Surgical treatment of tertiary hyperparathyroidism: does one fit for all?

Background: Tertiary hyperparathyroidism (3HPT) is defined as a condition of excessive autonomous excretion of intact parathyroid hormone (iPTH) with persistent hypercalcemia (>10.5 mg/dL) that lasts for more than 12 months after a successful kidney transplantation, in the context of a long course secondary hyperparathyroidism (2HPT). The chronic high levels of iPTH cause a worsening of graft function, accompanied by systemic symptoms of hypercalcemia. The only curative therapy is parathyroidectomy (PTX). It remains unclear whether total parathyroidectomy with autotransplantation (TPTX-AT) or subtotal parathyroidectomy (SPTX) lead to better outcomes. Aims: The aim of this retrospective, single-institution cohort study is to evaluate the rate of persistent or recurrent disease and postoperative calcium/iPTH disturbances in patients treated with TPTX-AT or SPTX for 3HPT. Methods: A single-center retrospective analysis of 3HPT patients submitted to TPTX-AT or SPTX between 2007-2020 with at least 24 months follow-up was conducted. The outcome parameters included persistence/recurrence of disease, incidence of transitory hypocalcemia, and temporary/permanent hypoparathyroidism. Results: A cohort of 52 patients was analyzed and divided in two groups: 38 (73%) were submitted for TPTX-AT, and 14 patients (27%) were submitted for SPTX. The TPTX-AT population showed lower plasmatic calcium concentrations compared with the SPTX group during the entire follow-up period (p<0.001). There were eight cases (21%) of transitory hypocalcemia in the TPTX-AT group and none in the SPTX group, with p=0.065. Two cases (5%) of temporary hypoparathyroidism occurred in the TPTX-AT group and none in the SPTX group, with p= 0.530. There were no cases of permanent hypoparathyroidism and no cases of persistent disease. No statistical difference was assessed for the recurrence of 3HPT between the TPTX-AT group and the SPTX group (N=1, 3% vs N=1, 7%) (p=0.470). Conclusion: No significative difference was registered between the TPTX-AT and SPTX groups in terms of persistence/recurrence of disease, incidence of transitory hypocalcemia, and temporary/permanent hypoparathyroidism. Mean calcium levels iPTH values were statistically lower among the TPTX-AT group compared with the SPTX group while remaining always in the range of normality.

Intrahepatic Cholangiocarcinoma and Hepatocellular Carcinoma: Real-life Data on Liver Disease, Treatment and Prognosis.

Background and Aims: Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) have common features and differences. This real-life study investigated their characteristics, treatment modalities, and prognoses. Methods: This retrospective comparative study was performed in 1,075 patients seen at one tertiary center between January 2008 and December 2020. Overall survival (OS) was estimated by the Kaplan-Meier method. Subclassification of iCCAs after histological and radiological review, and molecular profiling was performed. Results: HCCs patients were more likely to have early-stage disease than iCCA patients. iCCA patients were more likely to be female, especially those patients without cirrhosis (43% vs. 17%). Cirrhosis was prominent among HCC patients (89% vs. 34%), but no difference in underlying liver disease among cirrhotic patients was found. OS of HCC patients was 18.4 (95% CI: 6.4, 48.3) months, that of iCCA patients was 7.0 (95% CI: 3.4, 20.1) months. OS of Barcelona Clinic Liver Cancer C HCC patients was 7.8 (95% CI: 4.3, 14.2) months, that of advanced/metastatic iCCA patients was 8.5 (95% CI: 5.7, 12.3) months. In patients treated with sorafenib, OS was longer in HCC patients who received subsequent tyrosine kinase inhibitor therapies. No significant OS difference was found between iCCA patients with and without cirrhosis or according to histological subtype. A targetable molecular alteration was detected in 50% of the iCCA patients. Conclusions: In this French series, cirrhosis was common in iCCA, which showed etiological factors comparable to those of HCC, implying a distinct oncogenic pathway. Both entities had a dismal prognosis at advanced stages. However, systemic therapies sequencing in HCC and molecular profiling in iCCA offer new insights.

Radiomics, a Promising New Discipline: Example of Hepatocellular Carcinoma.

Radiomics is a discipline that involves studying medical images through their digital data. Using "artificial intelligence" algorithms, radiomics utilizes quantitative and high-throughput analysis of an image's textural richness to obtain relevant information for clinicians, from diagnosis assistance to therapeutic guidance. Exploitation of these data could allow for a more detailed characterization of each phenotype, for each patient, making radiomics a new biomarker of interest, highly promising in the era of precision medicine. Moreover, radiomics is non-invasive, cost-effective, and easily reproducible in time. In the field of oncology, it performs an analysis of the entire tumor, which is impossible with a single biopsy but is essential for understanding the tumor's heterogeneity and is known to be closely related to prognosis. However, current results are sometimes less accurate than expected and often require the addition of non-radiomics data to create a performing model. To highlight the strengths and weaknesses of this new technology, we take the example of hepatocellular carcinoma and show how radiomics could facilitate its diagnosis in difficult cases, predict certain histological features, and estimate treatment response, whether medical or surgical.

Perioperative Cetuximab with Cisplatin and 5-Fluorouracil in Esogastric Adenocarcinoma: A Phase II Study.

PURPOSE: While perioperative chemotherapy provides a survival benefit over surgery alone in gastric and gastroesophageal junction (G/GEJ) adenocarcinomas, the results need to be improved. This study aimed to evaluate the efficacy and safety of perioperative cetuximab combined with 5-fluorouracil and cisplatin. PATIENTS AND METHODS: Patients received six cycles of cetuximab, cisplatin, and simplified LV5FU2 before and after surgery. The primary objective was a combined evaluation of the tumor objective response (TOR), assessed by computed tomography, and the absence of major toxicities resulting in discontinuation of neoadjuvant chemotherapy (NCT) (45% and 90%, respectively). RESULTS: From 2011 to 2013, 65 patients were enrolled. From 64 patients evaluable for the primary endpoint, 19 (29.7%) had a morphological TOR and 61 (95.3%) did not stop NCT prematurely due to major toxicity. Sixty patients (92.3%) underwent resection. Sixteen patients (/56 available, 28.5%) had histological responses (Mandard tumor regression grade ≤3). After a median follow-up of 44.5 months, median disease-free and overall survival were 24.4 [95% CI: 16.4-39.4] and 40.3 months [95% CI: 27.5-NA], respectively. CONCLUSION: Adding cetuximab to the NCT regimen in operable G/GEJ adenocarcinomas is safe, but did not show enough efficacy in the present study to meet the primary endpoint (NCT01360086).

Optimizing Patient Pathways in Advanced Biliary Tract Cancers: Recent Advances and a French Perspective.

Biliary tract cancers (BTCs) are a heterogeneous group of tumors that are rare in Western countries and have a poor prognosis. Three subgroups are defined by their anatomical location (intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma and gallbladder carcinoma) and exhibit distinct clinical, molecular, and epidemiologic characteristics. Most patients are diagnosed at an advanced disease stage and are not eligible for curative-intent resection. In addition to first- and second-line chemotherapies (CisGem and FOLFOX, respectively), biologic therapies are now available that target specific genomic alterations identified in BTC. To date, targets include alterations in the genes for isocitrate dehydrogenase (IDH) 1, fibroblast growth factor receptor (FGFR) 2, v-raf murine sarcoma viral oncogene homolog B1 (BRAF), human epidermal growth factor receptor 2 (HER2 or ERRB2), and neurotrophic tyrosine receptor kinase (NTRK), and for those leading to DNA mismatch repair deficiency. Therapies targeting these genomic alterations have demonstrated clinical benefit for patients with BTC. Despite these therapeutic advancements, genomic diagnostic modalities are not widely used in France, owing to a lack of clinician awareness, local availability of routine genomic testing, and difficulties in obtaining health insurance reimbursement. The addition of durvalumab, a monoclonal antibody targeting the immune checkpoint programmed cell death ligand-1, to CisGem in the first-line treatment of advanced BTC has shown an overall survival benefit in the TOPAZ-1 trial. Given the high mortality rates associated with BTC and the life-prolonging therapeutic options now available, it is hoped that the data presented here will support updates to the clinical management of BTC in France.

Second-line therapy for advanced hepatocellular carcinoma with regorafenib or cabozantinib: Multicenter French clinical experience in real-life after matching.

BACKGROUND: Starting a second-line systemic treatment for hepatocellular carcinoma (HCC) is a common situation. The only therapeutic options in France are two broad-spectrum tyrosine kinase inhibitors (TKIs), regorafenib (REG) and cabozantinib (CBZ), but no comparative real-life studies are available. AIM: To evaluate the progression-free survival (PFS) of patients treated with REG or CBZ, we investigated the disease control rate (DCR), overall survival (OS), and safety of both drugs. To identify the variables associated with disease progression over time. METHODS: A retrospective multicenter study was performed on the clinical data of patients attending one of three referral centers (Avignon, Marseille, and Nice) between January 2017 and March 2021 using propensity score matching. PFS and OS were assessed using the Kaplan-Meier method. Multivariate analysis (MA) of progression risk factors over time was performed in matched-pair groups. RESULTS: Fifty-eight patients 68 (62-74) years old with HCC, Barcelona clinic liver cancer (BCLC) B/C (86%), Child-Pugh (CP)-A/B (24%) received REG for 3.4 (1.4-10.5) mo as second-line therapy. Twenty-eight patients 68 (60-73) years, BCLC B/C (75%), CP-A/B (25%) received CBZ for 3.7 (1.8-4.9) mo after first-line treatment with sorafenib [3 (2-4) (CBZ) vs 4 (2.9-11.8) mo (REG), P = 0.0226]. Twenty percent of patients received third-line therapy. After matching, PFS and DCR were not significantly different after a median follow-up of 6.2 (2.7-11.7) mo (REG) vs 5.2 (4-7.2) mo (CBZ), P = 0.6925. There was no difference in grade 3/4 toxicities, dose reductions, or interruptions. The OS of CP-A patients was 8.3 (5.2-24.8) vs 4.9 (1.6-11.7) mo (CP-B), P = 0.0468. The MA of risk factors for progression over time identified C-reactive protein (CRP) > 10 mg/L, neutrophil-to-lymphocyte ratio (NLR) > 3, and aspartate aminotransferase (AST) > 45 IU as predictive factors. CONCLUSION: This multicenter indirect comparative study found no significant difference in PFS between REG and CBZ as second-line therapy for advanced HCC. Elevated levels of inflammatory markers (CRP and NLR) and AST were associated with non-control of TKIs over time. A 2-mo online progression risk calculation is proposed.

Response to immunotherapy plus anti-angiogenic agent combination challenges hepatocellular carcinoma prognostic scores.

This new UHPI score identifies three groups with different prognosis, but with no clear therapeutic guidance. Moreover, this model's predictive ability is now challenged in the era of combination therapies where durable responses are more commonly observed, and where response criteria remain to be defined.

Expected outcomes and patients' selection before chemoembolization-"Six-and-Twelve or Pre-TACE-Predict" scores may help clinicians: Real-life French cohorts results.

BACKGROUND: Careful selection of hepatocellular carcinoma (HCC) patients prior to chemoembolization treatment is a daily reality, and is even more necessary with new available therapeutic options in HCC. AIM: To propose two new models to better stratify patients and maximize clinical benefit: "6 and 12" and "pre/post-TACE-predict" (TACE, transarterial chemoembolization). METHODS: We evaluated and compared their performance in predicting overall survival with other systems {Barcelona Clinic Liver Cancer (BCLC), Albumin-Bilirubin (ALBI) and NIACE [Number of tumor(s), Infiltrative HCC, alpha-fetoprotein, Child-Pugh (CP), and performance status]} in two HCC French cohorts of different stages enrolled between 2010 and 2018. RESULTS: The cohorts included 324 patients classified as BCLC stages A/B (cohort 1) and 137 patients classified as BCLC stages B/C (cohort 2). The majority of the patients had cirrhosis with preserved liver function. "Pre-TACE-predict" and "6 and 12" models identified three distinct categories of patients exhibiting different prognosis in cohort 1. However, their prognostic value was no better than the BCLC system or NIACE score. Liver function based on CP and ALBI grades significantly impacted patient survival. Conversely, the "post-TACE-predict" model had a higher predictive value than other models. The stratification ability as well as predictive performance of these new models in an intermediate/advanced stage population was less efficient (cohort 2). CONCLUSION: The newly proposed "Pre-TACE-predict" and "6 and 12" models offer an interesting stratification into three categories in a recommended TACE population, as they identify poor candidates, those with partial control and durable response. The models' contribution was reduced in a population with advanced stage HCCs.

"Six-and-twelve" score for outcome prediction of hepatocellular carcinoma following transarterial chemoembolization. In-depth analysis from a multicenter French cohort.

The "six-and-twelve" (6&12) score is a new hepatocellular carcinoma (HCC) prognostic index designed for recommended transarterial chemoembolization (TACE) candidates. Quick and easy to use by the sum of tumor size (cm) and number, this model identifies three groups with different survival time (the sum is ≤ 6; or > 6 but ≤ 12; or > 12); a survival benefit with TACE can be expected for HCC patients with a score not exceeding twelve. Recently, Wang ZW et al showed that the "6&12" model was the best system correlated with radiological response after the first TACE. Thus, we wanted to assess its survival prediction ability as well as its prognostic value and compared it to other systems (Barcelona Clinic Liver Cancer, Hong Kong Liver Cancer (HKLC) staging, Albumin-Bilirubin grade, tumor nodularity, infiltrative nature of the tumor, alpha-fetoprotein, Child-Pugh class, and Performance Status score, Cancer of the Liver Italian Program, Model to Estimate Survival for HCC scores, up-to-seven criteria) different from Wang ZW et al study in a multicenter French cohort of HCC including only recommended TACE candidates retrospectively enrolled. As previously demonstrated, we show that the "6&12" score can classify survival within this French cohort, with a prognostic value comparable to that of other systems, except HKLC staging. More importantly, the "6&12" score simplicity and ability in patients' stratification outperform other systems for a routine clinical practice.

Sorafenib: Experience and Better Manage-ment of Side Effects Improve Overall Survival in Hepatocellular Carcinoma Patients: A Real-Life Retrospective Analysis.

BACKGROUND: Sorafenib is the first-line treatment for advanced hepatocellular carcinoma (HCC). The management of its side effects is improving. This study aimed to assess, in real life, if this translates into a better prognosis. METHODS: This was a retrospective study of advanced HCC patients treated with sorafenib between 2007 and 2017. RESULTS: 188 advanced HCC patients received > 4 weeks of sorafenib. Median treatment duration was 5.4 months and median overall survival (mOS) 10 months (95% confidence interval 15-27). Sorafenib was initiated in 65 patients in 2007-2012 and 123 in 2013-2017. Both groups were comparable except for Barcelona Clinic liver cancer class. Tumor progression, disease control (DC) rate, and incidence of toxicity were similar in the 2 periods, but the duration of treatment (4.3 vs. 5.9 months; p < 0.01) and mOS (8 vs. 12 months; p < 0.002) differed. Among progressive disease patients, mOS was similar (7 months) but for those who had DC at 8 weeks, mOS was longer in the recent period (13 vs. 27 months; p < 0.0001). In the univariate analysis of OS, the period of treatment had a prognostic value. CONCLUSION: When comparing 2 periods of treatment in advanced HCC patients under sorafenib, duration of treatment and mOS were higher in the recent period. While mOS did not differ for patients who progressed, it was 2-fold higher in the recent period for those who had tumor control. Improvements in the use of sorafenib seem to be associated with better outcomes limited to patients with DC.

NIACE score refines the overall survival of hepatocellular carcinoma by Barcelona clinic liver cancer staging.

BACKGROUND AND AIM: The NIACE score provides prognostic values for hepatocellular carcinoma (HCC) in European studies. We aim to evaluate the prognostic value of the NIACE score in Asian patients. METHODS: Patients with HCC were retrospectively enrolled from a tertiary medical center in Taiwan during 2009-2014, and their clinical information were collected. The NIACE score was calculated according to the Nodular numbers, tumor Infiltration, Alpha-fetoprotein level, Child-Pugh score, and Eastern Cooperative Oncology Group score. The prognostic values of NIACE score for overall survival according to individual treatment and the Barcelona clinic liver cancer (BCLC) staging were analyzed. RESULTS: A total of 468 patients were included with a median follow-up of 30 months. A greater NIACE score correlated with lower median survival and higher BCLC staging. Regardless of treatment modalities, NIACE scores (0, 1-1.5, 2.5-3, and 4-7) significantly predicted survival between groups (log-rank P < 0.001). Specifically, NIACE score (0, 1-1.5, 2.5-3, and 4-7) significantly predicted survival in patients receiving transarterial chemoembolization (log-rank P < 0.001). NIACE score 1, 2.5, and 4 further distinguished overall survival in BCLC A, B, and C patients, respectively (all log-rank P < 0.01). After adjustment of the confounders and the BCLC staging, NIACE score of 2.5-3 and 4-7 (vs 0) had a significantly increased risk of mortality with a hazard ratio of 4.04 (95% confidence interval: 2.14-7.64, P < 0.001) and 7.45 (95% confidence interval: 3.22-17.23, P < 0.001), respectively. CONCLUSIONS: The NIACE score helps refine differential prognosis among BCLC A, B, and C subgroups of Asian patients with HCC, especially in those receiving transarterial chemoembolization.

Hepatocellular carcinoma macroscopic gross appearance on imaging: predictor of outcome after transarterial chemoembolization in a real-life multicenter French cohort.

BACKGROUND: Conventional transarterial chemoembolization (cTACE) with lipiodol is widely performed in patients with hepatocellular carcinoma (HCC) unsuitable for curative treatment. Additional tumor parameters such as HCC macroscopic appearance based on imaging might be helpful for transarterial chemoembolization prognostication and management. PATIENTS AND METHODS: A total of 405 patients with HCC who underwent cTACE between 2008 and 2016 from a real-life multicenter French cohort were retrospectively reviewed. Tumors were classified into two macroscopic types according to HCC gross appearance on imaging: nodular versus non-nodular. The study population was stratified into two groups: derivation and validation cohorts. Independent prognostic factors of survival based on multivariate cox regression models were determined and then assessed in the validation set. Thereafter, time to progression (TTP) and radiological response rate were investigated for each prognostic factors of survival. RESULTS: Median overall survival (OS) was 35 months for Barcelona Clinic Liver Cancer (BCLC) stage A, 22 months for BCLC stage B and 12 months for BCLC stage C patients (P < 0.0001). The corresponding TTP for these patients was 12 (7-17) months, 5 (3-6) months and 1.2 (1.2-3) months (P < 0.0001). Multivariate analysis revealed that tumors size and number, non-nodular type, alpha-fetoprotein, aspartate aminotransferase serum levels and impairment of performance status-1 were independent predictors of survival among the study groups. Non-nodular type was the most powerful factor that influences OS, TTP and radiological response rate for the recommended transarterial chemoembolization candidates. TTP was consistent with OS within each stage. CONCLUSION: HCC macroscopic appearance on imaging is a determinant predictor of outcome after cTACE in a real-life multicenter cohort.

Sofosbuvir, velpatasvir and voxilaprevir: a new triple combination for hepatitis C virus treatment. One pill fits all? Is it the end of the road?

The advent of oral direct-acting antiviral agents (DAAs) has dramatically improved the hepatitis C virus (HCV) treatment landscape in the last 4 years, providing cure rates over 95% with a shorter duration of treatment and a very good safety profile. This has enabled access to treatment in nearly all HCV infected patients. The launch of two pangenotypic fixed dose combinations (FDCs) in 2017 made a new step forward in HCV treatment by slightly increasing efficacy and more importantly allowing the treatment of patients without HCV genotyping, and in some cases without fibrosis assessment. However, retreatment of the few DAA failure patients was still an issue for some HCV genotypes. The launch of the triple regimen FDC, sofosbuvir/velpatasvir/voxilaprevir, solves this issue by providing a cure rate over 96% regardless of HCV genotype. In this review, we describe the current HCV treatment landscape and focus on the development of this triple FDC either in treatment-naïve or treatment-experienced patients with previous failure on a DAA regimen.

[Hepatocellular carcinoma: Increase in incidence or future plague?] / Épidémiologie du carcinome hépatocellulaire : simple augmentation d'incidence ou futur drame ?

Hepatocellular carcinoma is the third most frequent cause of cancer death worldwide, particularly in Asia and Africa. Most cases complicate an underlying liver cirrhosis due to hepatitis B or C chronic virus infection or alcoholic abuse. But, following the current epidemics of obesity and type 2 diabetes, it appears that these diseases, associated in metabolic syndrome, are responsible for non alcoholic fatty liver disease at risk of HCC frequently before the stage of cirrhosis. Recent hypotheses consider that in the near future, cancer deaths due to HCC will overpass in USA those due to breast or colorectal cancers. Governments should develop policies to prevent obesity, type 2 diabetes and the metabolic syndrome as well as fight against alcoholism and hepatitis B and C virus infections.

Hepatocellular carcinoma recurrence in hepatitis C virus-related cirrhosis treated with direct-acting antivirals: a case-control study.

BACKGROUND: Direct-acting antivirals (DAAs) therapy against hepatitis C viral (HCV) infection has markedly improved the sustained viral response. However, recent studies have suggested an unsuspected high rate of hepatocellular carcinoma (HCC) recurrence. PATIENTS AND METHODS: A retrospective case-control study was carried out to investigate the impact of DAAs on tumor recurrence in patients with complete response to HCC treatment within our HCV-related cirrhosis cohort. Patients who received [group 1 (G1), n=22] or not [group 2 (G2), n=49] a DAAs therapy were matched 1 : 2 for age, sex, liver function, HCC stage, and treatment. RESULTS: Initial HCC were mostly Barcelona Clinic Liver Cancer stage A (95% G1, 94% G2). Sustained viral response with DAAs was achieved in 86% of patients. After a similar median overall follow-up time with similar radiologic surveillance after HCC treatment, 41% of patients developed radiologic tumor recurrence in G1 versus 35% of patients in G2 (P=0.7904). There was no significant difference in time to progression between the two groups [12 (9-16) months G1 vs. 14 (8-21) months G2, P=0.7688], or Barcelona Clinic Liver Cancer stage at recurrence. However, the interval between HCC treatment and antiviral therapy was significantly different among DAAs patients with recurrence and those without recurrence [7.0 (2.5-9.0) months vs. 36.0 (9.0-58.0) months, P=0.0235, respectively]. CONCLUSION: In our case-control study, HCV therapy with DAAs does not accelerate or prevent early HCC recurrence compared with untreated patients. The rate of recurrence, time to progression, and HCC pattern are similar. Early DAAs treatment (<12 months) after HCC cure should be discouraged considering the HCC recurrence rate during this period.

[Hepatitis B virus infection: control or cure?] / Hépatite B : contrôler ou guérir ?

Hepatitis b virus infection: control or cure? Hepatitis B virus infection remains a global public health issue with changing epidemiology due to several factors including vaccination policies and migration. Approximately 254 million individuals are chronic HBsAg carrier worldwide including around 300 000 individuals in France. Host immune response plays a key role in hepatitis B pathogenesis and clinical manifestations. Hepatitis B screening should be performed in all individual with risk factors and in patients with elevated ALT. Hepatitis B vaccination should be implemented at birth or during early childhood and in individuals with risk factors. The needs for curative treatment depend mainly on the stage of the disease. Current HBV treatment are based on long term use of nucleos(t)ide analogue and rarely on the use of finite duration of pegylated interferon. The endpoints of therapy are long-term suppression of HBV replication, biochemical response and optimally durable loss of HBsAg and anti-HBs seroconversion. Current and future research aim to develop combination with antiviral therapy targeting multiple steps in the HBV lifecycle that rapidly suppress viral replication and viral antigen production and immune modulatory therapy to restore immune response to HBV in order to achieve the goal of HBV cure.

Hépatite b : contrôler ou guérir ? L'infection par le virus de l'hépatite B (VHB) est un problème majeur de santé publique. avec 254 millions de personnes porteuses de ce virus dans le monde et près de 300 000 en France. Le rôle de la réponse immunitaire est essentiel au cours de l'infection par le VHB et responsable de l'essentiel des lésions hépatiques et des manifestations cliniques. Le dépistage de l'hépatite chronique, qui est le plus souvent asymptomatique, doit être fait devant tout sujet ayant des facteurs de risque de contamination et devant toute augmentation des transaminases. La vaccination, qui est très efficace, doit être effectuée de façon systématique dans la petite enfance et chez les patients ayant des facteurs de risque de contamination. La nécessité du traitement dépend essentiellement de la phase de l'histoire naturelle du VHB où se situe le patient. Le traitement actuel de l'hépatite chronique B repose essentiellement sur un traitement prolongé par les analogues nucléosidiques ou nucléotidiques et plus rarement par un traitement de durée finie par l'interféron alpha pégylé. L'objectif de ces traitements est d'obtenir une virosuppression prolongée, une réponse biochimique et, de façon optimale, une perte de l'antigène HBs et une séroconversion anti-HBs durable, définissant la guérison fonctionnelle. Les recherches actuelles visent à développer de nouveaux antiviraux directs et des traitements immunomodulateurs dont les combinaisons permettront peutêtre d'obtenir une guérison de l'hépatite B.