Thrombocytopenia is frequent among patients with chronic hepatitis C virus and cirrhosis and is further aggravated by the IFN-based antiviral therapy. The development of DAA has significantly improved tolerability of treatment and cure rates. In Egypt, with the approval of sofosbuvir (SOF), different SOF-based therapies became the standard of care. We performed a retrospective study to compare the incidence of thrombocytopenia during treatment with three of the DAA regimens available for HCV treatment in Egypt. We found more noticeable lowering of mean platelet count in the 2nd week and 4th week of treatment followed by the rise of platelet count again in all the studied groups. Patients on triple therapy (group 1) showed earlier drop of platelet count (1st week) and did not return to baseline till the end of treatment.
On the evaluation of the overall number of patients with platelet count decrement, we found that most of the enrolled patients (76.2%, 71.4%) demonstrated platelet count decrement in the 2nd and 4th weeks with mean platelet counts of 87.65 ± 25.17 × 103/μl and 88.46 ± 32.08 × 103/μl, respectively, which improved towards the end of treatment: 54.8% of patients demonstrated platelet decrement with a mean platelet count of 99.46 ± 41.84.
In comparing the 3 therapeutic groups, the triple therapy group showed the highest proportion of patients with platelet decrement. While the SOF/RBV group showed the lowest mean platelet count at the 2nd week, 4th week and end of treatment. This could be explained by the lower pre-treatment platelet count in the SOF/RBV group in comparison with the other groups and the presence of more unfavourable features as higher proportion of patients with splenomegaly and those who received previous treatment. It is worth mentioning that the percentage of patients affected by this significant thrombocytopenia was lower in this group compared with the other two groups in all stages of assessment.
In a large study involving 125 patients with chronic hepatitis C and baseline thrombocytopenia who received antiviral therapy with peg-IFN-a and ribavirin, it was found that platelet count was less than 100,000 before onset of treatment, and rapid early drop of platelet count on treatment are predictors of high risk of developing on-treatment severe thrombocytopenia [8, 9].
But both studies were done on peg-INF/RBV, and this arm in our study had baseline platelet count of more than 100,000/l unlike the other two arms, but still the rule of 100,000/μl could be applicable.
We compared response to therapy in the 3 subgroups of antiviral therapy and noticed that rapid virological response was in the triple antiviral therapy group, but this was not statistically significant to the other arms as well as associated with more cases that required dose modification due to thrombocytopenia in this arm. Five of six patients who required dose modification were noticed in the triple antiviral therapy group and no dose modification was needed for the SIM/SOF group.
All the three arms were associated with SVR above 95% at week 12 with no statistical difference in between. There are data that support better SVR on SOF/REB [7, 10]. Others proved less efficacy for SOF/REB vs other different combinations of DAAs or even IFN-based therapies [11,12,13].
On studying the demographic data of the patients, we found that the lower the baseline weight of the patients, the more the development of thrombocytopenia during SOF/RBV therapy. However, BMI did not show significant correlation in our study. This is not in agreement with Lin et al., who found that low body mass index (p = 0.022) was significantly correlated with the development of thrombocytopenia but they used the INF/Rib combination [8].
In our study, we found that the lower the baseline albumin of the patients, the more the development of thrombocytopenia during triple therapy. This is in agreement with Lin et al., who also found that low albumin was significantly correlated with the development of thrombocytopenia [8]. This was not applicable for the other two arms. The interpretation may be because this arm has more thrombocytopenia with lower hepatic synthetic functions from the start. But this confirms that poorer baseline liver function is a predictor of thrombocytopenia during antiviral therapy.
It was found that cirrhosis was associated with thrombocytopenia during antiviral therapy which did not show significant correlation in our study [9].
We found that the lower baseline absolute neutrophil count was not associated with significant decrement in platelet count. On the contrary, Nachnani et al., reported that lower white blood cell count was associated with thrombocytopenia during antiviral therapy [14]. The reason could be that the interferon arm patients were chosen with good CBC from the start and that the other two drug combinations have less side effects on CBC. Larger studies on patients with chronic hepatitis C and thrombocytopenia should be conducted for further studying of the suggested predicting factors and follow-up for platelet counts after end of antiviral therapy is very important with the DAAs. We also found that by the end of treatment (EOT), all patients had normalized platelet (PLT) count regardless of the initial count.