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Rewisha et al. 16 case series of HCC post DAAs

Table 2: Descriptive laboratory data of the studied with cirrhosis or advanced fibrosis has concluded that
patients (n = 16) IFN-treated CHC cirrhotic patients showed a lower
Laboratory HCC incidence than non-IFN-treated controls after
investigations Before treatment On HCC diagnosis 5-years follow-up. The same review examined the
[12]
Total bilirubin outcome of antiviral treatments in 6 RCTs with a total
(mg/dL) 0.80 ± 0.66 4.84 ± 2.14
Direct bilirubin of 374 HCV-related HCC patients who had received
(mg/dL) 0.50 ± 0.20 1.82 ± 1.68 curative therapy for HCC. After a more than 25 months
AST (IU) 88.40 ± 34.34 79.00 ± 75.42 (median) follow-up, IFN-treated patients showed a
ALT (IU) 74.30 ± 23.60 74.63 ± 52.12 lower recurrence rate of HCC, than non-IFN-treated
ALK (IU) 45.00 ± 17.25 172.25 ± 156.19 controls. [12]
GGT (IU) 36.00 ± 12.00 69.06 ± 72.15
Serum albumin
(mg/dL) 3.40 ± 0.50 2.20 ± 0.88 Although the exact mechanism behind the anti-tumor
Hemoglobin properties of IFN has not been yet fully elucidated, it
(gm/L) 12.30 ± 2.20 11.81 ± 2.37 has been widely used for the treatment of numerous
3
WBCs (10 /L) 4.60 ± 6.10 8.63 ± 4.32 types of cancer, including certain hematological
Platelet (10 /L) 123.00 ± 32.50 102.50 ± 45.10 [13]
3
Prothrombin malignancies and solid tumors. A recent in vivo
concentration (%) 87.20 ± 12.40 44.94 ± 25.47 study reported the IFN’s ability to synergize the
INR(s) 1.20 ± 0.30 1.50 ± 0.46 apoptotic, autophagic as well as the anti-proliferative
Serum HCV-RNA action of cisplatin. [14] Autophagy has been shown to
average levels 517,229.10
(IU) be induced in HCC cell lines when treated with IFN-
Serum AFP α2b in a dose-dependent manner. [15]
(ng/mL) 20.00 ± 12.46 479.46 ± 588.96
HCC: hepatocellular carcinoma; AST: aspartate aminotransferase; Of note, autophagic cell death had been suggested
ALT: alanine aminotransferase; ALK: alkaline; GGT: gamma as one of the anti-cancer actions of anti-cancer
glutamyl transpeptidase; WBC: white blood cell; INR: international therapeutics. [16] Supporting these postulations was
normalized ratio; AFP: alpha fetoprotein
the recent study by Liang et al. [17] who concluded that
of concept. DAAs induced HCV elimination with treatment by pegylated IFN was associated with a
subsequent disturbance of immune functions and less lower HCC incidence than nucleos(t)ide analogues in
anti-tumoral potency is the most proposed explanation chronic HBV infection. They described the oncogenic
for developing HCC. Also, deprivation of the hepatic surface antigen truncation mutations to be detected
microenvironment from the inflammatory scene in entecavir-treated patients with HCC but not in
containing endogenous IFN-inducible natural killer cell/ pegylated IFN-treated patients. [17]
cytotoxic T lymphocytes and many other antiviral tumor
molecules; definitely has a pro-oncogenic effect. [9] Unlike IFN, DAAs have neither anti-angiogenic nor
anti-proliferative properties and have no effect on
The reported downregulation of IFN and IFN stimulated oncogenic buds that already would reside cirrhotic
genes following dual sofosbuvir-ribavirin induced viral livers.
eradication might add another explanation. In pre- For the time being, risk assessment for HCC should
[10]
clinical studies, IFN alpha had demonstrated activity be rigorously undertaken before DAAs, and those
against several tumor types including HCC. Many at risk should have attentive surveillance during
reports had demonstrated the beneficial effects of treatment and afterward. For people at risk, it is
IFN alpha in reducing incidence of HCC in cirrhotic noteworthy to explain the importance of continued
patients who achieved sustained virological response. surveillance after HCV eradication. Also, physicians
van der Meer et al. in their sizeable multinational in the outreach clinics should know by heart that in
[11]
study, with longstanding follow-up periods had proved HCV-positive patients, the risk of HCC is reaching
the positive effect of post IFN SVR on reducing higher figures compared with those eliminated the
morbidity and mortality and in diminishing HCC virus, yet sustained responders having advanced
incidence rates in HCV-related cirrhosis patients. They fibrosis are still at high HCC risk.
reported that only 4% of those who achieved SVR had
experienced HCC development against 76% in those Liver fibrosis has been proven to be regressive in
who didn’t. [11] some patients who eliminated the virus; hence
[18]
post treatment transient elastography would be
A recent systematic review had examined the HCC beneficial in defining patients within the surveillance
incidence in 5 randomized controlled trials (RCTs) program. Moreover, surveillance programs had to
including 1,926 chronic hepatitis C (CHC) patients be strengthened by predictive genetic as well as
180 Hepatoma Research ¦ Volume 3 ¦ August 11, 2017