People with hepatitis C and cirrhosis are at increased risk of HCC. Therefore, all people with hepatitis C and cirrhosis should be enrolled in surveillance for HCC, involving 6-monthly liver ultrasound with or without measurement of serum alpha-fetoprotein level.
The eradication of HCV is associated with a > 70% reduction in the risk of HCC. This was first shown in the setting of IFN-based treatment.[135-137]
The risk of HCC in people with cirrhosis is also reduced after cure of hepatitis C with DAA therapy. [138-143] Therefore, we strongly recommend DAA therapy for all individuals with advanced liver disease who do not have a history of HCC.
HCV treatment should not suspend HCC surveillance. We recommend a liver ultrasound within 1 month before starting DAA therapy for all individuals with cirrhosis to ensure that HCC surveillance remains up to date during the treatment and follow-up period. Importantly, although the risk of HCC is reduced after SVR, it is not abolished in people with cirrhosis, and HCC surveillance should continue long term for these people. There are no data to suggest that HCC risk is increased in people with no cirrhosis after SVR. We do not recommend HCC surveillance for people with no cirrhosis who are treated for HCV infection.
Treatment of HCV in patients with hepatocellular carcinoma
Important clinical questions to consider in deciding when to treat hepatitis C in a patient with HCC include:
i) Will DAA therapy influence the natural history of HCC?;
ii) Is the likelihood of SVR lower in patients with active HCC?;
iii) Will DAA therapy improve liver synthetic function and increase tolerability of HCC treatment options?;
iv) In patients who are candidates for liver transplantation, will DAA therapy influence waiting list time or waiting list dropout?; and
v) Will DAA therapy influence the risk of recurrence of HCC after successful HCC treatment?
Reports from Europe soon after DAAs were introduced raised concerns about the possibility of DAA therapy being associated with early recurrence or rapid progression of HCC.144,145 However, these concerns have not been borne out in subsequent studies. A 2017 systematic review, meta-analysis and meta-regression, which included 13 875 patients from 26 studies on HCC occurrence and 17 studies on HCC recurrence, concluded that there was no evidence for a difference in the incidence of de novo or recurrent HCC after achieving SVR.  A large retrospective cohort study of 797 North American patients with HCV-related HCC who achieved a complete response to local treatment (resection, ablation, transarterial chemo- or radio-embolisation or radiation therapy) reported a significant reduction in the overall risk of death associated with DAA therapy.147 More recently, an expert review produced by the American Gastroenterological Association concluded that DAA therapy is associated with a reduction in the risk of de novo HCC and that there were no conclusive data that DAA therapy is associated with risk of recurrent HCC or rapid progression of HCC in patients with a complete response to HCC therapy. Therefore, patients with early- or intermediate-stage HCC (Barcelona Clinic Liver Cancer [BCLC] stage A/B) should be considered for DAA therapy.
People with hepatitis C who have a diagnosis of HCC should be treated with standard DAA regimens according to liver synthetic function (compensated versus decompensated) and whether they have had liver transplantation. Protease inhibitor therapy should not be prescribed for patients with decompensated (Child–Pugh class B/C) liver disease. There are reports that HCC is associated with a lower SVR rate. For example, in one meta-analysis of studies that compared SVR between patients with and without HCC, the SVR rate was 88% in patients with HCC compared with 92% in those without HCC. Whether the lower rate of SVR can be attributed to the unique biology of HCC or whether it reflects the presence of more advanced liver disease in patients with HCC is not clear.
The timing of DAA therapy should be individualised after discussion in a multidisciplinary meeting. In patients with early-stage HCC who have good synthetic function, DAA therapy may be deferred until complete response to HCC treatment is achieved. In patients who are being considered for liver transplantation, the timing of DAA therapy should be decided by considering the likelihood of SVR before versus after transplantation and the potential for DAA treatment to improve tolerance of locoregional therapy, to prevent tumour progression and reduce waiting list dropout, as well as the potential for improvement in liver synthetic function to extend waiting list time. In patients with advanced HCC (BCLC-C/D) who are receiving palliative management, treatment decisions should also be individualised, considering the potential for DAA therapy to improve liver synthetic function, the systemic treatment options for HCC and the patient’s quality of life and life expectancy.