The Accuracy of Serum Biomarkers in the Diagnosis of Steatosis, Fibrosis, and Inflammation in Patients with Nonalcoholic Fatty Liver Disease in Comparison to a Liver Biopsy.

Background and Objective: This study was conducted to evaluate the diagnostic performance of various biomarkers for steatosis, fibrosis, and inflammation in comparison to a liver biopsy (LB) in patients with nonalcoholic fatty liver disease (NAFLD). Materials and Methods: This was a cross-sectional study that included 135 patients with biopsy-proven NAFLD. Fatty liver index (FLI), hepatic steatosis index (HSI), cell death markers (CK-18 M30 and CK-18 M65), FIB-4 index, NAFLD fibrosis score (NFS), BARD, and AST to platelet ratio index (APRI) were calculated and analysed. Results: FLI, HSI scores, and the cell death biomarkers showed poor diagnostic accuracy for steatosis detection and quantification, with an area under the curve (AUC) of <0.70. The cell death biomarkers likewise did not perform well for the detection of nonalcoholic steatohepatitis (NASH) (AUC < 0.7). As for the fibrosis staging, only APRI and the cell death biomarkers had moderate accuracy (AUC > 0.7) for advanced fibrosis, whereas FIB-4, BARD, and NFS scores demonstrated poor performance (AUC < 0.70). However, a combination of FIB-4 and NFS with the cell death biomarkers had moderate accuracy for advanced (≥F3) fibrosis detection, with an AUC of >0.70. Conclusions: In this first study on Croatian patients with NAFLD, serum biomarkers demonstrated poor diagnostic performance for the noninvasive diagnosis of liver steatosis and NASH. APRI and the cell death biomarkers had only moderate accuracy for diagnosing advanced fibrosis, as did the combination of FIB-4 and NFS with the cell death biomarkers. Further studies regarding serum biomarkers for all NAFLD stages are needed.

Metabolism of Direct-acting Antiviral Agents (DAAs) in Hepatitis C Therapy: A Review of the Literature.

BACKGROUND: Hepatitis C virus (HCV) infection is still one of the leading causes of chronic liver disease, with chronically infected making up approximately 1% of the global population. Of those infected, 70% (55-85%) will develop chronic HCV infection. Chronic HCV infection causes substantial morbidity and mortality, with complications including cirrhosis, end-stage liver disease, hepatocellular carcinoma, and eventually death. OBJECTIVE: Therapeutic options for chronic HCV infection have evolved dramatically since 2014, with a translation from pegylated interferon and ribavirin (associated with suboptimal cure and high treatment-related toxicity) to oral direct-acting antiviral treatment. There are four classes of direct-acting antivirals which differ by their mechanism of action and therapeutic target. They are all pointed to proteins that form the cytoplasmic viral replication complex. Multiple studies have demonstrated that direct-acting antiviral therapy is extremely well tolerated, highly efficacious, with few side effects. METHODS: We performed an indexed MEDLINE search with keywords regarding specific direct-acting antiviral regimes and their pharmacokinetics, drug-drug interactions, and metabolism in specific settings of pregnancy, lactation, liver cirrhosis, liver transplantation and HCC risk, kidney failure and kidney transplantation. RESULTS: We present a comprehensive overview of specific direct-acting antiviral metabolism and drug-drug interaction issues in different settings. CONCLUSION: Despite its complex pharmacokinetics and the possibility of drug-drug interactions, direct-acting antivirals are highly efficacious in providing viral clearance, which is an obvious advantage compared to possible interactions or side effects. They should be administered cautiously in patients with other comorbidities, and with tight control of immunosuppressive therapy.

Urgent Surgical Treatment of GIST of Esophago-Gastric Junction in a Patient with Giant Hiatal Hernia.

Gastrointestinal stromal tumors (GISTs), being the most common mesenchymal tumors of the gastrointestinal tract, arise most commonly in stomach (60-70%) and small intestine (20-25%) while other sites of origin are rare. In most cases, they are diagnosed accidentally due to their indolent clinical course; however, 10-30% have malignant potential. Gastric and esophageal GISTs carry a better prognosis than small bowel GISTs of similar size and mitotic rate. Complete surgical resection is the only potentially curative procedure, but despite its success, at least 50% of patients develop recurrence or metastases. Tyrosine kinase inhibitor imatinib gave positive results in treatment of unresectable, metastatic or recurrent GISTs. We present the case of a 69-year-old woman with a large unresectable GIST of esophago-gastric junction with multiple bilobar liver metastases who underwent an emergent palliative surgery due to diffuse bleeding from the tumor. Twelve months after the surgery, patient is still alive and stable under imatinib therapy with no signs of local recurrence of the disease. This example suggests that patients with locally advanced GISTs with distant metastases may benefit from surgery in terms of prolonged survival and quality of life.