Occult HBV Infection Reactivation in Non-Hodgkin’s Lymphoma: An Update on Prevalence and Management

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

Telemedicine Improves HCV Elimination among Italian People Who Use Drugs: An Innovative Therapeutic Model to Increase the Adherence to Treatment into Addiction Care Centers Evaluated before and during the COVID-19 Pandemic

People who use drugs (PWUDs) are generally considered “hard-to-treat” patients, due to adherence to HCV antiviral therapy or re-infection concerns. Linkage-to-care still remains a significant gap for HCV elimination, worsened by the COVID-19 pandemic. To reduce time-to-treat and improve treatment adherence, we have developed a patient-tailored model-of-care, decentralized within the addiction center and supervised remotely by hepatologists. From January 2017 to December 2020, patients were enrolled in one addiction care center in Southern Italy, where a complete hepatologic assessment, including blood chemistry, ultrasound, and transient elastography examination, was provided. DAAs treatment has been adapted on clinical features, also performing a daily administration during an outpatient visit, and monitored remotely by specialists via telemedicine interactions. Adherence was evaluated on the accomplishment of therapy or on the percentage of attended visits. From a total of 690 PWUDs, 135 had an active HCV infection and were enrolled in the study. All patients started the treatment within 3 weeks after HCV diagnosis. Six drop-outs were recorded, obtaining a sustained virological response at week 12 (SVR12) in 98.5% of PWUDs. There were only two cases of treatment failure, one of which is re-infection. No differences were found between the SVR12 rates before and during the COVID-19 pandemic. We obtained a high SVR12 rate, providing a comprehensive assessment within the addiction care center, tailoring the drug administration with a hepatologic remote stewardship. Our therapeutic model should improve the time-to-treat and treatment adherence in PWUDs

Coronavirus Disease 2019 (COVID-19) in autoimmune hepatitis: a lesson from immunosuppressed patients

Chronic immunosuppression is associated with increased and more severe viral infections. However, little is known about the association between immunosuppression and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Our aim was to describe the clinical course of patients with immunosuppressed autoimmune hepatitis (AIH) during coronavirus disease 2019 (COVID-19) infection in Italy. Our study is a case series of patients with AIH treated with immunosuppression, who tested positive for SARS-CoV-2 in March 2020 during the outbreak of COVID-19. Ten patients from seven different hospitals in Italy were diagnosed with COVID-19 during the outbreak of SARS-CoV-2 in March 2020. Seven subjects were female (70%), and age ranged from 27 to 73 years. Before the onset of SARS-CoV-2 infection, all patients were taking immunosuppressive therapy for AIH, and eight of them were on biochemical remission. Two other patients had recent acute onset of their AIH, and consequently started high-dose steroids, as per induction protocol. All patients had a respiratory syndrome and a positive nasal swab for SARS-CoV-2. Five patients developed a computed tomography-confirmed COVID-19 pneumonia. Six subjects received a combination of antiretroviral and antimalarial drugs. In seven patients, the dosage of immunosuppressive medication was changed. Liver enzymes were repeated during SARS-CoV-2 infection in all hospitalized cases; they remained within the normal range in all cases, and improved in the two acute cases treated with high-dose steroids. The clinical outcome was comparable to the reported cases occurring in non-immunosuppressed subjects.Conclusion:Patients under immunosuppressive therapy for AIH developing COVID-19 show a disease course presumptively similar to that reported in the non-immunosuppressed population. These data might aid in medical decisions when dealing with SARS-CoV-2 infection in immunocompromised patients

Can Telemedicine Optimize the HCV Care Cascade in People Who Use Drugs? Features of an Innovative Decentralization Model and Comparison with Other Micro-Elimination Strategies

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

Predictors of early and late hepatocellular carcinoma recurrence

: Hepatocellular carcinoma (HCC) is the most frequent liver neoplasm, and its incidence rates are constantly increasing. Despite the availability of potentially curative treatments (liver transplantation, surgical resection, thermal ablation), long-term outcomes are affected by a high recurrence rate (up to 70% of cases 5 years after treatment). HCC recurrence within 2 years of treatment is defined as "early" and is generally caused by the occult intrahepatic spread of the primary neoplasm and related to the tumor burden. A recurrence that occurs after 2 years of treatment is defined as "late" and is related to de novo HCC, independent of the primary neoplasm. Early HCC recurrence has a significantly poorer prognosis and outcome than late recurrence. Different pathogenesis corresponds to different predictors of the risk of early or late recurrence. An adequate knowledge of predictive factors and recurrence risk stratification guides the therapeutic strategy and post-treatment surveillance. Patients at high risk of HCC recurrence should be referred to treatments with the lowest recurrence rate and when standardized to combined or adjuvant therapy regimens. This review aimed to expose the recurrence predictors and examine the differences between predictors of early and late recurrence

Can telemedicine optimize the HCV care cascade in people who use drugs? features of an innovative decentralization model and comparison with other micro-elimination strategies.

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

Sustained virological response by direct antiviral agents in HCV leads to an early and significant improvement of liver fibrosis

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. Aim of the present study was to evaluate the SVR impact on LSM and clinical parameters of DAA-therapy on a real-life population of HCV patients with F3/F4 fibrosis. METHODS: 749 HCV genotype 1-4 patients with F3/F4 hepatitis undergoing antiviral therapy, were consecutively enrolled in four centers of Hepatology of Italy. Clinical, biochemical and imaging data were collected at the baseline(T0), at the End of Therapy(EoT) and after 12 weeks(SVR12). RESULTS: Out of 749 patients, 69.7% was F4 and 30.3% was F3. SVR12 was reached in 97,5%. LSM significantly decreased from T0 to EoT(p<0.001) whereas it did not from EoT to SVR12(p:ns). Moreover, in F4 no significant differences were found in Child and MELD between T0, EoT and SVR12(p=ns). At the univariate analysis of clinical and liver parameters, baseline high glucose(p<0.005), type 2 diabetes(p<0.001), low ALT(p<0.001), low PLTs(p<0.005), and the presence of esophageal varices (EV)(p<0.001) were found to be associated with a lack of a significant EoT LSM improvement. At a multiple regression, ALT(p<0.05), Diabetes(p<0.005) and EV(p<0.05), were inversely associated with significant LSM reduction. CONCLUSIONS: 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 overtime and seems to be negatively influenced by diabetes and E

Impact of telaprevir in HCV patients with cirrhosis and RVR: Real-life data from boceprevir or telaprevir based “triple therapy” experience in southern Italy

Background and Rationale of Study: The real-life data of triple therapy-based treatment in patients with chronic hepatitis C were investigated in this survey of 12 clinical centers of southern Italy. This retrospective study analyzed data from 176 consecutive patients. Methods: 125 (70%) patients were treated with telaprevir, and 51(30%) with boceprevir. There were no differences in demographic characteristics between the groups. The degree of Liver Fibrosis (LF) was evaluated according to Liver Biopsy (LB) and/or Transient Elastography (TE). 53/176 patients (30%) had liver cirrhosis. Sixteen patients (9%) were treatment naïve, and the remaining were not: 92 were non-responders (52, 84%), 63 relapsed (35,79%), and 5 discontinued treatment (2, 8%). Results: Overall, the rapid Virological Response (RVR) rate was 67.6%. Of the 103 patients who had follow-up for at least 12 weeks after the end of treatment, 61 (59, 2%) achieved a Sustained Virological Response (SVR). According to multivariate analysis for SVR, RVR was the only independent predictive factor of SVR, irrespective of the degree of LF and the type of response to previous treatments. In telaprevir-treated patients, the rate of RVR was similar in patients with F0-F2, F3 and F4 fibrosis (85%, 84%, 78%, respectively), and the SVR rates among RVR patients was similar irrespective of LF. Conclusions: Data from this real-life study confirm the efficacy reported in clinical trials, although cirrhosis appears to play a smaller role in influencing treatment efficacy. Moreover, RVR is the only independent predictive factor of response regardless of cirrhosis. Based on RVR and for patients with cirrhosis, a shorter therapy might be considered, at least with telaprevir-based therapy