Elia Gigante

HCV-positive status and hepatitis flares in patients with B-cell non-Hodgkin's lymphoma treated with rituximab-containing regimens.

BACKGROUND Rituximab has provided a revolutionary contribution to the treatment of B-cell non-Hodgkins lymphomas (NHL). A high prevalence of hepatitis C virus (HCV) infection has been described in B-cell NHL patients. Cases of liver dysfunction in HCV-positive patients have been reported with rituximab-containing regimens. AIM to evaluate the liver-related effects of rituximab-containing regimens on HCV-positive CD20-positive B-cell NHL patients. PATIENTS AND METHODS Retrospective analysis of 104 consecutive patients. HCV status was determined, and development of hepatitis flares analysed. RESULTS Nine patients (8.6%) were HCV-positive. No correlation was shown between viral load and alanine transaminase levels. Three of the 9 HCV-positive, and none of the 95 HCV-negative developed hepatitis flares (p<0.001). At the 12-month follow-up hepatitis flare patients were alive and in remission for their haematological disease and no hepatitis flares, liver-related death had developed. CONCLUSIONS HCV-positive status may represent a risk factor for the development of hepatic flares in B-cell NHL patients receiving rituximab-containing regimens. Despite the increase in liver function tests, there were no major clinical events.

Sarcopenia predicts reduced survival in patients with hepatocellular carcinoma at first diagnosis.

BACKGROUND Sarcopenia is a complication and independent risk factor for mortality in patients with liver cirrhosis. AIM To assess the prevalence and influence of sarcopenia on overall survival in a cohort of cirrhotic patients with hepatocellular carcinoma managed in a tertiary center. MATERIAL AND METHODS Abdominal computed tomography of 92 consecutive hepatocellular carcinoma cirrhotic patients, enrolled and followed from 2004 to 2014, were retrospectively studied with a software analyzing the cross-sectional areas of muscles at third lumbar vertebra level. Data was normalized for height, skeletal muscle index (SMI) calculated and presence of Sarcopenia measured. Sarcopenia was defined by SMI ≤ 41 cm2/m2 for women and ≤ 53 cm2/m2 for men with body mass index (BMI) ≥ 25, and ≤ 43 cm2/m2 for men and women with BMI < 25, respectively. RESULTS Median age at diagnosis was 71.9 years (30.7-86.4) and BMI 24.7 (17.5-36.7), comparable in women 23.1, (17.5-36.7) and men 24.7 (18.4-36.7). A class of CHILD score and BCLC A prevailed (55.4% and 41.3%, respectively); metastatic disease was found in 12% of cases. Sarcopenia was present in 40.2% of cases, mostly in females (62.9%; p = 0.005). Mean overall survival was reduced in sarcopenic patients, 66 (95% CI 47 to 84) vs. 123 (95% CI 98 to 150) weeks (p = 0.001). At multivariate analysis, sarcopenia was a predictor of reduced overall survival, independent of age (p = 0.0027). CONCLUSIONS This retrospective study shows high prevalence of sarcopenia among cirrhotic patients with hepatocellular carcinoma. Presence of sarcopenia was identified as independent predictor of reduced overall survival. As easily measurable by CT, sarcopenia should be determined for prognostic purposes in this patient population.

Patients with hematological malignancies and serological signs of prior resolved hepatitis B.

Hepatitis B virus (HBV) infection affects a large part of the world population. Within the different virological HBV categories that have been identified, patients with occult HBV infection represent a peculiar group. These individuals harbor a replication competent virus, inhibited in its replicative function. Accordingly, cases of reactivations have been observed in immunosuppressed individuals who lose immunological control over the infection. Patients with hematological malignancies (HM) are treated with intense myelo- and immunosuppressive chemotherapy regimens which favor HBV reactivation. This event can have severe consequences, such as hepatitis flare, hepatic failure and even death. In addition, it can lead to delays or interruptions of curative treatments, resulting in a decreased disease free and overall survival. In this review, we will examine the event of HBV reactivation in patients with signs of resolved HBV infection undergoing treatment for HM and propose possible management strategies.

Perception of hepatitis B virus infection reactivation-related issues among specialists managing hematologic malignancies: result of an Italian survey

Abstract Hepatitis B virus (HBV) reactivation strongly affects the practice of physicians dealing with hematological malignancies. In this respect, in collaboration with the Italian Lymphoma Foundation we developed a descriptive study of the real-life approach of physicians caring for patients with these diseases. A questionnaire was designed to explore the perception of HBV reactivation-related issues. Fifty-nine Italian Lymphoma Foundation-affiliated institutions participated, and 504 questionnaires were sent out. Forty institutions (67.8%) returned 154 (30.5%) completed questionnaires. The largest majority (91.5%, 141/154) were aware of possible HBV reactivation as a consequence of immunosuppression. Most of the participants providing an answer (93.3%; 126/135) performed universal screening, and were aware of strategies for managing reactivation (96.4%, 132/137). Specialists treating lymphoma show a high level of awareness concerning the management of HBV reactivation under immunosuppression. However, uncertainties regarding the issue of HBV reactivation still emerge in this setting, and thus continuing collaborative effort between hepatologists and hematologists is necessary.

Liver biopsy: Analysis of results of two specialist teams

AIM To analyze the safety and the adequacy of a sample of liver biopsies (LB) obtained by gastroenterologist (G) and interventional radiologist (IR) teams. METHODS Medical records of consecutive patients evaluated at our GI unit from 01/01/2004 to 31/12/2010 for whom LB was considered necessary to diagnose and/or stage liver disease, both in the setting of day hospital and regular admission (RA) care, were retrieved and the data entered in a database. Patients were divided into two groups: one undergoing an ultrasonography (US)-assisted procedure by the G team and one undergoing US-guided biopsy by the IR team. For the first group, an intercostal approach (US-assisted) and a Menghini modified type needle 16 G (length 90 mm) were used. The IR team used a subcostal approach (US-guided) and a semiautomatic modified Menghini type needle 18 G (length 150 mm). All the biopsies were evaluated for appropriateness according to the current guidelines. The number of portal tracts present in each biopsy was assessed by a revision performed by a single pathologist unaware of the previous pathology report. Clinical, laboratory and demographic patient characteristics, the adverse events rate and the diagnostic adequacy of LB were analyzed. RESULTS During the study period, 226 patients, 126 males (56%) and 100 females (44%), underwent LB: 167 (74%) were carried out by the G team, whereas 59 (26%) by the IR team. LB was mostly performed in a day hospital setting by the G team, while IR completed more procedures on inpatients (P < 0.0001). The groups did not differ in median age, body mass index (BMI), presence of comorbidities and coagulation parameters. Complications occurred in 26 patients (16 G team vs 10 IR team, P = 0.15). Most gross samples obtained were considered suitable for basal histological evaluation, with no difference among the two teams (96.4% G team vs 91.5% IR, P = 0.16). However, the samples obtained by the G team had a higher mean number of portal tracts (G team 9.5 ± 4.8; range 1-29 vs IR team 7.8 ± 4.1; range 1-20) (P = 0.0192) and a longer mean length (G team 22 mm ± 8.8 vs IR team 15 ± 6.5 mm) (P = 0.0001). CONCLUSION LB can be performed with similar outcomes both by G and IR. Use of larger dimension needles allows obtaining better samples, with a similar rate of adverse events.

‘Les liaisons dangereuses’: Hepatitis C, Rituximab and B-cell non-Hodgkin’s lymphomas

Rituximab has provided a revolutionary contribution to the treatment of B-cell non-Hodgkins lymphomas (NHL). A high prevalence of hepatitis C virus (HCV) infection has been described in B-cell NHL patients. Cases of liver dysfunction in HCV-positive patients have been reported with Rituximab-containing regimens. In this paper we review the recent data regarding the effects of Rituximab in NHL patients with HCV infection. We also added a section devoted to improving communication between oncohaematologists and hepatologists. Furthermore, we propose a common methodological ground to study hepatic toxicity emerging during chemotherapy.

Effectiveness of entecavir in the management of acute hepatitis B developing in a patient with Hodgkin's lymphoma: A case report

Abstract We describe a case of severe acute hepatitis B developing in a patient with Hodgkins lymphoma after chemotherapy and before radiotherapy. Entecavir was administered leading to virological and biochemical response, which allowed the scheduled treatment to be completed. The patient had complete haematological remission and made a complete recovery from hepatitis B.

Sarcopenia is associated with reduced survival in patients with advanced hepatocellular carcinoma undergoing sorafenib treatment

Background Sarcopenia has been associated with poor outcomes in patients with cirrhosis and solid tumours. Objective Analyse the influence of sarcopenia on survival and treatment duration in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib. Methods We conducted a multicentre, retrospective study on 96 patients with advanced HCC treated with sorafenib, all with available abdominal computed tomography (CT) scan within 30 days from treatment start. Anthropometric, laboratory, treatment and follow-up data were collected. Sarcopenia was defined by reduced skeletal muscle index calculated from an L3 section CT image. Results Sarcopenia was present in 49% of patients. Patients were divided into two groups according to sarcopenia: age was significantly higher in the sarcopenic group (SG) (66 years (31–87) versus 72 years (30–84), p = 0.04], with no difference in other baseline characteristics. The SG showed shorter overall survival (OS) (39 (95% confidence interval (CI) 26–50) versus 61 (95% CI 47–77) weeks (p = 0,01)) and shorter time on treatment (12.3 (95% CI 8–19) versus 25.9 (95% CI 15–33) weeks (p = 0.0044)). At multivariate analysis, sarcopenia was independently associated to reduced OS (p = 0.03) and reduced time on treatment (p = 0.001). Conclusion Sarcopenia is present in almost half of patients with advanced HCC, and is associated with reduced survival and reduced duration of oral chemotherapy.

SARCOPENIA IS ASSOCIATED WITH A REDUCED SURVIVAL IN PATIENTS WITH HEPATOCARCINOMA UNDERGOING SORAFENIB TREATMENT

P0367 SARCOPENIA IS ASSOCIATED WITH A REDUCED SURVIVAL IN PATIENTS WITH HEPATOCARCINOMA UNDERGOING SORAFENIB TREATMENT E. Gigante, G. Antonelli, P. Begini, F. Carbonetti, E. Iannicelli, P. Marchetti, A. Pellicelli, L. Miglioresi, G. Delle Fave, M. Marignani. Digestive and Liver Diseases unit, Radiology unit, Oncology unit, St. Andrea Hospital, Faculty of Medicine and Psychology, University ’Sapienza’, Liver Unit, San Camillo Forlanini Hospital, Rome, Italy E-mail: elia.gigante@hotmail.it

Different hepatitis B carrier categories need different management strategies in case of immunosuppressive chemotherapeutic regimens

We read Evens et al. [1] meta-analysis, which provides useful aggregated data about hepatitis B virus (HBV) reactivation in rituximab-treated oncohematology patients. However, some definitions and management strategies could be clarified using the specific Italian guidelines developed on this issue [2, 3]. In fact, the definition ‘ hepatitis B surface antigen (HBsAg)positive’ is not complete if the HBV DNA level is not reported, since it identifies different virological HBV categories and management. HBsAg-positive patients with HBV DNA levels >2000 IU/ml, defined active carriers, should be treated as immune competent patients, and nucleo(s)tide analogues (NA) with high potency and low resistance (entecavir, tenofovir or telbivudine) should be used to control the effects of immune suppression on viral replication while receiving chemotherapy. HBsAg positive, HBV DNA negative or £2000 IU/ml individuals, defined inactive carriers, undergoing high-risk immune suppressive treatment should be prophylaxed with an NA preferably 2–4 weeks before starting immune suppressive treatment. Considering that baseline viremia in this group is usually undetectable and that resistance risk is low, a low cost NA (i.e. lamivudine, LAM) should be used. The preemptive approach has been proven superior to delayed treatment. Curiously, in the paper by Pei et al. [4] a significantly protective effect of LAM is described, but in the discussion of the paper by Evens et al. [1], the same article is cited to underline LAM ineffectiveness in the prevention of HBV reactivation. In this study, HBV reactivated after LAM stopping, thus it can be argue that treatment duration, and not LAM per se, was inadequate to control viral replication. In fact, it has been suggested that antiviral treatment should be extended up to 12 months after immunochemotheraphy [3]. Thus, the negative perspective regarding LAM use in prophylaxis of HBsAg positive should be carefully discussed and detailed presenting the positive evidences supporting its use in this setting [3]. Differentiating the management of active versus inactive carriers is crucial to start treatment with NA of adequate potency/resistance and to prevent ineffective replication control, development of viral resistances and breakthrough. Occult hepatitis B carriers (OBI) are HBsAgand HBV DNA-negative individuals, usually anti-HBc and/or anti-HBs positive [5], in which liver HBV DNA can be detected by specific PCR probes. These individuals harbor replication competent virus, inhibited in its replicative function by immunological/epigenetic mechanisms, and are at increased risk for HBV reactivation if treated with immunochemotheraphy for oncohematological malignancies as monoclonal antibodies. Prophylaxis has been strongly suggested in this setting [2, 3]. Alternative strategies to manage OBI are monitoring for HBsAg reexpression or HBV DNA increase and consequential targeted prophylaxis before biochemical signs of hepatitis develop [2, 3]. The authors presented the effects of rituximab exposure by pooling a large group of patients from different HBV categories. Thus, even if acknowledging the intrinsic limits to all meta-analysis, the heterogeneity due to different virological HBV categories pooling and retrieval of data from different studies, since there are few large studies on this issue, the authors should be complimented for having provided useful