Double guidewire endoscopic technique, a major evolution in endoscopic retrograde cholangiopancreatography: Results of a retrospective study with historical controls comparing two therapeutic sequential strategies.

BACKGROUND AND AIM: Endoscopic access to the common bile duct (CBD) remains difficult in 10% of cases, requiring alternative techniques .CBD access was difficult after either five unsuccessful attempts, five unintentional insertions into the pancreatic duct or >10-min-long unsuccessful attempts. This retrospective study with historical controls aimed to evaluate the benefit of the double guidewire (DGW) technique after failure of standard CBD cannulation. METHODS: From January 2012 to December 2014, all patients requiring therapeutic endoscopic retrograde cholangiopancreatography (ERCP) with difficult access to CBD were included in a Studied group. This group was compared to a historical ERCP control group from January 2009 to December 2011. In the Studied group, a sequential strategy including DGW technique was done when the guidewire was unintentionally passed into the pancreatic duct. In the control group, only pre-cut technique was used. RESULTS: Among the 538 patients with naive papilla eligible for ERCP, 73 had difficult CBD access. Successful CBD access rate was higher in the Studied group: 91% (50/55) versus 67% (12/18) P = 0.0215. Complication rates were similar in both groups: 28% versus 20%, P = 0.5207. LOS was shorter in the Studied group (9.2 ± 8.5 vs 14.4 ± 7.4 days, P = 0.0028). Post-ERCP cholangitis were lower in the Studied group: 2% (1/55) versus 22% (4/18), P = 0.0118. CONCLUSION: After standard cannulation failure, DGW technique increased successful CBD access rate and decreased LOS without increasing complications.

Retreatment with TACE: the ABCR SCORE, an aid to the decision-making process.

BACKGROUND & AIMS: Transarterial chemoembolization (TACE) is the standard of care for intermediate stage hepatocellular carcinoma (HCC) and it is the most commonly used treatment for HCC worldwide. However, no prognostic indices, designed to select appropriate candidates for repeat conventional TACE, have been incorporated in the guidelines. METHODS: From January 2007 to April 2012, 139 consecutive HCC patients, mainly with an alcohol- or viral-induced disease, were treated with TACE. Using a regression model on the prognostic variables of our population, we determined a score designed to help for repeat TACE and we validated it in two cohorts. We also compared it to the ART score. RESULTS: In the multivariate analysis, four prognostic factors were associated with overall survival: BCLC and AFP (>200 ng/ml) at baseline, increase in Child-Pugh score by ⩾2 from baseline, and absence of radiological response. These factors were included in a score (ABCR, ranging from -3 to +6), which correlates with survival and identifies three groups. The ABCR score was validated in two different cohorts of 178 patients and proofed to perform better than the ART score in distinguishing between patients' prognosis. CONCLUSIONS: The ABCR score is a simple and clinically relevant index, summing four prognostic variables endorsed in HCC. An ABCR score ⩾4 prior to the second TACE identifies patients with dismal prognosis who may not benefit from further TACE sessions.

How to optimize current therapy of HCV genotype 1 infection with boceprevir.

Treatment with first generation protease inhibitors (PIs) is a milestone in the history of HCV therapy. Triple therapy with boceprevir (BOC) improves sustained virological response (SVR) by 30% in treatment naïve genotype 1 patients and by 50-60% in relapsers, 40-45% in partial responders and 25% in null responders compared with the Pegylated Interferon (PEG-IFN) and ribavirin regimen. To optimize BOC treatment, screening and access to treatment must be improved in genotype 1 patients. To select the ideal candidate for immediate treatment with triple therapy, an individual risk/benefit ratio must be assessed. Recent data have shown that patients with compensated cirrhosis and more advanced disease may also benefit from this regimen. Moreover, in HCV patients with extrahepatic manifestations, patients with HCV recurrence after liver transplantation and HIV-HCV co-infected patients, immediate treatment with triple therapy should be discussed. There is growing evidence that triple therapy with BOC is cost-effective in genotype 1 patients. Finally, the treatment design of BOC must be optimized in relation to baseline characteristics, so that optimal stopping rules can be followed, Drug-drug interactions (DDIs) can be prevented and AEs can be accurately prevented and managed.

Outcomes and safety of atezolizumab plus bevacizumab in the treatment of hepatocellular carcinoma: treatment prognosis and comparison with tyrosine kinase inhibitors in a French multicenter matched real-life study.

BACKGROUND AND AIMS: The combination of atezolizumab plus bevacizumab (Atz/Bev) has radically changed the treatment strategy for advanced hepatocellular carcinoma (HCC) but raises questions. Our objectives were to determine survival outcomes and safety in a real-life multicenter French cohort, to investigate the on-treatment prognostic value of the bioinflammatory RECA score, and to perform a matched comparison with patients who previously received tyrosine kinase inhibitors (TKIs). METHODOLOGY: A retrospective analysis of 109 consecutive patients enrolled from September 2020 to January 2023 and a post matched comparison with a TKI cohort (n = 79) by the propensity score matching method. RESULTS: The Atz/Bev population was mainly nonviral disease patients (69%) with Child-Pugh grade A (90%), performance status 0/1 (90%), and Barcelona Clinic Liver Cancer stage B (38%) or stage C (62%) classification. After a median follow-up of 6.5 months (3.6-11.7), overall survival (OS) was 13.0 (5.1-28.7) months. OS was independently associated with metastasis, increased alkaline phosphatase, and serum bilirubin levels. Treatment-related adverse events were reported in 78% of patients, mostly grade 1 or 2. The RECA score clearly revealed two different prognosis groups after three cycles. No difference in OS was observed after matching between sequential treatment with TKIs and Atz/Bev. CONCLUSION: This real-life study highlights the importance of liver function when using Atz/Bev combination and the necessity of identifying predictive markers of response to HCC therapies. Our findings suggest a change in practices, with a marked proportion of intermediate stages, and support the on-treatment prognostic value of an inflammatory score.

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.

Future treatment of patients with HCV cirrhosis.

Of all hepatitis C virus (HCV) patients, those with cirrhosis are most in need of treatment because of increased morbidity and mortality. Treatment with pegylated-interferon (PEG-IFN) and ribavirin (RBV) (PR) has definitely shown the benefits of successful treatment by improving fibrosis, causing the regression of cirrhosis and reducing and preventing cirrhosis-related complications. However, the sustained virological response (SVR) is lower in patients with cirrhosis. First generation protease inhibitors (boceprevir and telaprevir) in combination with PR are a major advancement in the treatment of both naïve and treatment-experienced genotype 1 patients. In naïve patients, the SVR rate with the triple regimen with boceprevir was increased by 14% in patients with severe fibrosis or cirrhosis compared with PR. This benefit was lower than that observed in patients with mild or moderate fibrosis (30%). The SVR rate of the triple regimen with telaprevir was increased by 10-30% compared with PR in patients with severe fibrosis or cirrhosis compared with nearly 30% in patients with mild or moderate fibrosis. In treatment-experienced patients, previous relapsers have the highest increase in SVR with the triple regimen compared with PR, whatever the status of fibrosis. Previous partial or non-responder patients with cirrhosis had lower SVR rates than those without cirrhosis. However, the benefits of telaprevir and boceprevir vs PR was maintained. Previous non-responder patients with cirrhosis benefited the least from treatment. The relapse rate was always higher and side effects were more frequent in patients with cirrhosis compared with those without. First generation protease inhibitors plus PR appear to be a new step forward in the management of HCV genotype 1 patients with cirrhosis.

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.

[Treatment of hepatitis C]. / Traitement de l'hépatite C.

Hepatitis C treatment has made a lot of progress in the last two decades. Treatment with pegylated interferon and ribarin is associated with sustained virological response in more than 50% of patients. This improvement is due in one part to the adaptation of treatment dose and duration according to genotype, liver fibrosis and response-guided therapy, fibrosis in another part to a better pretreatment management of co-morbidities and a better prevention and management of side effects. New direct antiviral agents will become soon available and will lead to an improvement of sustained virological response with maybe more complex therapy leading to a new management of patients.

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.

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.

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 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.

NIACE score for hepatocellular carcinoma patients treated by surgery or transarterial chemoembolization.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) prognostic scores could be useful in addition to the Barcelona Clinic Liver Cancer (BCLC) system to clarify patient prognosis and guide treatment decision. The NIACE (tumor Nodularity, Infiltrative nature of the tumor, serum Alpha-fetoprotein level, Child-Pugh stage, ECOG performance status) score distinguishes different prognosis groups among BCLC A, B, and C HCC patients. Our aims are to evaluate the NIACE score and its additive value in two HCC cohorts treated either by surgery or by chemoembolization, and then according to the BCLC recommendations. PATIENTS AND METHODS: This was a retrospective multicenter study with two BCLC A, B, and C HCC cohorts treated either by surgery (n=207) or by chemoembolization (n=168) carried out between 2008 and 2013. We studied survival time according to the baseline NIACE score and compared it with the Cancer of the Liver Italian Program score and the BCLC system. RESULTS: The NIACE score differentiates between subgroups of patients with different prognosis within each BCLC class. Among BCLC A patients treated by surgery and BCLC B patients treated by chemoembolization, the NIACE score differentiates between two subgroups with a significant difference in survival time: 68 (55-81) months versus 35 (21-56) months (P=0.0004) and 20 (17-24) months versus 13 (7-17) months (P=0.0008), respectively. Among those subgroups, the NIACE score has a significantly better prognostic value than the BCLC system or the Cancer of the Liver Italian Program score. CONCLUSION: In this study, among HCC patients treated according to the BCLC recommendations, the NIACE score predicts more accurately than any other system the survival time.

Barcelona clinic liver cancer nomogram and others staging/scoring systems in a French hepatocellular carcinoma cohort.

AIM: To compare the performances of the Barcelona clinic liver cancer (BCLC) nomogram and others systems (BCLC, HKLC, CLIP, NIACE) for survival prediction in a large hepatocellular carcinoma (HCC) French cohort. METHODS: Data were collected retrospectively from 01/2007 to 12/2013 in five French centers. Newly diagnosed HCC patients were analyzed. The discriminatory ability, homogeneity ability, prognostic stratification ability Akaike information criterion (AIC) and C-index were compared among scoring systems. RESULTS: The cohort included 1102 patients, mostly men, median age 68 [60-74] years with cirrhosis (81%), child-Pugh A (73%), alcohol-related (41%), HCV-related (27%). HCC were multinodular (59%) and vascular invasion was present in 41% of cases. At time of HCC diagnosis BCLC stages were A (17%), B (16%), C (60%) and D (7%). First line HCC treatment was curative in 23.5%, palliative in 59.5%, BSC in 17% of our population. Median OS was 10.8 mo [4.9-28.0]. Each system distinguished different survival prognosis groups (P < 0.0001). The nomogram had the highest discriminatory ability, the highest C-index value. NIACE score had the lowest AIC value. The nomogram distinguished sixteen different prognosis groups. By classifying unifocal large HCC into tumor burden 1, the nomogram was less powerful. CONCLUSION: In this French cohort, the BCLC nomogram and the NIACE score provided the best prognostic information, but the NIACE could even help treatment strategies.

[Sarcoidosis following pegylated interferon therapy: two cases]. / Sarcoïdose chez deux malades traités par interféron pégylé pour une hépatite chronique C.

One side effect of the immunomodulatory effect of interferon is the possible triggering or exacerbation of systemic or cutaneous sarcoidosis. We report two new cases and offer an exhaustive review of the literature. A 39-year-old man with type C chronic active hepatitis developed new respiratory symptoms and pulmonary infiltrates with hilar and mediastinal adenopathy after 7 months of treatment with pegylated interferon. The evolution was favourable after stopping treatment. The second patient developed cutaneous lesions after 6 months of treatment. Resolution occurred after the discontinuation of the treatment. In these two cases ribavirin was stopped before the first signs of sarcoidosis.

Usefulness of staging systems and prognostic scores for hepatocellular carcinoma treatments.

Therapeutic management of hepatocellular carcinoma (HCC) is quite complex owing to the underlying cirrhosis and portal vein hypertension. Different scores or classification systems based on liver function and tumoral stages have been published in the recent years. If none of them is currently "universally" recognized, the Barcelona Clinic Liver Cancer (BCLC) staging system has become the reference classification system in Western countries. Based on a robust treatment algorithm associated with stage stratification, it relies on a high level of evidence. However, BCLC stage B and C HCC include a broad spectrum of tumors but are only matched with a single therapeutic option. Some experts have thus suggested to extend the indications for surgery or for transarterial chemoembolization. In clinical practice, many patients are already treated beyond the scope of recommendations. Additional alternative prognostic scores that could be applied to any therapeutic modality have been recently proposed. They could represent complementary tools to the BCLC staging system and improve the stratification of HCC patients enrolled in clinical trials, as illustrated by the NIACE score. Prospective studies are needed to compare these scores and refine their role in the decision making process.

Clinical relevance of the HCV protease inhibitor-resistant mutant viral load assessed by ultra-deep pyrosequencing in treatment failure.

BACKGROUND: The detection of low frequency mutants in patients with hepatitis C virus (HCV) receiving direct-acting antivirals (DAAs) is still debated. The clinical relevance of the mutant viral load has not yet been evaluated. OBJECTIVES: To assess the viral load of resistance associated variants (RAVs) in patients at different time points, including the baseline, virological failure and one year after the cessation of therapy. STUDY DESIGN: The study included 22 patients who were previously treated with protease inhibitors (PI) (with telaprevir and boceprevir). For each patient, three time points were assessed using ultra-deep pyrosequencing (UDPS). RESULTS: Baseline mutations were observed in 14/22 patients (64%). At virological failure, RAVs were detected in 18/22 patients (82%). Persistent RAVs were observed in four HCV GT 1a patients (18%). Persistence mutations were found only in HCV GT 1a patients. The baseline relative V36M, R155K, R155T and A156T mutation load of patients with persistent RAVs was significantly higher (P<0.001) than those of patients without persistent RAVs. CONCLUSION: The UDPS follow-up analysis demonstrated that the presence of BOC or TLP-RAVs persist one year after therapy cessation only in HCV GT 1a patients. The relative mutant viral load should be considered prior to any PI based re-treatment. This concept of the baseline mutation viral load must be validated using current therapy and must be validated on a larger cohort.

Management of gastric varices: a French national survey.

BACKGROUND AND AIMS: Bleeding from gastric varices is more severe than that from esophageal varices, but its management remains debated. We aimed to determine how French hepatogastroenterologists manage cirrhotic patients with gastric varices. METHODS: Hepatogastroenterologists (n=1163) working in general or university hospitals received a self-administered questionnaire. RESULTS: Overall, 155 hepatogastroenterologists (13.3%) from 112 centers (33.3%; 39/40 university hospitals, 73/296 general hospitals) answered. Primary prophylaxis was used by 98.1% of hepatogastroenterologists as follows: ß-blockers 96.1% (93.8 vs. 97.0%; university vs. general hospitals respectively; P=0.57), glue obliteration 16.9% (17.2 vs. 16.3%; P=0.88), and transjugular intrahepatic portosystemic shunt (TIPS) 8.0% (12.7 vs. 4.6%; P=0.12). To manage bleeding, university hospitals had greater local access to glue obliteration (95.4 vs. 68.2%; P<0.001) and TIPS (78.5 vs. 3.5%; P<0.001). Early TIPS was proposed by 53.6% (72.1 vs. 39.2%; P<0.001). Glue obliteration was performed under general anesthesia (86.1%) using Glubran (43.1%) or Histoacryl (52.9%), and lipiodol (78.8%) with varying degrees of dilution (1 : 10 to 3 : 4). The injected volume per varix varied widely (1-20 ml). Glue obliteration, band ligation, or both were used by, respectively, 64.2, 18.2, and 17.5% of practitioners. Almost all hepatogastroenterologists (98%) performed secondary prophylaxis: ß-blockers 74.7% (75.0 vs. 74.4%, university vs. general hospitals; P=0.93), glue obliteration 66.0% (76.9 vs. 57.6%; P=0.013), and TIPS 30.0% (39.1 vs. 23.3%; P=0.037). CONCLUSION: The management of gastric varices in France is heterogeneous across centers. University hospitals have better access to techniques such as glue obliteration and TIPS. As bleeding from gastric varices has a poor outcome, guidelines should be established to standardize clinical practices and design further studies.

Prognosis of advanced hepatocellular carcinoma: a new stratification of Barcelona Clinic Liver Cancer stage C: results from a French multicenter study.

BACKGROUND: Advanced hepatocellular carcinoma (HCC) includes a wide spectrum of tumors and patients' prognosis after treatment is highly variable. Moreover, therapeutic options based on the Barcelona Clinic Liver Cancer (BCLC) staging system algorithm are restricted to one systemic therapy. AIM OF THE STUDY: To refine the stratification among BCLC C HCC patients by establishing a new simple prognostic score. PATIENTS AND METHODS: A regression model based on a BCLC stage C population and validated with an external cohort of BCLC C HCC patients defined the score. It was therefore validated among three external cohorts of BCLC C HCC patients treated with sorafenib. RESULTS: Five variables had independent prognostic values: the number of nodules, the infiltrating nature of the HCC, α-fetoprotein serum level, Child-Pugh score, and Eastern Cooperative Oncology Group Performance Status grade. They were integrated into a new score named NIACE ranging from 0 to 7, well correlated with survival. With the use of one threshold value, this score enables defining of two populations with different survivals among BCLC C patients and specifically among those treated with sorafenib. CONCLUSION: The NIACE score defines different prognostic subgroups after palliative treatment of HCC. It could be an additional tool for BCLC C HCC before inclusion in clinical trials or for the management of patients. These results must be validated in a prospective study.