Nicolina Capoluongo

Reactivation of overt and occult hepatitis B infection in various immunosuppressive settings

The aim of the study was to evaluate clinical and virological differences in HBV reactivation between patients with overt and occult HBV infection. Twenty‐three consecutive patients with symptomatic HBV reactivation occurring during or after immunosuppressive therapy were enrolled in a retrospective study: 10 with reactivation of overt HBV infection (overt group) and 13 of occult HBV infection (occult group). Twenty‐one patients were treated with nucleot(s)ide analogues after HBV reactivation. Regimens including rituximab or fludarabine were administered more frequently in the occult group (61% vs. 31%, respectively). HBV reactivation was severe frequently in the overt (40%) and occult groups (38.4%). Patients in the overt group showed higher HBV‐DNA titers (1.1 × 108 ± 1.4 × 108 vs. 5.1 × 105 ± 6.8 × 105 IU; P < 0.005). Seven patients died during HBV reactivation, two in the overt and five in the occult group. Of these seven patients, two remained untreated and five had been treated with Lamivudine; of the 16 patients showing remission of HBV reactivation, four had been treated with Lamivudine, four with Entecavir, two with Telbivudine, and six with Lamivudine plus Adefovir. It is concluded that HBV reactivation is life‐threatening in patients with diseases inhibiting the immune response and/or receiving immunosuppressive drugs. Supportive therapy without antiviral drugs or Lamivudine monotherapy may not be effective for treating patients with HBV reactivation. J. Med. Virol. 83:1909–1916, 2011.

A Simple Noninvasive Score Based on Routine Parameters can Predict Liver Cirrhosis in Patients With Chronic Hepatitis C

Background Liver biopsy has remained the gold standard for the diagnosis of chronic hepatitis C; even though, it has a low but non-negligible rate of both false negative and complications. Several authors have proposed noninvasive tools to diagnose cirrhosis. But none of them showed complete concordance with liver biopsy. Objectives To devise a score based on noninvasive routine parameters that discriminate between patients with a high risk, and those with a low risk of cirrhosis among patients with chronic hepatitis C without performing liver biopsy, and to compare this score with other ones using routine parameters devoted to this aim. Patients and Methods We reviewed the charts of patients with chronic hepatitis C who performed a liver biopsy between 2000 and 2004. Multivariate analysis was used to identify independent predictors of cirrhosis. An independent group of patients with chronic hepatitis C admitted for a liver biopsy between 2007 and 2012 constituted the validation set. Results We enrolled 249 patients who had complete laboratoristic data, and sufficient liver tissue for fibrosis staging. Age, AST, prothrombin activity, and platelets were identified as independent predictors of histological cirrhosis. We categorized these variables, and devised a novel score called CISCUN (Cirrhosis Score University of Naples), giving one point to each of the following predictors: age > 40 years; AST > 2 upper normal values; platelet count < 160.000/mmc; prothrombin activity < 100%. Cirrhosis rate was 2.9% for the 103 patients with a CISCUN = 0 or 1, 23.4% for the 124 patients with a CISCUN of 2 or 3, and 86.4% for the 22 patients with a CISCUN = 4. These results were confirmed in the independent validation group of 285 patients with similar characteristics. Conclusions Patients with chronic hepatitis C and with a CISCUN ≤ 1 had a very low rate of cirrhosis while those with a CISCUN = 4 had a high risk of cirrhosis. Patients with CISCUN = 2 or 3 had an intermediate rate of cirrhosis, and therefore needed to perform a liver biopsy to receive a reliable diagnosis.

Cannabinoid Receptor 2-63 QQ Variant Is Associated with Persistently Normal Aminotransferase Serum Levels in Chronic Hepatitis C

Background and Aim To evaluate in anti-HCV-positive patients the clinical impact of the rs35761398 variant of the CNR2 gene leading to the substitution of Gln (Q) of codon 63 of the cannabinoid receptor 2 (CB2) with Arg (R). Patients and Methods 253 consecutive anti-HCV-/HCV-RNA-positive patients were enrolled, of whom 53 were HCV carriers with persistently normal ALT (PNALT group) and 200 had a history of steadily abnormal serum ALT values (abnormal ALT group). All patients were naive for antiviral therapy and were screened for the CNR2 rs35761398 polymorphism by a TaqMan assay. Results Subjects in the PNALT group, compared with those in the abnormal ALT group were older (58.5±12 vs. 50.7±12.4 years, p = 0.001), more frequently female (66% vs. 42%, p = 0.003), with lower body massindex (BMI) (24.5±3.1 vs. 26.6±4.6, p = 0.003), and more frequently with HCV genotype 2 (43.1% vs 17.7%, p = 0.0002) and CB2-63 QQ variant (34% vs. 11%, p = 0.0001). Considering all 253 patients, no difference in the demographic, biochemical, or virological data was observed between patients in the different CB2-63 variants. The logistic regression analysis identified CB2-63 QQ, HCV genotype 2, older age and lower BMI as independent predictors of PNALT (p<0.00001). Discussion The CB2-63 QQ variant in HCV patients was independently associated with the PNALT status.

The impact of the CB2-63 polymorphism on the histological presentation of chronic hepatitis B

The impact of the cannabinoid receptor 2 (CB2) rs35761398 polymorphism on chronic hepatitis B (CHB) was evaluated in 106 consecutive biopsy-proven CHB patients naive for antiviral therapy. A histological activity index (HAI) > 8 (Ishak scoring) was more frequent in patients with CB2-63 RR than in those with CB2-63 QR or QQ (37% vs. 16.7%, p < 0.05). The logistic regression analysis identified CB2-63 RR (p < 0.05) and a fibrosis score >3 (p < 0.005) as independently associated with an HAI >8. The observation that the CB2-63 RR variant is an independent predictor of extensive necroinflammation opens up new prospects in the study of CHB.

CB2-63 polymorphism and immune-mediated diseases associated with HCV chronic infection

AIMS To evaluate whether CB2 variants are associated with the presence of immune-mediated disorders (IMDs) in patients with chronic HCV infection. METHODS One hundred and sixty-eight anti-HCV/HCV-RNA-positive patients were enrolled, 81 with signs of IMDs and 87 without. In the IMDs group, 22 (27.2%) showed ANA positivity (titers ≥1:160), 3 (3.7%) SMA positivity (titers ≥1:160), 24 (29.6%) had cryoglobulinemia, 25 (30.9%) autoimmune thyroiditis, 4 (4.9%) psoriasis, 2 (2.5%) B-cell non-Hodgkin lymphoma and 1 (1.2%) autoimmune hemolytic anemia. All patients were screened for the CNR2 rs35761398 single nucleotide polymorphism using a TaqMan Assay. RESULTS Compared with the 87 patients without IMDs, the 81 with IMDs were more frequently females (65% vs. 45%, p=0.01), but no significant difference was found in the initial demographic, epidemiological, serological, biochemical or virological data. Instead, the prevalence of patients with the CB2-63 RR variant was significantly higher in the IMD than in the non-IMD group (49.4% vs. 24.1%, p=0.001). A logistic regression analysis including the CB2-63 receptor (RR vs. QR or QQ), age and sex identified the CB2-63 RR as the only independent predictor of IMDs (p=0.005). CONCLUSIONS The data suggest a significant, previously unknown, independent association between the CB2-63 RR variant and IMDs in anti-HCV-positive patients. The study was approved by the Ethics Committee of the Azienda Ospedaliera Universitaria of the Second University of Naples (n° 214/2012).

Eighteen-month lamivudine prophylaxis on preventing occult hepatitis B virus infection reactivation in patients with haematological malignancies receiving immunosuppression therapy

This study evaluated the long‐term efficacy and safety of an 18‐month lamivudine prophylaxis in 68 HBsAg‐negative/anti–HBc‐positive patients with oncohaematological disease.

The reactivation of occult HBV infection emerging with the case of acute hepatitis B in the wife of a subject treated with rituximab-based chemotherapy.

It is still a matter of debate whether nucleoside/nucleotide analogues should be administered as prophylaxis to hepatitis B surface antigen (HBsAg)-negative/antibodies against hepatitis B core antigen (anti-HBc)-positive patients with immunosuppression or whether these patients should be closely monitored and early treatment administered to those who become HBsAg-positive. We describe a reactivation of occult HBV infection emerging with the case of acute hepatitis B in the wife of an HBsAg-negative/anti-HBc-positive subject treated with rituximab-based chemotherapy for chronic lymphocytic leukaemia.