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"Immunosuppression"

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Harnessing the microbiome: unveiling the influence of the gut microbiota on hepatobiliary cancer therapeutic strategies
Melody Yusong Li, Xue Qian Wu, Terence Kin Wah Lee
Clin Mol Hepatol 2026;32(1):91-126.
Published online August 25, 2025
DOI: https://doi.org/10.3350/cmh.2025.0476
The gut microbiota significantly influences hepatobiliary cancer therapeutics. Growing evidence indicates that shifts in the gut microbial ecosystem are hallmarks of hepatocellular carcinoma and cholangiocarcinoma, strongly correlating with tumor development, therapeutic resistance, and patient survival. The composition of gut microbiota has emerged as a biomarker associated with treatment outcomes across various modalities, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy. Beneficial bacterial communities enhance antitumor immunity, while pathogenic taxa are linked to reduced therapeutic efficacy. Multi-omics analyses have identified microbial metabolite signatures, such as short-chain fatty acids and bile acids, as potential targets for boosting antitumor responses. This review highlights the transformative potential of leveraging the gut microbiota to enhance precision oncology in hepatobiliary cancer. Future directions should prioritize personalized microbiota modulation approaches, combinatorial therapies targeting gut-liver axis crosstalk, and large-scale validation of microbial biomarkers across diverse populations.
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Hepatic neoplasm

The management of post-transplantation recurrence of hepatocellular carcinoma
Luckshi Rajendran, Tommy Ivanics, Marco PAW Claasen, Hala Muaddi, Gonzalo Sapisochin
Clin Mol Hepatol 2022;28(1):1-16.
Published online October 5, 2021
DOI: https://doi.org/10.3350/cmh.2021.0217
The annual incidence of hepatocellular carcinoma (HCC) continues to rise. Over the last two decades, liver transplantation (LT) has become the preferable treatment of HCC, when feasible and strict selection criteria are met. With the rise in HCC-related LT, compounded by downstaging techniques and expansion of transplant selection criteria, a parallel increase in number of post-transplantation HCC recurrence is expected. Additionally, in the context of an immunosuppressed transplant host, recurrences may behave aggressively and more challenging to manage, resulting in poor prognosis. Despite this, no consensus or best practice guidelines for post-transplantation cancer surveillance and recurrence management for HCC currently exist. Studies with adequate population sizes and high-level evidence are lacking, and the role of systemic and locoregional therapies for graft and extrahepatic recurrences remains under debate. This review seeks to summarize the existing literature on post-transplant HCC surveillance and recurrence management. It highlights the value of early tumour detection, re-evaluating the immunosuppression regimen, and staging to differentiate disseminated recurrence from intrahepatic or extrahepatic oligo-recurrence. This ultimately guides decision-making and maximizes treatment effect. Treatment recommendations specific to recurrence type are provided based on currently available locoregional and systemic therapies.

Citations

Citations to this article as recorded by  Crossref logo
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    Mizelle D’Silva, Jai-Young Cho, Ho-Seong Han, Yoo-Seok Yoon, Hae-Won Lee, Bo-Ram Lee, Mee-Young Kang, Ye-Shong Park, Jin-Ju Kim
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  • Commentary: Case Report: Lenvatinib for the treatment of recurrent hepatocellular carcinoma in people living with HIV: a report of two cases
    Cuiming Sun, Ying Wen, Jin Zhou
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    Jing Xu, Yuanyuan Zhao, Zhishui Chen, Lai Wei
    Journal of Personalized Medicine.2024; 14(4): 420.     CrossRef
  • Atypical case of hepatoma recurrence two years post-transplant
    Syed Muhammad Sinaan Ali, Abdul Haseeb, Muhammad Ashir Shafique, Muhammad Saqlain Mustafa, Naeemullah Arbani, Syeda Zainab Fatima
    Journal of Medicine, Surgery, and Public Health.2024; 3: 100101.     CrossRef
  • FOXM1 Upregulates O-GlcNAcylation Level Via The Hexosamine Biosynthesis Pathway to Promote Angiogenesis in Hepatocellular Carcinoma
    Xiaorong Zhang, Yifan Zhong, Qing Yang
    Cell Biochemistry and Biophysics.2024; 82(3): 2767.     CrossRef
  • Statin, aspirin and metformin use and risk of hepatocellular carcinoma related outcomes following liver transplantation: A retrospective study
    William Chung, Kevin Wong, Noel Ravindranayagam, Lauren Tang, Josephine Grace, Darren Wong, Danny Con, Marie Sinclair, Avik Majumdar, Numan Kutaiba, Samuel Hui, Paul Gow, Vijayaragavan Muralidharan, Alexander Dobrovic, Adam Testro
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Editorial

Hepatic neoplasm

Can hepatocellular carcinoma recurrence be prevented after liver transplantation?
Jong Man Kim
Clin Mol Hepatol 2021;27(4):562-563.
Published online September 23, 2021
DOI: https://doi.org/10.3350/cmh.2021.0276

Citations

Citations to this article as recorded by  Crossref logo
  • Everolimus Personalized Therapy: Second Consensus Report by the International Association of Therapeutic Drug Monitoring and Clinical Toxicology
    Satohiro Masuda, Florian Lemaitre, Markus J. Barten, Stein Bergan, Maria Shipkova, Teun van Gelder, Sander Vinks, Eberhard Wieland, Kirsten Bornemann-Kolatzki, Mercè Brunet, Brenda de Winter, Maja-Theresa Dieterlen, Laure Elens, Taihei Ito, Kamisha Johnso
    Therapeutic Drug Monitoring.2025; 47(1): 4.     CrossRef
  • Association between the early high level of serum tacrolimus and recurrence of hepatocellular carcinoma in ABO-incompatible liver transplantation
    Ji Won Han, Jong Young Choi, Eun Sun Jung, Ji Hoon Kim, Hee Sun Cho, Jae-Sung Yoo, Pil Soo Sung, Jeong Won Jang, Seung Kew Yoon, Ho Joong Choi, Young Kyoung You
    World Journal of Gastrointestinal Surgery.2023; 15(12): 2727.     CrossRef
  • Optimal imaging criteria and modality to determine Milan criteria for the prediction of post-transplant HCC recurrence after locoregional treatment
    Nieun Seo, Dong Jin Joo, Mi-Suk Park, Seung-seob Kim, Hye Jung Shin, Yong Eun Chung, Jin-Young Choi, Myoung Soo Kim, Myeong-Jin Kim
    European Radiology.2022; 33(1): 501.     CrossRef
  • 8,033 View
  • 144 Download
  • 4 Web of Science
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Original Article

Liver Transplantation

Impact of everolimus on survival after liver transplantation for hepatocellular carcinoma
Incheon Kang, Jae Geun Lee, Sung Hoon Choi, Hyun Jeong Kim, Dai Hoon Han, Gi Hong Choi, Myoung Soo Kim, Jin Sub Choi, Soon Il Kim, Dong Jin Joo
Clin Mol Hepatol 2021;27(4):589-602.
Published online July 23, 2021
DOI: https://doi.org/10.3350/cmh.2021.0038
Background/Aims
This study aimed to investigate whether everolimus (EVR) affects long-term survival after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC).
Methods
The data from 303 consecutive patients with HCC who had undergone LT from January 2012 to July 2018 were retrospectively reviewed. The patients were divided into two groups: 1) patients treated with EVR in combination with calcineurin inhibitors (CNIs) (EVR group; n=114) and 2) patients treated with CNI-based therapy without EVR (non-EVR group; n=189). Time to recurrence (TTR) and overall survival (OS) after propensity score (PS) matching were compared between the groups, and prognostic factors for TTR and OS were evaluated.
Result
s: The EVR group exhibited more aggressive tumor biology than the non-EVR group, such as a higher number of tumors (P=0.003), a higher prevalence of microscopic vascular invasion (P=0.017) and exceeding Milan criteria (P=0.029). Compared with the PS-matched non-EVR group, the PS-matched EVR group had significantly better TTR (P<0.001) and OS (P<0.001). In multivariable analysis, EVR was identified as an independent prognostic factor for TTR (hazard ratio [HR], 0.248; P=0.001) and OS (HR, 0.145; P<0.001).
Conclusions
Combined with CNIs, EVR has the potential to prolong long-term survival in patients undergoing LT for HCC. These findings warrant further investigation in a well-designed prospective study.

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Reviews

Liver Transplantation

Immunologic strategies and outcomes in ABO-incompatible living donor liver transplantation
Jongwook Oh, Jong Man Kim
Clin Mol Hepatol 2020;26(1):1-6.
Published online March 26, 2019
DOI: https://doi.org/10.3350/cmh.2019.0023
Antibody mediated rejection (AMR) after adult ABO-incompatible living donor liver transplantation (ABO-I LDLT) induced hepatic necrosis or diffuse intrahepatic biliary complications, which were related with poor graft and patient survival. Various desensitization protocols have been used to overcome these problems. Since using rituximab, the outcomes of ABO-I LDLT show a similar survival rate to those of ABO-compatible living donor liver transplantation. However, diffuse bile duct complications still occur after ABO-I LDLT. We have reviewed the past and current immune strategies for desensitization and to provide outcomes and ABO incompatibility-related complications in ABO-I LDLT.

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Autoimmune liver disease

The use of immunosuppression in autoimmune hepatitis: A current literature review
Angela Cropley, Martin Weltman
Clin Mol Hepatol 2017;23(1):22-26.
Published online March 14, 2017
DOI: https://doi.org/10.3350/cmh.2016.0089
Autoimmune hepatitis (AIH) is an organ specific autoimmune condition which can manifest at any age of life. The heterogeneous nature of this condition means that great variation can be seen in severity, progression of disease and response to treatment within this patient group. Since the 1980s prednisolone and azathioprine have been used for induction and remission of the disease and remain the mainstay of treatment. Other immunosuppressive agents have been employed in difficult to treat cases. While there is less published data regarding these agents compared with the conventional treatments of steroid and azathioprine, there is mounting evidence to support the use of mycophenolate mofetil as a second-line agent. The calcineurin inhibitors, though less studied, additionally show promise. More data is needed on the use of biological agents in refractory disease. This review focuses on our centre’s approach to treatment of AIH in the context of a contemporary review of the literature.

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Original Article

Liver Transplantation

Immunosuppression status of liver transplant recipients with hepatitis C affects biopsy-proven acute rejection
Jong Man Kim, Kwang-Woong Lee, Gi-Won Song, Bo-Hyun Jung, Hae Won Lee, Nam-Joon Yi, ChoonHyuck David Kwon, Shin Hwang, Kyung-Suk Suh, Jae-Won Joh, Suk-Koo Lee, Sung-Gyu Lee
Clin Mol Hepatol 2016;22(3):366-371.
Published online September 25, 2016
DOI: https://doi.org/10.3350/cmh.2016.0022
Background/Aims
The relationship between patient survival and biopsy-proven acute rejection (BPAR) in liver transplant recipients with hepatitis C remains unclear. The aims of this study were to compare the characteristics of patients with and without BPAR and to identify risk factors for BPAR.
Methods
We retrospectively reviewed the records of 169 HCV-RNA-positive patients who underwent LT at three centers.
Result
s: BPAR occurred in 39 (23.1%) of the HCV-RNA-positive recipients after LT. The 1-, 3-, and 5-year survival rates were 92.1%, 90.3%, and 88.5%, respectively, in patients without BPAR, and 75.7%, 63.4%, and 58.9% in patients with BPAR (P<0.001). Multivariate analyses showed that BPAR was associated with the non-use of basiliximab and tacrolimus and the use of cyclosporin in LT recipients with HCV RNA-positive.
Conclusions
The results of the present study suggest that the immunosuppression status of HCV-RNA-positive LT recipients should be carefully determined in order to prevent BPAR and to improve patient survival.

Citations

Citations to this article as recorded by  Crossref logo
  • Early use of everolimus improved renal function after adult deceased donor liver transplantation
    Seohee Lee, Jong Man Kim, Sangjin Kim, Jinsoo Rhu, Gyu-Seong Choi, Jae-Won Joh
    Korean Journal of Transplantation.2021; 35(1): 8.     CrossRef
  • 13,964 View
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Review

Viral hepatitis

Prevention of Hepatitis B reactivation in the setting of immunosuppression
Venessa Pattullo
Clin Mol Hepatol 2016;22(2):219-237.
Published online June 13, 2016
DOI: https://doi.org/10.3350/cmh.2016.0024
Advances in the treatment of malignant and inflammatory diseases have developed over time, with increasing use of chemotherapeutic and immunosuppressive agents of a range of drug classes with varying mechanism and potency in their effects on the immune system. These advances have been met with the challenge of increased risk of hepatitis B virus (HBV) reactivation in susceptible individuals. The magnitude of risk of HBV reactivation is associated with the individual’s HBV serological status and the potency and duration of immunosuppression. Individuals with chronic hepatitis B (CHB) and previously infected but serologically cleared HBV infection are both susceptible to HBV reactivation. HBV reactivation in the setting of immunosuppression is a potentially life threatening condition leading to liver failure and death in extreme cases. It is important to recognize that HBV reactivation in the setting of immunosuppression is potentially preventable. Therefore, identification of patients at risk of HBV reactivation and institution of prophylactic antiviral therapy prior to initiation of immunosuppression is essential.

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Original Articles

Impact of immunosuppressant therapy on early recurrence of hepatocellular carcinoma after liver transplantation
Ju-Yeun Lee, Yul Hee Kim, Nam-Joon Yi, Hyang Sook Kim, Hye Suk Lee, Byung Koo Lee, Hyeyoung Kim, Young Rok Choi, Geun Hong, Kwang-Woong Lee, Kyung-Suk Suh
Clin Mol Hepatol 2014;20(2):192-203.
Published online June 30, 2014
DOI: https://doi.org/10.3350/cmh.2014.20.2.192
Background/Aims

The most commonly used immunosuppressant therapy after liver transplantation (LT) is a combination of tacrolimus and steroid. Basiliximab induction has recently been introduced; however, the most appropriate immunosuppression for hepatocellular carcinoma (HCC) patients after LT is still debated.

Methods

Ninety-three LT recipients with HCC who took tacrolimus and steroids as major immunosuppressants were included. Induction with basiliximab was implemented in 43 patients (46.2%). Mycophenolate mofetil (MMF) was added to reduce the tacrolimus dosage (n=28, 30.1%). The 1-year tacrolimus exposure level was 7.2 ± 1.3 ng/mL (mean ± SD).

Results

The 1- and 3-year recurrence rates of HCC were 12.9% and 19.4%, respectively. Tacrolimus exposure, cumulative steroid dosages, and MMF dosages had no impact on HCC recurrence. Induction therapy with basiliximab, high alpha fetoprotein (AFP; >400 ng/mL) and protein induced by vitamin K absence/antagonist-II (PIVKA-II; >100 mAU/mL) levels, and microvascular invasion were significant risk factors for 1-year recurrence (P<0.05). High AFP and PIVKA-II levels, and positive 18fluoro-2-deoxy-d-glucose positron-emission tomography findings were significantly associated with 3-year recurrence (P<0.05).

Conclusions

Induction therapy with basiliximab, a strong immunosuppressant, may have a negative impact with respect to early HCC recurrence (i.e., within 1 year) in high-risk patients.

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Immune Response of Peripheral Blood Mononuclear cells to Core and NS3 Protein in Chronic Hepatitis C Virus (HCV) Infecton
Sook-Hyang Jeong, Min-Jin Yang*, Kee-Ho Lee*, Yeon-Sook Yun†, and Yo Han Choi‡
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Background/Aims
The aims of our study are to assess the frequency of peripheral blood mononuclear cell (PBMC) proliferation and cytokine profiles to hepatitis C virus(HCV) core protein and NS3 protein to search the potential immunosuppressive effect of HCV core in chronically HCV-infected patients.Subjects and Methods:Thirty two anti-HCV-positive patients with chronic liver diseases, eight HBsAg-positive patients with chronic liver diseases, and six healthy adults were the subjects of our study. Using recombinant HCV core and NS3, proliferative response of PBMC and cytokine production were determined.Results:Fifty nine percent and thirteen percent of patients with HCV-related chronic liver diseases showed positive PBMC proliferation to HCV core and NS3, respectively. Thirty four percent and fifty nine percent of patients with HCV-related chronic liver diseases showed significant production of interferon-gamma to HCV core and NS3, respectively. IL-4 production was negligible. When the PBMC were treated with HCV core and NS3 concurrently, or HCV core and phytohemagglutinin concurrently, the stimulation indices were significantly decreased compared to those treated either with NS3 or PHA without core.Conclusions:Although about two thirds of chronically HCV-infected patients with liver diseases showed the PBMC proliferation and Th 1 type cytokine profile, they could not eradicate the viral infection. This ineffective immune response seems to play a role in the pathogenesis of chronic inflammatory liver disease resulting in liver cirrhosis and hepatocellular carcinoma. HCV core showed a potential immunosuppressive effect, which has important meaning for the mechanism of HCV persistence.(Korean J Hepatol 2001;7:292-298)
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Review
Treatment of Chronic Hepatitis B ; Antiviral Therapy in Hepatitis B Carriers Undergoing Immunosuppressive Treatment or Cytotoxic Chemotherapy
Jung Hwan Yoon
Korean J Hepatol 2005;11(1):17-20.
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  • 12 Download
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