Editor’s Note: Chronic HCV infection is a global public health issue. With the widespread use of direct-acting antiviral agents (DAAs), chronic hepatitis C (CHC) has become a curable disease. However, after successful HCV clearance and achieving sustained virological response (SVR), do CHC patients still face risks of liver-related events? Currently, there is a significant gap in reaching the World Health Organization’s goal of eliminating viral hepatitis as a major public health threat by 2030. How can we achieve near-elimination of HCV? At the 32nd annual meeting of the Asia-Pacific Association for the Study of the Liver (APASL), Professor Rao Huiying from Peking University People’s Hospital, China, was invited as our special correspondent to bring four significant research findings in this field to our readers, providing insightful interpretations and summaries.
Study 1: Metabolic Dysfunction Increases Liver-Related Event Risk in Hepatitis C Patients Post-Cure, Not Ultrasonographic Hepatic Steatosis
Background
CHC has become a leading cause of liver-related deaths. A significant number of patients die from HCV-related liver diseases annually. It’s estimated that up to 74% of CHC patients may develop at least one extrahepatic manifestation, with diabetes mellitus (DM) being one of the more common. Previous studies have indicated that DM is a risk factor for the progression of liver fibrosis and liver-related events (LREs). HCV and DM have a complex bidirectional relationship. However, the impact of metabolic associated fatty liver disease (MAFLD) or metabolic dysfunction on LREs in CHC patients with sustained virological response (SVR) post-DAA treatment remains unclear. This study aims to analyze predictive factors for LREs in SVR patients post-DAA treatment, based on MAFLD or metabolic dysfunction.
Methods
The study, conducted from September 2012 to April 2022, included 924 CHC cured patients. Exclusion criteria were HBV or HIV infection, non-SVR, prior LREs (including esophageal or gastric variceal bleeding, ascites, hepatic encephalopathy, and hepatocellular carcinoma), and end-stage renal disease. Hepatic steatosis was defined as follows: ultrasonographic fatty liver (uFL, Group 1) or hepatic steatosis index >36 (eFL, Group 2). MAFLD was defined as hepatic steatosis with at least one of the following: overweight or obesity (BMI >23 kg/m^2), DM, and non-DM metabolic dysfunction. Factors related to LREs were collected at baseline and at 12 weeks post-treatment (PW12).
Results
Out of the 924 patients, 418 were male (45.2%), with a median age of 58 years (range 49-65 years). There were 174 diabetic patients (18.8%) and 156 with cirrhosis (16.9%). Group 1 and Group 2 MAFLD patients numbered 404 (43.7%) and 573 (62.0%), respectively. The median follow-up time after DAA treatment was 34.09 months (range 17.31-50.20).
Due to collinearity between the definition of MAFLD and fatty liver, the researchers used hepatic steatosis (uFL or eFL) and metabolic dysfunction instead of MAFLD in the multivariate Cox regression analysis. For Group 1, age, gender, albumin, total bilirubin, alpha-fetoprotein (AFP), uFL (HR=0.347, 95% CI: 0.176-0.683, P=0.002), and metabolic dysfunction (HR=1.737, 95% CI: 1.241-2.432, P=0.001) were independent predictors of LREs post-SVR in CHC patients. In Group 2, age, albumin, total bilirubin, AFP, and metabolic dysfunction (HR=1.676, 95% CI: 1.137-2.469, P=0.009) were independent predictors of LREs. Multivariate Cox regression analysis showed that neither MAFLD (Group 1: P=0.246; Group 2: P=0.256) nor FIB-4 were predictors of hepatocellular carcinoma in CHC patients post-SVR.
Conclusion
Metabolic dysfunction increased the risk of LREs in CHC patients who achieved SVR, but ultrasonographic fatty liver suggested a decreased risk of LREs, the reasons for which require further research.
Expert Commentary
Currently, CHC can be completely cured with DAA treatment regimens. However, even after HCV clearance, CHC patients may still experience progression of LREs and other extrahepatic manifestations, including metabolic abnormalities and DM. This study analyzed the situation of MAFLD and other metabolic dysfunctions in CHC patients who achieved SVR after DAA treatment. The results suggest that for CHC patients with fatty liver, monitoring of LREs is still necessary after HCV clearance.
Study 2: HCV Micro-Elimination in the Diabetic Population of a Medical Center
Background
Previous clinical studies have shown an association between chronic HCV infection and DM. Data indicate that the prevalence of HCV is twice as high in DM patients compared to the general population. There has been little reporting on HCV micro-elimination in the DM population. This study aims to examine the HCV elimination strategy for the DM population in a medical center.
Methods
The study was based on a DM care registration system used in Taiwan since 2007, focusing on DM cases from Kaohsiung Chang Gung Memorial Hospital between 2018 and 2020. A total of 14,759 DM cases were registered, and they were screened and treated for HCV. The study analyzed completion rates of various steps in the HCV management cascade and differences in HCV infection and treatment rates under various influencing factors.
Results
Compared with baseline characteristics, DM patients were older (P<0.05), had a higher proportion of females (P<0.05), higher proteinuria (P<0.005), higher HbA1c (P=0.004), higher fasting blood sugar (P=0.010), higher ALT levels (P<0.0005), lower eGFR (P=0.011), and lower TG levels (P<0.003). After excluding those who died, aged, or were highly mobile, 14,759 individuals were targeted for screening. The HCV antibody screening rate was 90.7% (13,387 individuals), with an HCV antibody positivity rate of 8.7% (1,172 individuals). The HCV RNA testing rate was 76.3% (895 individuals), with a detectable HCV RNA rate of 68.3% (612 individuals), and the final treatment rate was 88.6% (542 individuals). Compared to pre-intervention, both screening and treatment rates significantly increased, achieving the goal of eliminating HCV.
Conclusion
A new model for HCV elimination in the hospital’s DM population was successfully implemented using a series of medical care cascade indicators.
Expert Commentary
It’s well known that the World Health Organization has set the goal of eliminating viral hepatitis as a major public health threat by 2030, including hepatitis C. Currently, in the main efforts to eliminate HCV, there’s a hope for more HCV-infected individuals to be identified, diagnosed, and treated with DAAs in a timely manner.
In the previous study, we discussed the extrahepatic manifestations of CHC and its association with DM. This research found that conducting HCV screenings and treating positive cases in the diabetic population visiting hospitals yielded good results. The study suggests that HCV screening, diagnosis, and treatment, based on the hospital’s special DM population registry, are beneficial for HCV elimination. It also established an effective model for HCV micro-elimination.
Study 3: Outcomes of the LEGA-C Project: Review of Implementation Science Projects for HCV Elimination by 2030 in Asia
Background
The World Health Organization has identified HCV infection as a public health threat and has set a global goal to eliminate the threat of hepatitis C by 2030. However, currently, only 11 countries are on track to achieve this goal. To meet the WHO’s objectives, many patients still need to be screened and linked to management. A project named “Local Elimination of Global Hepatitis C” (LEGA-C) is underway to support the implementation of scientific projects aimed at eliminating HCV. This study explores the impact of the LEGA-C project, particularly on HCV-infected individuals in Asia.
Methods
The results and impact were measured by examining the number of studies and the number of patients involved; the steps in the medical care cascade and the effectiveness of each model were assessed.
Results
LEGA-C supported over 120 studies, with 18 completed or ongoing in Asia. As of July 2022, 175,192 individuals were screened, identifying 6,287 HCV-infected patients, of whom 3,768 received treatment. Eight studies investigated simplified HCV screening and its connection to care/minimal monitoring models.
Among these, four trial and treatment studies showed that active screening and on-site treatment could promote HCV micro-elimination. Three outreach and recall studies demonstrated the feasibility of recruiting personnel for HCV screening programs in community settings. Seven studies focused on special populations, with four describing the characteristics of special groups with higher HCV infection rates. Publications from these Asian studies included 14 full-text articles, which were collectively cited 56 times.
Conclusion
The LEGA-C project has contributed to raising public awareness about HCV and promoting micro-elimination efforts. The projects featured innovative ideas, aggressive promotion of HCV testing, disease education, patient navigation, and healthcare coordination, all of which collectively enhanced screening and treatment rates for HCV.
Expert Commentary
This study demonstrates that by adopting and adjusting effective HCV screening, diagnosis, and treatment strategies, and simplifying the execution process as much as possible, we can improve HCV screening and treatment rates. It is hoped that with joint efforts, we can first achieve the goal of eliminating HCV in Asia, and then push forward to meet the global objective of eliminating hepatitis C by 2030.
Study 4: Simplified Strategies for Baseline Testing and Minimal Monitoring in the Treatment of HCV Infection
Background
The advent of highly effective and well-tolerated DAAs has made the global elimination of HCV possible. This survey study aimed to: 1) gather opinions on simplified DAA treatment strategies from the perspectives of doctors, case managers, and patients; 2) assess the feasibility of implementing simplified treatment methods; 3) understand patient compliance with HCV treatment.
Methods
This survey study collected questionnaires from 100 HCV-infected individuals, 50 hepatology and gastroenterology doctors, and 20 case managers in Taiwan. The questionnaire, designed by IQVIA and reviewed by gastroenterologists, aimed to address factors affecting patient treatment.
Results
This is an interim report of the study, presenting questionnaire results from 50 HCV-infected individuals, 43 doctors, and 12 case managers. Over 85% of doctors believed it necessary to assess baseline CBC, PT/INR, bilirubin, albumin, and creatinine, while considering FIB-4, FibroScan, and biopsy as optional. 80% of doctors recommended monitoring AST/ALT and bilirubin during and after DAA treatment. 93% and 98% of doctors deemed it necessary to test for HCV RNA at EOT (End of Treatment) and SVR 12, respectively. 53% of doctors suggested simplifying or abolishing the VPN system requirement.
To manage drug interactions, 83% of case managers planned to track assessments from doctors and pharmacists through treatment visits, phone care, or regular personal visits. To improve HCV treatment compliance, case managers recommended same-day testing and treatment, as well as follow-up at the same medical institution where HCV infection was diagnosed.
Among the 50 surveyed HCV-infected individuals, common comorbidities included cardiovascular disease (36%), renal disease (26%), and diabetes (18%). Regarding HCV treatment plans, 78% of patients started the DAA treatment prescribed by their doctor, while 22% chose treatment plans based on a shared decision-making model with their doctor. 68% of patients were overall satisfied with their HCV treatment. 28% reported that routine follow-ups or medication collection were major obstacles during HCV treatment. 30% experienced treatment interruptions or discontinued treatment because they perceived chronic HCV infection as not severe.
Conclusion
The study suggests that adopting simplified DAA treatment and monitoring strategies can accelerate the global elimination of HCV.
Expert Commentary
This study highlights a consensus between medical professionals and patients towards accelerating the global elimination of HCV. There is a shared understanding of minimizing monitoring for non-complex HCV infections and implementing more simplified HCV treatment strategies. This approach not only reduces the burden of medical costs but also helps improve patient compliance with treatment, thereby empowering us in the fight to eliminate HCV.
TAG: APASL 2023, Review, HCV
