2020 EASL Recommendations: Treatment of Hepatitis C

2020 EASL Recommendations: Treatment of Hepatitis C (Final Update). Hepatitis C is a major cause of chronic liver disease, and there are approximately 71 million people chronically infected with HCV worldwide.

Hepatitis C is a major cause of chronic liver disease, and there are approximately 71 million people chronically infected with HCV worldwide. Due to the continuous deepening of the understanding of the pathophysiology of the disease, the optimization of the diagnosis process, and the advancement in treatment and prevention, the clinical treatment of HCV-related liver diseases has made considerable progress, making the goal of “eliminating hepatitis C” called by the World Health Organization possible. . This is the final update of the European Society of Hepatology’s recommendations for the treatment of hepatitis C, and provides the best management plan for new and chronic HCV infections in 2020 and beyond.

1 Methodology

The evidence-based level used in this recommendation is still the GRADE system. The strength of recommendation reflects the strength of relevant evidence. The level of evidence is divided into high quality (A), medium quality (B), and low quality (C); the recommendation strength is divided into: strong recommendation ( 1) and weak recommendation (2) (Table 1). The higher the quality of the evidence, the higher the strength of the recommendation; the greater the variability or uncertainty of the value and recommendation, the lower the strength of the recommendation.

2 Anti-HCV drugs available in Europe

3 Recent HCV infection, chronic hepatitis C and HCV reinfection

• Recommendation 1: All patients suspected of being newly infected with HCV should be tested for anti-HCV antibodies and HCV RNA or HCV core antigen (A1) in serum or plasma.
• Recommendation 2: For patients who are suspected of being newly infected with HCV, if anti-HCV antibodies are positive and HCV RNA or HCV core antigen is negative, HCV RNA should be rechecked after 12 or 24 weeks to confirm whether the virus has been cleared (A1).
• Recommendation 3: Serum or plasma anti-HCV antibody detection should be used as the first-line test for all suspected chronic HCV infections (A1).
• Recommendation 4: Patients with suspected chronic HCV infection with positive anti-HCV antibodies should be further tested for HCV RNA or HCV core antigen (A1).
• Recommendation 5: After obtaining sustained virological response (SVR), HCV RNA or HCV core antigen is detected again, and patients with risk factors for infection should be alert to HCV reinfection by confirming that the infection is of a different genotype or the same gene as the original infection Type of distant relatives (applied systematic evolution analysis sequencing) confirmed diagnosis (A1).
• Recommendation 6: Anti-HCV antibodies should be tested using plasma or serum samples and enzyme immunoassay (EIA) (A1).
• Recommendation 7: HCV RNA should be determined using serum or plasma specimens with a sensitive, lower detection limit of ≤15 IU/ml (A1).
• Recommendation 8: The HCV core antigen in serum or plasma detected by EIA is a marker of HCV replication and can replace HCV RNA to diagnose HCV viremia (A1).
• Recommendation 9: In areas where sensitive HCV RNA is not accessible or affordable, qualitative detection of HCV RNA with a lower detection limit of ≤1000 IU/ml (3.0 log10IU/ml) can be used to broaden the diagnosis and treatment of HCV (B1).

4 Screening for chronic hepatitis C

• Recommendation 1: The screening strategy for HCV infection should be formulated based on the local epidemiology of HCV and fit the local, regional and national action plan framework (A1).
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• Recommendation 2: Anti-HCV antibody screening and diagnosis should be linked to prevention, health care and treatment (A1).
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• Recommendation 3: Screening for HCV infection should use serum or plasma anti-HCV antibodies, EIA detection method (A1).
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• Recommendation 4: Whole blood dried blood spot samples can replace intravenous plasma or serum samples to detect anti-HCV antibodies, and the samples should be sent to a central laboratory (A1) that can achieve EIA.
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• Recommendation 5: Rapid diagnostic testing based on serum, plasma, whole blood or cervical fluid, or saliva can replace traditional EIA as a real-time medical testing method, thereby simplifying the screening of anti-HCV antibodies and improving medical accessibility (A1).
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• Recommendation 6: If the anti-HCV antibody is positive, molecular testing of HCV RNA or HCV core antigen of EIA should be used to further confirm whether the patient has viremia (A1).
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• Recommendation 7: Whole blood dried blood spot samples can replace intravenous plasma or serum samples for HCV RNA testing, and the samples need to be sent to a central laboratory (A1) that can achieve molecular testing.
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• Recommendation 8: Whole blood dried blood spot samples cannot replace venous blood plasma or serum samples for HCV core antigen detection, because their low sensitivity leads to more missed diagnosis (B1).
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• Recommendation 9: A simple procedure (A1) should be used for HCV RNA and HCV core antigen confirmation testing for patients with positive anti-HCV antibodies.
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• Recommendation 10: If low-cost viremia immediate detection (low detection limit ≤1000 IU/ml, 3.0 log10 IU/ml) or HCV core antigen detection is available, and it is better than anti-HCV antibody screening in people with low HCV incidence More economical, these tests can be used instead of anti-HCV antibodies to screen for HCV (C2).

The goal of 5HCV treatment

The goal of HCV treatment is to cure HCV infection. The purpose: (1) Prevent HCV-related liver and extrahepatic complications, including hepatic necrotizing inflammation, liver fibrosis, cirrhosis, decompensated cirrhosis, liver cells Cancer (HCC), severe extrahepatic manifestations and death; (2) Improve the quality of life and remove the HCV hat; (3) Prevent the continued spread of HCV through treatment (A1).

6 End point of treatment

• Recommendation 1: The endpoint of treatment is that HCV RNA in plasma or serum cannot be detected at 12 or 24 weeks after the end of treatment (the lower limit of detection is less than or equal to 15 IU/ml) (A1).
• Recommendation 2: 12 or 24 weeks after the end of treatment, no HCV core antigen test can be used as an alternative treatment endpoint for HCV core antigen-positive patients before treatment (A1).
• Recommendation 3: In areas where sensitive HCV RNA is not accessible or affordable, serum or plasma HCV RNA (qualitative detection, lower limit of detection ≤1000 IU/ml, 3.0 log10 IU/ml) cannot be detected 12 or 24 weeks after the end of treatment. As an alternative treatment endpoint (B1).
• Recommendation 4: Patients with advanced fibrosis (METAVIR score F3) or liver cirrhosis (METAVIR score F4) still need to be monitored for HCC, because SVR can only reduce but not eliminate the risk of HCC (A1).

7 Indications for treatment: Who should receive treatment?

• Recommendation 1: All newly-infected or chronic HCV infection patients should be treated immediately (A1).
• Recommendation 2: The following situations require emergency treatment. (1) Patients with significant fibrosis or cirrhosis (METAVIR score F2, F3, or F4), including cirrhosis in the compensatory phase (Child-Pugh A grade) and decompensated phase (Child-Pugh B or C grade); (2 ) Patients with significant extrahepatic clinical manifestations (such as HCV-related mixed cryoglobulinemia and clinical symptoms of vasculitis, HCV immune complex-related nephropathy and non-Hodgkin’s lymphoma); (3) HCV after liver transplantation Patients who relapse; (4) Patients who are at risk of rapid progression of liver disease due to comorbidities (patients after non-liver solid organs or stem cell transplantation, HBV and HIV co-infection, diabetes); (5) Individuals who are at risk of transmitting HCV (such as Intravenous addicts, high-risk men who have sex with men, women of childbearing age who are willing to become pregnant, hemodialysis patients and prisoners) (A1).
• Recommendation 3: It is not recommended to treat patients with limited life expectancy due to non-liver disease-related comorbidities (B2).

8 treatment contraindications

• Recommendation 1: Current DAA-based treatment has almost no contraindications (A1).
• Recommendation 2: If specific P450/P-gp inducing drugs (such as carbamazepine, phenytoin and phenobarbital) are used and cannot be replaced by other drugs, all HCV DAA regimens are contraindicated because these drugs will be obvious Reduce the blood concentration of HCV DAA (A1).
• Recommendation 3: The treatment plan contains HCV protease inhibitors, such as Glarevir, Gcarrevir, and Vocirevir. It is contraindicated in decompensated liver cirrhosis (Child-Pugh grade B or C) or previous degeneration Compensated patients (A1).

9 Evaluation before treatment

9.1 Looking for liver complications

• Recommendation 1: Before treatment, it is necessary to evaluate the impact of comorbidities on the progression of liver disease, and take appropriate treatment measures (A1).
• Recommendation 2: Assess and quantify alcohol consumption and drug abuse, and give specific guidance (A1).
• Recommendation 3: Identify the extrahepatic manifestations of HCV infection (A1).
• Recommendation 4: Assess renal function, including creatinine and glomerular filtration rate (eGFR) (A1).
• Recommendation 5: All patients should be tested for past or current HBV infection, HIV infection and HAV antibodies (A1).
• Recommendation 6: Patients without HBV and HAV antibodies need to be injected with HBV and HAV vaccines (A1).

9.2 Assess the severity of liver disease

• Recommendation 1: The severity of liver disease should be assessed before treatment (A1).
• Recommendation 2: Determine whether there is liver cirrhosis, because it will involve adjustment of the treatment plan, and patients with liver cirrhosis must be monitored for HCC after treatment (A1).
• Recommendation 3: Patients with advanced fibrosis (METAVIR score F3) must also be monitored for HCC after treatment (B1).
• Recommendation 4: The initial assessment of fibrosis grade requires non-invasive testing, including liver stiffness measurement or serological markers, such as APRI and FIB-4 and other economical and reliable biomarker scoring systems (A1).
• Recommendation 5: If the above-mentioned non-invasive tests cannot be determined or patients with potential additional causes should be confirmed by liver puncture (A1).
• Recommendation 6: Non-invasive detection methods should not be used for the evaluation of fibrosis after treatment, because the detection after treatment is unreliable (B1).

9.3 Detection or quantification of HCV RNA or HCV core antigen

• Recommendation 1: HCV RNA or HCV core antigen should be perfected to confirm viremia (A1) before starting treatment.
• Recommendation 2: The detection of serum or plasma HCV RNA requires a sensitive detection method with a detection limit of ≤15 IU/ml (A1).
• Recommendation 3: EIA (A1) is used for the detection of HCV core antigen.
• Recommendation 4: In areas where sensitive HCV RNA testing is unavailable or unaffordable, HCV RNA can also be detected with a low-cost, immediate, detection limit ≤1000 IU/ml (3.0 log10 IU/ml) test (B1).

9.4 Determination of HCV genotype

• Recommendation 1: The full genotyping program includes Sofosbuvir/Vipatavir, Gcareivir/Pirentavir, and treatment can be initiated when the genotype and subtype are unknown, because the cure rate is high ( A1).
• Recommendation 2: It is possible to detect genotypes and subtypes with unlimited visits. Determining HCV genotypes and subtypes can help identify patients who can benefit from individualized treatment (A1).
• Recommendation 3: Patients from HCV subtype endemic areas with clear treatment insensitive, clear genotype and subtype can benefit, through sampling or deep sequencing of NS5B sequence or analysis of another coding region using phylogenetic analysis methods to find NS5A Inhibitors are naturally resistant to HCV subtypes (subtypes 11, 4r, 3b, 3g, 6u, 6v and other undetermined subtypes) to avoid treatment failure (B1).
• Recommendation 4: In some regions with HCV subtypes (subtypes 11, 4r, 3b, 3g, 6u, 6v and other unidentified subtypes) that are naturally resistant to NS5A inhibitors, sampling or deep sequencing of NS5B sequence is required Or use phylogenetic analysis to analyze another coding region to determine the HCV genotype and subtype (but in most low- or middle-income countries with these HCV subtypes, sampling or deep sequencing methods are not available) (B2).

9.5 HCV resistance test

• Recommendation 1: HCV resistance testing (A1) is not recommended before first-line treatment.
• Recommendation 2: In some areas, the only treatment plan needs to be optimized based on pre-treatment resistance testing, and the evaluation of HCV for NS5A inhibitors (from amino acids 24 to 93) is reliable and convenient. These can be used to guide treatment decisions. For details, see the 2016 European Society of Hepatology recommendations for hepatitis C treatment (B2).

9.6 Evaluation of drug interactions before initiating treatment

• Recommendation 1: Before starting HCV treatment and other drugs in HCV treatment, all patients treated with DAA need to conduct a comprehensive drug interaction evaluation based on the prescription information of each DAA (www.hepdruginteractions.org will regularly update the recommendations ) (A1).
• Recommendation 2: In the treatment of patients with HIV and HCV co-infection, it is necessary to focus on drug interactions, and be aware of antiretroviral drugs that are contraindicated with specific DAA treatments, are not recommended, or require dose adjustment (A1).
• Recommendation 3: The following education should be given to patients. The importance of treatment compliance, use recommended dosages and report application of other prescription drugs, over-the-counter drugs, drugs purchased online and drugs (A1).

10. Treatment of hepatitis C patients with liver cirrhosis without liver cirrhosis or compensated stage (Child-Pugh A)

10.1 General treatment principles

• Recommendation 1: The virological effect, safety and tolerability of the whole-genotype DAA regimen are good, and the application is simple. Therefore, it is recommended to be used in patients without cirrhosis or compensated cirrhosis (Child-Pugh A), including initial treatment ( That is, never received treatment for HCV infection) and after treatment (that is, once received peginterferon combined with ribavirin, peginterferon, ribavirin and sofosbuvir, or sofosbuvir And ribavirin treatment) patients (A1).
• Recommendation 2: The following is the recommended full genotyping program (A1).

1. Sofosbuvir (400 mg)/Vipatavir (100 mg), 1 tablet per day;
2. Gcarevir (300 mg)/pirentavir (120 mg), 3 tablets each time (each tablet contains Gcarevir 100 mg and pirentavir 40 mg), once a day, with food Same server
3. Sofosbuvir (400 mg)/Vipatavir (100 mg)/Vociravir (100 mg), take 1 tablet a day with food.

• Recommendation 3: Non-genotype fixed-dose Glarevir (100 mg)/Albavir (50 mg) can be used for patients with genotype 1b, 1 tablet per day (A1).
• Recommendation 4: DAA treatment regimen without interferon and ribaviri is also suitable for HIV co-infected patients, because the drug virological response in this population is the same as that in HIV-free population (A1).
• Recommendation 5: Among HIV co-infected patients, if there are drugs that interact with antiretroviral drugs, the treatment plan or the dose needs to be changed (A1).
• Recommendation 6: In areas where the interferon-free and ribavirin-free program recommended in this recommendation is not accessible, the previous version of the recommended program can still be used for patients who may have an effect on it, until the full-genotype DAA program is accessible Or affordable (A1).
• Recommendation 7: If the supplier can ensure that the quality control is up to standard, generic drug therapy can be used (A1).
• Recommendation 8: In low- or middle-income countries, that is, areas where the interferon-free and ribavirin-free regimens recommended in this recommendation are not accessible or affordable, a generic drug of sofosbuvir combined with dacatavir of the whole genotype It is safe, efficient, and affordable. For details, refer to the 2016 European Society of Hepatology recommendations for hepatitis C treatment (A1).
• Recommendation 9: When HCC treatment can be timely, patients with advanced fibrosis (F3) or compensated cirrhosis (Child-Pugh A, F4) still need to be monitored and followed up (A1) for HCC after SVR.

10.2 Simplified, genotype- and subtype-free whole-genotype treatment plan

• Recommendation 1: Where the detection of any genotype and subtype is unavailable, and the treatment cannot be afforded and/or restricted, a simplified, non-genotype and subtype all-gene anti-HCV therapy should be adopted to improve the accessibility of HCV treatment. Increase the global infection treatment rate (A1).
• Recommendation 2: Pre-treatment assessment can be limited to the confirmation of HCV viremia (HCV RNA or HCV core antigen positive) and the presence of cirrhosis (using non-invasive testing methods) (A1).
• Recommendation 3: Confirm whether there is an interaction between drugs, and adjust the dose of drugs if necessary (A1).
• Recommendation 4: Patients who are initially treated without cirrhosis or compensated cirrhosis (Child-Pugh Class A) or treated without cirrhosis can start treatment without testing their genotype. The treatment plan can be one of the following: (1) Sophos Buvir combined with Vipatavir for 12 weeks; (2) Geckarivir combined with Pirentavir for 8 weeks (B1).
• Recommendation 5: After treatment, patients with compensatory liver cirrhosis can start treatment without genotype testing. The following options can be used: (1) Sofosbuvir combined with vepatavir for 12 weeks; (2) Gcarevir combined with piperazine Rentavir for 12 weeks (B1).
• Recommendation 6: If these treatment plans are well adhered to, the SVR12 rate is very high in all patients, so SVR testing can also be omitted (except for high-risk groups and patients at risk of reinfection, SVR should be tested 12 weeks after the end of treatment. Annual monitoring if possible) (B1).

10.3 Treatment options based on genotype or subtype

11 Treatment options for patients with chronic hepatitis C decompensated cirrhosis (Child-Pugh B or C) with or without indications for liver transplantation

11.1 General treatment principles

• Recommendation 1: Patients with decompensated liver cirrhosis should receive antiviral therapy in an experienced center that can perform liver transplantation (A1).
• Recommendation 2: Patients with decompensated liver cirrhosis should be closely monitored during treatment. If decompensation worsens during treatment, the drug may be discontinued (A1).
• Recommendation 3: Protease inhibitors are contraindicated in patients with decompensated cirrhosis and patients with decompensated cirrhosis (A1).
• Recommendation 4: Patients with decompensated cirrhosis and compensatory cirrhosis who have experienced decompensation should use sofosbuvir/vipatavir combined with ribavirin (body weight <75 kg, 1000 mg/d ; Body weight ≥75 kg, 1200 mg/d) 12 weeks (A1).
• Recommendation 5: For patients with decompensated liver cirrhosis, ribavirin can start at 600 mg/d and gradually adjust the dose according to tolerance (B1).
• Recommendation 6: For patients with decompensated cirrhosis and compensated cirrhosis who have experienced decompensated cirrhosis, if ribavirin is contraindicated or cannot tolerate ribavirin, a ribavirin-free cord should be used Fosbuvir/Vipatavir 24-week program (A1).

11.2 Treatment options for patients with decompensated cirrhosis with or without liver transplantation indications

• Recommendation 1: Patients with decompensated liver cirrhosis, who are not on the waiting list for liver transplantation, and have no comorbidities affecting survival should be treated as soon as possible (A1).
• Recommendation 2: Patients with decompensated liver cirrhosis, no HCC, waiting for liver transplantation and MELD score <18-20 points should start treatment before transplantation (A1).
• Recommendation 3: Patients with decompensated liver cirrhosis who are indicated for treatment should use Sofosbuvir/Vipatavir combined with body weight-based ribavirin (body weight <75 kg, 1000 mg/d, body weight ≥75 kg, 1200 mg/d) for 12 weeks; Ribavirin can start at 600 mg/d and gradually adjust the dose according to tolerance (A1).
• Recommendation 4: Patients with decompensated liver cirrhosis and treatment indications who have contraindications to ribavirin or cannot tolerate ribavirin should use ribavirin-free sofosbuvir/Vipata Wei’s 24-week program (B1).
• Recommendation 5: Patients with decompensated liver cirrhosis, no HCC, waiting for liver transplantation and MELD score ≥18-20 points should be transplanted first without anti-virus, and then treated for HCV infection after transplantation (B1).
• Recommendation 6: No HCC, waiting for liver transplantation and MELD score ≥18-20 points, waiting time for transplantation list exceeds 6 months, antiviral treatment should be based on local conditions before transplantation (B1).

12 Treatment options for hepatitis C patients undergoing solid organ transplantation including liver transplantation

12.1 Treatment of HCV-positive liver transplant patients with HCV recurrence after transplantation

• Recommendation 1: All patients with recurrence of HCV infection after transplantation should be treated (A1).
• Recommendation 2: Treatment must be started early after liver transplantation. The ideal time is to start as soon as possible after the patient is stabilized (usually 3 months after transplantation), because SVR12 will decrease in patients with advanced liver disease after transplantation (A1).
• Recommendation 3: Fibrotic cholestatic hepatitis, moderate to extensive fibrosis, or portal hypertension require emergency antiviral therapy (A1).
• Recommendation 4: Patients with HCV recurrence after transplantation, no cirrhosis or compensated cirrhosis can use the following treatment options. (1) Sofosbuvir/Vipatavir for 12 weeks; (2) Gocarrevir/pirentavir for 12 weeks (the blood concentration of immunosuppressants needs to be monitored and adjusted as needed during or after treatment Dose) (B1).
• Recommendation 5: After transplantation, patients with HCV recurrence and decompensated liver cirrhosis should be treated with sofosbuvir/vipatavir combined with ribavirin (body weight <75 kg, 1000 mg/d; body weight ≥75 kg, 1200 mg/d) 12 weeks; Ribavirin can start from 600 mg/d and gradually adjust the dose according to tolerance (B1).
• Recommendation 6: For patients with HCV recurrence and decompensated liver cirrhosis after transplantation, if ribavirin is contraindicated or cannot tolerate ribavirin, sofosbuvir/vipatas without ribavirin should be used Wei’s 24-week program (B1).

12.2 Treatment of HCV-positive non-liver solid organ transplant patients

• Recommendation 1: Patients with non-liver solid organ transplants including kidney, heart, lung, pancreas or small intestine should be treated for HCV infection before or after transplantation (A1).
• Recommendation 2: Before kidney, heart, lung, pancreas, or small bowel transplantation, patients on the waiting list can start anti-HCV therapy according to the above general population recommendations (A1).
• Recommendation 3: After solid organ transplantation, patients (including kidney, heart, lung, pancreas, and small intestine) should be treated with sofosbuvir/Vipatavir for 12 weeks, and there is no need to adjust the dose of immunosuppressants (B1).
• Recommendation 4: After transplantation of solid organs (including kidney, heart, lung, pancreas, and small intestine), gecarevir/pirentavir can be treated for 12 weeks, and the blood concentration of immunosuppressants should be monitored during and after treatment. , Adjust the dose if necessary (B1).

12.3 Treatment of HCV-negative patients receiving HCV-positive organ donors

• Recommendation 1: Organs of anti-HCV antibody-positive and HCV RNA-positive donors can be transplanted to HCV RNA-positive patients (B1).
• Recommendation 2: Organs of HCV RNA-positive donors can be used for HCV RNA-negative patients, but local regulations and full informed consent are required to ensure that DAA treatment can be initiated quickly after transplantation (B1).
• Recommendation 3: HCV RNA-positive liver with moderate or advanced liver fibrosis (F2 or F3) is not recommended for transplantation (B2).
• Recommendation 4: The HCV treatment for HCV RNA-negative patients receiving HCV RNA-positive organs is the same as the HCV-infected solid organ transplant patient program (B1).
• Recommendation 5: For HCV RNA-negative patients receiving HCV RNA-positive organs, preventive anti-HCV treatment can be performed before transplantation, but more research is needed to determine the ideal plan and treatment duration before or after transplantation (C2).

13 Treatment plan for chronic hepatitis C patients with HCC

13.1 Anti-HCV treatment plan for patients with HCC and indications of cure, no cirrhosis or compensated cirrhosis (including liver transplantation)

• Recommendation 1: For patients with HCC, no cirrhosis, or compensated cirrhosis, if radical treatment such as partial liver resection or radiofrequency ablation can be performed, DAA treatment should be postponed until the end of HCC treatment (A1).
• Recommendation 2: The timing of antiviral treatment for patients with HCC, HCV infection and waiting for transplantation (before transplantation or after transplantation) should not be interfered with by the management of transplant patients, and an individualized plan should be developed through multidisciplinary discussion (B1).
• Recommendation 3: If patients with HCC, HCV infection and waiting for liver transplantation are waiting for a long time in the center, HCV treatment should be initiated before liver transplantation, so as to speed up local treatment and reduce waiting list drop due to tumor progression (B2).
• Recommendation 4: Patients with HCC, no cirrhosis or compensated cirrhosis, and waiting for liver transplantation should be treated with anti-HCV treatment according to the recommendations of the general population before and after liver transplantation (A1).

13.2 Treatment of chronic hepatitis C patients with HCC after treatment and no indication for liver transplantation

• Recommendation 1: The treatment of patients with complete remission of HCC is the same as that of the general population without HCC (A1).
• Recommendation 2: Patients who have achieved complete remission of HCC and have reached SVR are still at risk of HCC recurrence. HCC needs to be monitored indefinitely after SVR, that is, ultrasound every 6 months (A1).
• Recommendation 3: Patients with only remission of HCC should decide whether to treat HCV based on the overall prognosis or potential benefit (B2).

14 Treatment of chronic hepatitis C in special epidemic groups

14.1 Treatment of chronic hepatitis C in adolescents and children

• Recommendation 1: All babies born to pregnant women with HCV infection should be tested for HCV infection from 18 months (A1).
• Recommendation 2: The treatment of adolescent patients with no cirrhosis or compensated cirrhosis should be selected according to the recommendation of the general adult population. (1) Sofosbuvir (400 mg) and Vipatavir (100 mg), 1 tablet orally per day; (2) Gcarevir (300 mg) and Pirentavir (120 mg), 3 each time Tablets (each tablet contains 100 mg of gorcarevir and 40 mg of pirentavir), once a day, taken with food (A1).
• Recommendation 3: 3~11 years old, newly treated, treated children without cirrhosis or compensated liver cirrhosis, should be treated with sofosbuvir and veptavir for 12 weeks according to their body weight, once a day: (1 ) Body weight ≥ 17 kg, 200 mg sofosbuvir and 50 mg vepatavir, 1 tablet (200 mg/50 mg) or 4 bags of granular preparations (each bag contains 50 mg sofosbuvir and 12.5 mg vipatavir) (this program is pending approval). (2) Body weight <17 kg, 150 mg of sofosbuvir and 37.5 mg of vepatavir, 3 bags of granular preparations, 50 mg of sofosbuvir and 12.5 mg of vepatavir per bag (this program is pending approval) ( B2).
• Recommendation 4: 3~11 years old, newly treated, after treatment, children with no liver cirrhosis or compensated liver cirrhosis can also be treated with Gcarevir and Pirentavir for 12 weeks, once a day, per bag according to body weight Contains 50 mg of Gecarivir and 20 mg of Pirentavir film-coated granules mixed with a small amount of food (this program is pending approval). (1) Body weight of 30~44 kg, 250 mg of Gcarevir and 100 mg of Pirentavir, namely 5 bags; (2) 20~29 kg, 200 mg of Gcarevir and 80 mg of Pirentavir, That is 4 bags; (3) 12-19 kg, 150 mg of gorcaravir and 60 mg of pirentavir, namely 3 bags (B2).

14.2 Treatment of chronic hepatitis C in pregnant women

• Recommendation 1: Due to lack of safe and effective data, anti-HCV therapy during pregnancy is not recommended (C2).
• Recommendation 2: Treatment can be considered during pregnancy, or unintended pregnancy during treatment, but it needs to be analyzed according to the specific situation, with the joint participation of liver disease and obstetricians and gynecologists, and fully discuss the potential risks and benefits with the patient (C2).
• Recommendation 3: HCV maternal breastfeeding is not contraindicated, unless there is bleeding or damage to the nipple, you need to seek specialist treatment (B1).

14.3 Treatment of people who inject drugs (PWID) and patients receiving opioid substitution therapy (OST)

• Recommendation 1: PWID should routinely detect anti-HCV antibodies and HCV RNA (A1).
• Recommendation 2: HCV RNA-negative PWID requires annual monitoring of HCV RNA, and close follow-up during the high-risk injection period (A1).
• Recommendation 3: As part of a comprehensive harm reduction plan, PWID, including prisoners, should have the opportunity to get OST and clean syringes (A1).
• Recommendation 4: All PWID infected with HCV, including those receiving OST, previous intravenous toxins or recent drug injections, should be treated according to the recommendation of the general population (A1).
• Recommendation 5: Education before treatment should include discussion and recommendations on HCV transmission, risk factors for liver fibrosis progression, treatment, risk of HCV reinfection, and harm reduction strategies (A1).
• Recommendation 6: For patients undergoing OST, DAA-based anti-HCV therapy does not require adjustment of the dose of methadone and buprenorphine (A1).
• Recommendation 7: PWIDs with high-risk behaviors should follow up with SVR, and test HCV RNA twice a year or at least once a year to monitor HCV reinfection (A1).
• Recommendation 8: If re-infection is found during follow-up after SVR, re-treatment is required (A1).
• Recommendation 9: Increasing the proportion of treatment in the PWID group, including treatment as prevention, can increase the possibility of achieving the goal of HCV elimination in this group (A1).

14.4 Treatment of chronic hepatitis C in prisoners

• Recommendation 1: All prisoners have the right not to participate in HCV infection screening (A1).
• Recommendation 2: HCV treatment should be provided to all patients with chronic hepatitis C, and the treatment is the same as the general population recommended program (A1) described above.
• Recommendation 3: OST should be accessible to all opioid dependent prisoners (B1).
• Recommendation 4: The needle and syringe exchange program should be open to prisoners and prison staff should provide support (B1).

15 Treatment of chronic hepatitis C in patients with comorbidities

15.1 Patients with immune complex-mediated extrahepatic manifestations of HCV

• Recommendation 1: Patients with mixed cryoglobulinemia and kidney disease associated with HCV infection should recommend the full-genotype DAA combination regimen (B1) according to the general population.
• Recommendation 2: Adverse reactions must be closely monitored during treatment (B1).
• Recommendation 3: Whether to use rituximab to treat HCV-related nephropathy needs to be discussed and decided by a multidisciplinary team (B1).
• Recommendation 4: HCV-related lymphoma is also recommended for the general population to adopt a whole-genotype DAA combination plan, combined with specific chemotherapy, and at the same time, be alert to drug interactions (B1).

15.2 Patients with renal insufficiency (including dialysis patients)

• Recommendation 1: Patients with severe renal insufficiency (eGFR<30 ml·min-1·1.73 m-2) and end-stage renal disease who have entered hemodialysis should be treated in a professional clinical center, requiring a multidisciplinary team during and after treatment Close monitoring (B1).
• Recommendation 2: Mild to moderate renal insufficiency (eGFR≥30 ml·min-1·1.73 m-2) or severe renal insufficiency (eGFR<30 ml·min-1·1.73 m-2) and end-stage renal disease HCV infected persons who have entered hemodialysis can refer to the recommended program for the general population without adjusting the DAA dose (A1).
• Recommendation 3: Gcarevir/pirentavir is only recommended for patients with HCV genotype 1b, severe renal insufficiency (eGFR<30 ml·min-1·1.73 m-2) and end-stage renal disease requiring dialysis The patient recommended the Glarevir/Elbavir combined regimen (B1).
• Recommendation 4: Decompensated liver cirrhosis and mild to moderate renal insufficiency should be treated with Sofosbuvir/Vipatavir combined with ribavirin for 12 weeks. Ribavirin can be started at 600 mg/d. Adjust the dose for tolerance and hemoglobin level (B1).
• Recommendation 5: Use Sofosbuvir/Vipatavir combined program without ribavirin for 24 weeks (B1) in decompensated liver cirrhosis and severe renal insufficiency.
• Recommendation 6: For patients with end-stage renal disease, indications for kidney transplantation, and before and after kidney transplantation, the benefits and risks of treatment need to be individually assessed (B1).

15.3 HBV/HCV co-infection

• Recommendation 1: HBV/HCV co-infected persons should undergo HIV testing if their HIV infection status is unknown (A1).
• Recommendation 2: Patients with HBV/HCV co-infection should adopt the same treatment plan and principles as a single HCV infection (A1).
• Recommendation 3: Patients with HBV/HCV co-infection and meeting the HBV treatment criteria need to receive nucleoside or nucleotide analog therapy (refer to the 2017 European Society of Hepatology HBV Management Clinical Guidelines) (A1).
• Recommendation 4: HBsAg-positive patients should receive nucleoside or nucleotide analog preventive treatment for at least 12 weeks after the end of anti-HCV treatment, and HBV should be monitored every month after the end of anti-HBV (B1).
• Recommendation 5: For HBsAg-negative and anti-HBc antibody-positive patients, serum ALT levels need to be monitored monthly to find possible HBV activation (B1).

15.4 Hemoglobinopathies and bleeding disorders

• Recommendation 1: Regardless of whether there is hemoglobinopathy or bleeding disorders, the indications for anti-HCV therapy remain unchanged (A1).
• Recommendation 2: For patients with hemoglobinopathy or bleeding disorders, the anti-HCV regimen and principles are the same as those with HCV single infection (B1).

Retreatment after 16DAA treatment fails

• Recommendation 1: Patients who have failed the DAA treatment plan should be treated again in the context of a multidisciplinary team composed of experienced therapists and virologists (B1).
• Recommendation 2: HCV resistance detection before retreatment can predict the possibility of retreatment response based on the observed resistance phenomenon (B1).
• Recommendation 3: Patients without liver cirrhosis or compensated liver cirrhosis, including DAA (protease inhibitor or NS5A inhibitor) regimen treatment failure should be treated with Sofosbuvir/Vipatavir/Vocirevir combined treatment for 12 weeks ( A1).
• Recommendation 4: No cirrhosis or compensated cirrhosis, after treatment failure with DAA regimens (protease inhibitors or NS5A inhibitors), and low response predictors (end-stage liver disease, based on multiple DAA treatments, complex NS5A RAS changes) Patients can be treated with sofosbuvir combined with Gcareivir/pirentavir for 12 weeks based on individualized treatment by a multidisciplinary team (B1).
• Recommendation 5: In very refractory patients (NS5A RAS, the combined regimen contains protease or NS5A inhibitor regimens for SVR failures of 2 or more times), based on the individualized treatment of a multidisciplinary team, triple DAA sofosbuvir/vipa can be given Tamivir/vocirevir, or sofosbuvir, gorcarevir/pirentavir, combined with ribavirin (<75 kg, 1000 mg/d; ≥75 kg, 1200 mg/d) treatment 12 Weeks, the treatment period can be extended to 16~24 weeks (B1).
• Recommendation 6: Triple DAA Sofosbuvir/Vipatavir/Vosirrevir, or Sofosbuvir, Gcarevir/Prentavir after re-treatment, patients with SVR failure can use Sofosbuvir, Goka Revir/pirentavir, combined with ribavirin (<75 kg, 1000 mg/d; ≥75 kg, 1200 mg/d) for 24 weeks (B1).
• Recommendation 7: In decompensated liver cirrhosis, protease inhibitors should be disabled for treatment failures with DAA regimens (protease inhibitors or NS5A inhibitors). Therefore, based on the individualized treatment of a multidisciplinary team, use Sofosbuvir/Vipatavir, Combined with ribavirin (<75 kg, 1000 mg/d; ≥75 kg, 1200 mg/d) for 24 weeks (B1).

17 Newly received treatment for HCV infection

• Recommendation 1: Patients who have recently re-infected with HCV should be treated with sofosbuvir/Vipatavir or Gcarevir/pirentavir for 8 weeks (B1).
• Recommendation 2: Due to reports of delayed recurrence, SVR12 and SVR24 should be monitored (B2).
• Recommendation 3: If there is no clear evidence of HCV transmission, post-exposure prophylactic antiviral therapy is not recommended (B1).

18 treatment monitoring

18.1 Evaluation of treatment effectiveness

• Recommendation 1: Test HCV RNA or HCV core antigen at 12 or 24 weeks after the end of treatment to assess whether the treatment is successful (A1).
• Recommendation 2: In view of the high SVR12 rate of the whole-genotype DAA program, SVR may not be tested unless the patient has high-risk behaviors or is at risk of reinfection (B1).

18.2 Treatment safety monitoring

• Recommendation 1: Patients receiving treatments that include DAA should be evaluated for clinical side effects at each visit (A1).
• Recommendation 2: Monitor ALT levels at baseline and 12 and 24 weeks after treatment to find patients with no overt symptoms (B1).
• Recommendation 3: Patients with decreased eGFR levels should monitor renal function every month (A1).

18.3 Drug interaction monitoring

• Recommendation 1: During treatment, the effectiveness and toxicity of comorbid drugs and potential drug interactions should be monitored (A1).
• Recommendation 2: If possible, discontinue the combined medications with interactions or replace them with drugs with less interactions during treatment (B1).

18.4 Reduction therapy

• Recommendation 1: Treatment should be stopped when there is a serious adverse event or the ALT level suddenly increases to 10 times the upper limit of normal (B1).
• Recommendation 2: In patients who need ribavirin therapy (decompensated cirrhosis), if the Hb level drops to 100 g/L, ribavirin should be reduced by 200 mg each time (A1); if If Hb drops to 85 g/L, ribavirin must be discontinued (A1).

18.5 Post-treatment follow-up of SVR patients

• Recommendation 1: Patients with no or mild fibrosis (METAVIR score F0~2), SVR and no persistent high-risk behaviors, and no other complications can stop follow-up (A1).
• Recommendation 2: SVR patients with advanced liver fibrosis (F3) and liver cirrhosis (F4) should be monitored for HCC every 6 months because the risk of HCC occurrence or recurrence after SVR is reduced but not completely eliminated (A1) .
• Recommendation 3: In patients with liver cirrhosis, if endoscopy finds esophageal varices before treatment, or the platelet count drops to <150 000, and the elastography value rises to >20 kPa, endoscopy is still needed to monitor varicose veins after treatment ( A1).
• Recommendation 4: The risk of recurrence should be clarified to high-risk groups to avoid high-risk behaviors (B1).
• Recommendation 5: Follow-up after SVR, among PWID or high-risk men who have sex with men, it is best to test HCV RNA at least once a year to detect re-infection (A1); if re-infected patients are found, timely antiviral treatment (A1) ).

18.6 Follow-up of untreated and clearly failed patients

• Recommendation 1: Patients with chronic HCV who have not been treated or who have failed the previous few treatments (incurable patients) should be followed up regularly (A1).
• Recommendation 2: Use non-invasive methods for fibrosis classification every 1 to 2 years (A1).
• Recommendation 3: Patients with advanced liver fibrosis and cirrhosis must undergo HCC monitoring every 6 months (indefinitely) (A1).

(source:chinanet, 2020 EASL Recommendations: Treatment of Hepatitis C. )

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