Etiology and Epidemiology
The primary causes of cirrhosis in China include viral hepatitis (HBV, HCV), alcoholic liver disease, and metabolic dysfunction-associated fatty liver disease (MAFLD). Less common etiologies encompass autoimmune liver diseases, genetic disorders (e.g., Wilson's disease, hemochromatosis), drug/toxin exposure, parasitic infections, and circulatory disorders. Cryptogenic cirrhosis is diagnosed after excluding identifiable causes. Epidemiologically, the burden of viral hepatitis-related cirrhosis has declined due to vaccination, screening, and antiviral therapies. In contrast, the prevalence of MAFLD-related cirrhosis is rising significantly, contributing to an increasing proportion of HCC cases. Many patients present with multiple overlapping etiologies, such as viral hepatitis combined with alcohol use or metabolic syndrome.
Pathophysiology
Cirrhosis results from chronic hepatocyte injury, activating hepatic stellate cells and leading to excessive extracellular matrix deposition. Key pathophysiological changes include:
Liver Dysfunction: Impaired synthesis of albumin and coagulation factors, reduced bilirubin metabolism, and inadequate estrogen inactivation.
Portal Hypertension: Caused by increased intrahepatic resistance from fibrosis and vascular distortion, compounded by visceral vasodilation and increased portal inflow.
Gut-Liver Axis Dysregulation: Gut microbiota dysbiosis and increased intestinal permeability promote endotoxin translocation, driving inflammation and fibrosis progression.
Progression Drivers: Persistent inflammation, alcohol, obesity, and metabolic syndrome accelerate disease progression and increase HCC risk.
Assessment of Liver Function and Portal Hypertension
1. Biochemical and Reserve Function Assessment:
Synthetic Function: Serum albumin, prealbumin, prothrombin time (PT), and INR.
Reserve Function: Child-Pugh score (grades A–C) and MELD/MELD-Na scores are used for prognosis stratification. The indocyanine green clearance test assesses hepatic blood flow and surgical risk.
2. Imaging and Non-Invasive Modalities:
Ultrasound: Evaluates liver morphology, surface nodularity, splenomegaly, portal vein dilation, and ascites.
Elastography: Liver stiffness measurement (LSM) and spleen stiffness measurement (SSM) are key non-invasive tools for fibrosis staging and portal hypertension assessment. SSM <21 kPa rules out portal hypertension, while >50 kPa indicates clinically significant portal hypertension.
CT/MRI: Provide detailed anatomical and vascular assessment, including 3D reconstruction. Magnetic resonance elastography (MRE) offers high accuracy for fibrosis staging, especially in obese patients or those with ascites.
Non-Invasive Models: Serological scores (APRI, FIB-4) combined with imaging improve fibrosis diagnosis.
3. Histopathological Assessment:
Liver biopsy remains the gold standard for diagnosing early cirrhosis and assessing inflammatory activity. The "Beijing Criteria" (PIR classification) categorize fibrosis as progressive (P-type), indeterminate (I-type), or regressive (R-type), aiding in monitoring treatment response. Adequate biopsy sample size (≥1.6 cm length, 8–10 portal tracts) is crucial for accuracy.
4. Portal Hypertension Assessment:
Endoscopy: Gold standard for diagnosing esophagogastric varices and portal hypertensive gastropathy.
HVPG Measurement: Invasive but valuable for staging and prognosis. HVPG >10 mmHg indicates clinically significant portal hypertension; >20 mmHg correlates with high mortality.
Portal Pressure Gradient (PPG): A newer technique via endoscopic ultrasound-guided transgastric puncture, useful for differentiating sinusoidal from non-cirrhotic portal hypertension.
5. Nutritional Assessment:
Malnutrition and sarcopenia are common and worsen prognosis. Assessment includes body composition analysis, grip strength, dietary intake evaluation, and screening tools.
Clinical Staging, Diagnosis, and Differential Diagnosis
1. Staging and Diagnostic Criteria:
Compensated Cirrhosis: Cirrhosis confirmed histologically, endoscopically (varices with non-cirrhotic portal hypertension excluded), or radiologically, without ascites, variceal bleeding, or HE. Alternative criteria include thrombocytopenia (<100×10⁹/L), hypoalbuminemia (<35 g/L), elevated INR, or APRI >2.
Decompensated Cirrhosis: Meets compensated cirrhosis criteria plus complications (ascites, variceal bleeding, HRS, HE). Subclinical decompensation includes minimal HE, minimal ascites (<2 cm), or occult gastrointestinal bleeding.
Recompensated Cirrhosis: Requires etiology control, absence of complications for ≥12 months off therapy, and stable liver function (MELD <10 or Child-Pugh A).
2. Differential Diagnosis:
Pseudocirrhosis: Conditions mimicking cirrhosis (e.g., metastatic liver cancer) with portal hypertension features.
Non-Cirrhotic Portal Hypertension (NCPH): Portal hypertension without cirrhosis, diagnosed via imaging and histology, with normal or mildly elevated HVPG.
Complications of Cirrhosis
Serous Cavity Effusions: Ascites (including chylous and hemorrhagic variants), hepatic hydrothorax (usually right-sided), and pericardial effusion.
Gastrointestinal Bleeding: Esophagogastric variceal bleeding (EVB) is most common; other sources include portal hypertensive gastropathy (PHG), enteropathy (PHE), cholangiopathy (PHC), and internal hemorrhoids.
Hepatic Encephalopathy (HE) and Neurological Syndromes: Ranges from minimal HE to overt neuropsychiatric symptoms. Differentiate from hepatic myelopathy and acquired hepatocerebral degeneration.
Infections: Spontaneous bacterial peritonitis (SBP) is frequent; others include urinary, respiratory, and soft tissue infections.
Renal Impairment: Includes acute kidney injury (AKI), HRS-AKI, HRS-non-AKI, and chronic kidney disease.
Hepatocellular Carcinoma (HCC): Cirrhosis is the primary risk factor; surveillance with ultrasound and AFP every 3–6 months is recommended.
Thrombocytopenia: Graded from mild (PLT 75–100×10⁹/L) to severe (<50×10⁹/L).
Portal Vein Thrombosis (PVT): Classified as acute (<6 months) or chronic (>6 months), requiring anticoagulation in select cases.
Hepatic Osteodystrophy: Mainly osteoporosis, correlated with liver disease severity.
Cirrhotic Cardiomyopathy (CCM): Characterized by systolic/diastolic dysfunction, with electrophysiological abnormalities.
Hepatopulmonary Syndrome (HPS) and Portopulmonary Hypertension (PoPH): Pulmonary vascular complications with distinct diagnostic criteria.
Sarcopenia and Malnutrition: Common, worsening outcomes; requires regular screening.
Treatment of Cirrhosis
1. Etiological Treatment:
Viral Hepatitis: Antiviral therapy per HBV/HCV guidelines. HBsAg clearance does not equate to "functional cure"; continued antiviral/anti-fibrotic therapy is often needed.
Alcohol and MAFLD: Abstinence and lifestyle intervention.
Autoimmune and Genetic Diseases: Specific therapies per respective guidelines.
Other Causes: Target underlying condition (e.g., heart failure in congestive cirrhosis).
2. Anti-inflammatory and Anti-fibrotic Therapy:
Hepatoprotectants: Glycyrrhizic acid, bicyclol, silymarin, etc., to reduce inflammation.
Traditional Chinese Medicine (TCM): Anluohuaxian pills, Fuzheng Huayu, compound Biejia Ruangan tablets show anti-fibrotic effects in combination with etiological therapy ("dual therapy"), improving fibrosis and reducing portal pressure.
3. Management of Complications:
Ascites: Salt restriction, diuretics, albumin, vasoconstrictors (terlipressin), large-volume paracentesis, or TIPS for refractory cases.
Variceal Bleeding: Acute management with vasoactive drugs, antibiotics, endoscopy (ligation/sclerotherapy), or TIPS. Secondary prevention with NSBBs (e.g., carvedilol) ± endoscopy.
HE: Lactulose, rifaximin, L-ornithine-L-aspartate; address precipitating factors.
Infections: Prompt empiric antibiotics, then targeted therapy; albumin for SBP.
HRS: Terlipressin plus albumin; consider TIPS or liver transplantation.
HCC: Multimodal treatment per liver cancer guidelines.
PVT: Anticoagulation with DOACs or LMWH; TIPS or thrombolysis in selected cases.
Nutritional Support: High-protein, frequent small meals; bedtime snacks to prevent catabolism.
Long-term Follow-up and Support
Regular monitoring (every 1–3 months) of liver function, AFP, and ultrasound is essential. Psychological support and nursing care (e.g., airway management during bleeding, HE precautions) are integral to comprehensive management.
Future Directions
Key research priorities include: non-invasive HVPG measurement, advanced elastography technologies, diagnostic markers for minimal HE, criteria for recompensation/reversal, TCM anti-fibrotic therapy, albumin use optimization, and multidisciplinary management leveraging artificial intelligence.
Conclusion
The 2025 guidelines provide a structured, evidence-based approach to cirrhosis management, emphasizing early diagnosis, etiology-directed therapy, anti-fibrotic strategies, and complication-specific interventions. They highlight the importance of individualized care, nutritional support, and long-term surveillance to improve patient outcomes and quality of life.
Full text
https://www.xiahepublishing.com/2310-8819/JCTH-2025-00517
The study was recently published in the Journal of Clinical and Translational Hepatology.
The Journal of Clinical and Translational Hepatology (JCTH) is owned by the Second Affiliated Hospital of Chongqing Medical University and published by XIA & HE Publishing Inc. JCTH publishes high quality, peer reviewed studies in the translational and clinical human health sciences of liver diseases. JCTH has established high standards for publication of original research, which are characterized by a study’s novelty, quality, and ethical conduct in the scientific process as well as in the communication of the research findings. Each issue includes articles by leading authorities on topics in hepatology that are germane to the most current challenges in the field. Special features include reports on the latest advances in drug development and technology that are relevant to liver diseases. Regular features of JCTH also include editorials, correspondences and invited commentaries on rapidly progressing areas in hepatology. All articles published by JCTH, both solicited and unsolicited, must pass our rigorous peer review process.
Follow us on X: @xiahepublishing
Follow us on LinkedIn: Xia & He Publishing Inc.
END