HCC risk post-SVR with DAAs in East Asians: findings from the REAL-C cohort

Tanaka, Yasuhito; Ogawa, Eiichi; Huang, Chung‐Feng; Toyoda, Hidenori; Jun, Dae Won; Tseng, Cheng‐Hao; Hsu, Yao-Chun; Enomoto, Masaru; Takahashi, Hirokazu; Furusyo, Norihiro; Yeh, Ming‐Lun; Iio, Etsuko; Yasuda, Satoshi; Lam, Carla Pui-Mei; Lee, Dong Hoon; Haga, Hiroaki; Yoon, Eileen L.; Ahn, Sang Bong; Wong, Grace Lai–Hung; Nakamuta, Makoto; Nomura, Hideyuki; Tsai, Pei‐Chien; Jung, Jang Han; Song, Do Seon; Dang, Hansen; Maeda, Manabu; Henry, Linda; Cheung, Ramsey; Yuen, Man‐Fung; Ueno, Yoshiyuki; Eguchi, Yuichiro; Tamori, Akihiro; Yu, Ming‐Lung; Hayashi, Jun; Nguyen, Mindie H.; Investigators, Real-C

doi:10.1007/s12072-020-10105-2

Cited by 54 publications

(64 citation statements)

References 26 publications

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“…Although not universally recommended for HCC surveillance by international guidelines due to its low sensitivity and specificity, broad application of αFP in routine clinical practice has led many authors to investigate its potential for de-novo HCC prediction. αFP was independently associated with HCC occurrence, either in patients with cirrhosis 32 , 38 , 42 or advanced fibrosis. 44 Some studies evaluated the predictive ability of αFP assessed at baseline, 32 , 42 , 44 while others analysed the EOT time-point.…”

Section: Predictors Of De-novo Hccmentioning

confidence: 99%

“…In F3-F4 patients, Alonso Lopez et al found that both baseline FIB-4 >3.7 and FIB-4 >3.3 one year after treatment were associated with de-novo HCC 45 ( Table 7 ). Other NITs had been investigated as predictors of HCC in several studies: the albumin-bilirubin (ALBI) score grade 2–3 29 , 37 , 42 and AST to platelet (PLT) ratio index (APRI) >2.5 11 emerged as independent risk factors for de-novo HCC in patients with cirrhosis and advanced fibrosis, respectively.…”

Section: Predictors Of De-novo Hccmentioning

confidence: 99%

“…Clinical scores incorporating these parameters, such as Child-Pugh-Turcotte (CPT) 25 , 36 and Model for End Stage Liver Disease (MELD) 41 or ALBI scores 29 , 37 , 42 were independently associated with de-novo HCC in cirrhotics ( Table 7 ). Some studies provided different CumI of de-novo HCC according to the combination of one or more variables associated with portal hypertension (see below).…”

Section: Predictors Of De-novo Hccmentioning

confidence: 99%

“… 44 Some studies evaluated the predictive ability of αFP assessed at baseline, 32 , 42 , 44 while others analysed the EOT time-point. 38 Most studies tried to identify a predictive αFP cut-off: overall, the proposed cut-offs resulted always higher than the reference standard 7 ng/mL (ie, >9 or ≥10 ng/mL, >20 mg/mL) 38 , 42 , 44 ( Tables 3 and 6 ).…”

Section: Predictors Of De-novo Hccmentioning

confidence: 99%

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Predicting Hepatocellular Carcinoma Risk in Patients with Chronic HCV Infection and a Sustained Virological Response to Direct-Acting Antivirals

D’Ambrosio¹,

Degasperi²,

Lampertico³

2021

JHC

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Chronic infection with hepatitis C virus (HCV) may complicate with hepatocellular carcinoma (HCC), especially in patients with cirrhosis. Although the achievement of a sustained virological response (SVR) had been associated with a reduction in the risk of HCC already in the Interferon era, some concerns initially raised following the use of direct-acting antivirals (DAA), as their use was associated with increased risk of HCC development and aggressiveness. However, studies demonstrated that the risk of HCC was strongly influenced by pre-treatment fibrosis stage and, eventually, prior HCC history more than the type of antiviral therapy. According to published studies, rates of de-novo HCC ranged between 1.4% and 13.6% in patients with cirrhosis or advanced fibrosis vs 0.9% and 5.9% in those with chronic hepatitis C (CHC). Conversely, rates of recurrent HCC were higher, ranging between 3.2% and 49% in cirrhotics vs 0% and 40% in CHC patients. Most studies tried to identify predictors of HCC development, either de-novo or recurrent, and some authors were also able to build predictive scores for HCC risk stratification, which however still need prospective validation. Whereas some clinical features, such as age, gender, presence of comorbidities and fibrosis stage, may influence both de-novo and recurrent HCC, previous tumour burden before DAA seems to prevail over these features in recurrent HCC risk prediction.

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Section: Predictors Of De-novo Hccmentioning

confidence: 99%

Section: Predictors Of De-novo Hccmentioning

confidence: 99%

Section: Predictors Of De-novo Hccmentioning

confidence: 99%

Section: Predictors Of De-novo Hccmentioning

confidence: 99%

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Predicting Hepatocellular Carcinoma Risk in Patients with Chronic HCV Infection and a Sustained Virological Response to Direct-Acting Antivirals

D’Ambrosio¹,

Degasperi²,

Lampertico³

2021

JHC

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“…More recently, similar results have been confirmed in long-term follow-up studies. A retrospective study from East Asia, involving a large cohort of 5814 HCV patients treated with DAA and followed up for a median of 2.9 years, reported a significant reduction in HCC risk in SVR patients compared with those without SVR[ 27 ].…”

Section: Is Daa-induced Svr Associated With An Appreciable Benefit In Hcc?mentioning

confidence: 99%

Direct antiviral agents in hepatitis C virus related liver disease: Don’t count the chickens before they’re hatched

Compagnoni¹,

Bruno²,

Madonia³

et al. 2021

WJG

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Since molecules with direct-acting antiviral (DAA) became available, the landscape of the treatment of hepatitis C virus (HCV) infection has completely changed. The new drugs are extremely effective in eradicating infection, and treatment is very well tolerated with a duration of 8-12 wk. This review aims to report the outstanding clinical benefits of DAA and to highlight their critical disadvantages, identifying some clinically relevant hot topics. First, do the rates of virological response remain as high when patients with more advanced cirrhosis are considered? Large studies have shown slightly lower but still satisfactory rates of response in these patients. Nevertheless, modified schedules with an extended treatment duration and use of ribavirin may be necessary. Second, does the treatment of HCV infection affect the risk of occurrence and recurrence of liver cancer? Incidence is reduced after viral eradication but remains high enough to warrant periodic surveillance for an early diagnosis. In contrast, the risk of recurrence seems to be unaffected by viral clearance; however, DAA treatment improves survival because of the reduced risk of progression of liver disease. Third, can HCV treatment also have favorable effects on major comorbidities? HCV eradication is associated with a reduced incidence of diabetes, an improvement in glycemic control and a decreased risk of cardiovascular events; nevertheless, a risk of hypoglycemia during DAA treatment has been reported. Finally, is it safe to treat patients with HCV/ hepatitis B virus (HBV) coinfection? In this setting, HCV is usually the main driver of viral activity, while HBV replication is suppressed. Because various studies have described HBV reactivation after HCV clearance, a baseline evaluation for HBV coinfection and a specific follow-up is mandatory.

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Association of Direct-Acting Antiviral Therapy With Liver and Nonliver Complications and Long-term Mortality in Patients With Chronic Hepatitis C

et al. 2023

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ImportanceChronic hepatitis C (CHC) and its complications are associated with high rates of morbidity and mortality. However, large-scale data analysis of the long-term liver and nonliver effects of direct-acting antiviral (DAA) treatment has been limited.ObjectiveTo assess the association of hepatitis C virus elimination through DAA treatment with the risk of liver and nonliver morbidity and mortality during long-term follow-up among a large nationwide cohort of insured patients with CHC in the US.Design, Setting, and ParticipantsThis was a retrospective cohort study of 245 596 adult patients with CHC using data from the Optum Clinformatics Data Mart database, 2010 to 2021. Of the total cohort, 40 654 patients had received 1 or more prescriptions for DAA medication (without interferon), and 204 942 patients were untreated.ExposureTreatment with a DAA.Main Outcomes and MeasuresIncidence of hepatocellular carcinoma (HCC), liver decompensation, relevant nonliver events (nonliver cancer, diabetes, chronic kidney disease, cardiovascular disease), and overall mortality.ResultsThe DAA-treated cohort (vs untreated) were older (mean [SD] age, 59.9 [10.8] vs 58.5 [13.0] years; P &lt; .001); more likely to be male (25 060 [62%] vs 119 727 [58%] men; P &lt; .001) and White (23 937 [59%] vs 115 973 [57%]; P &lt; .001) individuals; and more likely to have diabetes (10 680 [26%] vs 52 091 [25%]; P &lt; .001) or cirrhosis (17 971 [44%] vs 60 094 [29%]; P &lt; .001). Comparing DAA-treated with untreated patients, the incidence (per 1000 person-years) of liver outcomes (eg, decompensation, 28.2 [95% CI, 27.0-29.4] vs 40.8 [95% CI, 40.1-41.5]; P &lt; .001, and HCC in compensated cirrhosis, 20.1 [95% CI, 18.4-21.9] vs 41.8 [95% CI, 40.3-43.3]; P &lt; .001) and nonliver outcomes (eg, diabetes, 30.2 [95% CI, 35.4-37.7] vs 37.2 [95% CI, 36.6-37.9]; P &lt; .001; and chronic kidney disease, 31.1 [95% CI, 29.9-32.2] vs 34.1 [95% CI, 33.5-34.7]; P &lt; .001) were significantly lower in treated patients. The all-cause mortality rates per 1000 person-years were also significantly lower in DAA-treated compared with untreated patients (mortality, 36.5 [95% CI, 35.4-37.7] vs 64.7 [95% CI, 63.9-65.4]; P &lt; .001). In multivariable regression analysis, DAA treatment was independently associated with a significant decrease in the risk of liver (adjusted hazard ratio [aHR] for HCC, 0.73; decompensation, 0.36), nonliver (aHR for diabetes, 0.74; chronic kidney disease, 0.81; cardiovascular disease, 0.90; nonliver cancer, 0.89), and mortality outcomes (aHR, 0.43).Conclusions and RelevanceThe findings of this retrospective cohort study indicate that DAA treatment for insured patients with CHC was associated with improved liver- and nonliver outcomes, and ultimately, with long-term overall survival.

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HCC risk post-SVR with DAAs in East Asians: findings from the REAL-C cohort

Cited by 54 publications

References 26 publications

Predicting Hepatocellular Carcinoma Risk in Patients with Chronic HCV Infection and a Sustained Virological Response to Direct-Acting Antivirals

Predicting Hepatocellular Carcinoma Risk in Patients with Chronic HCV Infection and a Sustained Virological Response to Direct-Acting Antivirals

Direct antiviral agents in hepatitis C virus related liver disease: Don’t count the chickens before they’re hatched

Association of Direct-Acting Antiviral Therapy With Liver and Nonliver Complications and Long-term Mortality in Patients With Chronic Hepatitis C

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