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The long-term changes of liver stiffness (LS) in patients who achieve viral clearance after direct-acting anti-HCV therapy remain undefined. We conducted a multicenter prospective study to investigate this aspect. Patients with HCV infection treated with DAAs were enrolled from six Italian centers; they underwent clinical, biochemical, ultrasound, and transient elastography evaluations before treatment (T0), 12 weeks (SVR12), and 24 months (T24) after the end of therapy. Among the 516 consecutive patients enrolled, 301 had cirrhosis. LS significantly decreased from T0 to SVR (14.3 kPa vs 11.1 kPa, p=0.002), with a progressive reduction until T24 (8.7 kPa, p

Hepatitis B virus (HBV) is a major cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Despite the advent of vaccines and potent antiviral agents able to suppress viral replication, recovery from chronic HBV infection is still an extremely difficult goal to achieve. Complex interactions between virus and host are responsible for HBV persistence and the risk of oncogenesis. Through multiple pathways, HBV is able to silence both innate and adaptive immunological responses and become out of control. Furthermore, the integration of the viral genome into that of the host and the production of covalently closed circular DNA (cccDNA) represent reservoirs of viral persistence and account for the difficult eradication of the infection. An adequate knowledge of the virus–host interaction mechanisms responsible for viral persistence and the risk of hepatocarcinogenesis is necessary for the development of functional cures for chronic HBV infection. The purpose of this review is, therefore, to analyze how interactions between HBV and host concur in the mechanisms of infection, persistence, and oncogenesis and what are the implications and the therapeutic perspectives that follow.

People who use drugs (PWUDs) are a crucial population in the global fight against viral hepatitis. The difficulties in linkage to care, the low adherence to therapy, the frequent loss to follow-up and the high risk of re-infection make the eradication process of the hepatitis C virus (HCV) really hard in this viral reservoir. Several management and treatment models have been tested with the aim of optimizing the HCV care cascade in PWUDs. Models of decentralization of the care process and integration of services seem to provide the highest success rates. Giving this, telemedicine could favor the decentralization of diagnostic-therapeutic management, key for the implementation of linkage to care, reduction of waiting times, optimization of adherence and results and reduction of the costs. The purpose of this literature review is to examine the role and possible impact of telemedicine in optimizing the HCV care cascade, comparing the different care models that have shown to improve the linkage to care and therapeutic adherence in this special population.

Background: Free-of-charge HCV screening in some key populations and in 1969–1989 birth cohorts has been funded in Italy as the first step to diagnosing individuals who are infected but asymptomatic. The aim of this study is to evaluate the feasibility of an opportunistic HCV screening and its linkage to care. Methods: A hospital-based HCV screening was conducted as a routine test for in-patients admitted to the Evangelical Hospital Betania of Naples from January 2020 to May 2021. All consecutive in-patients were screened for the HCV antibody (HCV-Ab) at the time of their admission to the hospital, and those born prior to year 2000 were included in the study. HCV-RNA testing was required for those not previously treated and without antiviral treatment contraindications. For in-patients with an active infection, treatment started soon after hospital admission. Results: Among 12,665 inpatients consecutively screened, 510 (4%) were HCV-Ab positive. The HCV-Ab positivity rate increased with age, reaching the highest prevalence (9.49%) in those born before 1947. Among patients positive for HCV, 118 (23.1%) had been previously treated, 172 (33.9%) had been discharged before being tested for HCV-RNA, and 26 (5.1%) had not been tested for short life expectancy. Of 194 (38% of HCV-Ab+) patients who were tested for HCV-RNA, 91 (46.2%) were HCV-RNA positive. Of patients with active infection, 33 (36%) were admitted to the liver unit with signs of liver damage either not previously diagnosed or diagnosed but unlinked to care for HCV infection. Of the patients positive for HCV-RNA, 87 (95.6%) started treatment; all achieved sustained virological response. Conclusion: HCV active infection has been frequently found in patients with comorbidities admitted in the hospital in Southern Italy. To achieve HCV elimination in Italy, broader screening strategies are required. In addition to screening of the 1969–1989 birth cohort of individuals unaware of their infection status, diagnosis and linkage to care of patients with known liver damage is strictly required. Hospital screening is feasible, but prompt reflex testing for identifying HCV-active infections is necessary to increase diagnosis and subsequent linkage to care.

Simple Summary Epidemiological data on viral hepatitis are essential to optimize screening programs. For HCV, the Italian Health Ministry planned a cohort screening for those born in 1969-1989. In order to update the epidemiological data of viral hepatitis in a highly endemic area of Southern Italy and assess whether the screening programs currently planned by the Italian government for those born between 1969-1989 will be effective, a retrospective multicenter study was carried out enrolling all COVID-19 hospitalized patients screened for markers of HCV and HBV infection. Indeed, the COVID-19 pandemic has resulted in access to the national health system of an unselected population similar to the general one. Among the 2126 patients evaluated, HBsAg and HCV-Ab prevalence was 1.6% and 5.1%, respectively. For HCV infection, a bimodal distribution was observed, with peaks in the birth cohorts 1930-1939 and 1960-1969 (11.6% and 5.6%, respectively). An analysis of the screening period imposed (born: 1969-1989) demonstrates that only 17% of HCV infection could be captured. Thus, an alignment of the screening period (i.e., birth cohort 1960-1984) would capture 40% of cases. Data show a high endemicity of hepatitis virus in our geographic area and the need for a tailored regional screening program. The COVID-19 pandemic led to the hospitalization of an unselected population with the possibility to evaluate the epidemiology of viral hepatitis. Thus, a retrospective multicenter study was conducted in an area of Southern Italy with the aim of assessing the prevalence of HCV and HBV markers and the ability of current screening program to capture cases. We evaluated 2126 hospitalized patients in seven COVID Centers of Naples and Caserta area in which 70% of the Campania population lives. HBsAg and HCV-Ab prevalence was 1.6% and 5.1%, respectively, with no differences between gender. Decade distribution for birth year shows a bimodal trend of HCV prevalence, with a peak (11.6%) in the decade 1930-1939 and a second peak (5.6%) for those born in 1960-1969. An analysis of the screening period imposed by the Italian government for those born between 1969 and 1989 shows that only 17% of cases of HCV infection could be captured. A small alignment of the screening period, i.e., those born from 1960 to 1984, would capture 40% of cases. The data confirm the high endemicity of our geographical area for hepatitis virus infections and underline the need for a tailored screening program according to the regional epidemiology.

INTRODUCTION: We assessed the performance of direct-acting antivirals (DAAs) in hepatitis C virus (HCV)-infected people who use drugs (PWUDs) in terms of sustained virological response (SVR) and adherence rates in comparison to a location-matched cohort of non-PWUD HCV patients. METHODS: All consecutive HCV RNA-positive PWUDs were enrolled between 2015 and 2019. All subjects underwent DAA treatment according to international guidelines and then followed, at least, up to 12 weeks after the end of treatment (SVR12). The SVR and adherence to treatment was compared with that of non-PWUD HCV patients observed at hepatological units of the CLEO platform. Intention-to-treat analysis was performed. RESULTS: A total of 1,786 PWUDs who were followed up were available for assessment. Most PWUDs (85.4%) were managed inside the specialized outpatient addiction clinics (SerDs). The overall SVR rate was 95.4%. The SerDs group achieved an SVR rate of 96.2% compared with 91.6% of the non-SerDs group (P < 0.001). Comparison with the non-SerDs group and the control HCV group showed a significant difference in the dropout rate (0.6% in the SerDs group versus 2.8% in the non-SerDs group and 1.2% in the control group; P < 0.001). At multivariate analysis, factors independently associated with SVR were use of the most recent regimens (elbasvir/grazoprevir, glecaprevir/pibrentasvir, and sofosbuvir/ velpatasvir; odds ratio: 3.126; P 5 0.000) and belonging to the SerDs group (odds ratio: 2.356; P 5 0.002). DISCUSSION: The performance of DAAs in PWUD is excellent, if 2 conditions are met: (i) that the latest generation drugs are used and (ii) that the patients are managed within the SerDs.

Background: We aimed to evaluate the factors associated with a virological response in a cohort of Hepatitis C virus (HCV)-infected people who inject drugs (PWID) treated with direct acting antivirals (DAAs). Methods: We conducted a multicenter retrospective cohort study enrolling HCV-infected PWID treated with DAAs. The primary outcome evaluated was the sustained virological response (SVR12) rate. Results: Five hundred and twenty HCV-infected PWID treated with all-oral DAA-based regimens were enrolled; a total of 168 (32.3%) patients presented genotype 1a, 109 (21.0%) genotype 1b, and 174 (33.5%) genotype 3; a total 152 of the 520 subjects (29.2%) were cirrhotics; a total 118 (22.7%) and 373 (71.7%) were treated with DAA regimens of second and third generation, respectively; a total 169 (33.6%) patients were receiving an opioid agonist at the start of antiviral therapy. Only 11 subjects (2.1%) did not show an SVR12. A significant correlation was found between treatment with opioid substitution therapy (p < 0.001), Human Immunodeficiency Virus (HIV) coinfection (p = 0.002), and treatment with first- or second-generation regimens (p = 0.0015) and HCV failure. Upon multivariate analysis, treatment with a first- or second-generation DAA was the only factor independently associated with failure (OR 10.4, 95% CI: 1.43 to 76.1, p = 0.02). Conclusions: Treatment with DAAs led to a high SVR12 rate (97.9%) in a large cohort of HCV-infected PWID. The only predictor of viral failure found in our analysis was treatment with first- and second-generation DAA.

Non-invasive ventilation is usually adopted as a support to medical therapy in patients with acute pulmonary edema, but which modality between Pressure Support Ventilation (PSV) and Continuous Positive Airway Pressure (CPAP) has better favourable effects is not been yet well known. Aim of this observational study was to provide data on these different non-invasive ventilation modalities in the management of acute cardiogenic pulmonary edema. One-hundred-fifty-three patients consecutively admitted to the Emergency Room of two different Center were enrolled and randomly assigned to CPAP or PSV. Data relative to mortality, need of endotracheal intubation, sequential blood gas analysis were compared. Furthermore, there were no significant differences regarding mortality in the two groups, but patients treated with PSV had a significant lower rate of endotracheal intubation and a higher improvement of blood gas analyses parameters. In conclusion, our data support only a slight advantage in favour to PSV versus CPAP.

Purpose: The aim of this study was to evaluate the effects of antiviral therapy on liver stiffness measurement (LSM). Methods: Two hundred HBV patients were enrolled from four hospital centers in southern Italy; median age was 50.7 (25–75) males were 68%; 171 patients underwent to liver biopsy and 200 patients had LSM at baseline and 189 at the end of follow-up. One hundred and forty-nine patients were treated with nucleos(t)ide analogs, while 51 patients were untreated. The cutoffs of the LSM, related to the fibrosis stages, were as follows: non-advanced fibrosis ≤ 8.1 kPa and advanced fibrosis ≥ 8.2 Kpa. Results: At baseline, the median value of LSM was 14.1 kPa for advanced fibrosis/cirrhosis and 6.9 kPa for non-advanced fibrosis. LSM was performed at 24 months from the start of therapy. The treated patients (68% received Entecavir and 32% Tenofovir) showed a decrease in liver stiffness measurement of 1.5 kPa (p < 0.001) in non-advanced fibrosis and of 6 kPa (p < 0.001) in advanced fibrosis/cirrhosis. In the patients not undergoing antiviral treatment, no statistically significant change of the LSM was observed (p = 0.26). A logistic binary regression model showed that the only independent factor associated with a significant change in the LSM was the liver stiffness value at baseline (odd ratio 2.855; 95% CI 1.456–5.788; (p = 0.007). Conclusion: Long-term antiviral therapy induced a significant reduction of liver stiffness measurement and this result may be related to the reduction of liver fibrosis. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.

Inflammatory bowel diseases, including Crohn’s disease and ulcerative colitis, are chronic inflammatory conditions involving primarily the gastrointestinal tract. However, they may be also associated with systemic manifestations and comorbidities. The relationship between chronic inflammation and endothelial dysfunction has been extensively demonstrated. Mucosal immunity and gastrointestinal physiology are modified in inflammatory bowel diseases, and these modifications are mainly sustained by alterations of endothelial function. The key elements involved in this process are cytokines, inflammatory cells, growth factors, nitric oxide, endothelial adhesion molecules, and coagulation cascade factors. In this review, we discuss available data in literature concerning endothelial dysfunction in patients affected by inflammatory bowel disease and we focus our attention on both pharmacological and nonpharmacological therapeutic targets.

A 72‐year‐old man with polycystic liver disease and unexplained shock was admitted to our Emergency Department. The presence of turgidity in the jugular veins and acute prerenal kidney failure led to a possible hypothesis of right ventricular heart failure. A massive hepatic cyst resulted in right atrial compression and, secondarily, a state of shock. Surgical decompression by drainage of the hepatic cyst resulted in rapid improvement in the patient's hemodynamics. We report the description of an extremely rare complication of polycystic liver disease., Polycystic liver disease (PCLD) is a rare autosomal‐dominant genetic condition characterized by the presence of multiple cysts in the liver tissue. When extremely massive, the induced mass effect can lead to abdominal distension, gastroesophageal reflux and/or dyspnoea. This is the description of an extremely rare manifestation of the disease: cardiac tamponade.

Non-alcoholic fatty liver disease (NAFLD) represents the result of hepatic fat overload not due to alcohol consumption and potentially evolving to advanced fibrosis, cirrhosis, and hepatocellular carcinoma. Fructose is a naturally occurring simple sugar widely used in food industry linked to glucose to form sucrose, largely contained in hypercaloric food and beverages. An increasing amount of evidence in scientific literature highlighted a detrimental effect of dietary fructose consumption on metabolic disorders such as insulin resistance, obesity, hepatic steatosis, and NAFLD-related fibrosis as well. An excessive fructose consumption has been associated with NAFLD development and progression to more clinically severe phenotypes by exerting various toxic effects, including increased fatty acid production, oxidative stress, and worsening insulin resistance. Furthermore, some studies in this context demonstrated even a crucial role in liver cancer progression. Despite this compelling evidence, the molecular mechanisms by which fructose elicits those effects on liver metabolism remain unclear. Emerging data suggest that dietary fructose may directly alter the expression of genes involved in lipid metabolism, including those that increase hepatic fat accumulation or reduce hepatic fat removal. This review aimed to summarize the current understanding of fructose metabolism on NAFLD pathogenesis and progression.

Alcohol represents the oldest substance of abuse known and Alcoholic Liver Disease (ALD) is the most common cause of chronic liver disease worldwide. The ALD includes a wide spectrum of injury and may lead progressively from simple steatosis to frank cirrhosis. The ALD diagnosis may be hard and it is mainly defined by the history of chronic alcohol intake, physical and laboratory abnormalities suggestive of liver disease. Abstinence is the cornerstone of ALD therapy. Although the burden on health of ALD is not negligible, in the last decades few therapeutic advances have been made. Because of the complex pathogenetic mechanisms, the therapy of ALD and especially of severe Alcoholic Hepatitis (AH), represents a thorny problem in the clinical practice. In severe forms of acute AH, some specific drug treatments, including glucorticoids or pentoxifylline, have been defined and are, at the moment, recommended by international guidelines. On the contrary, specific long-term treatments of ALD, aimed at stopping the progression of fibrosis, are not yet approved.

Occult hepatitis B virus infection (OBI) is characterised by the persistence of hepatitis B virus (HBV) genome in the liver, without any evidence of overt infection: without HBV surface antigen (HBsAg) and HBV DNA detectable in the serum, or fugacious spots of very low levels of viraemia. OBI, a possible phase in the natural history of chronic hepatitis B, is mainly due to the strong suppression of viral replication by host’s immunity. Although every condition inducing a strong immunosuppression may cause an OBI reactivation, onco-haematological patients, particularly those affected by non-Hodgkin’s lymphoma (NHL), are at the highest risk of this occurrence. This is mostly due to the primary involvement of the immune system that characterises these diseases, and the strong immunosuppressive treatments used for their cure. OBI reactivation represents a life-threatening risk, because of the possible development of an overt acute hepatitis that may lead to hepatic failure. Prophylaxis with lamivudine can prevent OBI reactivation and, when it occurs, the prompt administration of an antiviral therapy with nucleos(t)ide analogues can stop it. Currently, no valid serological tests for occult HBV detection are available, in this way every HBsAg-negative patient undergoing treatment for NHL is to be considered at risk of a ‘probable OBI reactivation’. The estimation of the real extent of this occurrence in a NHL setting is a difficult challenge, mostly due to the difficulty of obtaining a definitive diagnosis (which involves the availability of a liver biopsy performed before its development) and the high variability of the literature reports on this issue. In fact, the data concerning this prevalence range from 2.3-27.7% among the different papers, according to different study designs, different diagnostic criteria, different study populations, and different geographical areas of origin of the patients. The aim of this review is to browse the available knowledge about occult HBV infection amongst NHL patients, focusing on the prevalence of OBI reactivations, their identification, and their management.

Background Direct antiviral agents (DAA) demonstrated high efficacy among HCV-infected patients in registered trials. Nevertheless, the impact of these therapies on liver stiffness measurement (LSM) and liver functionality in ‘real-life’ is not well-known. The aim of the present study was to evaluate the sustained virological response (SVR) impact on LSM and clinical parameters of DAA-therapy on a real-life population of HCV patients with F3/F4 fibrosis. Methods A total of 749 HCV genotype 1–4 patients with F3/F4 hepatitis undergoing antiviral therapy were consecutively enrolled in four centres of hepatology in Italy. Clinical, biochemical and imaging data were collected at the baseline (T0), at the end of treatment (EoT) and after 12 weeks (SVR12). Results Out of 749 patients, 69.7% were F4 and 30.3% were F3. SVR12 was reached in 97.5%. LSM significantly decreased from T0 to EoT ( PConclusions Virological response to DAA is associated with fibrosis regression and recovery of liver functionality and this can be detected as early as EoT. HCV eradication is associated with a rapid and significant clinical improvement that lasts over time and seems to be negatively influenced by diabetes and EV.

SummaryAims Alcohol is the most commonly used addictive substance and alcoholic liver disease (ALD) is a major cause of chronic liver disease worldwide, responsible for 47.9% of all liver chronic deaths. Despite ALD has a significant burden on the health, few therapeutic advances have been made in the last 40 years, particularly in the long-term management of these patients. Methods we searched in PubMed, Scopus, Google Scholar, and MEDLINE databases to identify relevant English language publications focused on long-term therapy of ALD. Results From the huge literature on this topic, including about 755 studies, 75 were selected as eligible including clinical trials and meta-analysis. Conclusions Abstinence remains the cornerstone of ALD therapy but it is also the most difficult therapeutic target to achieve and the risk of recidivism is very high at any time. Several drugs (disulfiram, naltrexone, acamprosate, sodium oxybate) have proven to be effective to prevent alcohol relapse and increase the abstinence, although the psychotherapeutic support remains crucial. Baclofen seems to be effective to improve abstinence, showing an excellent safety and tolerability. ALD is often complicated by a state of malnutrition, which is related to a worst mortality. A nutritional therapy may improve survival in cirrhotic patients, reversing muscle wasting, weight loss and specific nutritional deficiencies. While in aggressive forms of alcoholic hepatitis are recommended specific drug treatments, including glucocorticoids or pentoxifylline, for the long-term treatment of ALD, specific treatments aimed at stopping the progression of fibrosis are not yet approved, but there are some future perspective in this field, including probiotics and antibiotics, caspase inhibitors, osteopontin and endocannabinoids.

Alcohol represents the oldest substance of abuse known, existed at least as early as the Neolithic period. In the present era, almost half of the world’s population consumes alcohol and it represents the third largest risk factor for disease and disability and the most prevalent cause of advanced liver disease worldwide. In fact, when alcohol consumption reaches "unsafe quantities" an Alcoholic Liver Disease (ALD) is very likely. ALD comprises a large spectrum of diseases, ranging from simple steatosis to steatohepatitis with fibrosis and cirrhosis. Alcohol related cirrhosis is responsible of almost 50% of all cirrhosis-related and 1% of all-cause deaths worldwide. Even if ALD and alcoholic cirrhosis represent a large part of liver diseases, to know exactly the global burden of these phenomena is very difficult. This is mostly due to diagnostic and nosological issues, being ALD represented by several types of diseases and the diagnosis very often based on voluntary questionnaires. Also the natural history of ALD is somewhat difficult to predict, since there is not a definite evolution between the various stages of the disease and, indeed, they may coexist in a single subject. In this brief review we will report on the global burden of ALD, the principal factors influencing its prevalence among populations and the different presentations of its natural history.

Background: Standard [i.e. pegylated interferon (Peg-IFN) + ribavirin] treatment of hepatitis C virus (HCV)-related chronic hepatitis is associated with a sustained virological response (SVR) in 50 - 90% of patients. A rapid virological response (RVR) (i.e. negative HCV-RNA after 4 weeks of treatment) predicts SVR in almost 90% of patients. Objectives: The main aim of this study was to assess the strength of RVR, as a predictive factor of antiviral treatment response. Patients and Methods: Using univariate and multivariate analysis, we retrospectively evaluated biochemical, metabolic, genetic and viral variables that might affect both RVR and SVR to Peg-IFN plus ribavirin, in 315 consecutive outpatients affected by HCV-related chronic hepatitis. Results: At univariate analysis, staging, body mass index, RVR, genotype and viral load were significantly related to SVR (P < 0.001). At multivariate analysis, RVR and genotype remained significant (P < 0.00001). The RVR had a predictive value of 83%. At univariate and multivariate analyses, diabetes (P = 0.003), genotype 2 (P = 0.000) and HCV-RNA values (P = 0.016) were independent predictors of RVR, even though at multivariate analyses, only genotype 2 was significantly related to RVR. When we stratified patients, according to genotype, no laboratory or clinical factors were predictive of RVR in genotype 1 patients at either univariate or multivariate analysis. In genotype 2 patients, staging (P = 0.029) and diabetes (P = 0.001) were the only significant predictors of RVR at univariate analyses, whereas no factor was independently related to RVR, at multivariate analysis. Conclusions: The RVR is the strongest factor of SVR and infection with HCV genotype 2 is significantly associated with RVR. Neither biochemical and/or metabolic factors seem to exert influence on RVR.

Recent studies report a prevalence of non-alcoholic fatty liver disease (NAFLD) of between 70% and 80% in patients with metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM). Nevertheless, it is not possible to differentiate between simple steatosis and non-alcoholic steatohepatitis (NASH) with non-invasive tests. The aim of this study was to differentiate between simple steatosis and NASH by liver biopsy in patients with hypertransaminasemia and MS or T2DM. Two hundred and fifteen patients with increased ALT levels and MS, and 136 patients at their first diagnosis of T2DM regardless of ALT values were consecutively admitted to a tertiary hepatology center between January 2004 and November 2014. Exclusion criteria were other causes of liver disease/ALT increase. Each patient underwent a clinical, laboratory and ultrasound evaluation, and a liver biopsy. Gender distribution, age, and body mass index were similar in the two groups of patients, whereas cholesterol levels, glycemia and blood pressure were significantly different between the two groups. The prevalence of NAFLD was 94.82% in MS patients and 100% in T2DM patients. NASH was present in 58.52% of MS patients and 96.82% of T2DM. Consequently, this study reveals that, by using liver biopsy, almost all patients with T2DM or MS have NAFLD, which in patients with T2DM means NASH. Importantly, it suggests that NASH may be one of the early complications of T2DM due to its pathophysiological correlation with insulin resistance.

Background: Occult HBV infection (OBI) is defined by the persistence of HBV in the liver without serum HBsAg and HBVDNA. It represents a life-threatening event during immunosuppressive chemotherapies. An OBI occurs in approximately 18% of HBcAb + patients. International guidelines suggest surveillance for HBV markers in immunosuppressed patients. In Non-Hodgkin Lymphoma (NHL), the prevalence of OBI reactivation remains to be established. Methods: In order to determine the prevalence of occult HBV reactivation in a large cohort of patients during chemotherapy for NHL, we analysed 498 NHL patients in a centre of Southern Italy. We evaluated HBV markers, NHL type, treatment type and occurrence of HBV reactivation. Results: Forty % of patients were treated with monoclonal antibodies and 60.3% without. Ninety-six patients were HBcAb+, HBsAg-. HBV reactivation occurred in ten subjects of this subgroup. All of them were successfully treated with Lamivudine. None of the patients experienced liver-related death. The prevalence of OBI reactivation was of 10.42% in HBcAb + HBsAb-patients. This event occurred in 50% of patients treated with mild immunosuppressive therapies. Each reactivation was treated with Lamivudine. Discussion: This report suggests that a strict surveillance is important and cost-effective in HBcAb + HBsAg- NHL patients treated with mild immunosuppressive therapies, in order to detect an occult HBV reactivation.