Quantitative assessment of liver fibrosis by digital image analysis: Relationship to Ishak staging and elasticity by shear-wave elastography.

OBJECTIVE: To analyze the relationship between fibrosis staged by Ishak stage and quantified by digital image analysis (DIA), and to reveal the optimum performance of shear-wave elastography (SWE) using quantitative DIA measurements as a comparative histological standard. METHODS: The proportionate area (PA) of fibrosis was measured by DIA from images of the PA of trichrome-stain (TPA) of 168 chronic hepatitis patients. SWE was performed in 105 patients. The accuracy of SWE for predicting the fibrosis defined by quantitative PA thresholds (≥ 2.5%, ≥ 5%, ≥ 10% and ≥ 20%, respectively) and by Ishak stages was measured using the area under the receiver operating characteristic curve (AUROC). RESULTS: DIA was proven to be highly reproducible (interclass correlation coefficient 0.926). The TPA range corresponding to each Ishak stage was large, widened as stages progressed, and reached its greatest extent in cirrhosis. TPA magnified at ×50 ranges 11.9-56% for Ishak stage F5-6. A good correlation between TPA and elasticity was presented for more advanced fibrosis (TPA ≥10%, rs = 0.732, P = 0.000) than milder fibrosis (TPA <10%, rs = 0.308, P = 0.006). With the advance of fibrosis either by stages or PA thresholds the discriminative accuracy of SWE gradually increased, but was less satisfactory for milder fibrosis. CONCLUSIONS: DIA may serve as a reproducible and reliable quantitative standard for surrogate tests for liver fibrosis. The performance and correlation of SWE with the fibrotic extent were better for advanced fibrosis, but less satisfactory for milder fibrosis.

Noninvasive assessment of liver fibrosis with the aspartate transaminase to platelet ratio index (APRI): Usefulness in patients with chronic liver disease: APRI in chronic liver disease.

BACKGROUND: The aspartate aminotransferases (AST) to platelet ratio index (APRI) may serve as a noninvasive marker to assess liver fibrosis. OBJECTIVES: To assess the diagnostic ability of the APRI for prediction of fibrosis in patients with chronic hepatitis B (CHB), chronic hepatitis C (CHC), and non-alcoholic fatty liver disease (NAFLD). PATIENTS AND METHODS: This retrospective study included 207 patients with CHB, 108 with CHC, and 140 patients with NAFLD. The APRI was calculated as (AST level/upper normal limit for AST)/platelet counts (109/L) × 100. The stage of liver fibrosis in patients with chronic viral hepatitis was graded using the METAVIR scale. The Kleiner system for grading fibrosis was used in patients with NAFLD. RESULTS: Bivariate correlation analyses showed that the APRI was significantly associated with fibrosis scores in patients with CHC (p = 0.2634, p = 0.0059) and NAFLD (p = 0.2273, p = 0.0069), but not in those with CHB (p = 0.1005, p = 0.1495). Receiver operating characteristic (ROC) curves were used for assessing the ability of the APRI as a predictor of the absence or presence of liver fibrosis (fibrosis score of 0 vs fibrosis scores of 1-4). In patients with CHC, the APRI showed a sensitivity of 72.7% and a specificity of 62.4% for detection of fibrosis (p<0.01). In the NAFLD group, the APRI showed a sensitivity of 60.0% and specificity of 73.3% for detection of fibrosis (p<0.01). In patients with CHB, the APRI showed a sensitivity of 55.0% and a specificity of 75.4% for fibrosis (p=NS). CONCLUSIONS: The APRI shows an acceptable accuracy for the assessment of liver fibrosis in patients with CHC and NAFLD, but not in those with CHB.

MELD score and clinical type predict prognosis in hepatorenal syndrome: relevance to liver transplantation.

Important progress has been made recently regarding the pathogenesis and treatment of hepatorenal syndrome (HRS). However, scant information exists about factors predicting outcome in patients with cirrhosis and HRS. Moreover, the prognostic value of the model of end-stage liver disease (MELD) score has not been validated in the setting of HRS. The current study was designed to assess the prognostic factors and outcome of patients with cirrhosis and HRS. The study included 105 consecutive patients with HRS. Forty-one patients had type 1 HRS, while 64 patients had type 2 HRS. Patients with type 1 HRS not only had more severe liver and renal failure than type 2 patients, they also had greater impairment of circulatory function, as indicated by lower arterial pressure and higher activation of vasoconstrictor factors. In the whole series, the median survival was 3.3 months. In a multivariate analysis of survival, only HRS type and MELD score were associated with an independent prognostic value. All patients with type 1 HRS had a high MELD score (> or =20) and showed an extremely poor outcome (median survival: 1 mo). By contrast, the survival of patients with type 2 HRS was longer and dependent on MELD score (> or =20, median survival 3 mo; <20, median survival 11 mo; P < .002). In conclusion, the outcome of patients with cirrhosis and HRS can be estimated by using two easily available variables, HRS type and MELD score. These data can be useful in the management of patients with HRS, particularly for patients who are candidates for liver transplantation.

In vivo inefficiency of pentoxifylline and interferon-alpha on hepatic fibrosis in biliary-obstructed rats: assessment by tissue collagen content and prolidase activity.

BACKGROUND AND AIM: To evaluate the possible antifibrotic effects of two drugs, pentoxifylline (PTX) and interferon (IFN)-alpha as well as their combination, on a bile-duct-ligated rat hepatic fibrosis model. METHODS: Bile ducts of 34 female Wistar rats were ligated, and 24 bile ducts were sham operated. Bile-duct-ligated rats were divided into four groups, in which either sterile saline, IFN-alpha (100 000 IU/3 days a week), PTX (50 mg/kg/day) or IFN-alpha + PTX were administered. Sham-operated rats were treated at the same doses. On the 28th day, rats were decapitated to obtain blood for the measurements of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT) and bilirubins. Serum prolidase was assayed at the beginning and at the end of the study by the modified Chinard's colorimetric method. Liver prolidase was assayed after tissue homogenization. Liver collagen content was determined by the dye elution method described by Lopez de Leon. Morphometric-densitometric measurements of hepatic fibrosis were quantified by computerized image analysis. RESULTS: The AST, ALT, ALP, GGT and bilirubins, liver prolidase enzyme activity, collagen content and hepatic collagen surface density were found to be increased in bile-duct-ligated rats on day 28. There was no statistically significant recovery or even a change in collagen turnover rate in rats treated with alternate regimens applied in the study (P > 0.05). CONCLUSION: Pentoxifylline, IFN-alpha and their combination have no beneficial effect on experimental fibrosis induced by biliary obstruction.