Research on many small molecule compounds targeting viral protein-targeted specific therapies in the HCV life cycle has been rapidly developed, and these drugs are uniformly named directly acting antivirals (DAAs), including non-structural (NS) 3/4A protease inhibitors, the NS3/4A protease inhibitors are more potent, but are genotype 1 specific, have a lower resistance barrier and have more drug interactions. NS5A protease inhibitors are more potent, target genotype 1 and 4, but have a lower resistance barrier and have more drug interactions. NS5B polymerase non-nucleoside analogue inhibitors have moderate antiviral activity, are genotype 1 specific, and have a low resistance barrier; nucleoside analogue inhibitors have a stronger antiviral effect, can target multiple genotypes, have a high resistance barrier, and have fewer drug interactions. Since 2011, a variety of drugs from the above three classes have been marketed in the United States and Europe, and have achieved relatively good efficacy in clinical trials and practice. This article briefly describes the clinical application protocols, applicable populations and efficacy of the marketed DAAs, and introduces the progress of DAAs treatment in special populations. 1.1 simeprevir simeprevir must be administered in combination with pegylated interferon (Peg-IFN) alpha and ribavirin (PR) and is only indicated for patients with genotypes 1 and 4. The specific dosing regimen is: Peg-IFN α (1 time/d) + ribavirin (1000 mg/d and 1200 mg/d for patients <75 kg and ≥75 kg, respectively) + simeprevir (150 mg 1 time/d) for 12 weeks, followed by 12 weeks of PR alone for primary treatment and for patients who have relapsed on previous PR therapy (total For patients with partial or no response to prior PR therapy, an additional 36 weeks of treatment should be given (48 weeks total). The combination regimen is not used for patients with genotype 1a with a variant of the NS3 protease sequence Q80K detected at baseline by direct sequencing. However, genotype 1a only accounts for about 1.4% of hepatitis C patients in China and is therefore not significantly affected by this variant [5]. Data from phase III clinical trials in China and Korea showed that patients with primary genotype 1 had a sustained virologic response (SVR) rate of 91% with this regimen and were well tolerated; SVR rates were 94% in patients with interleukin 28B genotype CC and 79% in non-CC patients; and METAVIR scores of F4 SVR was achieved in all five cases [6]. Patients treated with this triplet regimen who are positive for HCV RNA (lower limit of detection 15 IU/ml) by sensitive reagents at weeks 4, 12, or 24 of treatment should be discontinued and replaced with an interferon-containing (IFN) regimen including another DAAs or an IFN-free regimen excluding protease inhibitors. If patients develop rash and elevated indirect bilirubin but not elevated ALT, it may be associated with simeprevir. 1.2 sofosbuvir Patients receiving sofosbuvir should be monitored regularly for renal function. 1.2.1 sofosbuvir + PR sofosbuvir + PR combination therapy is indicated for patients of all genotypes. The dosing regimen is Peg-IFN α (1 dose/d) + ribavirin (<< span="">1000 mg/d, 1200 mg/d for patients with 75 kg or ≥75 kg, respectively) + sofosbuvir (400 mg, 1 dose/d) for 12 weeks of treatment. Foreign data showed an overall SVR rate of 89% in genotype 1 primary patients with this regimen, 92% in genotype 1a, and 82% in genotype 1b [7]; the SVR rate in genotype 1 patients who failed previous PR therapy was expected to be 78% [8]. This option is available for patients with genotype 2 cirrhosis and/or treated patients. 1.2.2 sofosbuvir + ribavirin combination therapy The combination of sofosbuvir and ribavirin is indicated for patients with genotype 2 and 3. The dosing regimen was sofosbuvir (400 mg, 1 time/d) + ribavirin (<< span="">1000 mg/d, 1200 mg/d for patients with 75 kg or ≥75 kg, respectively). The duration of therapy is 12 weeks in patients with genotype 2, but the duration should be extended to 16-20 weeks in cirrhosis, especially in patients with cirrhosis undergoing treatment. This regimen treats genotype 2 patients with an overall SVR rate of 95% and up to 97% in patients without cirrhosis compared to 83% in patients with cirrhosis [7]. The course of treatment for patients with genotype 3 is 24 weeks and the SVR rate with this regimen is 94% in non-cirrhotic primary patients and 87% in non-cirrhotic treated patients, while the SVR rate in cirrhotic treated patients is only 60%, so this regimen is not recommended for genotype 3 cirrhotic treated patients [9]. 1.2.3 sofosbuvir+simeprevir combination therapy The combination of sofosbuvir and simeprevir is indicated for patients with genotype 1 and 4. The dosing regimen is: sofosbuvir (400 mg, 1 time/d) + simeprevir (150 mg, 1 time/d) combination therapy for 12 weeks. Ribavirin is added for patients with cirrhosis, and the regimen must be extended to 24 weeks for patients with cirrhosis in whom ribavirin is contraindicated. Foreign data show that this regimen treats genotype 1 SVR rates of 93% to 96% [10]. 1.2.4 sofosbuvir + daclatasvir combination therapy The combination of sofosbuvir and daclatasvir is indicated for patients with all genotypes. The dosing regimen was: sofosbuvir (400 mg, 1 time/d) + daclatasvir (60 mg, 1 time/d) combination therapy for 12 weeks. However, ribavirin was added for patients with genotypes 1, 4, 5, and 6 cirrhosis, and the regimen had to be extended to 24 weeks for patients with cirrhosis contraindicated to ribavirin. Patients with genotype 3 cirrhosis were treated with ribavirin for an additional 24 weeks. Data from a foreign phase IIb clinical trial showed SVR rates of 95% to 100% in genotype 1 patients [11]. 1.3 sofosbuvir/ledipasvir combination tablet sofosbuvir/ledipasvir is indicated for patients with genotypes 1, 4, 5 and 6 and is administered as a combination sofosbuvir (400 mg)/ledipasvir (90 mg) tablet (1 tablet, 1 time/d). Patients without cirrhosis should be treated for 12 weeks, and patients with compensated cirrhosis should be treated with a combination of ribavirin for 12 weeks. If ribavirin is contraindicated or intolerant, ribavirin is not administered but the course is extended to 24 weeks; in patients with compensated cirrhosis who are treated and in the presence of adverse response factors, ribavirin should be combined and the course extended to 24 weeks. Patients with genotype 1 without cirrhosis and a low baseline viral load (HCV RNA < 6 x 10^6 IU/ml) in primary treatment may be considered for a shorter course of treatment up to 8 weeks. Foreign data show an overall SVR rate of 93% to 99% in genotype 1 patients treated with this regimen [12-14]. 1.4 paritaprevir/ombitasvir/ritonavir combination tablets and dasabuvir 1.4.1 paritaprevir/ombitasvir/ritonavir combination tablets + ribavirin combination therapy Paritaprevir/ombitasvir/ ritonavir combination tablet (2 tablets, 1 time/d) combined with ribavirin (<< span="">1000 mg/d and 1200 mg/d for patients with 75 kg or ≥75 kg, respectively) was used in patients with genotype 4 for 12 weeks in patients without cirrhosis and 24 weeks in patients with cirrhosis [15]. 1.4.2 paritaprevir/ombitasvir/ritonavir combination tablet + dasabuvir combination therapy aritaprevir/ombitasvir/ritonavir combination tablet (2 tablets, 1 time/d) + dasabuvir (250 mg, 1 time/d) is indicated for Patients with gene type 1. Patients with genotype 1b without cirrhosis are treated for 12 weeks without ribavirin; patients with genotype 1b cirrhosis are treated for 12 weeks with ribavirin; patients with genotype 1a without cirrhosis are treated for 12 weeks with ribavirin; and patients with genotype 1a cirrhosis are treated for 24 weeks with ribavirin. Foreign data show overall SVR rates of 91% to 100% in genotype 1 patients treated with this regimen [16-20]. Patients should be monitored for efficacy and safety during the treatment of DAAs. Due to the teratogenic effects of ribavirin, women of childbearing age and/or their partners must use effective contraception at the time of ribavirin use and for 6 months after discontinuation of the drug. Use effective contraception. If possible, interactions should be discontinued during HCV treatment or switched to a combination with fewer interactions. DAAs have been used in special populations with good antiviral effects because of their ease of administration and low adverse effects, but the impact of viral clearance on the medium to long-term prognosis of patients needs to be further investigated. 2.1 Treatment of DAAs in patients with genotype 1/4 decompensated cirrhosis and liver transplantation The SOLAR-2 study included 329 patients with genotype 1/4 decompensated cirrhosis and/or relapse after liver transplantation, randomized in a 1:1 ratio to 12-week and 24-week sofosbuvir/ledipasvir combined with ribavirin treatment groups, with the primary efficacy endpoint of 12 weeks of drug discontinuation SVR rate (SVR12) [21]. SVR12 at 12 and 24 weeks of treatment in the non-cirrhotic (F0 to F3) and compensated cirrhosis (CTP grade A) groups and in the decompensated cirrhosis (CTP grade B+C) group were 95%, 98% and 85% and 88%, respectively; in the genotype 1 CTP B+C group SVR12 at 12 and 24 weeks of treatment were 88% and 89%, respectively; in the genotype 4 CTP B+C group SVR12 at 12 weeks The SVR12 was 57% and 86% at 12 and 24 weeks, respectively, in the genotype 4 CTP B+C group. At 4 weeks of follow-up, 31 cases (35%) were reduced from CTP B to CTP A at baseline and 20 cases (48%) were reduced from CTP C to CTP B at baseline. 24 cases in the F0-F3 and CTP A groups and 3 cases in the CTP B+C group were considered treatment-related; 45 cases in the CTP B+C group and 6 cases in the CTP B+C group were considered treatment-related. Regardless of the patient’s liver transplant status, sofosbuvir/ledipasvir in combination with ribavirin resulted in a high SVR12 with good safety and tolerability in patients with advanced liver disease. In patients with genotype 1, there was no significant difference in SVR12 between 12 and 24 weeks of treatment. 2.2 Treatment of DAAs in patients with genotype 1/3 decompensated cirrhosis A study included 467 patients with genotype 1/3 decompensated cirrhosis, 252 receiving sofosbuvir/ledipasvir combined with ribavirin for 12 weeks and 172 receiving sofosbuvir + daclatasvir + ribavirin for 12 weeks. 43 cases did not apply ribavirin [22]. In patients with genotype 1, SVR12 in the sofosbuvir/ledipasvir + ribavirin group, sofosbuvir/ledipasvir group, sofosbuvir + daclatasvir + ribavirin group, and sofosbuvir + daclatasvir group were 86%, 81%, 82%, 60%; in genotype 3 patients, SVR12 was 59%, 43%, 70%, 71% in the four groups, respectively. 92 cases (41.8%) had MELD score improvement >2 and 23 cases (10.5%) had MELD worsening >2. A total of 175 serious adverse events occurred in 119 cases, 78.9% of which could be related to liver disease and/or HCV treatment. In patients with decompensated cirrhosis, sofosbuvir combined with ledipasvir or daclatasvir had an antiviral effect in patients with genotype 1 or 3 decompensated cirrhosis, and liver function improved in 40% of patients. 2.3 Interim report of DAAs in patients with decompensated cirrhosis A study included 253 patients with cirrhosis and MELD score ≥10 to assess the efficacy and safety of DAAs, and 216 completed treatment and 12-week follow-up [23]. Among genotype 1 patients, SVR12 was 52%, 74%, and 66% in the Sofosbuvir+ribavirin, Sofosbuvir+simeprevir, and Sofosbuvir+simeprevir+ribavirin groups, respectively. The SVR12 was 81% and 39% for Sofosbuvir + ribavirin treatment in patients with genotype 2 and 3, respectively. The relapse rates were 26%, 7%, and 46% for genotypes 1, 2, and 3, respectively. A total of 44 serious adverse events occurred, including 16 cases of liver failure, 10 infections, 3 deaths (1 without special, 1 death from liver failure, 1 death from shock), and 12 cases received liver transplantation during the course of treatment. Patients with cirrhosis and MELD scores ≥10 were safe for oral DAAs, with genotype 1, 2, and 3 SVR12 of 52% to 74%, 81%, and 39%, respectively. negative SVR predictors were genotype 1a and higher bilirubin, while higher levels of albumin were associated with a good prognosis. 2.4 Patients with recurrence after genotype 1 liver transplantation paritaprevir/ombitasvir/ritonavir combination tablet + dasabuvir + ribavirin for patients with recurrence after genotype 1 hepatitis C liver transplantation [24], 34 patients without liver fibrosis or mild liver fibrosis received treatment for 24 weeks, and the dose of ribavirin at baseline and during treatment adjustment was at the discretion of the investigator. The primary study endpoint was SVR12. 97% (33 cases) achieved SVR12 and sustained it until 24 weeks after the end of treatment. The most common adverse events were malaise, headache, and cough. 5 cases (15%) required erythropoietin and none required blood transfusion. Calcium-regulated phosphatase inhibitor levels were monitored during treatment, and no graft rejection occurred. The study included patients with mild liver fibrosis, all of whom were treated 1 year after transplantation, and no patients with acute rapid progression in the early post-transplant period, which contributed to the high response rate. The immunosuppressive agents used by the patients in this study were limited to tacrolimus and cyclosporine. 3 Conclusion The above treatments bring new options for patients with decompensated liver cirrhosis, and the application of DAAs is a breakthrough in antiviral therapy as patients with decompensated cirrhosis are intolerant to Peg-IFN + ribavirin. In an era of liver transplantation donor shortage, the above treatment options may improve the quality of life of patients with hepatitis C cirrhosis in decompensated and post-liver transplantation, providing new feasible options to reduce overall medical needs and costs, etc., and improve prognosis to some extent. In conclusion, the launch of multiclass DAAs has led a new pattern of antiviral therapy for hepatitis C with excellent efficacy and a good safety profile, providing an alternative treatment option for those with refractory hepatitis C, those with contraindications to or intolerant of IFN and ribavirin therapy, as well as new hope for antiviral therapy in special populations such as decompensated cirrhosis, organ transplantation, and immunosuppressed states.