruction, and, in rare cases, malignancy arising within cysts Long-term monitoring is crucial in high-risk patients, particularly those with ADPKD and a high liver cyst burden (Masyuk et al., 2021). Management of these complications often requires a multidisciplinary approach. Interventions include sclerotherapy, surgical fenestration, or, in severe cases, liver transplantation. Experimental pharmacological approaches targeting signaling pathways involved in cyst growth, such as mTOR inhibitors, are promising avenues for reducing complications (Ellis et al., 2022; Cai, 2024). 4 Molecular and Pathophysiological Mechanisms 4.1 Ciliary signaling and cellular pathways Ciliary signaling plays a pivotal role in maintaining biliary epithelial homeostasis, and its disruption is central to the pathogenesis of liver cysts. The PKD1 and PKD2 genes, encoding polycystin-1 and polycystin-2, respectively, are critical for ciliary function in cholangiocytes. These proteins regulate intracellular calcium signaling, which in turn modulates cellular proliferation, differentiation, and fluid secretion. In Autosomal Dominant Polycystic Kidney Disease (ADPKD) and Polycystic Liver Disease (PLD), mutations in these genes lead to defective calcium signaling, promoting cystogenesis (Lee-Law et al., 2019). Ciliary dysfunction Also Activates Cyclic AMP (cAMP) pathways, which are critical in cyst enlargement. Elevated cAMP levels drive fluid secretion and cellular proliferation through the activation of protein kinase A (PKA) and downstream signaling cascades, including the Ras/ERK pathway (Spirli et al., 2017). Targeting cAMP signaling with adenylyl cyclase inhibitors represents a potential therapeutic approach to mitigate cyst growth. The Wnt signaling pathway also plays a role in hepatic cystogenesis. Aberrant activation of Wnt/β-catenin signaling has been implicated in increased cholangiocyte proliferation and cyst expansion, further emphasizing the role of cellular pathways in cyst development (van de Laarschot and Drenth, 2017).
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