Paola Begini

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.

Hepatitis B in patients with hematological diseases: An update

Hepatitis B virus (HBV) reactivation (HBVr) in patients undergoing immunosuppressive therapy is still a hot topic worldwide. Its prevention and management still represents a challenge for specialists dealing with immunosuppressed patients. Aim of this paper is to provide a critical review of the relevant information emerged in the recent literature regarding HBV reactivation following immunosuppressive treatments for oncohematological tumors. A computerized literature search in MEDLINE was performed using appropriate terms arrangement, including English-written literature only or additional relevant articles. Articles published only in abstract form and case reports not giving considerable news were excluded. Clinical manifestation of HBVr can be manifold, ranging from asymptomatic self-limiting anicteric hepatitis to life-threatening fulminant liver failure. In clusters of patients adverse outcomes are potentially predictable. Clinicians should be aware of the inherent risk of HBVr among the different virological categories (active carriers, occult HBV carriers and inactive carriers, the most intriguing category), and classes of immunosuppressive drugs. We recommend that patients undergoing immunosuppressive treatments for hematological malignancies should undergo HBV screening. In case of serological sign(s) of current or past infection with the virus, appropriate therapeutic or preventive strategies are suggested, according to both virological categories, risk of HBVr by immunosuppressive drugs and liver status. Either antiviral drug management and surveillance and pre-emptive approach are examined, commenting the current international recommendations about this debated issue.

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.

Lean body mass wasting and toxicity in early breast cancer patients receiving anthracyclines

Background Sarcopenia refers to the reduction of both volume and number of skeletal muscle fibers. Lean body mass loss is associated with survival, quality of life and tolerance to treatment in cancer patients. The aim of our study is to analyse the association between toxicities and sarcopenia in early breast cancer patients receiving adjuvant treatment. Materials and Methods Breast cancer patients who have received anthracycline-based adjuvant treatment were retrospectively enrolled. CT scan images performed before, during and after adjuvant chemotherapy were used to evaluate lean body mass at third lumbar vertebra level with the software Slice Omatic V 5.0. Results 21 stage I–III breast cancer patients were enrolled. According to the skeletal muscle index at third lumbar vertebra cut-off ≤38.5 cm2/m2, 8 patients (38.1%) were classified as sarcopenic before starting treatment, while 10 patients (47.6%) were sarcopenic at the end of treatment. A lower baseline L3 skeletal muscle index is associated with G3-4 vs G0-2 toxicities (33.4 cm2/m2 (31.1–39.9) vs 40.5 cm2/m2 (33.4–52.0), p = 0.028). Similarly skeletal muscle cross sectional area was significantly lower in patients with G3-4 toxicities (86.7 cm2 (82.6–104.7) vs 109.0 cm2 (83.3–143.9), p = 0.017). L3 skeletal muscle index is an independent predictor of severe toxicity (p = 0.0282) in multivariate analysis. Conclusion Lean body mass loss is associated with higher grade of toxicity in early breast cancer patients receiving adjuvant chemotherapy.

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.