Diagnostic accuracy of an uncorrected native T1 mapping sequence for liver fibrosis and inflammation in autoimmune hepatitis: a prospective study using histopathology as reference standard.

PURPOSE: There is an unmet clinical need for non-invasive imaging biomarkers that could replace liver biopsy in the management of patients with autoimmune hepatitis (AIH). In this study, we sought to evaluate the diagnostic accuracy of a simple uncorrected, non-contrast T1 mapping for detecting fibrosis and inflammation in AIH patients using histopathology as a reference standard. MATERIAL AND METHODS: Over 3 years, 33 patients with AIH were prospectively studied using a multiparametric liver MRI protocol which included T1 mapping. Biopsies were performed up to 3 months before imaging, and a standardized histopathological score for fibrosis (F0-F4) and inflammatory activity (PPA0-4) was used as a reference. Statistical analysis included independent t test, Mann-Whitney U-test, and ROC (receiver operating characteristic) analysis. RESULTS: T1 mapping values were significantly higher in patients with advanced fibrosis (F0-2 vs. F3-4; p < 0.015), significant fibrosis (F0-1 vs. F2-4; p < 0.005), and significant inflammatory activity (PPA 0-1 vs. PPA 2-4 p = 0.048). Moreover, the technique demonstrated a good diagnostic performance in detecting significant (AUC 0.856) and advanced fibrosis (AUC 0.835), as well as significant inflammatory activity (AUC 0.763). CONCLUSION: A rapid, simple, uncorrected, non-contrast T1 mapping sequence showed satisfactory diagnostic performance in comparison with histopathology for detecting significant tissue inflammation and fibrosis in AIH patients, being a potential non-invasive imaging biomarker for monitoring disease activity in such individuals.

Advanced Magnetic Resonance Imaging for Detection of Liver Fibrosis and Inflammation in Autoimmune Hepatitis: A State-of-the-Art Review.

Autoimmune hepatitis is a rare chronic liver disease, associated with a high level of morbidity and high mortality; approximately 40% of patients with severe untreated disease die within 6 months of diagnosis. It should be treated to achieve complete biochemical and histologic resolution of the disease using corticosteroids and immunosuppression to prevent further progression to cirrhosis. The use of invasive liver biopsy is recommended for the staging and assessment of inflammation and fibrosis for treatment decision-making in the face of an unsatisfactory response or clinical remission, including being a determinant for withdrawal of immunosuppression. On the other hand, liver biopsy is invasive, costly, and not free of complications. It also has potential sampling error and poor interobserver agreement. The limitations of liver biopsy highlight the importance of developing new imaging biomarkers that allow accurate and non-invasive assessment of autoimmune hepatitis in terms of liver inflammation and fibrosis, developing the virtual biopsy concept. Therefore, we review the state-of-the-art of Magnetic Resonance Imaging sequences for the noninvasive evaluation of autoimmune hepatitis, including historical advances and future directions.

Renal dysfunction during treatment of chronic hepatitis B with tenofovir disoproxyl fumarate and associated risk factors.

OBJECTIVES: To analyze the evolution of glomerular filtration rate (GFR) and the presence of renal tubular dysfunction during the treatment of chronic hepatitis B virus (HBV) infection with tenofovir disoproxil fumarate (TDF) and to determine the risk factors involved. METHODS: Retrospective cohort observational study of adults with chronic hepatitis B. Exclusion: hepatitis C virus-HBV coinfection, diabetes, baseline GFR less than 60 ml/min. Measurements of serum and urinary creatinine and phosphate; urinary albumin, retinol-binding protein (RBP) and neutrophil gelatinase-associated lipocalin (NGAL) were performed. Univariate and multivariate analyses tracked factors associated with worsening GFR. RESULTS: A total of 120 individuals were included: 35% NAÏVE (G1); 49.2% HBV using TDF (G2); 15.8% HBV-HIV using TDF (G3); 63.3% men; 60.8% white; 30% hypertensive. Average age was 50.5 years (SD ±â€…12.9 years). Reactive HBeAg predominated in G3 ( P  < 0.001) and cirrhosis in G2 ( P  < 0.036). NGAL was elevated in 5.3% of cases (G1 = 3.2%; G2 = 8.7%; G3 = 0%; P  = 0.582), RBP in 6.7% (G1, G3 = 0%; G2 = 13.6%; P  = 0.012), urinary phosphate/creatinine ratio in 16.2% (G1 = 15.2%; G2 = 14.5%; G3 = 23.5%; P  = 0.842) and urinary albumin/creatinine ratio in 12.9% (G1 = 12.2%; G2 = 10.7%; G3 = 21.1%; P  = 0.494). Worsening of renal function occurred in 22.5% of the population (G1 = 11.9%; G2 = 28.8%; G3 = 26.3%; P  = 0.122), independently associated only with systemic arterial hypertension [adjusted odds ratio (AOR) = 4.14; P  = 0.008], but not to TDF (AOR = 2.66; P  = 0.110) or male sex (AOR = 2.39; P  = 0.135). However, the concomitance of these variables generated a high estimated risk for this outcome (51%). CONCLUSIONS: Renal tubular dysfunction was uncommon according to NGAL, RBP or urinary phosphate/creatinine ratio. TDF was not an independent factor for worsening renal function, significantly associated only with systemic arterial hypertension. However, in hypertensive men, the use of TDF should be monitored.

Role of gamma-glutamyl transferase activity in patients with chronic hepatitis C virus infection.

BACKGROUND: Increased serum gamma-glutamyl transferase (GGT) levels are frequently observed in chronic hepatitis C virus (HCV) infection. However, the significance of this finding remains unclear. The purpose of the present paper was to assess the relationship between GGT levels and clinical, biochemical and histological features in chronic HCV-infected carriers. METHODS: Patients with a liver biopsy presenting anti-HCV and HCV-RNA were evaluated. Age, gender, risk factors of transmission, serum alanine aminotransferase (ALT), GGT and alkaline phosphatase (ALP) levels and histological features were assessed in all. Data were analyzed statistically by the chi2 test and multivariate logistic regression analysis. RESULTS: Among 201 patients studied, elevated GGT levels and bile duct damage were observed in 48% and 35% of them, respectively. No association was seen between GGT level and bile duct damage or between GGT level and hepatic steatosis. Initially, age >40 years (P=0.007), elevated ALT (P=0.01), grading of inflammatory activity (P=0.004) and staging of fibrosis (P<0.001) were found to be associated with elevated GGT levels. After multivariate regression analysis, histology grading 3 and 4 inflammation activity (P=0.01) and staging 3 and 4 fibrosis (P=0.01) remained independently associated with elevated GGT level. CONCLUSIONS: A significant number of patients with chronic HCV infection had elevated serum GGT levels. Furthermore, this enzyme seemed to be useful as an indirect marker of more advanced liver disease in chronic hepatitis C.