The risk of hepatocellular carcinoma decreases after the first 5 years of entecavir or tenofovir in Caucasians with chronic hepatitis B

Papatheodoridis, George V.; İdilman, Ramazan; Dalekos, George Ν.; Buti, María; Chi, Heng; Boemmel, Florian van; Calleja, José Luís; Sypsa, Vana; Goulis, John; Manolakopoulos, Spilios; Loglio, Alessandro; Siakavellas, Spyros I.; Keskın, Onur; Gatselis, Nikolaos; Hansen, Bettina E.; Lehretz, Maria; Revilla, Juan de la; Savvidou, Savvoula; Κourikou, Αnastasia; Vlachogiannakos, Jiannis; Galanis, Kostantinos; Yurdaydın, Cihan; Berg, Thomas; Colombo, Massimo; Esteban, Rafael; Janssen, Harry L.A.; Lampertico, Pietro

doi:10.1002/hep.29320

Cited by 259 publications

(261 citation statements)

References 30 publications

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“… • All independent predictive factors for HCC occurrence were related to host conditions (age > 50 years and comorbidities represented either by obesity in the whole cohort or elevated baseline serum GGT level in the subgroup of HBV monoinfected patients) or linked to severity of the underlying cirrhosis (low platelet count), and none comprised virological markers. These results are in line with those observed in European cohorts of viral‐suppressed patients chronically infected with HBV or in patients with advanced fibrosis following hepatitis C virus eradication or more largely in Western patients • Two published HCC risk scores were validated as previously suggested in a heterogeneous population of American patients; both had 100% negative predictive values, and the most discriminant at 1 year was PAGE‐B, which is a score specifically constructed and validated in a cohort of patients living in Europe, chronically infected by HBV and mostly receiving effective antiviral treatment by nucleos(t)ide analogs …”

Section: Discussionsupporting

confidence: 81%

“…As Fibroscan was not recommended by French Guidelines at the time of inclusion in HBV chronic liver disease, especially in treated patients, a limited number of LSM was available either at baseline (n = 139) or during follow‐up (n = 44 at year 5), ruling out the opportunity to validate LSM‐HCC score and the predictive value for HCC of persistent elevated LSM under long‐term NA treatment …”

Section: Discussionmentioning

confidence: 99%

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Non‐virological factors are drivers of hepatocellular carcinoma in virosuppressed hepatitis B cirrhosis: Results of ANRS CO12 CirVir cohort

Brichler

Nahon

Zoulim

et al. 2019

Journal of Viral Hepatitis

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Summary Worldwide, hepatocellular carcinoma (HCC) occurs mainly in Asian patients with hepatitis B virus (HBV) infection. This study aimed to decipher the environmental and virological factors associated with HCC occurrence and validate risk scoring systems in a French multicentre prospective cohort of HBV cirrhotic patients. Patients with biopsy‐proven Child‐Pugh A viral cirrhosis included in the ANRS CO12 CirVir cohort who were HBsAg(+) without hepatitis C coinfection were selected for: (a) interview through a standardized questionnaire reporting coffee consumption and HCC familial history; (b) HBsAg quantification using baseline and sequential 2‐year frozen sera; (c) baseline HBV genotype determination; and (d) assessment of risk factors and applicability of HCC risk scores (Kaplan‐Meier analysis, Cox models). Among 317 patients studied (261 men, median age 53 years, past or ongoing antiviral treatment 93.3% and baseline detectable HBV DNA in 88 patients), the baseline and 2‐year median HBsAg levels were 810 and 463 IU/mL, respectively. After a median follow‐up of 65.2 months, 27 HCC cases were diagnosed (annual incidence: 1.6%). Three factors were independently associated with HCC occurrence: age > 50 years, platelets ≤ 150 × 103/mm3 and body mass index ≥ 30 kg/m2. Two out of five risk scores were validated, and the most accurate was PAGE‐B at 1 year. Moreover, HCC in patients without maintained virological suppression seems more aggressive and less accessible to curative treatment. In conclusion, in French patients with HBV cirrhosis mostly virally suppressed, independent HCC risk factors were host‐related (age, obesity) or linked to the severity of cirrhosis (thrombopenia), and the European PAGE‐B score was the most accurate risk score.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Non‐virological factors are drivers of hepatocellular carcinoma in virosuppressed hepatitis B cirrhosis: Results of ANRS CO12 CirVir cohort

Brichler

Nahon

Zoulim

et al. 2019

Journal of Viral Hepatitis

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“…Therefore, early treatment intervention may be desired for the prevention of early‐onset HCC. The administration of nucleoside/nucleotide analogs has been shown to suppress the development of HCC in adults . Although there is insufficient data on the efficacy and safety of the administration of nucleoside/nucleotide analogs to children or young people, the suppression of HBV with nucleoside/nucleotide analogs may be considered for HBV‐infected children or young people (Table ).…”

Section: Discussionmentioning

confidence: 99%

Hepatitis B virus‐related hepatocellular carcinoma in young adults: Efficacy of nationwide selective vaccination

Yotsuyanagi

Takano

Tanaka

et al. 2020

Hepatology Research

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Aim Hepatitis B vaccination in infancy was carried out in Japan only when the mother was persistently infected from 1986 to 2016. The aim of the present study was to elucidate the results of vaccination for the prevention of hepatocellular carcinoma in young adults. Methods We studied the number of patients who had liver cancer and died from 1976 to 2017 using a national database. Furthermore, we carried out a nationwide survey focusing on patients with hepatitis B virus‐related hepatocellular carcinoma who were diagnosed when aged <40 years from 2007 to 2016. Results The national database showed that the number of deaths of patients aged <40 years decreased from 337 in 1986 to 61 in 2016. Among the 122 patients with hepatocellular carcinoma (HCC) who were registered in the survey, just three patients were born after the start of the vaccination in 1986. Liver cirrhosis, defined by a high Fib‐4 index (≥3.25), was found in just 12.5% of the patients at the time of the survey. HCC was incidentally diagnosed in 85 of the 122 (69%) patients. More than 60% of the patients (54/88) were dead at the time of the study, which may be attributed to the delay in diagnosis. Conclusions Selective vaccination was effective for the prevention of hepatitis B virus‐related HCC. In contrast, many young adults who missed the chance of hepatitis B vaccination and HCC surveillance developed HCC and died. Hepatitis B virus screening in young adults and careful follow up of infected patients are important to prevent HCC development.

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“…It is unlikely that future placebo-controlled studies will be performed due to ethical reasons. However, there is increasing circumstantial evidence to suggest that long term antiviral therapy will reduce or delay HCC [100,101] . The key to antiviral therapy therefore is starting early, as the presence of advanced fibrosis and cirrhosis at the time of starting therapy is already associated with higher risk of HCC [102,103] .…”

Section: Discussionmentioning

confidence: 99%

The role of oral antiviral therapy in hepatitis B-related hepatocellular carcinoma

Fung¹,

Chok²

2017

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Hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC) in places where chronic hepatitis B infection is endemic. Oral nucleos(t)ide analog (NA) therapy can reduce the risk of HCC, but cannot completely prevent its development. For HBV-related HCCs, viral inhibition by NAs can preserve or improve liver function, thereby increasing the chance of therapeutic intervention. After surgical resection, NAs can prevent reactivation of HBV, and also reduce the chance of de novo development of HCC in the remnant liver. For those who undergo liver transplantation, NAs are essential to prevent reactivation and graft hepatitis, but is not likely to prevent HCC recurrence, which is due to metastatic disease. The role of NAs for non-curable advanced HCC is less well defined. These include patients undergoing locoregional therapy, chemotherapy, or palliation. Although antiviral therapy can preserve liver function, which may be compromised by HBV, it is unable to prevent disease progression from HCC. At the time of HCC diagnosis, most patients will already be receiving NAs, and these patients should be maintained on therapy. For patients not on antiviral therapy at the time of HCC diagnosis, the decision to commence therapy is often determined by the stage of HCC and life expectancy. Patients undergoing curative therapy, or locoregional therapy/chemotherapy with reasonable life expectancy, should be commenced on antiviral therapy. Key words:Antiviral therapy, hepatitis B virus, hepatocellular carcinoma ABSTRACTArticle history:

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The risk of hepatocellular carcinoma decreases after the first 5 years of entecavir or tenofovir in Caucasians with chronic hepatitis B

Cited by 259 publications

References 30 publications

Non‐virological factors are drivers of hepatocellular carcinoma in virosuppressed hepatitis B cirrhosis: Results of ANRS CO12 CirVir cohort

Non‐virological factors are drivers of hepatocellular carcinoma in virosuppressed hepatitis B cirrhosis: Results of ANRS CO12 CirVir cohort

Hepatitis B virus‐related hepatocellular carcinoma in young adults: Efficacy of nationwide selective vaccination

The role of oral antiviral therapy in hepatitis B-related hepatocellular carcinoma

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