Comparison of serum fibrosis biomarkers for diagnosing significant liver fibrosis in patients with chronic hepatitis B.

Chronic hepatitis B (CHB) virus continues to be a leading cause of morbidity and mortality worldwide. The diagnosis of liver fibrosis has a key role in selecting patients with CHB for antiviral treatment. However, serum biomarkers demonstrate limited diagnostic utility. The present study aimed to compare the performances of fibrosis biomarkers for diagnosing significant liver fibrosis that indicates the need for antiviral therapy in patients with CHB and to identify the most appropriate biomarker for these patients. The current study included 96 antiviral-naïve patients with CHB who underwent liver biopsy. METAVIR scoring system was used to assess liver fibrosis and necroinflammation. The diagnostic performances were evaluated of the platelet (PLT) count; the levels of hyaluronan, serum 7S domain of type 4 collagen, procollagen type III N-terminal peptide, tissue inhibitor of metalloproteinases 1, Mac-2 binding protein glycosylation isomer (M2BPGi) and N-terminal type III collagen propeptide (Pro-C3); the fibrosis index based on four factors; the aspartate aminotransferase-to-platelet ratio index; and enhanced liver fibrosis score for identifying significant liver fibrosis [≥fibrosis stage 2 (F2)]. All fibrosis biomarkers, except the Pro-C3 level, correlated with the fibrosis stage. M2BPGi was better than other biomarkers for diagnosing ≥F2, with the highest area under the curve of 0.902. M2BPGi demonstrated a higher diagnostic accuracy for significant fibrosis than mild/severe fibrosis or cirrhosis. However, no significant correlation was observed between the M2BPGi level and fibrosis stage in patients with CHB having significant liver necroinflammation defined as ≥ necroinflammatory activity 2. The M2BPGi level and PLT count were exclusively correlated with the fibrosis stage in 73 patients without significant liver necroinflammation. M2BPGi demonstrated the highest diagnostic performance for significant fibrosis in patients having significant liver fibrosis with no significant liver necroinflammation. In conclusion, the M2BPGi level can accurately diagnose significant liver fibrosis that indicates the need for antiviral therapy in patients with CHB.

Isolated Pancreatic Sarcoidosis Diagnosed by Endoscopic Ultrasound-guided Fine-needle Aspiration.

We herein report a 52-year-old man with multiple hypoechoic lesions in the body and tail of the pancreas detected during a screening ultrasound. Computed tomography (CT) showed no lesions other than those in the pancreas and peripheral lymph nodes. Contrast-enhanced CT identified hypovascular tumors in the pancreas. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) demonstrated partial fibrosis and noncaseating granulomas with Langhans giant cells. To our knowledge, this is the first report of isolated pancreatic sarcoidosis diagnosed by EUS-FNA. Although pancreatic sarcoidosis is very rare, clinicians should be aware of this possibility in patients presenting with multiple hypovascular pancreatic tumors.

Late-Evening Snack with Branched-Chain Amino Acid-Enriched Nutrients Does Not Always Inhibit Overt Diabetes in Patients with Cirrhosis: A Pilot Study.

Cirrhosis patients often have abnormal glucose metabolism. We investigated the effects of a late-evening snack (LES) with branched-chain amino acid-enriched nutrients (BCAA-EN) on glucose metabolism in cirrhosis patients. LES with BCAA-EN was administered for 1 week in 13 patients with cirrhosis and hypoalbuminemia. Blood glucose (BG) levels were measured every 15 min. The patients were divided into two groups based on BG levels: group 1 (G1, n = 11): nocturnal BG levels <200 mg/dL and group 2 (G2, n = 2): nocturnal BG levels ≥200 mg/dL. G1 had nocturnal BG levels <200 mg/dL, whereas G2 had nocturnal BG levels ≥200 mg/dL. The average BG levels did not significantly change after BCAA-EN administration in G1 (before 91.9 ± 29.0 mg/dL; after 89.0 ± 24.3 mg/dl). However, the average BG levels significantly increased after BCAA-EN administration in G2 (before 153.6 ± 43.3 mg/dL; after 200.9 ± 59.7 mg/dL) (p < 0.01). The glycated albumin level (16.6 ± 0.9% vs. 16.2 ± 2.1%), fasting immunoreactive insulin (F-IRI) level (53.9 ± 34.0 µU/mL vs. 16.5 ± 11.0 µU/mL), and homeostasis model assessment of insulin resistance (HOMA-IR) score (17.85 ± 10.58 vs. 4.02 ± 2.59) were significantly higher in G2 than in G1 (p < 0.05, p < 0.05, and p < 0.01, respectively). The quantitative insulin sensitivity check indices (0.32 ± 0.03 vs. 0.27 ± 0.02) were significantly higher in G1 than in G2 (p < 0.01). One patient in G2 was obese and had type 2 diabetes. The other patient was obese and had a high HOMA-IR score and F-IRI level. A LES with BCAA-EN does not inhibit overt diabetes in most cirrhosis patients. However, close attention should be paid to fluctuations in BG levels in cirrhosis patients who present with obesity and severe insulin resistance.

A histologically proven case of progressive liver sarcoidosis with variceal rupture.

Sarcoidosis is a chronic multi-systemic granulomatous disease, and liver involvement frequently occurs. in most cases, no evidence of liver dysfunction is observed, and portal hypertension due to sarcoid liver diseases is a rareoccurrence. Moreover, no case of liver sarcoidosis has ever been reported with confirmation of the disease progression. Herein we describe a patient having hepatic sarcoidosis with severe portal hypertension and liver dysfunction. The diagnosis was histologically confirmed from granulomatous status to established liver cirrhosis over 10 years. A 46-year-old woman developed massive hematemesis due to the rupture of gastric cardial varices. She underwent emergency endoscopic injection sclerotherapy, and clear evidence of chronic hepatic failure. Twelve years ago, she was diagnosed as having sarcoidosis with respiratory clinicalsymptoms. Liver biopsy revealed asymptomatic incidental granulomas without fibrosis development. After a couple of years, features of liver dysfunction were manifest and progressed. Ten years after the first biopsy, a second liver biopsy was performed, and well established dense fibrosis was revealed. Although significant liver dysfunction with portal hypertension is rarely seen in sarcoidosis, this case indicates that we have to consider the possibility that sarcoidosis may cause end-stage liver cirrhosis.

Time course and spacial distribution of UV effects on human skin in organ culture.

Apoptosis plays an important role in eliminating cells from populations when cells have been exposed to UV irradiation and damaged. Studies of cells in culture have provided some details of the mechanisms involved when stress response genes act after exposure to UV irradiation and other environmental stresses. However, little is known about the responses of intact sections of human skin growing in organ culture to UV irradiation. In the work reported here, it was found that the response of organ-cultured human skin after exposure to UV irradiation is different than the response of cultured cells. At wavelengths below 300 nm, the action spectrum obtained from organ-cultured skin samples showed a lower sensitivity than that observed at 300 nm, indicating that the overlying stratum corneum and upper epidermal cell layers had probably caused a selective absorption of incident UV radiation at some wavelengths. At 3 hours after UV irradiation, p53 was phosphorylated at Ser 15 and Ser 46, and accumulated in the cell nuclei, notably after exposure to 280-320 nm wavelengths. Accumulations of Bax, active Caspase-3 and cleaved PARP were detected in apoptotic cells at 24 hours post-exposure, along with a reduction of Bcl-2 levels, notably after exposure to 300-365 nm light. This difference in apoptotic responses may result from the characteristics of the different irradiation wavelengths used, and from details in the skin's structure. The data obtained in this study using an organ-culture system utilized direct measurements of the biological effects of different wavelengths of UV lights.