This study reports safety and efficacy of SOF/DCV combination regimen for treating patients with chronic hepatitis C-induced cirrhosis with Child-Pugh class B7–B9. An overall SVR12 rate of 82.9% (81.8% among treatment naïve and 87% among treatment experienced patients) is reported; this unexpected higher response rate among treatment experienced patients may be due to small number of patients in this subset; non-response rate was 2.7%, and relapse rate was 2.7% while 8.1% of patients discontinued therapy due to adverse events. Patients with decompensated cirrhosis (Child-Pugh B/C) have lower response rates than patients with compensated cirrhosis (Child-Pugh A). Reasons for these lower response rates may include reduced drug delivery due to shunting leading to HCV reservoirs, altered drug metabolism and uptake due to impaired liver synthetic function, or impaired immune responses which are present in cirrhotic patients. Relatively few patients with decompensated liver disease have been enrolled in DAA trials or real-life studies [12,13,14,15,16,17].
In the present study, the mean age of patients was 55.83 years ± 7.9. Similarly, in Maan et al.’s study the mean age was 57.1 years, and in Fernández Carrillo et al.’s study the mean age was 55 years [15, 16]. While in Calvaruso et al.’s study the mean age was 65.4 years [17].
Regarding gender distribution: our study showed female predominance (60.8%), in contrast to Maan et al. 2016, Fernández Carrillo et al. 2017, and Calvaruso et al. 2018 who showed male predominance (62.3%), (67%), and (56.9%) respectively [14,15,16]. Our patients were recruited from governmentally supported program (non-health insurance) who is concerned with treating unemployed persons mostly housewives.
In the currently discussed study, 80.8% of patients were treatment naïve while only 19.2% were treatment experienced. This was similar to El-khayat et al.’s study where 78.4% of patients were treatment naïve and 21.6% were treatment experienced [13]. While in Maan et al.’s study 41.2% of patients were treatment naïve and 58.8% were treatment experienced among CTP class B/C patients [16], and in Fernández Carrillo et al.’s study treatment experienced patients represent 57% of CTP class B/C patients [15].
Baseline mean serum albumin level was 2.85 gm/dl, median serum bilirubin level was 1.37 mg/dl, and median platelet count was 92.5 × 103/ml; these were different from other studies where Fernández Carrillo et al.’s study showed a median serum albumin level of 3.2 gm/dl, a median serum bilirubin level of 2.1 mg/dl, and a median platelet count of 62 × 103/ml [15], and in Mann et al.’s study, the baseline mean serum albumin level for CP class B/C patients was 3.1 gm/dl and the median platelet count was 75 × 103/ml [16].
Baseline trans-abdominal ultrasonography revealed that 50% of patients had mild ascites and that 2 patients had FHLs one of them (0.83%) was hemagnioma and the other was an ablated HCC as confirmed by triphasic C.T. This was different from Omar et al.’s study who reported that ascites was present in only 0.1% of patients who received SOF/DAC and 0.3% of patients who received SOF/DAC/RBV and that ablated FHLs was present in 0.1% of patients who received SOF/DAC and in 0.6% of patients who received SOF/DAC/RBV [12].
Patients in our study were more tolerant to ribavirin, 71.6% of them received treatment for 12 weeks this was higher than that reported by Fernández Carrillo et al. 2017 who stated that 46% of patients received treatment for 12 weeks [15]. In other studies, Omar et al. treated-naïve patients without cirrhosis without RBV, and those who had cirrhosis or were treatment-experienced (interferon experienced or SOF experienced) received RBV, and El-Khayat et al. reported a multicenter study of patients with liver cirrhosis genotype 4; in his study all patients received SOF (400 mg) and DCV (60 mg) daily in addition to weight-based ribavirin (RBV) for 12 weeks and when RBV is contraindicated the treatment duration was extended to 24 weeks [12, 13].
In current study, 3 patients (2.7%) relapsed. This was similar to that reported by El-khayat et al. who reported an overall relapse rate of 2%, and was lower than that reported by Fernández Carrillo et al. who concluded that relapse rate among CP class B/C patients was 14% [13, 15]. The ETR was higher among treatment naïve and treatment experienced patients than that reported by El-Khayat et al.’s study after excluding Child’s class A patients [13].
In our study, 9 patients (8.1%) discontinued therapy due to development of adverse events most of them suffered from worsening decompensation (rising serum bilirubin, development of hepatic encephalopathy or development of massive ascites) and some of them suffered from anemia. Similarly, Fernández Carrillo et al. also reported that incident decompensation was the most common serious adverse event and that it occurred in overall 7% of patients [15]. While Omar et al. found that treatment was prematurely discontinued in only 1.5% of patients and that the most common events leading to discontinuation were patient withdrawal and pregnancy. They also reported that the most frequent reported adverse events were hematological, decompensation, and/or development of ascites and that serious adverse events were reported in six patients receiving SOF/DCV [12].
In our study, 4 patients (3.6%) died during follow-up. This was lower than that reported by Fernández Carrillo et al. who reported a death rate of 6.4% among CTP class B/C patients [14] and was slightly lower than that reported by Maan et al. who reported a death rate of 5/114 (4.4%) among CP class B/C patients [16].
Our analysis of data showed that age, gender, prior HCV treatment status, did not have a significant effect on SVR12, while baseline WBCs count was significantly higher among patients who achieved SVR12 (may have a better immunological response) and that serum creatinine level was significantly higher among intolerant patients who discontinued therapy due to adverse events, the presence of ascites also increased the risk of intolerance (possibly more advanced liver disease). El-Khayat et al. also reported that age, treatment experience, and viral load did not have a significant effect on SVR but reported that female gender, MELD score < 10, and platelet count > 150,000/mm3 were significantly associated with higher rate of SVR12 [13]. Omar et al. reported that treatment experience and viral load did not have a significant effect on SVR12 but reported that age, gender, ALT, AST, albumin, bilirubin, WBCs count, hemoglobin, platelet, and INR were significantly different between patients who achieved SVR12 and those who did not [12]. In Maan et al.’s study analysis of data among patients with CP class B/C revealed that age, gender, prior treatment status, serum bilirubin level, and platelet count did not increase the risk for hepatic decompensation, but they reported that serum albumin level < 35 g/l and MELD score ≥ 14 increased the risk of hepatic decompensation [16].
To assess the safety during treatment, a comparison between results of laboratory investigations at baseline and at the end of treatment revealed that there was a significant improvement in liver biochemical profile in the form of reduction in the level of AST (P < 0.001), ALT (P < 0.001), and serum bilirubin (P = 0.019), and an increase in the level of serum albumin (P < 0.001). There was also a significant decline in the level of hemoglobin (P < 0.001) and AFP (P < 0.001), this was in agreement with Fernández Carrillo et al. 2017 who reported that treatment was associated with improvements in MELD scores, particularly in CTP class B/C patients [15].
As previously reported and described in the literature, few cases of recurrence of formerly treated HCC or even de novo lesions after HCV treatment are expected [17]. We repeated the trans-abdominal ultrasonography for 65 patients 12 weeks post-therapy, and revealed that the patient with previously ablated HCC did not develop any new FHLs and that new FHLs developed in 2/65 patients (3%). Thus, we concluded that treatment did not increase the risk of development of HCC. This was similar to that reported by Waziry et al. and Bang and Song [18, 19]. But contrasted with that reported by Reig et al. who reported an unexpected increase in the incidence of both de novo (i.e., incident) HCC, recurrent HCC, and more aggressive and faster progression of HCC in patients treated with DAAs [20]. The 2 patients who developed new FHLs have achieved SVR12 which means that eradication of the virus did not abolish the risk of HCC development. This finding was consistent with that reported by Cardoso et al. 2016 who suggests that we need to consider patients with cirrhosis remain at risk of HCC in spite of eradication of HCV [21].
In the present study, one patient developed rising serum creatinine showing that patients with high baseline serum creatinine may be at risk of worsening renal functions when they receive DAA therapy. This was in agreement with Carrier et al., 2016 who recommended that close monitoring of renal function is required, particularly for at-risk patients (transplanted, HIV-coinfected, CKD, hypertensive, or diabetic patients) [22]. While in another Egyptian study which included patients eligible for treatment with sofosbuvir-based regimens, the reported side effects were fatigue and headache, whereas the liver function tests were significantly improved at SVR12 [23].
