The etiology of liver cirrhosis has transformed from hepatitis B virus-driven to metabolic dysfunction-associated steatotic liver disease (MASLD) . In this context, researchers have compared the viral and metabolic cirrhosis, highlighting the differences in their key pathogenic mechanisms and the limited applicability of viral therapeutic strategies for treatment of MASLD. This necessitates the development of new strategies for diagnosis and treatment of MASLD.
Cirrhosis represents the end stage of chronic liver disease, characterized by extensive hepatocyte necrosis and fibrous tissue proliferation, which disrupt the liver's architecture and lead to the liver damage. The causes of liver damage may include alcohol use, hepatitis B virus (HBV) infection, or metabolic dysfunction like obesity. HBV vaccination drives have succeeded in reducing global incidence of viral cirrhosis; unfortunately, the leading cause of cirrhosis has shifted to metabolic dysfunction-associated steatotic liver disease (MASLD). Increasingly poor lifestyle choices, unhealthy diet, and low physical activity may escalate MASLD to one of the biggest health problems in the future. Thus, better understanding the underlying disease-causing mechanisms may help develop early diagnostic biomarkers and targeted therapeutic strategies.
In a new review, a team of researchers led by Professor Yuan Ding from Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, China, and Professor Weilin Wang from Department of Hepatobiliary and Pancreatic Surgery, Zhejiang University School of Medicine, China, compared the pathogenic mechanisms between viral and MASLD cirrhosis. The study was published in the journal of Portal Hypertension & Cirrhosis on February 15, 2026.
“Our study clarifies the distinct pathogenesis and clinical management challenges of MASLD cirrhosis versus HBV cirrhosis and aims to establish a precise framework for prevention, diagnosis, treatment, and monitoring of MASLD cirrhosis,” says Prof. Ding.
The authors note that the primary trigger of disease onset is distinct. Viral persistence and immune dysregulation trigger HBV cirrhosis, whereas insulin resistance and lipotoxicity trigger MASLD. Yet, both conditions also share several pathogenic pathways that drive liver fibrosis. First, chronic inflammation that increases production of inflammatory cytokines. Second, persistent metabolic stress that increases fibrosis. Third, dysregulation of the gut microbiota and increased intestinal permeability that leads to endotoxemia. Taken together, these pathways lead to liver injury and fibrosis progression in both conditions.
Diagnostic differences between HBV cirrhosis and MASLD cirrhosis stem from their underlying etiologies. HBV cirrhosis can be diagnosed directly through routine blood tests due to the presence of definitive serological virological markers (such as HBsAg and HBV DNA), whereas MASLD cirrhosis lacks specific biomarkers and currently still relies on percutaneous liver biopsy as the gold standard. Current serological biomarkers and advanced imaging modalities, while highly accurate, are ineffective in detecting early-stage fibrosis, making the diagnosis of MASLD cirrhosis a challenge. Consequently, patients with MASLD frequently present late for metabolic interventions.
Treatment for viral cirrhosis involves the sustained suppression of viral replication and other antiviral interventions which delay disease progression, whereas the management of metabolism‐related cirrhosis focuses on reversing the underlying metabolic disorders. Current pharmacological approaches have shown the potential for treating fatty liver, inflammation, and fibrosis. Interventions in glucose and lipid metabolism, addressing body weight, interventions in gut microbiota, and interventions that reduce the inflammatory and fibrogenic microenvironments are considered effective and essential to halt MASLD disease progression.
The study identifies the challenges in timely diagnosis and treatment of MASLD cirrhosis and lists potential means of overcoming these obstacles. Moreover, it emphasizes the need for further research focusing on developing and validating highly sensitive and specific noninvasive biomarkers.
“Our study by synthesizing the epidemiological transition, key mechanisms, and emerging therapies offers a strategic framework for the MASLD cirrhosis. A major challenge is the absence of a dominant pathogenic driver and disease heterogeneity. This highlights the need for personalized treatment strategies that combine metabolic, anti‐inflammatory, and anti‐fibrotic approaches,” concludes Prof. Wang.
About Zhejiang University School of Medicine
Zhejiang University School of Medicine pursues high-quality education and aims to develop extraordinary medical practitioners. It is composed of 11 schools focusing on basic medicine, brain science, public health, and clinical medicine. Affiliated hospitals and 8 cooperated hospitals provide a health care network to the local and nation-wide community. Zhejiang University School of Medicine has many international collaborations and exchange programs. Among 966 full-time professors, there are 3 members of the China Academy of Sciences, 4 members of China Academy of Engineering, 9 members of the Cheung Kong Chair Professor, 43 State “1000-elite Program” Experts (including “1000 Young Talent Plan” Professors), and 14 winners of National Science Funds for Distinguished Young Scholar.
Website: http://www.cmm.zju.edu.cn/cmmenglish/
About Professor Yuan Ding from Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province
Prof. Yuan Ding is the leader of the Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province. He is also the Vice President of the Second Affiliated Hospital of Zhejiang University School of Medicine (SAHZU). He has published more than 100 articles and over 40 papers were published in Nature Cancer , Gastroenterology , Hepatology , Signal Transduction and Targeted Therapy , Nature Communications , Advanced Materials , and Advanced Science as a corresponding author.
About Professor Weilin Wang from Zhejiang University School of Medicine
Dr. Weilin Wang is a Professor and Vice Dean of the Faculty of Medicine and Pharmaceutic Sciences of Zhejiang University. He is also the President of Hepato-Biliary-Pancreatic (HBP) Surgery Hospital and Director of the Organ Transplantation Center of the Second Affiliated Hospital of Zhejiang University School of Medicine (SAHZU). His works mainly focus on precision diagnosis & treatment of HBP tumors, liver transplantation, and combined organ transplantation. By so far, he has published more than 300 articles and over 100 papers were published in Nature Nanotechnology , Gastroenterology , Hepatology , Advanced Materials , and Advanced Science as a corresponding author.
Funding information
The research was supported by the Key Research and Development Program of Zhejiang Province (No. 2024C03143), the National Natural Science Foundation of China (Nos. U23A202181, 82472844), and the Special Financial Support for Zhejiang Traditional Chinese Medicine Innovation Teams, Zhejiang Provincial Natural Science Foundation of China (No. LQN25H160026).
Portal Hypertension & Cirrhosis
Literature review
Not applicable
From HBV to MASLD Cirrhosis: Mechanistic Insights and Therapeutic Strategies
15-Feb-2026
The authors declare no conflicts of interest.