A NOVEL AND SIMPLIFIED SCORE FOR DETERMINING TREATMENT ELIGIBILITY FOR PATIENTS WITH CHRONIC HEPATITIS B

Introduction:
Chronic hepatitis delta (CHD) typically leads to cirrhosis and hepatic decompensation. The only treatment option for CHD patients with decompensated cirrhosis is liver transplantation with associated short- and long-term complications. REP 2139-Mg is a nucleic acid polymer (NAP) that blocks the assembly and secretion of HBV subviral particles and hepatitis delta antigen function, providing multiple effects against both HBV and HDV infection. The objective of this study is to describe the safety and efficacy of REP 2139-Mg in CHD patients with decompensated cirrhosis.

Patients & Methods:
Compassionate use access in the first two European CHD patients with decompensated cirrhosis to receive REP 2139-Mg 250 mg QW subcutaneously (SC) and tenofovir disoproxil fumarate (TDF) 300 mg QD orally for a planned total duration of 48 weeks was approved in France by the ANSM. Clinical, biological, virological and imaging data were collected at baseline and every week for the first month, then every month. Safety and tolerance were continuously evaluated.

Results:
Patient #1 is a Caucasian, 56-year old female, HDV treatment-naïve, with CHD decompensated cirrhosis (Child Pugh B8, portal hypertension and ascites) with HDV RNA 7.04 log10 IU/mL and HBsAg 1177 IU/mL at baseline. At week 4 of therapy, reversal of ascites was confirmed by ultrasound (minimal diuretic dose was maintained due to mild bilateral leg edema). HBsAg loss occurred at week 10 with HBsAg seroconversion (27 mIU/mL) at week 14 increasing to 168 mIU/mL at week 18. HDV RNA has been undetectable since week 20.
Patient #2 is an African, 56-year old female with arterial hypertension awaiting liver transplant. She experienced HDV relapse 1 year after discontinuing bulevirtide 2mg and pegIFN 180ug and progressed to decompensated cirrhosis (Child Pugh C11, portal hypertension, ascites and hepatocellular carcinoma) with accompanying edema, and pronounced fatigue. Baseline HDV RNA was 3.64 log10 IU/mL and HBsAg 4270 IU/mL. At Week 4, abdominal CT confirmed significant reduction of clinical ascites and peripheral edema and fatigue were markedly reduced.

Both patients have no side effects and present a good tolerance to subcutaneous injections of REP 2139-Mg to date.

Conclusion:
REP 2139-Mg in association with TDF is safe and well tolerated in patients with CHD and decompensated cirrhosis. Liver function improvement with significant ascites reversal was rapid, occurring after only 4 weeks of treatment. HBV-HDV functional cure with HBsAg loss and HBs seroconversion appears achievable in this special population which could prevent the need for a future liver transplant.

Background & Aims: International treatment guidelines for hepatitis B infection (HBV) recommend initiating antiviral therapy based on viral replication with significant inflammation or fibrosis. However, HBV viral load and liver fibrosis measurements are not widely available in resource-limited countries. We aimed to develop a simple scoring system for selecting patients for treatment in these countries.

Methods: We examined 602 and 420 treatment-naive HBV mono-infected patients for derivation and validation cohorts, respectively. We performed logistic regression analysis to identify independent liver-related complication parameters associated with the initiation of antiviral treatment based on the European Association for the Study of the Liver clinical practice guideline. The scores in our system were based on these parameters and converted to integer points. The scoring system’s performance was validated and compared with the Treatment Eligibility in Africa for HBV (TREAT-B) system, World Health Organization (WHO) simplified criteria, and Risk Estimation for HCC in Chronic Hepatitis B (REACH-B) system.

Results: The novel scoring system (HePAA score) was based on HBeAg (0 point; negative, 1 point; positive), platelet count (0 point; ≥150,0000, 1 point; <150,0000 /mm³), alanine transaminase (0 point; <30, 1 point; 30 - 39, 2 points; 40 – 49, 3 points; ≥ 50 IU/L), and albumin (0 point ≥ 4, 1 points; < 4 g/dL). The system showed excellent performance, with an area under the receiver operating characteristic curve of 0.926 (95% CI, 0.901–0.950) for the derivation cohort and 0.872 (95% CI, 0.833–0.910) for the validation cohort. The optimal cutoff was ≥3 points (sensitivity, 84.9%; specificity, 92.6%). The HePAA scoring system performed better than the WHO criteria and REACH-B scoring system and performed similarly to the TREAT-B system. The HePAA system demonstrated similar performance when using all guidelines (AASLD; American Association for the Study of Liver Diseases, APASL; Asian-Pacific Association for the Study of Liver, and THASL; Thai Association for the Study of the Liver) as gold standards.

Conclusions: The HePAA scoring system is simple and accurate for chronic hepatitis B treatment eligibility in resource-limited countries.