Immunological modifications during treatment with thymosin alpha1 plus antiviral therapy in chronic hepatitis C.

The current standard therapy for the treatment of chronic hepatitis C virus (HCV) is the combination of peginterferon and ribavirin, although many patients fail to clear the virus and their retreatment options are still unsatisfactory. Thymosin alpha1 (Talpha1) is an immunomodulating agent that has been proposed as complementary therapy for chronic HCV, especially in the setting of difficult-to-treat patients. The aim of this study was to evaluate, in patients nonresponsive to previous Peg-based therapy, the effect of standard antiviral therapy with or without Talpha1 on peripheral lymphocyte subsets. Twenty-four patients, 12 receiving Talpha1 and 12 standard therapy, were enrolled. Peripheral subpopulations were analyzed by flow cytometry. Although the addition of Talpha1 did not seem to significantly modify the T-lymphocyte subpopulations, as comparable behaviors were observed in the CD4 and CD8 longitudinal evaluation, Talpha1 produced an earlier increase of natural killer cells. An accurate selection of HCV patients who can benefit from immunomodulation is needed.

Hepatitis C Virus-related chronic liver disease in elderly patients: an Italian cross-sectional study.

Chronic hepatitis C virus (HCV) infection has been poorly investigated in the elderly. The aim of this study was to identify the age-specific characteristics of chronic hepatitis C by comparing patients > or =65 years with those <65 years. A cross-sectional study was performed on data collected from consecutive outpatients referred for the first time to two tertiary outpatient clinics for liver diseases located in Bologna (Northern Italy) and Paola, Cosenza (Southern Italy) over a two-year period. A total of 560 anti-HCV and HCV-RNA positive patients were enrolled, of whom 174 (31%) were 65 years or older. The proportion of older patients was significantly higher in the Southern Italy centre, accounting for more than 40%. Comparison of younger and older groups showed that 51% patients > or =65 years had advanced liver disease (liver cirrhosis or hepatocellular carcinoma) compared with 26% younger patients (P < 0.0001). About half of the patients > or =65 years were not aware of their anti-HCV positive status, even if they tended to be more symptomatic than the younger group. By multivariate analysis, age > or = 65 years, alcohol consumption and diabetes were independently associated with advanced liver disease. Overall, 34 out of 174 patients (20%) > or =65 years had received antiviral treatment compared with 122 out of 386 (32%) younger patients (P = 0.003). Our results further emphasize the notion that chronic hepatitis C is becoming a disease of the elderly and that elderly patients with chronic HCV infection often have severe and underestimated disease.

Pharmacokinetics and efficacy of intravenous or intramuscular hepatitis B immunoglobulins in prophylaxis of hepatitis B after liver transplantation.

AIM: The use of hepatitis B immunoglobulin (HBIg) combined with nucleos(t)ide analogues (NUCs) has improved outcomes in post-hepatitis B (PHB) liver transplant (LT), reducing the 1-year recurrence rate below 10%. The aim of this study was to evaluate efficacy and pharmacokinetics of prophylaxis with NUC(s) and intravenous (iv-) or intramuscular (im-) HBIg in 33 PHBLTs, transplanted for more than 1 year. METHODS: During the first six months of the study, 18 subjects received 5000 IU of iv-HBIg every four weeks and 15 patients 2160 IU/12 mL of im-HBIg every two weeks. In the following six months, 31 subjects were switched to two different concentrations of im-HBIg, 2160/12 mL (16 patients) or 2000 IU/6 mL every two weeks (15 patients). RESULTS: All patients remained HBsAg-negative and 30/31 maintained anti-HBs >100 IU/L. Overall mean anti-HBs titer during treatment was 363 IU/mL. Mean HBIg half-life was 21.4, 27.3 and 26 days with intravenous, diluted or concentrated im-preparations, respectively. CONCLUSION: These results confirm an analogue efficacy and tolerance of iv- and im-HBIg combined with antivirals in prophylaxis of hepatitis B after LT. Anti-HBs titers three times higher than aimed and four weeks mean half-life could suggest the reduction of doses and the elongation of the interval of administration of im-HBIg.

Ultrasound detection of abdominal lymph nodes in chronic liver diseases. A retrospective analysis.

AIM: To retrospectively evaluate the prevalence of lymph nodes of the hepato-duodenal ligament in a group of patients with chronic liver disease of various aetiologies and to investigate what clinical, aetiological and laboratory data may lead to their appearance. MATERIALS AND METHODS: One thousand and three patients (554 men, 449 women) were studied, including 557 with chronic hepatitis and 446 with liver cirrhosis. The presence of lymph nodes near the trunk of the portal vein, hepatic artery, celiac axis, superior mesenteric vein and pancreas head was investigated using ultrasound. RESULTS: Lymph nodes were detected in 394 out of the 1003 study patients (39.3%); their number ranged from one to four, with a diameter ranging between 0.8 and 4 cm. The highest prevalence was in the subgroup of patients with primary biliary cirrhosis (87.5%), followed by patients with hepatitis C virus (HCV; 42%), patients with HCV and hepatitis B virus (HBV; 41.3%), autoimmune hepatitis (40%), and HBV alone (21.2%). In the alcoholic and idiopathic subgroups prevalence was 9.5%, while in the non-alcoholic steatohepatitis and haemochromatosis subgroups it was 0%. HCV RNA was present in 97 out of 103 lymph node-positive patients and in 141 out of 168 lymph node-negative HCV-negative patients (p<0.003). Lymphadenopathy frequency increased as the liver disease worsened (chi(2) MH=74.3; p<0.0001). CONCLUSION: Despite the limitations of a retrospective study, our data indicate a high prevalence of lymphadenopathy in liver disease patients; ultrasound evidence of lymph nodes of the hepato-duodenal ligament in a given liver disease may most likely suggest a HCV or an autoimmune aetiology and a more severe histological picture.

Hemodynamic changes in splanchnic circulation after orthotopic liver transplantation in patients with liver cirrhosis.

BACKGROUND: Liver cirrhosis increases portal vein pressure and alters the splanchnic circulation. With Doppler sonography, we investigated the hemodynamic changes in the portal vein, superior mesenteric artery, hepatic and splenic arteries and spleen size in a group of patients with end-stage liver disease before and after orthotopic liver transplantation (OLT). METHODS: Ten patients (seven male, three female; mean age = 48.8 +/- 7.6 years) who underwent OLT for liver cirrhosis mainly associated with hepatitis C virus infection completed the study. The control group consisted of 10 patients matched by sex and age who had no gastroenterologic or vascular diseases. All patients underwent duplex Doppler sonography (Toshiba SSA 270A with a 3.5-MHz probe) after 24 h of fasting (baseline) and then 6 and 12 months after OLT. The following parameters, expressed as the mean of three measurements, were evaluated: portal flow velocity (PFV), pulsatility index of the superior mesenteric artery (MAPI), resistance indexes of the hepatic (HARI) and splenic (SARI) arteries, and longitudinal diameter of the spleen (LDS). RESULTS: PFV in the pre-OLT phase was significantly lower in the patients than in the controls ( p < 0.0001); it progressively and significantly increased over baseline levels at 6 and 12 months ( p < 0.0001), approaching control values. LDS in the pre-OLT phase was significantly higher than in controls ( p < 0.0001); after OLT, it decreased significantly compared with baseline values ( p < 0.005). The MAPI of patients in the pre-OLT phase was lower than that in controls ( p < 0.0001); post-OLT, it progressively increased and reached values that were significantly above baseline at 12 months ( p < 0.005). In the pre-OLT phase, the HARI and SARI were significantly higher than in controls ( p < 0.04); 6 and 12 months after OLT, those values were significantly below baseline values ( p < 0.001), and there was no significant difference from control values. CONCLUSION: These data show that many of the hemodynamic parameters typical of decompensated cirrhosis improve progressively within 12 months after transplantation.