Newly diagnosed hepatocellular carcinoma in patients with advanced hepatitis C treated with DAAs: A prospective population study

Romano, A.; Angeli, Paolo; Piovesan, Sara; Noventa, Franco; Anastassopoulos, George; Chemello, Liliana; Cavalletto, Luisa; Gambato, Martina; Russo, Francesco Paolo; Burra, Patrizia; Vincenzi, V.; Scotton, Pier Giorgio; Panese, Sandro; Tempesta, Diego; Bertin, T.; Carrara, M.; Carlotto, Antonio; Capra, Franco; Carolo, Giada; Scroccaro, Giovanna; Alberti, Alfredo

doi:10.1016/j.jhep.2018.03.009

Cited by 149 publications

(173 citation statements)

References 38 publications

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“…Furthermore, there was no indication of a downtrend in HCC risk at least over the first 3.6 years. These results are in contrast to recent data from 139 patients with HCV‐related cirrhosis who were followed for an average of 15 months and reported a sharp decline in HCC risk in the second year of follow‐up, suggesting that HCC risk may indeed fall as time from treatment ensues . However, this study was limited by small sample, rendering the estimates unreliable especially during the second year of follow‐up.…”

Section: Discussioncontrasting

confidence: 98%

“…Although successful treatment resulting in SVR represents a cure from the standpoint of chronic infection, studies suggest that subsequent risk of hepatocellular carcinoma (HCC), while considerably reduced compared with active HCV infection, persists after treatment with DAAs. The absolute risk of HCC ranged from 1.8%‐3.5% in the first 12 months following SVR in published studies . However, these studies were limited by short‐term follow up.…”

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confidence: 99%

“…The long‐term risk of HCC may not be similar in different subgroups of patients with SVR. For example, although cirrhosis is the most important risk factor for HCC, the risk of HCC is not uniform among patients with cirrhosis and most patients with cirrhosis do not progress to HCC. Some of this heterogeneity in risk may come from the variation in the extent to which markers of inflammation and fibrosis change over time .…”

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confidence: 99%

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Long‐Term Risk of Hepatocellular Carcinoma in HCV Patients Treated With Direct Acting Antiviral Agents

et al. 2019

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Sustained virologic response (SVR) after direct acting antiviral agents (DAAs) holds promise for reducing hepatocellular cancer (HCC). DAAs have recently been available long enough to estimate the long‐term risk. We conducted a retrospective cohort study of hepatitis C virus (HCV) patients who achieved SVR with DAAs from 129 Veterans Health Administration hospitals between January 1, 2015, and December 31, 2015, with follow‐up through September 30, 2018. We calculated the overall and quarterly HCC incidence rates. We examined the effect of demographic, clinical, and behavioral factors and the decline or increase of FIB‐4 and aspartate aminotransferase to platelet ratio index (APRI) on HCC risk. Among the 18,076 patients with SVR, 544 incident cases of HCC were diagnosed during the mean 2.9 years of follow‐up. The cumulative 1, 2, and 3‐year risks of HCC were 1.1%, 1.9% and 2.8%, respectively. Cirrhosis was strongly associated with HCC risk (adjusted hazard ratio = 4.13, 95% confidence interval = 3.34‐5.11). The quarterly incidence rate of HCC remained stable between 1.00 and 1.23/100 person‐years (PY) and 1.5 to 2.3/100 PY in patients with cirrhosis. The risk of HCC was the highest in patients who had persistently high FIB‐4/APRI and both with and without cirrhosis. HCC risk fell in patients with cirrhosis who experienced a decrease of FIB‐4/APRI scores yet remained higher than the accepted threshold for HCC surveillance. HCC risk was also higher in patients with alcohol use, older age, and infection with HCV genotype 3. Most patients treated at an early stage of liver fibrosis had a stable low risk. Conclusion: Patients successfully treated with DAAs and at risk of HCC did not regress after 3.6 years of follow‐up. HCC risk remained above the accepted thresholds for surveillance in patients with cirrhosis. These data have important implications for HCC surveillance in cured HCV patients.

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Section: Discussioncontrasting

confidence: 98%

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confidence: 99%

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confidence: 99%

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Long‐Term Risk of Hepatocellular Carcinoma in HCV Patients Treated With Direct Acting Antiviral Agents

et al. 2019

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“…An Italian prospective study including 3917 patients with a F3‐F4 fibrosis score treated by DAA between January 2015 and June 2016 (SVR12 in 97.2% of F3, in 92.7% of F4 Child‐Pugh A and 80% of F4 Child‐Pugh B) also denied an increased HCC risk associated with DAAs: the HCC incidence of 1.18% person/y (95% CI: 0.92‐1.49) in the whole cohort of cirrhotic patients was not different than that of an historical control group . Incidence of HCC was related to the severity of the underlying liver disease (0.46% (95% CI: 0.12‐0.17) in F3, 1.49% (95% CI: 1.03‐2.08) in CTP‐A and 3.61% (95% CI: 1.86‐6.31) in CTP‐B during the first year and 0%, 0.2% and 0.69%, respectively in the second year.…”

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confidence: 99%

“…Thus, if we consider that the DAA‐associated risk of HCC is not an issue anymore, the issue of an impact of DAA on the tumour growth and aggressiveness previously suggested is still a matter of debate. The influence of DAA therapy on the timing (early or late), frequency and aggressiveness of HCC recurrence after a so‐called “curative” treatment clearly needs further investigation.…”

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confidence: 99%

Direct‐acting antivirals and the risk of hepatocellular carcinoma: The end of a polemic?

Pol

Vallet-Pichard

Fontaine

et al. 2019

Liver International

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Assessment of Incidence of and Surveillance Burden for Hepatocellular Carcinoma Among Patients With Hepatitis C in the Era of Direct-Acting Antiviral Agents

et al. 2020

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IMPORTANCEIn the US, hepatocellular carcinoma (HCC), primarily associated with hepatitis C virus (HCV) infection, is the fastest rising cause of cancer-related death. Wider use of highly effective direct-acting antiviral agents (DAAs) substantially reduces the burden of chronic HCV infection, but the subsequent impacts with HCV-associated HCC remain unknown. OBJECTIVETo assess projected changes in the incidence rate of and surveillance burden for HCC in the era of DAA treatment for HCV. DESIGN, SETTING, AND PARTICIPANTSThis decision analytical model study was performed from January 2019 to February 2020, using an individual-level state-transition simulation model to simulate disease progression, screening, and different waves of antiviral treatments for HCV in the US from 2012 to 2040. INTERVENTIONS Current clinical management for chronic HCV infection. MAIN OUTCOMES AND MEASURES Model outcomes were projected temporal trends and age distribution of incident HCC cases and candidates for HCC surveillance among patients with viremia and patients with virologically cured HCV. RESULTSThe simulation model projected that the annual incidence of HCC among patients with viremia and patients with virologically cured HCV will continue increasing to 24 000 (95% uncertainty interval [UI], 18 000-31 000) cases until 2021. In patients with virologically cured HCV, incident HCC cases are projected to increase from 1000 (95% UI, 500-2100) in 2012 to the peak of 7000 (95% UI, 5000-9600) in 2031 with a subsequent decrease to 6000 (95% UI, 4300-8300) by 2040. The proportion of incident HCC cases that occur in individuals with virologically cured HCV is estimated to increase from 5.3% in 2012 to 45.8% in 2040. The number of candidates for HCC surveillance in the population with virologically cured HCV is projected to increase from 106 000 (95% UI, 70 000-178 000) in 2012 to the peak of 649 000 (95% UI, 512 000-824 000) in 2030 and decrease to 539 000 (95% UI, 421 000-687 000) by 2040, while the proportion of all candidates for surveillance who are virologically cured is estimated to increase from 8.5% to 64.6% during the same period. The average age of HCC incidence and surveillance candidates is estimated to increase from 55 in 2012 to 72 and 71, respectively, by 2040. CONCLUSIONS AND RELEVANCEThe results of this study suggest that the burden of HCC will shift from patients with viremia to patients with virologically cured HCV, and to older populations. Appropriate management may be warranted for early detection of HCC in patients who may no longer be receiving specialty care for liver conditions.

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Newly diagnosed hepatocellular carcinoma in patients with advanced hepatitis C treated with DAAs: A prospective population study

Cited by 149 publications

References 38 publications

Long‐Term Risk of Hepatocellular Carcinoma in HCV Patients Treated With Direct Acting Antiviral Agents

Long‐Term Risk of Hepatocellular Carcinoma in HCV Patients Treated With Direct Acting Antiviral Agents

Direct‐acting antivirals and the risk of hepatocellular carcinoma: The end of a polemic?

Assessment of Incidence of and Surveillance Burden for Hepatocellular Carcinoma Among Patients With Hepatitis C in the Era of Direct-Acting Antiviral Agents

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