Red blood cell distribution width as a non-invasive marker for the assessment of inflammation in non-alcoholic steatohepatitis.

BACKGROUND/AIMS: The aim of this study was to assess the association between red cell distribution width and inflammation in biopsy proven non-alcoholic steatohepatitis. METHODOLOGY: Fifty four subjects with non-alcoholic steatohepatitis and thirty nine controls were enrolled for the study. Liver biopsy specimens were scored by using non-alcoholic fatty liver disease activity score by a single experienced liver pathologist. RESULTS: Red cell distribution width was higher in the severe inflammation group in non-alcoholic steatohepatitis (p < 0.05). The areas under the receiver operating characteristic curves for the predictive performance of aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase and red cell distribution width in identifying inflammation in non-alcoholic steatohepatitis were 0.55 (0.41-0.68), 0.51 (0.37-0.64), 0.53 (0.39-0.67) and 0.73 (0.59-0.84) respectively and the differences of these values between red cell distribution width and other parameters were found to be statistically significant (p < 0.05). To determine the grading of inflammation, the specificity for using the red cell distribution width as an indicator in non-alcoholic steatohepatitis patients was calculated to be 73.3%, with 79.5% sen- sitivity. CONCLUSION: Red cell distribution width was a sensitive and specific method for the assessment of the inflammation in patients with non-alcoholic steatohepatitis.

[Results of the participation of 360 laboratories of Russia in the external quality assessment program for HBsAG tests].

During their first participation in the external quality assessment program (EQAP), 78-81% of the laboratories detect positive samples of control panels containing 0.125 IU/ml of HBsAg; 95-97% of them identify negative samples of the control panels. The high efficiency of EQAP was established when the results of the same laboratories that had participated in two cycles were compared. For correct detection of positive samples of the control panel, it is necessary to use disposable containers and tips for example for solutions of conjugate concentrate, tetramethylbenzidine, buffer for conjugate dilution, and citrate-phosphate solution. The ranges of 95% confidence interval were established for the individual values of CV values of the commercial preparation ILC-HBsAg in the laboratories: from 0 to 11.3% with estimated convergence and from 0 to 14.2% with estimated reproducibility. In making an intralaboratory control of the quality of HBsAg test using ILC-HBsAg, one should be guided by the test accuracy indices given in the application sheet.

Assessment of platelet activation in coupled schistosomiasis and viral hepatitis infection: contribution to complexity of course and development of complications.

This study assessed platelet activation and its possible contribution to the pathogenesis of liver cirrhosis (LC), hepatocellular carcinoma (HCC) and portal vein thrombosis (PVT). Forty-five patients with LC caused by dual schistosomiasis and viral hepatitis infections were enrolled in the study, 15 had LC only, 15 were complicated with HCC, and 15 were complicated with PVT, in addition to 15 healthy controls. Platelet morphological parameters including platelet count, platelet crit, mean platelet volume (MPV) and platelet distribution width (PDW), as well as platelet activation as evidenced by measuring soluble platelet selectin (sP-selectin) level and the release of beta-thromboglobulin (beta-TG), transforming growth factor beta-1 (TGF-beta1) and platelet derived growth factor-AA (PDGF-AA) were evaluated. The results obtained revealed significant reduction in platelet count, platelet crit and MPV while PDW was significantly increased in all LC patients in comparison to controls. sP-selectin, beta-TG, TGF-beta1 & PDGF-AA revealed significant increase in all diseased groups when compared to control group. Patients complicated with HCC or PVT demonstrated significant increase in the aforementioned parameters in comparison to patients with LC only. Patients with PVT showed significant increase versus HCC patients. These findings indicate that platelet activation is a prominent feature in LC and its serious complications HCC & PVT. This activation can play an important role in the pathogenesis of LC, HCC & PVT in patients with mixed schistosomiasis and viral hepatitis infections. Such patients need careful medical attention and effective treatment. Stabilization of the activated platelets and the dual suppression of PDGF & TGF-beta1 could be new therapeutic strategies against LC and its sequels.

Improvement of liver cancer detection with simultaneous assessment of circulating levels of free alpha-fetoprotein (AFP) and AFP-IgM complexes.

We assessed the presence of alpha-fetoprotein (AFP) complexed with IgM (AFP-IgM IC) in serum of patients affected by hepatocellular carcinoma (HCC), cirrhosis and chronic hepatitis as well as in healthy subjects by means of a dedicated ELISA assay. The amount of AFP-IgM IC was expressed in arbitrary units (AU) on a reference standard curve. Free AFP (FAFP) levels were determined in parallel in each sample by means of an automated immunoassay system. The mean serum concentration of AFP-IgM IC was significantly higher in HCC patients (mean +/- SD: 1378.3 +/- 2935.7 AU/mL) than in cirrhotic patients (129.8 +/- 261.4 AU/mL) and in patients with chronic hepatitis (80.9 +/- 168.9 AU/mL) (p < 0.01). HCC patients had FAFP values above the 20 ng/mL cutoff in 44% of cases (22/50) and AFP-IgM IC values above the 120 AU/mL cutoff in 60% of cases (30/50). The occurrence of the free and IgM-complexed form of circulating AFP did not overlap, and 82% of patients (41/50) were positive for at least one marker. The results indicate that AFP-IgM IC is a complementary serological marker to FAFP and that the combination of these biomarkers may be useful in the diagnosis of liver cancer.

Assessment of insulin resistance and effect of metformin in nonalcoholic steatohepatitis--a preliminary report.

INTRODUCTION: Insulin resistance plays a major role in the pathogenesis of nonalcoholic steatohepatitis (NASH). Insulin-sensitizing drugs like metformin may have a role in the treatment of this disease. OBJECTIVE: To determine insulin resistance and the role of metformin in the treatment of NASH. METHODS: We prospectively studied 25 patients with NASH over a period of one and a half years. In addition to clinicopathological profile, we studied the insulin resistance by insulin tolerance test in 10 of them; seven of them, who did not respond to 3 months of low-calorie, low-fat diet, exercise, weight reduction and ursodeoxycholic acid (UDCA), were treated with metformin for six months. Results were compared with control groups. RESULTS: All 10 patients with NASH tested had low insulin sensitivity; there was significant difference in the rate constant for insulin sensitivity (Kitt) between patients with NASH and normal volunteers. Thirteen (52%) patients responded to dietary restriction, exercise, weight reduction and UDCA. Four of 7 patients treated with metformin had normalization of ALT. CONCLUSION: Patients with NASH have insulin resistance. Metformin may have a role in the treatment of these patients.

Uncertainty in liver function assessment on the basis of single-point galactose concentration.

The uncertainty in liver function assessment based on single-sample galactose levels after galactose injection, in comparison to the standard procedure using the galactose elimination capacity (GEC), was assessed in 905 tests performed in a wide range of liver functions. The 45-min galactose levels significantly correlated with GEC, the correlation being better in subjects with a good liver function. In cirrhosis, the prediction using the 60-min galactose value was better than when the 45-min value was used. In the whole series, the 95% confidence interval of GEC predicted by 45-min galactose was as large as +/- 1.55mg x kg(-1) x min(-1) as absolute value, corresponding to a range from -41 to +47% of measured GEC. In cirrhosis, the 95% confidence interval was +/- 1.42 mg x kg(-1) x min(-1) and between -40 and +46% of measured GEC. The 60-min values were more predictive, but in Child class C patients the average error was 0.42 mg x kg(-1) x min(-1) (95% confidence interval -0.64 to +1.49, corresponding to -39 to +76% of measured GEC). The uncertainty was maintained within +/- 10% of measured values only in 50% of the tests. We conclude that the single-point galactose test introduces a considerable error, mainly in patients with more advanced liver disease, which may bias the decision-making process.

Comparison of serum 7S fragment of type IV collagen and serum central triple-helix of type IV collagen for assessment of liver fibrosis in patients with chronic viral liver disease.

BACKGROUND/AIMS: A competitive radioimmunoassay for serum 7S fragment of type IV collagen (7S collagen) using a polyclonal antibody against 7S collagen and a sandwich enzyme immunoassay for serum central triple-helix of type IV collagen (IV collagen) using two monoclonal antibodies against the pepsin-solubilized type IV collagen may be used as diagnostic aids for liver fibrosis in clinical medicine. We compared the clinical usefulness for assessing liver fibrosis of serum 7S collagen and IV collagen tests in chronic viral liver diseases, and also examined the elution pattern of 7S collagen- and IV collagen-related antigens in serum by gel filtration analysis. METHODS: Serum 7S collagen and IV collagen levels were assayed in 151 patients with chronic viral liver disease and 30 healthy control subjects. RESULTS: Gel filtration on the Sephacryl S400HR column revealed that the 7S collagen antigenicity in serum was heterogeneous, whereas the IV collagen antigen in serum was uniform in size. Serum levels of 7S collagen and IV collagen showed increases closely correlated with the severity of liver disease. The abnormal percentage of 7S collagen in three patient groups was similar to that of IV collagen in the corresponding groups. Serum 7S collagen and IV collagen levels were strongly correlated with the histological degree of liver fibrosis; the correlation coefficients were r = +0.675 for 7S collagen and r = +0.665 for IV collagen. When we assessed the ability of each test to detect cirrhosis with a receiver operating curve, the serum 7S collagen test was a slightly better marker than the serum IV collagen test. For the detection of cirrhosis, serum 7S collagen was 83% sensitive and 88% specific at a cutoff value of 9 ng/ml, and serum IV collagen was 80% sensitive and 81% specific at a cutoff value of 160 ng/ml. CONCLUSIONS: These findings suggested that serum 7S collagen and IV collagen tests are similarly useful for assessing liver fibrosis in patients with chronic viral liver disease, although the former is slightly better for diagnosing cirrhosis than the latter.

Assessment of bilirubin clearance capacity of a newly developed ion-exchange adsorption column and its possible use as a supportive therapy in hepatorenal syndrome.

We assessed the bilirubin reduction capacity of three different types of devices in vitro: a high-permeable membrane column for double-filtration plasmapheresis (DFP) (Evaflux 2A, Kuraray, Japan), and non-coated charcoal column for hemoperfusion (HP) (N-180, Asahi Medical, Japan), and ion-exchange columns for plasma adsorption (PA) (BR-350, Asahi Medical, Japan, and B-001, Kuraray, Japan). A column for DFP reduced the concentration of low-molecular proteins effectively such as plasma bilirubin and bile acids in an albumin-dependent manner. A charcoal column adsorbed low-molecular substances preferentially. But in these two columns, the loss of fibrinogen is a limiting factor for determining the processing plasma volume. Ion-exchange columns for PA adsorbed bile acids, disconjugated bilirubin, and monoconjugated bilirubin more efficiently compared with delta-bilirubin and unconjugated bilirubin. Pretreatment of the column with heparin reduced the loss of fibrinogen to less than 10%. We applied the BR-350 ion-exchange column in vivo for treatment of three patients with hyperbilirubinemia. After treatment, an alcoholic hepatitis patient with the hepatorenal syndrome (HRS) recovered from acute renal failure. However, in a patient with primary biliary cirrhosis and in a patient with fulminant hepatitis, the decrease of serum bilirubin was transient and no obvious beneficial responses were noted. The capacity and ability of the BR-350 column to adsorb plasma bilirubin was shown sufficient to treat deeply jaundiced patients, because 4 liters of the plasma of a patient with 108 mg/dl of initial total bilirubin concentration was able to be processed continuously without an obvious decrease in bilirubin adsorption capacity.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of an oral bile acid loading test for assessment of liver function in chronic hepatitis. A comparison with fasting serum bile acids and i.v. galactose elimination test.

In 40 patients with histologically verified chronic hepatitis, (chronic persistent hepatitis, n = 13; chronic active hepatitis without, n = 14; or with cirrhosis, n = 13), of viral and autoimmune origin, serum bile acids (SBA) were measured before and during 3 h after oral ingestion of 1 g chenodeoxycholic acid (CDA). Fasting SBA were elevated in 22 (55%) patients, whereas the CDA loading test was abnormal in 15 (38%) patients and the galactose elimination was prolonged in 16 (40%) patients. In patients with chronic active hepatitis, 20/27 had elevated SBA either in the fasting state (18/27) or after the CDA loading test (13/27). Normal SBA values were found in 9/13 (70%) patients with chronic persistent hepatitis. Thus, fasting SBA is not sensitive enough to detect mild chronic inflammatory liver disease as chronic persistent hepatitis, but seems to be as sensitive as the galactose elimination or CDA loading tests in detecting potential severe liver disease. Fasting SBA may thus be used as a complement of conventional liver tests in the follow-up of chronic hepatitis as assessment of liver function. An oral CDA loading and an i.v. galactose elimination test add no further information to that given by fasting serum bile acids.