Chronic hepatitis C virus infection and lymphoproliferative disorders: mixed cryoglobulinemia syndrome, monoclonal gammopathy of undetermined significance, and B-cell non-Hodgkin lymphoma.

BACKGROUND AND AIM: Chronic hepatitis C (CHC) has been associated with lymphoproliferative disorders (LPD) such as mixed cryoglobulinemia syndrome (MCS), monoclonal gammopathy of undetermined significance (MGUS), and B-cell non-Hodgkin lymphoma (B-NHL). The aim of the present study is to assess MCS, MGUS, and B-NHL prevalence in a cohort of CHC-infected patients and to evaluate the association of demographic, clinical, and virologic factors with the presence of LPDs. METHODS: A total of 121 CHC patients with LPDs (50 M, 71 F; mean age 61.5 ± 11.8) and 130 CHC patients without extrahepatic manifestations (60 M, 70 F; mean age 60.4 ± 9.2) were retrospectively enrolled from a cohort of 1313 CHC patients between January 2006 and December 2013. Patients with LPDs included: 25 patients with MCS (9 M, 16 F; mean age 60.2 ± 1.4), 55 patients with MGUS (18 M, 37 F; mean age 61.3 ± 12.1), and 41 patients with B-NHL (23 M, 18F; mean age 62.5 ± 11.0) RESULTS: Patients with MCS (25/1313; 1.9%), MGUS (55/1313; 4.2%), and B-LNH (41/1313; 3.1%) did not differ in age, severity of liver disease, HCV genotype, and response to antiviral therapy. Using multivariate logistic regression analysis, a positive association was found between the presence of cirrhosis and MGUS (odds ratio [OR] = 2.8924, 95% confidence interval [CI] 1.2693-6.5909; P = 0.012) and between cirrhosis and B-NHL (OR = 3.9407, 95% CI 1.7226-9.0153; P = 0.001), whereas no association with MCS diagnosis emerged. CONCLUSION: Despite the pathogenetic mechanism of HCV-associated LPDs is still unclear, cirrhosis is an additional risk factor for the development of lymphoproliferative disorders in patients with chronic HCV infection.

Circulating erythropoietin in microalbuminuric type 2 diabetic patients with normal renal function: a pilot study.

To verify the hypothesis of an early impairment of erythropoietin (Epo) production and to assess the adequacy of its circulating levels in diabetic nephropathy, we investigated Epo values in 18 microalbuminuric type 2 diabetic patients with normal renal function (7 anaemic and 11 nonanaemic), 24 subjects with uncomplicated iron-deficiency anaemia, and 15 healthy controls comparable for sex and age. Mean+/-S.D. plasma Epo level was 56.4+/-12.7 mU/mL in iron-deficient patients and 9.3+/-2.6 mU/mL in controls. In diabetic groups, mean+/-S.D. Epo level was 11.38+/-3.65 mU/mL in nonanaemic and 49.12+/-6.44 mU/mL in anaemic subjects. No significant difference (P>.05) in Epo values was found between controls and nonanaemic diabetic patients. Anaemic diabetics and iron-deficient subjects had significantly higher values than the nonanaemic groups (P>.001). An inverse significant relation between Epo levels and Hb concentration resulted in both anaemic diabetics (r=-.44, P>.05) and iron-deficient patients (r=-.61, P=.001). Analysis of covariance (P>.05) and comparison of the two regression lines (t=0.4, df=29, P>.05) did not show any significant difference between diabetic patients with anaemia and iron-deficient patients. These results suggest that normochromic anaemia observed in microalbuminuric diabetic patients with normal renal function is not due to Epo deficiency, and circulating levels of this hormone are suitably increased with regard to Hb concentration.

Circulating adhesion molecules in patients with virus-related chronic diseases of the liver.

AIM: In the inflammatory state, intercellular adhesion molecule-1 (ICAM-1) and vascular cellular adhesion molecule-1 (VCAM-1) play a key role in promoting migration of immunological cells from the circulation to target site. Aim of our study was to investigate soluble forms of these molecules in patients with virus-related chronic liver diseases, to assess their behavior in different pathologies and correlation with severity of liver damage. METHODS: Circulating ICAM-1 and VCAM-1 were assayed by EIA commercial kits (R and D System Co., Abington, UK) in 23 patients with chronic active hepatitis (CH), 50 subjects affected by liver cirrhosis (LC) and 15 healthy controls comparable for sex and age. In patients, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were also detected by autoanalyzer. RESULTS: LC patients had significantly higher ICAM-1 values than CH patients (38.56+/-7.4 ng/mL vs 20.89+/-6.42 ng/mL; P < 0.001) and these ones had significantly higher values than controls (12.92+/-1.08 ng/mL; P < 0.001). In CH group, ICAM-1 levels were significantly related to inflammatory activity (P = 0.041) and ALT values (r = 0.77; P < 0.05). VCAM-1 values were significantly increased only in LC patients (P < 0.001) and related to severity of liver impairment. CONCLUSION: These findings suggest that the determination of serum ICAM-1 can be considered as an additional useful marker of hepatocellular necrosis and inflammatory activity in chronic hepatitis, while serum VCAM-1 is an indicator of liver fibrogenesis and severity of disease in cirrhosis.

Plasma erythropoietin levels in anaemic and non-anaemic patients with chronic liver diseases.

AIM: To investigate the serum erythropoietin (Epo) levels in patients with chronic liver diseases and to compare to subjects with iron-deficiency anaemia and healthy controls. METHODS: We examined 31 anaemic (ALC) and 22 non-anaemic (NALC) cirrhotic patients, 21 non- anaemic subjects with chronic active hepatitis (CAH), 24 patients with iron-deficiency anaemia (ID) and 15 healthy controls. Circulating Epo levels (ELISA; R and D Systems, Europe Ltd, Abingdon, UK) and haemoglobin (Hb) concentration were determined in all subjects. RESULTS: Mean+/-SD of Epo values was 26.9+/-10.8 mU/mL in ALC patients, 12.5+/-8.0 mU/mL in NALC subjects, 11.6+/-6.3 mU/mL in CAH patients, 56.4+/-12.7 mU/mL in the cases of ID and 9.3+/-2.6 mU/mL in controls. No significant difference (P>0.05) was found in Epo levels between controls, CAH and NALC patients. ALC individuals had higher Epo levels (P<0.01) than these groups whereas ID subjects had even higher levels (P<0.001) than patients suffering from ALC. CONCLUSION: Increased Epo values in cirrhotics, are only detectable when haemoglobin was lesser than 12 g/dL. Nevertheless, this rise in value is lower than that observed in anaemic patients with iron-deficiency and appears blunted and inadequate in comparison to the degree of anaemia.