**3. Results**

#### *3.1. Study Group*

Between August 2019 and December 2020, 37 patients qualified for treatment with LDV/SOF. Most of them were infected with genotype 1 HCV (26 with 1b; 4 with 1a; and 2 with undefined 1). Two patients were coinfected with human immunodeficiency virus (HIV) and had received effective antiretroviral treatment. One patient had evidence of previous hepatitis B virus infection (HBV): detectable anti-HBc antibodies with negative HBs antigen testing. Baseline liver stiffness measurement (LSM) revealed significant fibrosis (F ≥ 2 points in METAVIR scale) in 4/37 (11%) patients, including 3/37 (8%) with compensated cirrhosis (Child–Pugh class A). Two of these cirrhotic patients were infected with genotype 1b HCV, and they had a history of previous ineffective treatment with interferon and ribavirin. Thus, they were qualified for 24 weeks of LDV/SOF therapy. The baseline characteristics of the study group are presented in Table 1.

#### *3.2. Efficacy of the Treatment*

After four weeks of treatment, HCV RNA was undetectable in 31/37 (84%) patients and detectable in 6/37 (16%) patients, ranging between 14 and 942 IU/L (Figure 1). At the EOT, HCV RNA was undetectable in 31/37 (84%) patients, including 4 of the 6 patients with detectable HCV viral load after 4 weeks of therapy. In the remaining 6 cases, the evaluation was not performed due to the ongoing coronavirus disease 2019 (COVID-19) pandemic. Assessment of SVR12 was performed in 36/37 cases; however, in 21 participants, the evaluation of the SVR was postponed from 3 to 12 months as a result of the disruption caused by the COVID-19 pandemic. One patient (infected with genotype 1b, with cirrhosis) was lost to follow-up after week 4 of treatment when his HCV RNA was undetectable. However, home delivery of LDV/SOF was arranged for him, and he completed the 24-week therapy.

The overall intention-to-treat SVR12 rate in this group was 36/37 (97%). All the patients who completed the full protocol and were evaluated at least 12 weeks after the end of treatment achieved SVR12 (36/36, 100%) (Table 2). Intention-to-treat and per-protocol analyses of SVR12 according to the HCV genotype, baseline liver fibrosis, duration of the treatment, and previous ineffective treatment with interferon and ribavirin are presented in Table 2. There were no cases of treatment nonresponse or relapse in our study group.


**Table 1.** Baseline characteristics of 37 patients with chronic HCV infection treated with ledipasvir/sofosbuvir (LDV/SOF).

> ALT—alanine aminotransferase; AST—aspartate aminotransferase; LSM—liver stiffness measurement.

**Figure 1.** HCV viral load in 37 patients treated with LDV/SOF at baseline, at 4 weeks of treatment, at the end of treatment, and ≥ posttreatment week 12. EOT—end of treatment. Data at EOT were available for 31 patients.


**Table 2.** Efficacy of LDV/SOF treatment in 37 adolescents with CHC (intention-to-treat and per-protocol analysis).

> ITT—intention-to-treat; PP—per-protocol analysis; SVR12—sustained virological response.

A significant decrease in both ALT and AST serum levels was observed in the subsequent weeks of the treatment and at SVR assessment compared to baseline (Figure 2A,B).

**Figure 2.** Box-and-whisker plots for alanine aminotransferase ( **A**) and aspartate aminotransferase (**B**) levels during and after treatment with LDV/SOF. The top and bottom of each box are the 25th and 75th percentiles. The line through the box is the median, and the error bars are the maximum and minimum. ( **A**) 0—start of treatment; EOT—end of treatment. (**B**) 0—start of treatment; EOT—end of treatment.

#### *3.3. Tolerability and Safety of the Treatment*

All 37 patients received treatment with the oral fixed-dose tablet of LDV/SOF (400/90 mg) once daily, and they all completed the treatment. No patient declared omission of any drug dose or delay in the admission of the drug dose longer than 3 h. The treatment was well tolerated. No serious adverse events were observed in this group. Overall, 11/37 (30%) patients complained of any adverse event, with fatigue as the most common (5/37, 14%). Other observed side effects of the treatment are listed in Table 3. Six patients (16%) suffered from upper respiratory tract infections during the treatment. In addition, two episodes of alcohol intoxication were reported in the study participants receiving treatment.


**Table 3.** Side effects of LDV/SOF treatment in 37 patients.
