Clinical and Molecular Hepatology

Correspondence to editorials (CMH-2025-0699) on “Safety and efficacy of HK-660S in patients with primary sclerosing cholangitis: A randomized double-blind phase 2a trial”: Woo Hyun Paik, Heon Se Jeong, Do Hyun Park; Received July 22, 2025 Accepted July 27, 2025 Published online July 29, 2025; DOI: https://doi.org/10.3350/cmh.2025.0816 [Accepted]

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Autoimmune liver disease

Correspondence to editorial on “Safety and efficacy of HK-660S in patients with primary sclerosing cholangitis: A randomized double-blind phase 2a trial”: Woo Hyun Paik, Do Hyun Park; Clin Mol Hepatol 2025;31(2):e158-e160.
Published online November 11, 2024; DOI: https://doi.org/10.3350/cmh.2024.0989

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Autoimmune liver disease

Safety and efficacy of HK-660S in patients with primary sclerosing cholangitis: A randomized double-blind phase 2a trial: Woo Hyun Paik, Joo Kyung Park, Moon Jae Chung, Gunn Huh, Ce Hwan Park, Sang Hyub Lee, Heon Se Jeong, Hee Jin Kim, Do Hyun Park; Clin Mol Hepatol 2025;31(1):119-130.
Published online September 24, 2024; DOI: https://doi.org/10.3350/cmh.2024.0629

Background/Aims
A clinical unmet need persists for medications capable of modulating the progression of primary sclerosing cholangitis (PSC). This study aimed to assess the clinical feasibility of HK-660S (beta-lapachone) in PSC.
Methods
In this multicenter, randomized, double-blind, placebo-controlled, parallel-group phase 2 trial, participants were assigned in a 2:1 ratio to receive either 100 mg of HK-660S or a placebo twice daily for 12 weeks. The primary outcomes were the reduction in serum alkaline phosphatase (ALP) levels and the percentage of participants showing improvements in PSC severity, as determined by magnetic resonance cholangiopancreatography with the Anali score. Secondary endpoints included changes in liver stiffness and adverse events.
Results
The analysis included 21 patients, 15 receiving HK-660S, and six receiving a placebo. Improvements in the Anali score were observed in 13.3% of the HK-660S group, with no improvements in the placebo group. HK-660S treatment resulted in a 15.2% reduction in mean ALP levels, compared to a 6.6% reduction in the placebo group. A stratified ad-hoc analysis based on baseline ALP levels showed a statistically significant response in the HK-660S group among those with ALP levels greater than twice the upper limit of normal, with a 50% responder rate (p=0.05). Additionally, 26.7% of the HK-660S group showed improvements in the enhanced liver fibrosis score, with no improvements in the placebo group. HK-660S was generally well tolerated.
Conclusions
HK-660S is well tolerated among patients with PSC and may improve bile duct strictures, decrease serum ALP levels, and reduce liver fibrosis (cris.nih.go.kr, Number KCT0006590).

Citations

Citations to this article as recorded by

Pruritus in Chronic Cholestatic Liver Diseases, Especially in Primary Biliary Cholangitis: A Narrative Review
Tatsuo Kanda, Reina Sasaki-Tanaka, Naruhiro Kimura, Hiroyuki Abe, Tomoaki Yoshida, Kazunao Hayashi, Akira Sakamaki, Takeshi Yokoo, Hiroteru Kamimura, Atsunori Tsuchiya, Kenya Kamimura, Shuji Terai
International Journal of Molecular Sciences.2025; 26(5): 1883. CrossRef
Future Treatment Options for Managing Primary Sclerosing Cholangitis and Cholestatic Pruritus
Taranika Sarkar Das, Raj Vuppalanchi
Clinics in Liver Disease.2025; 29(4): 781. CrossRef

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Viral hepatitis

Acute pancreatitis associated with pegylated interferon-alpha-2a therapy in chronic hepatitis C: Jong Wook Choi, June Sung Lee, Woo Hyun Paik, Tae Jun Song, Jung Wook Kim, Won Ki Bae, Kyung-Ah Kim, Jung Gon Kim; Clin Mol Hepatol 2016;22(1):168-171.
Published online March 28, 2016; DOI: https://doi.org/10.3350/cmh.2016.22.1.168

Abstract
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Chronic hepatitis C virus (HCV) infection is a major cause of liver cirrhosis and hepatocellular carcinoma. Combination therapy of pegylated interferon-alpha (PEG-IFN-α) and ribavirin (RBV) is a current standard treatment for chronic HCV infection in Korea, which has considerable adverse effects. Acute pancreatitis is a rare complication of PEG-IFN-α administration. We report a case of a 62-year-old female who experienced acute pancreatitis after 4 weeks of PEG-IFN-α-2a and RBV combination therapy for chronic HCV infection. The main cause of the acute pancreatitis in this case was probably PEG-IFN-α rather than RBV for several reasons. A few cases have been reported in which acute pancreatitis occurred during treatment with PEG-IFN-α-2b. This is the first report of acute pancreatitis associated with PEG-IFN-α-2a in Korea.

Citations

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Drug-Induced Acute Pancreatitis: An Evidence-Based Classification (Revised)
Jasmine Saini, Daniel Marino, Nison Badalov, Melanie Vugelman, Scott Tenner
Clinical and Translational Gastroenterology.2023; 14(8): e00621. CrossRef
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Dianna Wolfe, Salmaan Kanji, Fatemeh Yazdi, Pauline Barbeau, Danielle Rice, Andrew Beck, Claire Butler, Leila Esmaeilisaraji, Becky Skidmore, David Moher, Brian Hutton, Francisco X. Real
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Bin Nie, Yongcan Guo, Kaijiong Zhang, Jinbo Liu, Sunguang Yun
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Imen Aouinti, Imen Hamza, Ons Charfi, Ghozlane Lakhoua, Sihem El Aidli, Riadh Daghfous, Ahmed Zaiem, Sarrah Kastalli
Therapies.2019; 74(3): 449. CrossRef
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Fateh Bazerbachi, Samir Haffar, Mohammad Tahir Hussain, Eric J. Vargas, Kymberly D. Watt, M. Hassan Murad, Suresh Chari, Barham K. Abu Dayyeh
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Viral hepatitis

Tenofovir disoproxil fumarate monotherapy for nucleos(t)ide analogue-naïve and nucleos(t)ide analogue-experienced chronic hepatitis B patients: Sang Kyung Jung, Kyung-Ah Kim, So Young Ha, Hyun Kyo Lee, Young Doo Kim, Bu Hyun Lee, Woo Hyun Paik, Jong Wook Kim, Won Ki Bae, Nam-Hoon Kim, June Sung Lee, Yoon Jung Jwa; Clin Mol Hepatol 2015;21(1):41-48.
Published online March 25, 2015; DOI: https://doi.org/10.3350/cmh.2015.21.1.41

Abstract
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Background/Aims

This study investigated the antiviral effects of tenofovir disoproxil fumarate (TDF) monotherapy in nucleos(t)ide analogue (NA)-naive and NA-experienced chronic hepatitis B (CHB) patients.

Methods

CHB patients treated with TDF monotherapy (300 mg/day) for ≥12 weeks between December 2012 and July 2014 at a single center were retrospectively enrolled. Clinical, biochemical, and virological parameters were assessed every 12 weeks.

Results

In total, 136 patients (median age 49 years, 96 males, 94 HBeAg positive, and 51 with liver cirrhosis) were included. Sixty-two patients were nucleos(t)ide (NA)-naïve, and 74 patients had prior NA therapy (NA-exp group), and 31 patients in the NA-exp group had lamivudine (LAM)-resistance (LAM-R group). The baseline serum hepatitis B virus (HBV) DNA level was 4.9±2.3 log IU/mL (mean±SD), and was higher in the NA-naïve group than in the NA-exp and LAM-R groups (5.9±2.0 log IU/mL vs 3.9±2.0 log IU/mL vs 4.2±1.7 log IU/mL, P<0.01). The complete virological response (CVR) rate at week 48 in the NA-naïve group (71.4%) did not differ significantly from those in the NA-exp (71.3%) and LAM-R (66.1%) groups. In multivariate analysis, baseline serum HBV DNA was the only predictive factor for a CVR at week 48 (hazard ratio, 0.809; 95% confidence interval, 0.729-0.898), while the CVR rate did not differ with the NA experience.

Conclusions

TDF monotherapy was effective for CHB treatment irrespective of prior NA treatment or LAM resistance. Baseline serum HBV DNA was the independent predictive factor for a CVR.

Citations

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Hui-Lian Wang, Xi Lu, Xudong Yang, Qilan Ning
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Xiaojun Xu, Hong Thai, Kathryn M. Kitrinos, Guoliang Xia, Anuj Gaggar, Matthew Paulson, Lilia Ganova-Raeva, Yury Khudyakov, James Lara
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Hyoung Su Kim
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Soo Ki Kim, Soo Ryang Kim, Susumu Imoto, Madoka Tohyama, Yumi Otono, Tomoko Tamura, Ke Ih Kim, Mana Kobayashi, Aya Ohtani, Kayo Sugimoto, Aya Mizuguchi, Yukiko Hiramatsu, Masatoshi Kudo
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