A Dietary Supplement (Epigallocatechin Gallate) for the Prevention of Liver Cancer in Patients with Liver Cirrhosis, CATCH-B Trial

Inclusion Criteria

• Diagnosis/disease status. Individuals with a clinical and/or histological diagnosis of compensated liver cirrhosis with (i) Child‐Pugh-Turcotte score of 7 or less, (ii) no evidence of active hepatic decompensation (e.g., variceal bleeding, uncontrolled hepatic encephalopathy, moderate to severe ascites), and (iii) no previous history of HCC diagnosis nor treatment within 2 years before enrollment.
• Age of participants. Participating individuals must be >= 18 years-old. There is no upper age limit as long as the individual fulfills the eligibility criteria.
• International normalized ratio (INR) or prothrombin time (PT) =<1.5 × the upper limit of normal (ULN) (within 14 days of registration).
• Platelets >= 100,000/uL (within 14 days of registration).
• Total bilirubin =< 3 × institutional ULN (within 14 days of registration).
• Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT) =< 5 × institutional ULN (within 14 days of registration).
• Creatinine =< 2 × institutional ULN (within 14 days of registration).
• Performance status: Must be Karnofsky performance status scale of 70 or above.
• Smoking. Willingness to discontinue smoking during the study two weeks prior to beginning the study and willingness to not smoke while taking study medication because smoking is associated with increased HCC risk.
• Not pregnant or breast feeding. The effects of EGCG on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately.
• Contraception. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: * Has not undergone a hysterectomy or bilateral oophorectomy; or * Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
• Blood specimens. Willingness to provide mandatory blood specimens as specified in the protocol.
• Absence of HLA-B*35:01 allele. Absence of HLA-B*35:01 associated with increased risk of green tea-derived products confirmed by Taqman genotyping assay using leukocytes isolated from the blood specimen.
• Clinical HCC risk status. Clinical-variable-based HCC risk will be assessed by using Fibrosis-4 (FIB-4) score > 3.25. We will prioritize patients with the FIB-4 score > 5 for further elevated HCC risk.
• High-risk PLSec. PLSec will be assayed using serum isolated from the blood specimen to further boost anticipated HCC incidence rate. In our previously analyzed cirrhosis patient cohort (n=2000), annual HCC incidences are 1.7% in patients with PLSec >= 3 and 2% in patients with PLSec score >= 4, both of which exceed the threshold to identify high risk patients for semi-annual HCC screening. In this trial, we will enroll patients with screening PLSec score >= 3, prioritizing patients with PLSec score >= 4.
• Liver biopsy (optional). Able to undergo (a) percutaneous or transjugular (in rare occasion) biopsy of cirrhotic liver within 6 months prior to EGCG treatment (can be archived liver biopsy tissue performed in the past) and within 1 month after completion of EGCG treatment. Willingness to authorize collection of tissue from clinical liver biopsy for analyses specified in the protocol.
• Informed consent. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

• Prior treatment. Any prior treatment with EGCG or other agent whose primary mechanism of action is known to inhibit cancer-promoting pathways. Any form of HCC treatment within 5 years before enrollment.
• Known diagnosis of HIV. Note: An HIV screening test does not have to be performed to evaluate this criterion.
• Use of antacids. Participants who regularly (>= 2 times per week) use drugs that alter the potential of hydrogen (pH) of the gastrointestinal (GI) tract, such as proton pump inhibitors (PPI) and antacids. Exceptions: Individuals who use prescription PPIs and have approval from their primary health care provider to discontinue for the duration of clinical trial participation may be enrolled. Alternate drug to control gastroesophageal reflux disease (GERD) and/or peptic ulcer disease (PUD) symptoms and/or alternative medication schedule will be suggested.
• Uncontrolled intercurrent illness. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.
• Severe obesity. Obesity defined as body mass index (BMI) >= 40 kg/m^2.
• Active alcohol drinking. Active alcohol drinking during the study period defined by the Alcohol Use Disorders Identification Test (AUDIT-C) score >= 4 for men and >= 3 for women.
• Allergy. History of allergic reactions attributed to compounds of similar chemical or biologic composition to EGCG.
• Use of anticoagulants. Participants who cannot have their warfarin, lovenox, plavix, or other comparable medications held for percutaneous or transjugular liver biopsy and surgery if so indicated.
• Lack of histologic abnormality. Pathology report from clinical liver biopsy (=< 6 months prior to registration) demonstrates no histologic abnormalities associated with chronic hepatitis, steatohepatitis, fibrosis, or cirrhosis.
• Use of other investigational agents. Receiving any other investigational agents =< 6 months prior to registration.
• Incomplete biopsy. Percutaneous or transjugular biopsy incomplete or not performed.
• Pregnancy. Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.