Acquired lecithin:cholesterol acyltransferase deficiency as a major factor in lowering plasma HDL levels in chronic kidney disease.

OBJECTIVES: It has been suggested that a low plasma high-density lipoprotein cholesterol (HDL-C) level contributes to the high cardiovascular disease risk of patients with chronic kidney disease (CKD), especially those undergoing haemodialysis (HD). The present study was conducted to gain further understanding of the mechanism(s) responsible for the low HDL-C levels in patients with CKD and to separate the impact of HD from that of the underlying CKD. METHODS: Plasma lipids and lipoproteins, HDL subclasses and various cholesterol esterification parameters were measured in a total of 248 patients with CKD, 198 of whom were undergoing HD treatment and 40 healthy subjects. RESULTS: Chronic kidney disease was found to be associated with highly significant reductions in plasma HDL-C, unesterified cholesterol, apolipoprotein (apo)A-I, apoA-II and LpA-I:A-II levels in both CKD cohorts (with and without HD treatment). The cholesterol esterification process was markedly impaired, as indicated by reductions in plasma lecithin:cholesterol acyltransferase (LCAT) concentration and activity and cholesterol esterification rate, and by an increase in the plasma preß-HDL content. HD treatment was associated with a further lowering of HDL levels and impaired plasma cholesterol esterification. The plasma HDL-C level was highly significantly correlated with LCAT concentration (R = 0.438, P < 0.001), LCAT activity (R = 0.243, P < 0.001) and cholesterol esterification rate (R = 0.149, P = 0.031). Highly significant correlations were also found between plasma LCAT concentration and levels of apoA-I (R = 0.432, P < 0.001), apoA-II (R = 0.275, P < 0.001), LpA-I (R = 0.326, P < 0.001) and LpA-I:A-II (R = 0.346, P < 0.001). CONCLUSION: Acquired LCAT deficiency is a major cause of low plasma HDL levels in patients with CKD, thus LCAT is an attractive target for therapeutic intervention to reverse dyslipidaemia, and possibly lower the cardiovascular disease risk in these patients.

Circulating levels of cytochrome C, gamma-glutamyl transferase, triglycerides and unconjugated bilirubin in overweight/obese patients with non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease, characterized by hepatocyte apoptosis, is distinct in fatty liver and non-alcoholic steatohepatitis, the more severe form. Apoptotic cell death is caspase-dependent and associated with mitochondrial membrane depolarization and cytochrome c release. Adhering to the hypothesis that the exposure of hepatocytes to free fatty acids, resulting in increased ROS production and mitochondrial damage, is balanced by the presence of antioxidant substances, circulating levels of gamma-glutamyl transferase, cytochrome c, triglycerides and unconjugated bilirubin were explored in patients suffering from non-alcoholic fatty liver disease with different severity. One hundred and eighty-six consecutive patients who presented recent ultrasound feature of bright liver without any liver disease of known origin were enrolled, eighty-nine of whom underwent liver biopsy. Forty-five subjects were allocated on the basis of histology in fatty liver group while 44 patients formed the group with non-alcoholic steatohepatitis. A cohort of 27 young, lean, apparently healthy individuals was selected as control group. The levels of gamma-glutamyl transferase were normal or slightly increased, while unconjugated bilirubin concentrations were elevated in all the spectra of non-alcoholic fatty liver disease. Comparing the present results with relevant findings from other studies dealing with diseases characterized by apoptosis, we did not find high circulating levels of cytochrome c in non-alcoholic fatty liver disease. What is more, our patients, categorized as suffering from simple fatty liver or from the more severe non-alcoholic steatohepatitis, had similar levels of cytochrome c and gamma-glutamyl transferase, p=0.19 and 0.11. Serum triglycerides were higher in patients with non-alcoholic fatty liver disease than in the healthy group, p=0.001. These findings likely reflect a balance between oxidative stress and anti-oxidant response rather than a lack of reliability of cytochrome c as a reliable biomarker of mitochondrial damage.

Successful lamivudine monotherapy in an elderly patient suffering from HBV-related decompensated cirrhosis associated with widespread leukocytoclastic vasculitis.

Hepatitis B virus (HBV) infection is known to be responsible for both hepatic and extrahepatic manifestations including dermatitis, polyarthralgias and arthritis, pulmonary disease, aplastic anemia, glomerulonephritis and vasculitis. The mechanism of these extrahepatic disorders is thought to be linked to immune complex disease, but their pathogenesis is poorly clarified. Immunosuppressive treatment could promote viral load and impair hepatic disease, also worsening the vasculitis by enhancing viral antigenemia. Lamivudine is a nucleoside analogue approved for treating chronic hepatitis B, that decreases the amount of viral antigens by suppressing HBV replication. Several reports have suggested lamivudine in the treatment of vasculitis associated with HBV infection, but, although significant inhibition of HBV is achieved in the short term, resistance develops in 15-32 percent annual risk rating. We report an elderly patient whose chronic hepatitis B decompensated cirrhosis with associated refractory hepatic hydrothorax and extensive leukocytoclastic vasculitis was successfully treated with ongoing long-term lamivudine monotherapy.

Does spleen volume play a role in patients with HCV-related chronic hepatitis?

As the lymphotropism of hepatitis C virus (HCV) has already been ascertained, and in the light of the fact that the immune defense system is an organized network composed of functionally interrelated tissues, this study was carried out to verify the possible involvement of spleen in HCV-related chronic hepatitis. In this cross-sectional study we measured spleen longitudinal diameter by ultrasound, beta2-microglobulin serum levels and splenic artery resistivity index (SARI) by Doppler in 51 patients treated with standard combined (Peg-Interferon plus Ribavirin) antiviral therapy. Thirty-three patients (17 females) completed the regimen and were compared to 31 controls (16 females). The mean basal values of spleen longitudinal diameter were higher in patients with chronic hepatitis than in controls, i.e., 116 mm (9.4) versus 102.7 mm (9.3), P = 0.0001. In the same patients a significant trend towards increased spleen longitudinal diameter was found after antiviral therapy, independently of the stage of HCV-related chronic hepatitis. The median values of the beta2-microglobulin concentrations were not significantly higher in the patients with HCV-related chronic hepatitis compared to controls, i.e., 1.3 (0.5-2.6) versus 1 (0.6-1.4), P = 0.16, although during the course of therapy they were significantly increased. SARI values of HCV-related chronic hepatitis patients were different from those of controls, but were unvaried compared to values at the end of treatment. Neither spleen measurements nor serum beta2-microglobulin levels were able to predict therapeutic response to antiviral therapy. A stimulation/expansion of lymphoid tissue was found in patients with HCV-related chronic hepatitis. Such evidence raises the question whether physicians should continue to prescribe antiviral therapy in non-responders and supports the use of a new scheme (SLD plus beta2-MG) to diagnose this ongoing, apparently reversible, but nevertheless dangerous immunologic process.

Rheumatoid factor after antiviral therapy in patients with HCV chronic hepatitis.

Positivity of rheumatoid factor (RF) in the course of Hepatitis C virus HCV infection has been described in many papers, with percentages between 30% and 80%, but no data are reported on the behaviour of this parameter during the treatment. In the present retrospective study, 66 patients with HCV infection and positivity for RF were observed between March 2001 and January 2004; they had received combined therapy with Peg-IFN alpha-2b 1.5 mcg/kg/weekly and ribavirin 800-1200 mg/daily (on the basis of body weight). Before treatment, all of them had presented hypertransaminasemia for at least 6 months and high viral load. No patient suffered from other hypersensitivity disorders. The follow-up period lasted for a mean period of 26+/-7 months, after which only 34 (51.5%) revealed normal transaminases activity with negativity of HCV-RNA (long-term responders, LTR), while the remaining 32 (48.5%) were classified as non responders (NR). In both groups significant variations of RF values were observed. Moreover, RF remained positive in 6 (17.6%) of the LTR group and in 17 (53.1%) of the NR group patients. These data suggest a possible inhibiting action of the combined therapy on the exaggerated immune response. This effect appears partially unrelated to the antiviral action of the therapy.

Do thyroid abnormalities detected in patients treated for HCV-related chronic hepatitis persist?

One hundred and twenty-one patients with HCV-related chronic hepatitis and normal baseline thyroid function were studied. Forty-six patients received IFN alpha-2b, while 75 patients had Peg-IFN alpha-2b with ribavirin more recently. Thirty patients (ten belonging to the standard IFN group) were re-treated. The pre-treatment prevalence of thyroid antibodies was 3.3%. At the end of the first antiviral treatment, the prevalence of laboratory alterations (presence of antibodies and abnormal hormonal levels) of thyroid was assessed to be 20.7% (25 patients), being quite similar for standard-interferon- and pegylated-interferon-treated patients (P = 0.63). TSH level alteration was seen in eleven patients (9.1% of the overall population and 44% of the antibodies positive patients), of whom ten were females. The anti-microsomal, anti-thyroperoxidase and anti-thyroglobulin antibodies, in combined or isolated presence, were detected in all 25 patients. During the re-treatment we noticed worsening only of previous thyroid abnormalities. No patient changed the antiviral schedule after the emerging of thyroid alterations. All eleven patients remained thyroid dysfunctional at the end of the follow-up (ten with Hashimoto's thyroiditis and one with Graves disease), meanwhile the near totality of patients with presence of antibodies remained positive. Interestingly, eight out the 14 patients who showed mood disorders after antiviral therapy, belonged to the aforementioned cohort.

Could the depression of obese patients suffering from chronic hepatitis C be temporarily improved?

Depression is an usual finding in patients suffering from chronic hepatitis C. Development of moderate to severe depressive symptoms occurs frequently during pegylated interferon/ribavirin treatment and is generally predicted by baseline depression scores. Furthermore, the obese patients have been found to be twice as likely to suffer from anxiety, impaired social interaction, and depression when compared with the no obese population. In order to evaluate the efficacy of a pharmacological treatment of depression, 68 obese patients with chronic hepatitis C, under or not antiviral therapy, were selected and enrolled into this open, controlled pilot study. Our population was divided in two groups: 'on Selective Serotonin Reuptake Inhibitors plus support', with individual titration of medication to adequate side-effects, including thirty seven patients, and 'on only support', involving thirty one patients. Both groups were well balanced for gender, age and antiviral treatment. The selected patients had, at entry, a Beck Depression Inventory score of 24.5 +/- 8.1 (mean +/- SD). Therapeutic successful outcomes (a decreased score of >or= 10 units compared to the baseline) were statistically more frequent in antidepressant drug-treated group (P = 0.005); they were well predicted by dose of Selective Serotonin Reuptake Inhibitors. Thirty five percent of patients were non-responder to Selective Serotonin Reuptake Inhibitors. The drug tolerability was good. Nearly twenty percent of patients were responder to only support.

Can serum TGF-beta 1 be used to evaluate the response to antiviral therapy of haemophilic patients with HCV-related chronic hepatitis?

Congenital coagulation disorders limit the use of liver biopsy, especially when repeated assessment is needed. TGF-beta 1 plays a pivotal role in inducing fibrosis and has been proposed as its surrogate marker. Aiming at validating the clinical utility of this cytokine, fifteen haemophilic patients suffering from HCV-related chronic hepatitis were treated with Peg-IFN alpha2beta plus Ribavirin. Serum TGFbeta 1, viral load and liver enzymes were analyzed at baseline and at six, twelve, and eighteen months. As expected, patients initially showed significantly higher TGF-beta 1 levels than age-matched controls (43.8 ng/mL, 28.7-46.4 vs. 26.9 ng/mL, 23.0-34.0, median and 95% CI; p=0.004). The end of therapy response rate was 67%. The main finding was a significant drop in TGF-beta 1 at six months compared to baseline values; this drop de facto predicted the levels reached in the following six months, which were fixed at lower concentrations (37.0 ng/mL, 21.9-43.8 and 27.0 ng/mL, 24.1-44.0 respectively; p<0.009), independently of treatment outcome (three patients were breakthrough, twelve were sustained virological responders (SVRs). During the treatment period none had clinical or biochemical signs of inflammation in other areas. Treatment was followed by a six-month follow-up, at the end of which TGF-beta 1 was increased compared to the previous values, reaching the initial levels in ten SVRs (45 ng/mL, 24.5-52.9). Interestingly, at a longer follow-up, two out of ten SVRs, who displayed the highest values of TGF-beta 1, relapsed. Serum TGF-beta 1 could be used to assess therapeutic outcome and short-term prognosis of HCV-related chronic hepatitis.

Serum concentrations of the tissue polypeptide specific antigen in patients suffering from non-alcoholic steatohepatitis.

BACKGROUND: Liver histology is the gold standard for diagnosis of non-alcoholic fatty liver disease. Ethical considerations and patient choice often preclude performing a liver biopsy, especially considering the rare but potential risk. Searching for a good serological marker substitute for the invasive procedure was the aim of our study. Keratins, mainly 8 and 18, play not only a mere structural role providing mechanical stability to hepatocytes, but also represent a target via toxic stress ultimately inducing apoptosis/necrosis. Tissue polypeptide-specific antigen (TPS), a serological mirror of keratin 18, is widely used as a marker for various cancers. This antigen was assessed in three different groups who were overweight or obese. MATERIALS AND METHODS: In this cross-sectional case-control study, 48 cancer-free patients with non-alcoholic steatohepatitis (NASH, Group 1), 48 patients with pure fatty liver (FL, Group 2), and 47 volunteers (Group 3) were studied. All of them were referred to our metabolic unit for routine evaluation. RESULTS: The median (range) TPS levels were 123 (56-286) ng mL(-1) in NASH patients. FL patients and volunteers had significantly lower TPS levels, 76 (38-98) ng mL(-1) and 64 (28-87) ng mL(-1), respectively (P = 0.0001). A value of 88 ng mL(-1) in patients with underlying bright liver was associated with a high probability of NASH (sensitivity and specificity = 92% and 96%, respectively). One patient (2.1%) with FL had a TPS value > 88 ng mL(-1), but in the same group, 29 FL patients (60.4%) had an alanine aminotransferase value > 40 U L(-1). Based on a recent classification of liver fibrosis, the median (range) TPS values were significantly different among the stages: F1 (n = 23) = 100 (76-264) ng mL(-1); F2 (n = 21) = 134 (56-276) ng mL(-1); and F3 (n = 4) = 199.5 (123-286) ng mL(-1), respectively (P = 0.014). CONCLUSIONS: Our study shows that TPS is a better marker than alanine aminotransferase activity, ultrasonography or the combination of both parameters in differentiating NASH from FL.

Exaggerated immune reactions predict the outcome of interferon therapy in patients with chronic hepatitis C.

HCV plays a key role as chronic antigenic driver in inducing a clonal expansion of B-lymphocytes. The hypothesis that previous immunological pattern, when expression of an exaggerated immune reaction, could affect the response to IFN therapy was tested. Using a longitudinal database, the outcomes of 124 HCV-positive patients, genotype 1b only, with circulating HCV RNA, were analyzed by a retrospective cohort design. Immunological disorder-related clinical features and visceral organ involvement were thoroughly investigated in addition to laboratory data focusing on the presence of cryoglobulins, rheumatoid factor, antinuclear antibody, complement, circulating immunocomplexes and mono-oligoclonal gamma-globulin expansion. Eighty-four patients with and forty patients without abnormal immunological status, presenting a low fibrosis score, were identified. The whole naive population was treated by IFN monotherapy at the classical schedule for six or, alternatively, up to twelve months. Of the 124 patients, 28 showed a sustained response while 50 were non-responders and 46 were relapsers. Particularly, among the 84 patients with abnormalities of the immunological status, skin involvement was detected in 71 patients and hypocomplementemia was found in 69 patients, emerging as independent predictors for the lack of response. Conclusively, a peculiar immunological phenotype, ascertained by clinical and/or laboratory findings, is associated to a lack of IFN response and could be considered a further predictive factor.

Long-term prophylaxis with intermediate-purity factor VIII concentrate (Haemate P) in a patient with type 3 von Willebrand disease and recurrent gastrointestinal bleeding.

Prophylaxis with von Willebrand factor (VWF)-containing concentrates is considered to be a potential approach for patients with von Willebrand disease (VWD) and severe bleeding tendency. We report the case of a 57-year-old man with type 3 VWD and a history of recurrent melaena. Bleeding frequency and severity had progressively increased and the patient showed chronic anaemia and persistent haemoglobin in the stools. Endoscopic examinations revealed multiple vascular mucosal abnormalities (MVA) of the stomach and large bowel. Photocoagulation of some actively bleeding lesions and octreotide did not significantly affect his clinical conditions: six red cell transfusions and >400 000 IU of intermediate-purity factor VIII (FVIII) concentrate (Haemate P) on-demand were needed during 2002. Prophylaxis with Haemate P 40 IU kg(-1) (102 IU kg(-1) VWF:RCo) thrice weekly was associated with improvement of his mean haemoglobin levels, cessation of clear-cut melaena and red cell transfusions and reduction of total Haemate P requirements (-20% over 2003-04). Prophylaxis with Haemate P is still ongoing without any adverse event over a 30-month period. Clinical course and pharmacokinetic evaluations led to administer Haemate P each 72-96 h. Possible vascular complications were excluded by a careful clinical follow up, as the patient suffered from arterial hypertension and diabetes mellitus; thrombophilic abnormalities were previously excluded and no signs of abnormal coagulation activation or FVIII:C levels >150% were detected thereafter. Long-term prophylaxis with Haemate P has been shown to be safe, effective (also in terms of quality of life) and cost saving in this patient with severe gastrointestinal bleeding due to MVA and VWD.

Non-alcoholic fatty liver disease in young adult severely obese non-diabetic patients in South Italy.

BACKGROUND/AIMS: In the absence of other causes, obesity increases the risk of liver disease. We evaluated the prevalence and degree of metabolic and hepatic abnormalities associated with non-alcoholic fatty liver disease (NAFLD) in type II-III obesity in a metropolitan area of South Italy. METHODS: 187 (81 M, 106 F) young adult non-diabetic obese patients, age range 18-50 years (mean 31.9 +/- 8.8), body mass index (BMI) > or =30 (mean 47.5 +/- 9.6), consecutively admitted from January 2000 to April 2003 to the Obesity Outpatients Clinic entered into the study. Patients were divided into two groups: (1) BMI 30.0-39.9, and (2) BMI> or =40. Ultrasound detected liver steatosis was classified as: (I) mild; (II) moderate, and (III) severe. RESULTS: All patients, except 4, showed a variable degree of steatosis: mild was more frequent among females, severe steatosis present only in grade III obesity, with higher prevalence in males than in females (p < 0.001). Mean serum transaminases, in particular alanine aminotransferase (ALT), increased according to BMI and degree of steatosis. Homeostasis Model Assessment (HOMA) index, ferritin and fibrinogen levels increased with BMI, particularly in severe steatosis. In group 2, patients with BMI> or =40 showed a positive correlation between ferritin, aspartate aminotransferase (AST) (r = 0.46, p < 0.018), ALT (r = 0.41, p < 0.036) and gamma-glutamyltransferase (gammaGT) (r = 0.51, p < 0.007), between serum triglycerides (TG) and AST (r = 0.28, p < 0.036), ALT (r = 0.30, p < 0.02) and between HOMA and ALT (r = 0.30, p < 0.03) and gammaGT (r = 0.35, p < 0.012). In group 2 patients with severe steatosis the prevalence of metabolic syndrome according to Adult Treatment Panel III (ATP III) was 40%. CONCLUSION: These data suggest that, in young adult non-diabetic grade III obese patients, fatty liver is always present and strictly related to insulin resistance which, in the presence of severe liver steatosis, is also related to serum ferritin.

A clinical-morphological study on cholestatic presentation of nonalcoholic fatty liver disease.

To determine the association among the clinical, biochemical, and histological features of cholestasis, we analyzed all the relevant data of the patients recorded in our non-alcoholic fatty liver disease (NAFLD) database. We selected 20 NAFLD patients with abnormal transaminase levels, with both alkaline phosphatase >500 U/L and gamma-glutamyl transpeptidase >250 U/L. Their histological features were compared with those of a group of patients with NAFLD matched for sex, age, and body mass index and of a group of patients matched for sex, body mass index and histological NAFLD grading/staging. Cases and controls satisfied, on histology, the criteria for NASH. The presence of cholestasis in our patients was correlated with injury of the bile duct epithelium, characterized by cholangitis, swelling, variable bile duct loss, and bile stasis. Compared to NAFLD patients of similar age, sex, and body mass index, the cholestatic group had total and severe histological liver impairment. When we analyzed the group of patients histologically identified on the basis of identical stage and grade severity, we could not find any evidence of significant bile damage, compared to cases, despite the control group's significantly older age. NAFLD patients with biochemical cholestasis have a histological picture of bile damage; they have more advanced histological impairment than patients matched for age, sex and body mass index.

Clinical presentation and prevalence of spontaneous bacterial peritonitis in patients with cryptogenic cirrhosis and features of metabolic syndrome.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) may progress to cirrhosis. The prevalence and clinical relevance that spontaneous bacterial peritonitis may have in complicating ascites due to NASH-related cirrhosis have yet to be defined. METHODS: Among 611 cases of cirrhosis-associated ascites, 45 patients with cryptogenic cirrhosis were retrospectively identified. Of these, 36 patients and a control group of subjects with viral- associated ascites were followed up and compared in a case control study. Information on the onset of ascites, with or without spontaneous bacterial peritonitis, history of risk factors for multimetabolic syndrome, and serological and ascitic laboratory data were compared between groups. RESULTS: Spontaneous bacterial peritonitis occurred significantly more often in patients with cryptogenic cirrhosis than in equally symptomatic viral controls. The prevalence of obesity, diabetes and spontaneous bacterial peritonitis was significantly higher in patients with cryptogenic cirrhosis. Although liver function was similar in both groups, cryptogenic cirrhosis patients had lower aminotransferase levels. Multivariate analysis identified diabetes, juvenile obesity and spontaneous bacterial peritonitis as independent factors associated with ascites due to cryptogenic cirrhosis. CONCLUSIONS: Features suggestive of NASH are more frequently observed in patients with ascites and cryptogenic cirrhosis than in age- and sex-matched ascitic patients with well-defined viral etiology. Ascites may be a presenting symptom of NASH-related cirrhosis, and affected patients have a twofold greater risk of spontaneous bacterial peritonitis.

Low daily dosage of interferon for 1 year after HCV-related end-therapy response. A randomized-controlled study.

This randomized controlled study involved 236 1b genotype (121 males) naive patients with chronic hepatitis C. After a course of interferon (IFN)-alpha2b plus ribavirin for 6 or 12 months, 117 (49.5%) of the end-therapy responders were equally divided into two groups and were assigned to receive either low daily doses of IFN-alpha2b (1.5 MU) 'consolidation therapy' (59 patients) for 1 year or no further treatment (58 patients). At the end of the follow-up period (6 months), the number of sustained responders in the consolidation group (83%) was significantly higher than in the control group (37.9%). The predicting factors of both end-therapy response and sustained response were the classic ones and a lower GGT/ALT ratio (GGT: gamma-glutamyl transpeptidase; ALT: alanine aminotransferase). The strongest predictors of sustained response alone were consolidation therapy and the longer period on combined treatment (12 vs 6 months). Consolidation therapy was better tolerated than the previously prescribed combined therapy in terms of side effects. In conclusion, genotype 1b naive end-therapy responders to usual combined therapy, after a period of daily consolidation therapy with a low dosage of IFN without ribavirin, achieved a better rate of sustained response than the control group.

Hepatic and peripheral T-lymphocyte patterns in patients with chronic hepatitis C infection: what correlation with histological activity?

The immunopathological processes involved in hepatic damage during chronic hepatitis C infection are not fully understood. Several works suggest the role of T helper 1 (Th1) immune response in both injury and fibrinogenesis. in this study, we have analyzed peripheral and intrahepatic T-lymphocyte subsets in liver biopsy specimens of 13 patients with definite chronic hepatitis C (CHC) to explore the possible direct role of these patterns in the evolution of necrotic inflammation and fibrogenesis scored according to the Knodell histological activity index. in particular, we have studied CD4+/CD7+ T-lymphocytes, as phenotypic marker of Th1 immune response, CD4+/CD7- as Th2 marker, and CD8+/CD38 as activated CD8+ lymphocytes. on statistical analyses we found a significant negative correlation in liver CD8+/CD38+ T-cells grading (r= -0.607; p<0.05) and staging index (r= -0.650; p<0.05) and between CD4+/CD7+ and grading (r= -0.626; p<0.05) index. in addition, we found a positive strong correlation between CD38+/CD8+ and CD4+/CD7+ T cells (r= 0.783; p<0.05) in liver tissue and between peripheral and liver resident CD8+/CD38+ (r= 683; p<0.05). moreover, the hepatic CD4+/CD7+ T-cells showed a positive correlation with peripheral CD 8+/CD38+ T-cells (r= 0.676; p<0.05). A strong positive correlation was also observed between grading and staging index (r= 0.921; p<0.01). we found no statistical correlation between the above variables and CD4+/CD7- T cells. our data could suggest that a preferential hepatic CD4+/CD7+ OR CD8+/CD38+ T cell subset was not directly associated with hepatic damage but, on the contrary, it could have been able to block liver injury. Concerning the peripheral subsets, the only CD8+/CD 38+ T-cells result reflect the CTL activity in the liver tissue. further studies are required to better understand the possible correlation between peripheral and liver resident T-helper, subset and other hepatic resident immunocompetent cells.

CD8+/CD38+: immune activity and clinical significance in HCV patients with and without interferon therapy.

At the light of the importance of cytotoxic T lymphocyte (CTL) response during chronic hepatitis C, we carried out a study in order to evaluate the CD8+/CD38+T-cells, immunophenotypic marker of CD8+ activated cells in a selected cohort of 22 patients for four months. The patients were subdivided in two groups: A (with IFN therapy), B (without IFN therapy). The results show that in IFN-treated subjects there is a significant reduction of ALT (sign test, z = .424;p < or = .05) and that the CD8+/CD38+ present a positive correlation with HCV-RNA (r = .894; p < .05). We hypothesize that during IFN therapy the CD8+/CD38+ activity is able to oppose HCV, probably by increasing MHC I expression on the infected cells due to the IFN modulatory action, that could strengthen the immune response of CD8+ activated T-lymphocytes. These events confer the capacity to specifically respond to any viral replication and probably take part in the reduction of ALT levels by decreasing the chronic inflammation present during a defective immune response. These data show think CD8+/CD38+ marker could be a good parameter to evaluate both the viral activity and immunological status in HCV+ patients undergoing IFN treatment.