What is Liver Cirrhosis?
Cirrhosis is a late stage of scarring (fibrosis) of the liver caused by many forms of liver diseases and conditions, such as hepatitis and chronic alcoholism.
Each time your liver is injured — whether by disease, excessive alcohol consumption or another cause — it tries to repair itself. In the process, scar tissue forms. As cirrhosis progresses, more and more scar tissue forms, making it difficult for the liver to function (decompensated cirrhosis). Advanced cirrhosis is life-threatening.
The liver damage done by cirrhosis generally can’t be undone. But if liver cirrhosis is diagnosed early and the cause is treated, further damage can be limited and, rarely, reversed.
What Causes Liver Cirrhosis?
Although the liver has a considerable inherent regenerative capacity, sustained and chronic injury results in the onset of liver fibrosis. Stimuli such as viral hepatitis, alcohol, drugs, metabolic disease, and autoimmune attack by hepatic cells trigger hepatocyte apoptosis (programed cell death), the impairment of the endothelial barrier, the recruitment of inflammatory cells and the activation of hepatic stellate cells (HSCs).
The fibrosis is the result of an imbalance in extracellular matrix (ECM) synthesis and degradation mediated by portal fibroblasts, bone marrow-derived fibroblasts, mesenchymal cells and activated HSCs.
Some conditions that can lead to liver cirrhosis include:
- Chronic alcohol abuse.
- Chronic viral hepatitis (hepatitis B, C and D).
- Non-alcoholic fatty liver disease.
- Hemochromatosis (iron buildup in the body).
- Autoimmune hepatitis.
- Primary biliary cirrhosis (destruction of the bile ducts).
What are Common Signs and Symptoms?
Cirrhosis often has no signs or symptoms until liver damage is extensive. When they occur they can include:
- Fatigue and weight loss.
- Easily bleeding or bruising.
- Loss of appetite.
- Swelling of legs, feet or ankles (edema).
- Itchy skin.
- Jaundice (yellow discoloration of the skin and eyes).
- Ascites (fluid accumulation in the abdomen).
- Spider-like blood vessels in the skin.
- Gynecomastia (breast enlargement in men).
- Confusion, drowsiness and slurred speech (hepatic encephalopathy).
Current Treatment Options
Treatment for cirrhosis depends on the cause and extent of the liver damage. The goals of treatment are to slow the progression of scar tissue in the liver and to prevent or treat symptoms and complications of cirrhosis.
In early stages, it may be possible to minimize damage to the liver by treating the underlying cause, some options include:
- Treatment of alcohol dependency. People with cirrhosis caused by excessive alcohol use should try to stop drinking.
- Weight loss. People with cirrhosis caused by non-alcoholic fatty liver disease may become healthier if they lose weight and control their blood sugar levels.
- Medications to control hepatitis. Medications may limit further damage to liver cells caused by hepatitis B or C through specific antiviral treatments.
- Medications to control other causes and symptoms. One example is for people with primary biliary cirrhosis that is diagnosed early, medication may significantly delay progression to cirrhosis.
Currently the most effective treatment for end-stage liver fibrosis is liver transplantation. However, transplantation is limited by a shortage of donor organs, surgical complications, immunological reaction and high medical costs.
Stem Cell Therapies
Recently, stem cell transplantation has been suggested as an effective alternative therapy for hepatic diseases. Stem cells, including embryonic, induced pluripotent, hematopoietic and mesenchymal stem cells (MSCs), can be differentiated into hepatocyte-like cells both in vitro and in vivo.
Of these stem cell types, MSCs have several advantages, such as easy acquisition, strong proliferative capacities and ex vivo expansion. In addition, MSCs have immune-modulatory properties and are able to migrate to damaged tissues. MSCs also secrete trophic factors, including growth factors and cytokines, which promote the regeneration of impaired tissues, including the liver.
MSCs can suppress inflammatory responses, reduce hepatocyte apoptosis, increase hepatocyte regeneration, regress liver fibrosis and enhance liver functionality.
Clinical Trials with MSCs
A study published in the journal Stem Cells Research & Therapy evaluated the use of umbilical cord mesenchymal stem cells (UCMSCs). The study was observational and considered a 3 year period during which 513 patients who received stem cell infusion and met the criteria of hepatic failure and liver cirrhosis were identified from databases of the Third Affiliated Hospital of Sun Yat-sen University.
The eligible patients were categorized into the liver failure group and liver cirrhosis group. The two groups were divided into different subgroups according to the duration of stem cell therapy. In the liver failure group, group A received more than 4 weeks and group B received less than 4 weeks of stem cell therapy.
In the liver cirrhosis group, patients who received more than 4 weeks of stem cell therapy belonged to group C, and the patients in group D received less than 4 weeks of stem cell therapy. The patients were followed up for 24 weeks. A total of 64 patients met the criteria of liver failure and 59 met the criteria of liver cirrhosis.
The researchers found that after the therapy with UCMSCs, the levels of alanine aminotransferase (ALT), glutamic-oxaloacetic transaminase (AST) and total bilirubin were significantly lower than those at baseline in both the liver failure and cirrhosis group.
Four weeks after treatment the patients who received prolonged treatment with UCMSs had a larger decrease in total bilirubin levels. After more than 4 weeks of treatment there were no significant differences in the changes.
The researchers concluded that peripheral infusion of UCMSCs shows good therapeutic effects for HBV-related liver failure and liver cirrhosis and that prolonging treatment courses can increase the curative effect of UCMSCs for end-stage liver disease, especially for patients with cirrhosis.
These and other clinical studies results are promising because they have shown that the therapies are safe and effective in the treatment of multiple conditions for which no other treatments offer good therapeutic results.
Eom YW, Shim KY, Baik SK. Mesenchymal stem cell therapy for liver fibrosis. Korean J Intern Med. 2015 Sep;30(5):580-9. doi: 10.3904/kjim.2015.30.5.580. Epub 2015 Aug 27. PMID: 26354051; PMCID: PMC4578027.
Jia, Y., Shu, X., Yang, X. et al. Enhanced therapeutic effects of umbilical cord mesenchymal stem cells after prolonged treatment for HBV-related liver failure and liver cirrhosis. Stem Cell Res Ther 11, 277 (2020). https://doi.org/10.1186/s13287-020-01787-4