Severe Acute Exacerbation of HCV Infection in Cancer Patients Who Undergo Chemotherapy Without Antiviral Prophylaxis

Yuan-Rung Li; Wen-Chi Chen; Wei-Lun Tsai; Jin-Shiung Cheng; Feng-Woei Tsay; Sung-Shuo Kao; Hui-Chun Chen; Ping-I Hsu

Disclosures

J Viral Hepat. 2020;27(9):873-879. 

In This Article

Discussion

While HBV reactivation is a recognized complication in HBsAg-positive cancer patients undergoing chemotherapy, the precise risk of severe acute exacerbation of HCV infection in HCV-infected cancer patients receiving chemotherapy remains unclear. The prevalence of HCV infection in cancer patients who underwent chemotherapy was 6.0% (337/5601) in this investigation. The incidence of severe acute exacerbation of HCV infection in cancer patients with haematological malignancy, HCC and non-HCC solid tumours who received chemotherapy was 9.4% (3/32), 1.9% (2/105) and 1.2% (2/169), respectively. HCV-infected cancer patients had a higher incidence of severe liver injury during chemotherapy than those without HCV infection. Rituximab-containing chemotherapy and haematological malignancy were the risk factors related to severe acute exacerbation of HCV infection in cancer patients undergoing chemotherapy. None of the cancer patients with acute exacerbation of HCV infection developed liver decompensation-related mortality. However, interruption of chemotherapy was observed in 57.1% (4/7) of those developing severe acute flare of HCV infection.

Chemotherapy may lead to immunosuppression and can reactivate quiescent infection or worsen the clinical effects of infection. To improve pre-chemotherapy HBV and HCV testing, our institute developed in 2012 a computerized order entry-based therapeutic control system (e-CONTROL) to notify healthcare providers of pre-chemotherapy HBV and HCV testing, as well as prophylaxis of HBV flare-up, when prescribing chemotherapy agents.[7] Under the e-CONTROL system, 5,601 out of 5,735 cancer patients undergoing chemotherapy during the study period received complete serological tests for HBsAg and anti-HCV, giving a high screen rate of 97.7%. Among them, the prevalence rates of HBV infection, HCV infection and co-infection were 15.1%, 5.4% and 0.6%, respectively. An epidemiological study by Chen et al[14] explored the prevalence of HBV and HCV infection in Taiwan by a large-scale survey, which showed that the seroprevalence rates of HBV and HCV infection in the general population were 17.3% and 4.4%, respectively. Aforementioned data indicate that HCV infection is present in a significant number (6.0%) of the cancer patients receiving chemotherapy in Taiwan. Cancer patients receiving chemotherapy have a slightly higher seroprevalence rate of HCV infection than the general population.

Data on acute exacerbation of chronic HCV infection following chemotherapy are very limited. A retrospective cohort study by Mahale et al showed that HCV-infected cancer patients did not have a higher incidence of acute liver injury during chemotherapy than noninfected patients.[3] In the current study, severe hepatic injury occurred in 2.3% (7/306) and 0.7% (32/4419) of HCV-infected and uninfected cancer patients undergoing chemotherapy. The data indicate that HCV-infected cancer patients have a higher risk of developing severe liver injury than those without HCV infection. This finding was consistent with an independent study by Zuckerman et al, which reported a significant difference in the incidence of liver dysfunction between HCV-infected and uninfected haematological malignancy patients who received chemotherapy (54% vs 36%).[5]

In one of our previous studies, fatal consequences occurred in 40% of those cancer patients who developed severe acute exacerbation of HBV infection during chemotherapy. The current study indicates that most of the cancer patients with acute exacerbation of HCV infection had a benign clinical course. None of the seven cancer patients developing acute flare of HCV infection developed hepatic decompensation or hepatitis-related mortality. This finding was compatible with another independent prospective observational study by Torres et al,[15] in which reactivation occurred in 23 out of 100 HCV-infected cancer patients receiving chemotherapy. Of the 23 patients with reactivation, 10 (43%) had hepatitis flare. No patient with acute flare of HCV infection experienced liver failure or liver-related death within 36 weeks after initiation of cancer treatment. However, importantly, acute exacerbation of HCV infection can result in discontinuation of potentially life-saving chemotherapy. In the current study, four out of seven patients (57.1%) developing severe acute flare of HCV infection discontinued chemotherapy due to liver dysfunction. Another study found that liver dysfunction led to discontinuation by 45% of the patients with exacerbation of HCV infection.[15]

In this investigation, the incidences of severe acute exacerbation of HCV infection in anti-HCV (+) cancer patients with haematological malignancy, HCC and non-HCC solid tumours were 9.4%, 1.9% and 1.2%, respectively. Haematological malignancy patients had a higher incidence of severe HCV flare than those with nonhaematological malignancy (9.38% vs 1.46%). Additionally, patients receiving rituximab-containing chemotherapy also had higher incidence of severe acute exacerbation of HCV infection than those receiving non-rituximab–containing chemotherapy (12.0% vs 1.4%). Rituximab is a chimeric mouse human anti-CD20 monoclonal antibody that can lower B-cell numbers and antibody levels. It is widely adopted as a single agent, or in combination with chemotherapy in the management of CD20 + lymphomas, such as DLBCL and follicular lymphoma. Several studies have also shown that chemotherapy with rituximab increases the risk of hepatitis in HCV-infected cancer patients.[5,16–18] In this investigation, two (67%) of the three haematological malignancy patients with acute flare of HCV infection discontinued chemotherapy due to liver dysfunction. Since chemotherapy is a potentially life-saving treatment for haematological malignancies, HCV testing is indicated before rituximab-containing chemotherapy for cancer patients, especially those with haematological malignancies. If pre-chemotherapy anti-HCV testing followed by serum HCV RNA assay finds active HCV infection, then direct-acting antiviral agents should be administered before or during chemotherapy.

Despite the useful contributions of this retrospective cohort study, there are several limitations. Firstly, the incidence of HCV reactivation during chemotherapy was unknown because serum HCV RNA data at baseline or during chemotherapy were unavailable in most cases. Secondly, the number of HCV-infected patients with severe acute exacerbation was small. Therefore, multivariate analysis was not possible to identify minor risk factors predicting severe acute exacerbation of HCV infection. Thirdly, it is a single-institute study in a non-HCV endemic area. Nonetheless, it proves that HCV-infected cancer patients had a higher incidence of severe liver injury during chemotherapy than those without HCV infection. Additionally, it provided the incidence of severe acute exacerbation of HCV infection in patients with haematological malignancies, HCC and non-HCC solid tumours, who had HCV infection and underwent chemotherapy without anti-HCV therapy.

In conclusion, HCV infection increases the risk of acute severe liver injury in cancer patients undergoing chemotherapy. Rituximab-containing chemotherapy and haematological malignancy are the risk factors related to severe acute exacerbation of HCV infection in cancer patients undergoing chemotherapy. More than half of the cancer patients with a severe flare of HCV infection had to discontinue potentially life-saving chemotherapy in this investigation. Therefore, pre-chemotherapy HCV testing is mandatory before rituximab-containing chemotherapy for the treatment of patients with haematological malignancy.

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