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( Jonggi Choi ),( Jina Park ),( Danbi Lee ),( Ju Hyun Shim ),( Kang Mo Kim ),( Young-suk Lim ),( Han Chu Lee ),( Young-hwa Chung ) 대한소화기기능성질환·운동학회 2022 Gut and Liver Vol.16 No.6
Background/Aims: The care cascade for hepatitis C virus (HCV) infection is impeded by multiple barriers, including suboptimal anti-HCV testing, link to care, and diagnosis. We explored the changes in the care cascade of HCV for the past 20 years and its current status in a large cohort from a tertiary referral center. Methods: We analyzed 1,144,468 patients who had anti-HCV testing between January 2001 and June 2020. Metrics related to the care cascade of HCV infection and the long-term prognosis of patients were explored. Results: The seroprevalence of anti-HCV positivity was 1.8%, with a recent decreasing trend. In all, 69.9% of anti-HCV positive patients performed HCV RNA testing, with a 65.7% positivity. Patients who did not have HCV RNA testing were older and more likely to have a non-hepatocellular carcinoma malignancy, normal alanine aminotransferase level, and good liver function. Linkage times for HCV RNA testing from the anti-HCV positivity and for antiviral treatment from HCV diagnosis decreased, notably after 2015, when highly efficacious oral antiviral treatment was introduced to Korea. The average treatment uptake rate was 35.4%, which increased to 38.9% after 2015. Of the 5,302 patients analyzed for long-term prognosis, the annual incidences of hepatocellular carcinoma were 1.02 or 2.14 per 100 person-years in patients with or without a sustained virological response, respectively. Conclusions: The care cascade of HCV infection has been suboptimal for the past 20 years, despite the recent changes. More effort should be made to increase HCV RNA testing and treatment uptake. (Gut Liver 2022;16:964-975)
( Jonggi Choi ),( Seungbong Han ),( Gi-ae Kim ),( Young-suk Lim ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1
Aims: HBeAg seroclearance is one of surrogate markers by current guidelines to predict the long-term outcomes in patients with chronic hepatitis B (CHB). However, whether HBeAg seroclearance in HBeAg-positive CHB patients under antiviral treatment can reflect the long-term outcomes remains unanswered in the era of high potency antiviral agents. Methods: A historical cohort of 2,829 treatment-naïve HBeAg-positive CHB patients who initiated treatment with entecavir or tenofovir disoproxil fumarate at a tertiary referral hospital in Korea from 2007 through 2016 were included. The risk of HCC was analyzed by multivariable Cox proportional hazards model and time-dependent Cox model. Results: The mean age was 45.0 years and 1,832 (64.8%) were male. Cirrhosis was present in 1,077 (38.1%) of patients. With the median follow-up of 56.8 months, HBeAg seroclearance was observed in 905 (32.0%) patients. HBeAg seroconversion and virologic response (HBV-DNA <60 IU/mL) were achieved in 694 (24.5%) and 2249 (79.5%) patients, respectively. During 13,526 person-years of follow-up, 238 patients developed HCC, with an annual incidence rate of 1.75/100PYs. The unadjusted cumulative incidence of HCC of patients experiencing HBeAg seroclearance during the first 2-year of antiviral treatment was not significantly different compared with that of patients who persisted HBeAg-positivity (P=0.15), regardless of presence of cirrhosis. By time-dependent Cox model, HBeAg seroclearance during overall treatment period was not a significant factor for predicting HCC development (adjusted hazard ratio: 0.92, 95% confidence interval: 0.58-1.44, P=0.70). In multivariable analysis, older age, male sex, lower ALT level, lower albumin, lower platelet count, and cirrhosis at baseline were independent predictive factors for HCC development. Conclusions: In a large historical cohort of HBeAg-positive CHB patients, HBeAg seroclearance during antiviral treatment was not a significant surrogate marker for predicting HCC.
( Jonggi Choi ),( Young-suk Lim ),( Woochang Lee ),( Sail Chun ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1
Aims: Current surveillance strategy for hepatocellular carcinoma (HCC) is based on the single point measurement rather than the serial change of alpha-fetoprotein (AFP). Methods: We performed a National Cancer Institute’s Early Detection Research Network(EDRN)-defined phase 3 biomarker, nested case-control study by using prospectively collected samples from cirrhotic patients at high risk for HCC development. Forty-two cases of HCC were included and matched to controls (N=168) without HCC in a 1:4 ratio by age, gender, etiology of liver disease, and cirrhosis. All patients were screened every 6 months with serum AFP and imaging modalities with a median follow-up of 24 months. Blood samples at the time of HCC diagnosis and months -6, and -12 and at corresponding time points form the matched controls were eval uated for AFP. Results: Of the 42 patients with HCC, 32 (76.2%) had very early-stage HCC (a single nodule <2 cm) and 4 (9.5%) had early-stage HCC (single 2-5 cm or 2-3 lesions each <3 cm). The mean of most recent AFP (ng/mL) was significantly higher in HCC cases than in controls (35.4±78.6 vs 5.0±17.1, respectively, p<0.001). HCC cases had a higher level of standard deviation of AFP than controls (17.1±42.8 vs 1.7±9.9, respectively, p=0.026), as well as rate of AFP increase (7.3±18.8 in HCC cases vs 0.0±4.1 in controls, p=0.017). Rate of AFP increase was the most strongly associated with the development of HCC (odds ratio [OR], 1.10; area under curve [AUC], 0.747; p=0.03), followed by standard deviation of AFP (OR, 1.03; AUC, 0.723; p=0.02) and most recent AFP (OR, 1.02; AUC, 0.740; p=0.03). Conclusions: Serial change pattern of AFP is better marker of early stage HCC than single point AFP.
만성 B 형 간염 면역 관용기: 치료 할 것인가 말 것인가?
최종기 ( Jonggi Choi ) 대한간학회 2020 Postgraduate Courses (PG) Vol.2020 No.1
Hepatitis B virus (HBV) infection is a major global health issue causing end-stage liver disease or hepatocellular carcinoma. Based on virus-host interactions, natural course of chronic hepatitis B (CHB) infection can be divided into four chronological phases. Immune tolerant (IT) phase, the first phase of natural course of CHB, is defined as normal alanine aminotransferase (ALT) and very high level of HBV DNA according to the current international guidelines and is traditionally considered “benign” disease due to host’s immune tolerance. However, evidences from basic and clinical studies argued that IT phase may not completely be a benign feature. Immunologic studies demonstrated that HBV-specific immune responses in patients with IT phase are as active as those in patients with immune clearance phase, which is indicated for antiviral treatment. In addition, recent large-scale observational studies also support this notion showing that higher and worse long-term clinical outcomes in patients with IT phase than patients with immune active phase under antiviral treatment. Therefore, issues of earlier antiviral treatment and treatment indication expansion beyond current treatment guidelines are currently under hot debate. Nevertheless, opinion deferring treatment for patients with IT phase still prevails given that possibility of spontaneous HBeAg seroclearance, poor response to current treatments in patients with IT phase, and expected good long-term clinical outcomes in patients with genuine IT phase. Evidences from prospective randomized trials warrant to re-determination of treatment indication.