Hepatology Forum最新文献

Rhabdomyosarcoma (RMS) comprises approximately 5% of all pediatric malignancies, and the biliary system is considered one of the rarest RMS locations. Awareness, knowledge, and early recognition of the disease are essential for accurate diagnosis and proper treatment of biliary RMS in a child with obstructive jaundice and suspicious radiological findings. We present two pediatric biliary RMS cases requiring different managements because of their primary evaluations at their referring facilities. A four-and-a-half-year-old boy was referred to our institution for liver transplantation following neoadjuvant chemotherapy for centrally located unresectable biliary RMS. The patient received a left lateral segment graft from a living donor with no complications during the post-transplant period. The second patient was a seven-year-old foreign boy with obstructive jaundice and a history of choledochal cyst resection. A tumoral mass was revealed during exploration, and macroscopic total resection of the lesion was performed. The final pathology result of the resected material was biliary RMS with microscopic residue on the bile duct margin and lymph node involvement. The patient was transferred to the Pediatric Oncology Division for systemic treatment following surgical recovery. Biliary RMS presents distinct challenges in terms of accurate diagnosis and successful management. A multidisciplinary approach is indispensable for effective treatment. Complete surgical resection has been proven to be the mainstay strategy in feasible cases. Contributions of pre- and postoperative chemotherapy and radiotherapy are crucial in extensive disease. Liver transplantation should be considered, with reasonable success rates, in persistent unresectable and non-metastatic cases.

Background and aim: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide and is strongly linked to metabolic comorbidities such as diabetes mellitus, hypertension, dyslipidemia, and coronary artery disease. Despite their cardiovascular benefits, statins are historically underused in patients with MASLD because of concerns regarding hepatotoxicity. This study aimed to evaluate the impact of statins on liver transaminase levels in patients with MASLD and assess whether statin type or dose influences these outcomes.

Materials and methods: We conducted a retrospective review of 104 patients with MASLD who attended outpatient clinics between January 2023 and December 2024. Patients on statins for ≥12 months were included, while those with viral hepatitis, autoimmune liver disease, or significant alcohol intake were excluded. The data collected included comorbidities, statin type/dose, and liver transaminase levels at baseline, 3, 6, and 12 months. Patients without baseline transaminase levels available at the time of statin initiation were excluded. Of the 104 patients recruited, only 21 underwent transient elastography, of which two had advanced chronic liver disease.

Results: The mean BMI was 34.26 kg/m². Most patients had diabetes mellitus (86%), hypertension (88.5%), and dyslipidemia (98.1%). Transaminase levels remained stable over 12 months (ALT, χ²(3)=0.340, p=0.952; AST, χ²(3)=0.342, p=0.926). Statin type and dose had no significant effects on transaminase levels.

Conclusion: Statins of different types and doses did not significantly affect transaminases in patients with MASLD, indicating that statins are safe for use in patients with MASLD who meet the criteria for lipid-lowering therapy. Further studies are warranted to explore the long-term hepatic effects of statins in patients with metabolic dysfunction-associated steatohepatitis (MASH), focusing on histological outcomes.

Wilson's disease (WD) is a genetic disease of autosomal recessive inheritance resulting in the mutation of the adenosine triphosphate 7B (ATP7B) gene. The estimated prevalence of WD is one in 30,000 to 100,000, with a wide age of presentation between 3 to 55 years. Initial manifestations of WD are mainly neurologic, hepatic, or a combination of both. Proximal myopathy, however, is a rare presenting feature, with only a limited number of cases described in the literature. Presenting features such as rhabdomyolysis, hypokalemic muscle paralysis, and spasmodic contractions have been documented, but, as per our knowledge, only one case of proximal myopathy as the initial complaint has been reported. The underlying mechanism of this phenomenon in untreated cases remains unclear and warrants further investigation. We report the case of a 9-year-old female who presented with difficulty in walking, difficulty standing from a sitting position, and jaundice, subsequently diagnosed as WD with proximal myopathy.

Background and aim: Resmetirom received conditional Food and Drug Administration (FDA) approval in 2024 for metabolic dysfunction-associated steatotic liver disease (MASLD) based on its promising liver-targeted therapy. Clinical trials required a histological diagnosis of metabolic dysfunction-associated steatohepatitis (MASH) with F2-F3 fibrosis, excluding cirrhosis, while real-world prescribing relies on non-invasive tests (NITs). This study evaluates their efficacy in identifying the target population within a biopsy-proven Turkish MASLD cohort.

Materials and methods: We analyzed 266 patients with biopsy-proven MASLD from the Turkish NAFLD Biobank. Inclusion required AST >17 U/L (females) or >20 U/L (males), and CAP ≥280 dB/m. Eligibility was defined by liver stiffness measurement (LSM) of 10-19.9 kPa (excluding cirrhosis or low platelet count) or a FAST score ≥0.67.

Results: Among the study population, 130 patients (48.9%) had histologically confirmed MASH with F2-F3 fibrosis. Based on LSM criteria applied to histologically eligible patients, 81 patients (62.3%) were underdiagnosed, compared to 95 patients (73.1%) when using the FAST score. Additionally, among patients who corresponded to NIT, 34 patients (41.0%) were overprescribed using LSM, while 23 patients (39.7%) were overprescribed using the FAST score. The kappa value as a measure of agreement showed poor compatibility for both LSM and FAST with liver biopsy (0.128 and 0.101, respectively). When treatment decisions were guided by either of the NITs, 44 patients (44.0%) received unnecessary prescriptions, and 74 patients (44.6%) had missed diagnoses.

Conclusion: The NITs defined for identifying the target population for resmetirom demonstrated poor performance in accurately detecting or excluding eligible patients. Therefore, performing a liver biopsy before starting resmetirom treatment will prevent unnecessary increases in cost and significantly reduce the economic burden of the treatment.

Keywords: Fibrosis; MASLD; MASH; non-invasive test; resmetirom.

Background and aim: Early detection, accurate evaluation, and proper follow-up of fibrosis in chronic liver disease are crucial for improving disease prognosis. Indirect biochemical fibrosis tests, such as the AST-to-Platelet Ratio Index (APRI) and Fibrosis-4 (FIB-4) score, have been developed, incorporating parameters like AST, ALT, and platelet count. However, the influence of factors such as Helicobacter pylori (H. pylori) on fibrosis tests such as APRI and FIB-4 remains unclear, and this study aimed to evaluate its impact.

Materials and methods: This study included 190 patients (aged ≥18 years) who underwent gastric and liver biopsies at a tertiary center between 2006 and 2021. Patients were categorized into three groups based on liver histopathological findings: mild (F0-1), moderate (F2-3), and advanced (F4-6) fibrosis. Additionally, patients were grouped based on H. pylori presence as determined by gastric histopathology. Demographic, clinical, laboratory, imaging, and histopathological characteristics were analyzed and compared between groups.

Results: Among the 190 patients, H. pylori was detected in 135 (71%) and was absent in 55 (29%). No significant differences were observed between H. pylori-positive and -negative groups in terms of AST, ALT, platelet count, INR, FIB-4, or APRI scores. For APRI, significant differences were found between mild-moderate and mild-advanced fibrosis groups (p<0.001), but not between moderate and advanced groups (p>0.05). For FIB-4, significant differences were observed across all fibrosis groups (p<0.001). The presence of H. pylori did not significantly affect the APRI or FIB-4 scores within any fibrosis group.

Conclusion: The presence of H. pylori did not significantly impact APRI or FIB-4 scores. These indices can reliably assess liver fibrosis, regardless of H. pylori status.

Background and aim: Numerous studies have demonstrated associations between hepatocellular carcinoma (HCC)-related features and markers such as glypican-3 (GPC3), heat shock protein 70 (HSP70), CD34, and glutamine synthetase (GS). In this study, we aimed to quantify these markers in the tissues of patients with cirrhosis or advanced fibrosis due to chronic hepatitis B (CHB).

Materials and methods: A retrospective review was conducted on patients with CHB who developed pathologically confirmed HCC and underwent surgical resection between 2003 and 2013. A total of 24 patients who had paired malignant and surrounding cirrhotic tissue samples were included. Liver tissues were categorized as pre-HCC cirrhotic tissue, peritumoral cirrhotic tissue, and malignant HCC tissue. Non-cirrhotic liver samples from CHB patients served as controls.

Results: GPC3 staining was observed to be strong in 80% of HCC tissues and was positive in 70% of cirrhotic tissue surrounding HCC. In cirrhotic tissue 44 months prior to HCC development, 60% of cases were GPC3 positive. In non-cirrhotic chronic viral hepatitis, 20% of cases were GPC3 positive. GPC3, CD34, and GS showed significantly stronger staining in malignant versus control tissue (p<0.05). CD34 showed the highest discriminatory performance for malignant versus cirrhotic tissue (sensitivity=91.7%, specificity=91.7%), while GPC3 had the highest sensitivity (83.4%) in differentiating malignant from non-cirrhotic tissue.

Conclusion: GPC3 expression may be a predictive marker for HCC development in patients with CHB-related cirrhosis. CD34 also has considerable accuracy in differentiating HCC from cirrhotic and non-cirrhotic tissues, supporting a role for use in HCC detection.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a persistent hepatic condition linked with cardiovascular disorders and metabolic disturbances. Characterized by inflammation, fat accumulation, and fibrosis within the liver, MASLD can develop into liver cancer and cirrhosis. With a global prevalence of 32.4%, the condition parallels rising obesity rates. Orlistat inhibits lipase enzymes and, therefore, reduces dietary fat absorption, which may benefit MASLD patients. The present systematic review and meta-analysis were performed in accordance with PRISMA guidelines. Searches of PubMed, Scopus, Web of Science, and Embase up to January 2025 were performed using specific keywords and MeSH terms. Bias assessment and data extraction were conducted using Joanna Briggs Institute (JBI) tools independently by two researchers. Statistical analyses were performed with Stata version 14, calculating standardized mean differences, 95% confidence intervals (CI), and heterogeneity (by performing Cochran's Q test and I² index). Moreover, meta-regression, subgroup analyses, and sensitivity analyses were conducted. Eleven studies featuring 582 participants were included. Orlistat treatment induced a significant reduction in levels of alanine transaminase (ALT) (SMD = -26.23; 95% CI = -34.70 to -17.76) and aspartate aminotransferase (AST) (SMD = -19.62; 95% CI = -28.33 to -10.92). Furthermore, reductions in HOMA-IR, body mass index, cholesterol, insulin, and waist circumference were observed. The included studies exhibited low to moderate heterogeneity for most outcomes, indicating consistent results across trials. Orlistat significantly improved AST, ALT, and some other metabolic parameters in MASLD patients, suggesting its potential as an additional treatment option. However, the outcome must be interpreted cautiously, considering study heterogeneity. Further high-quality, multicenter research is necessary to confirm these results.