Ratio of circulating follistatin and activin A reflects the severity of acute liver injury and prognosis in patients with acute liver failure.

BACKGROUND AND AIM: The activin A-follistatin system is known to play a critical role in hepatocyte regeneration during the repair of liver tissue. However, the relationship between blood levels of these compounds and the severity and prognosis of acute liver injury remains unclear. The aim of this study was to evaluate the clinical significance of circulating activin A and follistatin in patients with acute liver disease. METHODS: Serum activin A and plasma follistatin levels were determined on admission by enzyme-linked immunosorbent assay in 32 patients with acute hepatitis (AH), 23 patients with acute severe hepatitis (ASH) and 16 patients with acute liver failure (ALF). RESULTS: Both serum activin A and plasma follistatin levels were significantly elevated in patients with ASH and ALF when compared with those in patients with AH and normal controls (NC). Although plasma follistatin levels were significantly and positively correlated with serum activin A levels (r = 0.413, P < 0.001), the follistatin and activin A (F/A) ratio showed distinct deviation from NC between AH and ALF patients. The F/A ratio in AH patients was significantly elevated when compared with NC, but was significantly reduced in ALF patients. Furthermore, the F/A ratio in non-surviving ALF patients was significantly lower than that in survivors. Levels of serum activin A and plasma follistatin were significantly and negatively correlated with prothrombin time (PT) and normotest (NT) levels, while the F/A ratio showed significant and positive correlations with PT and NT. CONCLUSIONS: Decreased blood F/A ratio in ALF patients may be a reliable indicator of the severity of acute liver injury and prognosis in ALF.

Association of virus infected-T cell in severe hepatitis caused by primary Epstein-Barr virus infection.

BACKGROUND: Infectious mononucleosis owing to primary Epstein-Barr virus (EBV) infection sometimes causes hepatitis, which is usually self-limiting with mildly elevated transaminases, but can rarely develop into severe hepatitis with jaundice. OBJECTIVE: To clarify the pathogenesis of severe hepatitis by primary EBV infection. METHODS: We experienced four cases of severe hepatitis with jaundice caused by primary EBV infection. These cases were analyzed virologically and histologically, and compared with infectious mononucleosis patients without jaundice. RESULTS AND DISCUSSION: Using real-time PCR, more EBV-DNA was detected in peripheral blood from patients with severe hepatitis, as compared to those without jaundice. Furthermore, CD3+, CD4+ or CD8+ cells contained more EBV DNA than did other cell populations, indicating that in severe hepatitis, T cells harbor most of the EBV. By contrast, mainly B cells were infected in infectious mononucleosis patients without jaundice. The liver was biopsied in three of the four cases. An in situ hybridization study showed that EBV infected lymphocytes, not hepatocytes. In addition, in one patient, it was confirmed that the infected lymphocytes were CD8+ T cells. These results suggest that a large EBV burden and T cell infection may play major roles in the mechanism of severe hepatitis caused by primary EB virus infection.

Liver fat content measured by magnetic resonance spectroscopy at 3.0 tesla independently correlates with plasminogen activator inhibitor-1 and body mass index in type 2 diabetic subjects.

We measured liver fat content by 3-Tesla magnetic resonance spectroscopy (MRS) in 34 non- to mild obese Japanese subjects with type 2 diabetes, who were not complicated with any liver diseases including clinical fatty liver (liver/spleen ratio of computed tomography [CT] < 0.9) and were not being treated with oral hypoglycemic agents, insulin, or lipid-lowering agents, and analyzed the relationship between liver fat content and body composition and plasma metabolite. The liver fat content is significantly correlated with variables relating to obesity (body mass index [BMI], body weight, fat mass, waist to hip ratio, visceral fat area, subcutaneous fat area, and serum triglyceride), insulin resistance (fasting plasma insulin and homeostasis model assessment of insulin resistance [HOMA-IR]), adipocytokines (serum plasminogen activator inhibitor-1 [PAI-1] and leptin), and serum cholinesterase, but not CT liver/spleen ratio, which is correlated only with fasting plasma glucose, BMI, and HOMA-IR. Multiple regression analysis revealed that the liver fat content is independently associated with serum PAI-1 level (p < 0.001) and BMI (p < 0.05), but not visceral fat area. MRS is a more sensitive method for quantifying liver fat content than CT in type 2 diabetic subjects with non- to mild obesity and without clinical fatty liver.

Branched-chain amino acid treatment in patients with liver cirrhosis.

We discuss branched-chain amino acid (BCAA) treatment for the management of hepatic encephalopathy (HE) and protein-energy malnutrition (PEM) in patients with liver cirrhosis (LC). PEM is closely associated with the prognosis of patients with LC independently of liver function. Therefore, adequate protein and energy intake is a fundamental management to improve the status of PEM in patients with LC. However, it is difficult to maintain good nutritional status with diet therapy alone in patients with LC, because the majority of these patients have disturbances of the nutritious metabolism including urea synthesis in the liver, together with the existence of portal-systemic shunt which is related with the pathogenesis of HE. BCAA enriched amino acid solution was administered at first to treat chronic HE based on amino acid imbalance and neurotransmitter theory. Furthermore, recent studies have suggested that the supplement of BCAA enriched oral mixture and BCAA granules with diet therapy might improve the status of PEM in patients with LC. However, as the effects of these BCAA supplements are basically related to the severity of liver damage, further investigations are required to identify the efficacy of these treatments.