F573 for Injection for the Treatment of Liver Injury/Failure

Inclusion Criteria:

（1）The first stage:

Participants who meet all of the following criteria will be enrolled in the study:

1. Age ≥18 and ≤60 years old, gender is not limited;

2. Patients with liver injury clinically diagnosed with hepatocyte injury or mixedliver injury or CHB patients with hepatitis B virus infection for more than 6 months (refer to the "Chronic Hepatitis B Prevention and Treatment Guidelines (2019edition)"). Screening patients with CHB may provide etiological (HBsAg positiveand/or HBV DNA positive) or clinical or pathological evidence (liver tissue biopsyresults) that HBV infection has been present for more than 6 months.

3. Serum ALT: 2~ 10× upper limit of normal (ULN), TBil: <5×ULN;

4. DILI patients: the abnormal duration of liver biochemical indexes [ALT, AST, ALP,gamma-glutamyltranspeptides (GGT), TBil, albumin, prothrombin time] does not exceed 90 days;

5. The subject (including the partner) is willing to take effective contraceptivemeasures from the screening until 6 months after the last test drug administration;

6. Sign informed consent and be able to comply with the requirements of the program; Ifthe subject is unable to sign the informed consent form, it must be signed by alegal guardian or witness as required by the regulations.

(2)The second stage:

Subjects meeting all of the following criteria will be included in the study:

1. Age ≥ 18 and ≤ 65 years old, with no gender restrictions;

2. According to the "Chinese Guidelines for the Diagnosis and Treatment of Drug-InducedLiver Injury (2023 Edition)", patients diagnosed with drug-induced liver injury (DILI) or those diagnosed with intrahepatic cholestasis type liver injury. Patientswith DILI and intrahepatic cholestasis type liver injury need to meet the followingcriteria separately;

3. Patients with DILI need to simultaneously meet the following conditions: ①Serum ALT > 3 times the upper limit of normal (ULN), and TBil > 2 times the ULN (the ULN of TBil refers to 17.1 μmol/L according to international standards); ②Abnormal liver biochemical indicators (ALT, AST, ALP, TBil) persist for no morethan 60 days;

4. Patients with intrahepatic cholestasis type liver injury need to simultaneouslymeet the following conditions: ① TBil > 2 times the ULN (the ULN of TBil refersto 17.1 μmol/L); ② ALP > 1.5 times the ULN; ③ALT>1×ULN;

5. The subjects (including their partners) are willing to voluntarily adopt effectivecontraceptive measures from the time of the initial screening until 6 months afterthe last administration of the investigational drug;

6. They have signed the informed consent form and can comply with the requirements ofthe protocol; if the subjects are unable to sign the informed consent form, it mustbe signed by a legal guardian or a witness as required by the regulations.

The third stage:

Subjects who meet all of the following criteria will be enrolled in the study:

1. Age ≥18 and ≤70 years old, gender is not limited; 2. Patients diagnosed with chronic and acute liver failure with TBil≥5×ULN according to the "Guidelines for Diagnosis and Treatment of Liver Failure (2018 Edition)" may have hepatic encephalopathy (Grade 1-2) or ascites (grade 1-2) 4 weeks before subject screening. And 5≤AARC score ≤10 (AARC rating I-II); 3. The subject (including the partner) is willing to take effective contraceptive measures from the screening until 6 months after the last trial drug administration; 4. Sign informed consent and comply with the requirements of the program; If the subject is unable to sign the informed consent form, it must be signed by a legal guardian or witness as required by the regulations.

Exclusion Criteria:

The first stage:

Subjects meeting one of the following conditions will not be included in the trial:

1. According to the investigator's judgment, the subjects were patients withcholestatic liver injury;

2. Previous diagnosis of cirrhosis or liver hardness determination (LSM) at screening ≥ 12.4kPa;

3. Patients with severe or life-threatening heart, lung, brain, kidney,gastrointestinal and systemic diseases, and patients with malignant tumors;

4. There are the following laboratory test values or abnormal test values:

5. Blood routine: platelet (PLT) <75× 109/L, hemoglobin (HGB) <90 g/L;

6. Prothrombin activity <40%, prothrombin time (PT) extended >5 s;

7. Left ventricular ejection fraction (LVEF) <50%;

8. Allergic or intolerant to the investigational drug, or allergic;

9. The subject is unable to express his main complaint, such as mental illness andsevere neurosis;

10. Poor compliance can not partner;

11. Pregnant women, breastfeeding women or women of childbearing age who are trying toconceive;

12. Participants in other clinical trials within 3 months;

13. Patients who had used liver protection drugs other than ursodeoxycholic acid oradenosylmethionine within 3 days before randomization;

14. The researcher considers any circumstances unsuitable for inclusion.

The second stage:

Subjects meeting one of the following conditions will not be included in the trial:

1. The diagnosis is advanced liver cirrhosis (with complications such as ascites andhepatic encephalopathy), or liver cancer, or when liver stiffness measurement (LSM)is ≥ 18.0 kPa during screening.

2. Patients with severe or life-threatening heart, lung, brain, kidney,gastrointestinal and systemic diseases are malignantTumor patients;

3. There are the following laboratory test values or abnormal test values:

4. Blood routine: platelet (PLT) <100×109/L, hemoglobin (HGB) <100 g/L;

5. INR>1.4, or as determined by the investigator to meet the criteria for severehepatitis;

6. Left ventricular ejection fraction (LVEF) <50%;

7. Allergic or intolerant to the investigational drug, or allergic;

8. The subject is unable to express his main complaint, such as mental illness andsevere neurosis;

9. Poor compliance can not partner;

10. Pregnant women, breastfeeding women or women of childbearing age who are trying toconceive;

11. Participants in other clinical trials within 3 months;

12. Patients who had used liver protection drugs other than ursodeoxycholic acid oradenosylmethionine and basic therapeutic drugs (polyene phosphatidylcholines andglutathione drugs) within 3 days before randomization;

13. Patients who had used glucocorticoids or interferon drugs within 3 days beforerandomization;

14. The researcher considers any circumstances unsuitable for inclusion.

The third stage:

Subjects meeting one of the following conditions will not be included in the trial:

1. Patients who have completed liver transplantation or plan to undergo livertransplantation within 1 month;

2. Severe grade 3 ascites or stubborn ascites;

3. Patients with ≥ grade 3 hepatic encephalopathy;

4. Patients who received artificial liver treatment within 1 week before screening;

5. Patients with severe underlying diseases, such as respiratory system, digestivesystem, circulatory system, endocrine and other diseases and malignant tumors, andpatients with severe infections that cannot be controlled by drugs;

6. During the screening period or within 1 month before screening, the results ofgastroscopy or imaging (abdominal B-ultrasound, CT or MRI) examination suggestsevere varicose veins with bleeding risk;

7. Patients with acute kidney injury (AKI), defined as meeting one of the followingconditions:

8. Serum creatinine (Scr) increased ≥26.5 μmol/L (0.3 mg/dL, 1 mg/dL=88.4 μmol/L)within 48 h;

9. The Scr increase exceeds 1.5 times or more of the base value within 7 days;

10. Decreased urine volume (<0.5 mL/kg/h) for more than 6 hours;

11. Allergic or intolerant to the investigational drug, or allergic;

12. The subject is unable to express his main complaint, such as mental illness andsevere neurosis;

13. Poor compliance can not partner; 11 Pregnant women, breastfeeding women or women ofchildbearing age who are trying to conceive;

14. Participants in other clinical trials within 3 months; 13. The researcher considers any circumstances unsuitable for inclusion.