Study of sex-biased differences in genomic profiles in East Asian hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is characterized by a notable sex disparity in incidence and tumor aggressiveness. Revealing differences in genetic landscapes between male and female HCCs may expand the understanding of sexual disparities mechanisms and assist the development of precision medicine. Although reports on the sex disparity of HCC are accumulated, studies focusing on sex-related biomarkers among Asian populations remain limited. Here, we conducted a comprehensive genomic profiling analysis to explore differences between male and female patients within a cohort of 195 Taiwanese HCC patients. We did not detect any sex-biased genomic alterations. However, when our investigation extended to the TCGA dataset, we found higher frequencies of gene copy gains in CCNE2 and mutations in CTNNB1 and TP53 among male patients. Besides, we further evaluated the associations between genomic alterations and patients' prognosis by sex. The results showed that female patients harboring tumors with STAT3 gain and alterations in the JAK-STAT pathway displayed a poor prognosis. These two factors remained independently associated with unfavorable prognosis even after adjusting for the patient's age and stage characteristics (Hazard ratio = 10.434, 95% CI 3.331-32.677, P < 0.001; Hazard ratio = 2.547, 95% CI 1.195-5.432, P = 0.016, respectively). In summary, this study provides valuable insights into understanding sex disparity in HCC in the East Asian population. Validation through larger cohorts and extensive sequencing efforts is warranted.

The efficacy of multi-disciplinary lifestyle modifications in Taiwanese nonalcoholic steatohepatitis patients.

Lifestyle modification is the standard of care for nonalcoholic fatty liver disease (NAFLD) patients. We aimed to investigate the efficacy of a short-term lifestyle modification program in the disease course of Taiwanese nonalcoholic steatohepatitis (NASH) patients with paired biopsies. All patients received a 6-month, strict multidisciplinary program of lifestyle modifications led by physicians, dieticians, and nursing staff. The histopathological and clinical features were assessed. The endpoints were normalization of transaminase levels, metabolic parameters, a decrease in the NAFLD activity score (NAS) ≥1, and a decrease in the fibrosis stage ≥1. We also aimed to elucidate the predictors associated with disease progression. A total of 37 patients with biopsy-proven NASH were enrolled. The normalization of transaminase levels increased from 0% to 13.5%. There were also significantly increased proportions of patients with normal total cholesterol, triglyceride, and hemoglobin A1c levels. Fifteen (40.5%) patients had an increased NAS ≥1, whereas 10 (27.0%) patients had NAS regression. Twelve (32.4%) patients had increased fibrosis ≥1 stage. Only 2 (5.4%) patients experienced fibrosis regression. A high fasting plasma glucose (FPG) level was associated with NAS progression. Older age and higher transaminase and FPG levels were factors associated with fibrosis progression. Seven (18.9%) patients achieved a body weight reduction >3%, and 4 (57.1%) of them experienced NAS regression. No significant effect of weight reduction on the progression of fibrosis was observed. The short-term lifestyle modification program significantly decreased liver enzymes and metabolic parameters in NASH patients. A more precise or intensive program may be needed for fibrosis improvement.

Hepatocellular Carcinoma with Gastric Metastasis Mimicking a 4 cm Gastrointestinal Stromal Tumor After a 3-year Disease-free Interval.

Hepatocellular carcinoma (HCC) is an aggressive tumor that usually occurs in patients with chronic liver disease and cirrhosis. Surgical resection is an optimal treatment for HCC, but the 5-year recurrence rates are significantly high. The majority of recurrent HCCs occur through intrahepatic metastasis with local tumor progression, and less than 20% of recurrences are extrahepatic metastases. HCC with gastric metastasis is extremely rare, and it is easily misdiagnosed as primary gastric cancer with liver metastasis. An 80-year-old male chronic hepatitis B virus carrier had received lamivudine and entecavir for years and was regularly followed up in the clinic. He had a 3.5 cm solitary HCC with microvascular invasion and received curative surgical resection in 2009. In 2013, he developed a 1.3 cm solitary HCC again and was treated with combination therapy with radiofrequency ablation and pure ethanol injection. Afterwards, he was followed every 3-6 months and was HCC-free. Three years later, in 2016, endoscopy for intermittent epigastralgia showed a solitary 4 cm intraluminal gastric subepithelial tumor without mucosal ulcers or erosions over the gastric fundus. All imaging studies, including computed tomography, favored the diagnosis of gastrointestinal stromal tumor (GIST), but the pathology of the tumor proved to be HCC. The patient did not receive any systemic anticancer therapy but only wedge resection of the stomach and remained tumor- and HCC-free until his latest clinic visit in 2023. The current case is unique and indicates the possibility of HCC with late solitary gastric metastasis mimicking GIST. Complete gastric tumor resection ensured an extremely good outcome for the patient, which is different from the devastating prognosis of most cases of HCC with gastric metastasis.

Primary biliary cholangitis with features of autoimmune hepatitis in a 19-year-old adolescent with 14q24.1q24.2 deletion: a case report.

Introduction: Primary biliary cholangitis (PBC) is a rare and chronic autoimmune liver disease characterized by the progressive destruction of small intrahepatic bile ducts that may eventually lead to cirrhosis. PBC with features of autoimmune hepatitis (AIH) has rarely been reported in pediatric patients with genetic defects. We present the case of an adolescent with chromosome 14q24.1q24.2 deletion who was given the diagnosis of stage IV PBC with features of AIH. Case presentation: A 19-year-old male adolescent with multiple congenital abnormalities and an intellectual disability presented with abnormal liver enzymes levels and pruritus for more than 5 years. Laboratory examinations revealed elevated levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma-glutamyl transpeptidase. After the exclusion of viral hepatitis, alpha-1 antitrypsin deficiency, Wilson's disease, and other genetic cholestatic liver diseases by laboratory tests and whole exome sequencing, a liver biopsy was performed and stage IV PBC was diagnosed. Notably, features of AIH were also noted in the histopathological report, indicating the presence of PBC with AIH features. The patient responded well to a combination therapy of ursodeoxycholic acid and steroids. Array comparative genomic hybridization analysis performed to study the congenital abnormalities revealed a 3.89 Mb 14q24.1q24.2 deletion. Conclusion: PBC with AIH features has rarely been reported in an adolescent with a chromosomal abnormality. The present case can increase awareness for early-onset PBC and its possible correlation with chromosomal defects.