GeneHealth - Your precision medicine

Hepatic Cirrhosis

Disease Details

Family Health Simplified

Buy Membership

Description: Hepatic cirrhosis is a chronic liver disease characterized by the replacement of healthy liver tissue with scar tissue, leading to impaired liver function.
Type: Hepatic cirrhosis is not typically classified under a specific "type" when it comes to its primary categorization, but it can be further classified based on the underlying cause, such as alcoholic cirrhosis, viral hepatitis-related cirrhosis, or non-alcoholic fatty liver disease-related cirrhosis.

Regarding genetic transmission, most cases of hepatic cirrhosis are not inherited. However, some genetic conditions that can lead to cirrhosis include hereditary hemochromatosis, Wilson's disease, and alpha-1 antitrypsin deficiency. These specific conditions have a genetic basis and can be inherited in an autosomal recessive manner.
Signs And Symptoms: Cirrhosis can take quite a long time to develop, and symptoms may be slow to emerge. Some early symptoms include tiredness, weakness, loss of appetite, weight loss, and nausea. People may also feel discomfort in the right upper abdomen around the liver.As cirrhosis progresses, symptoms can include neurological changes. This can consist of cognitive impairments, confusion, memory loss, sleep disorders, and personality changes.Worsening cirrhosis can cause a build-up of fluid in different parts of the body such as the legs (edema) and abdomen (ascites). Other signs of advancing disease include itchy skin, bruising easily, dark urine, and yellowing of the skin.
Prognosis: Prognosis for hepatic cirrhosis varies depending on the underlying cause, stage at diagnosis, and presence of complications. Early-stage cirrhosis might be managed effectively with treatment and lifestyle changes, potentially slowing progression. Advanced cirrhosis can lead to life-threatening complications, such as liver failure, gastrointestinal bleeding, and liver cancer. Prognosis worsens significantly with these complications. Lifespan estimates can be gauged using the Child-Pugh score or Model for End-Stage Liver Disease (MELD) score, which assess the severity of liver dysfunction.
Onset: Hepatic cirrhosis has no specific onset age as it varies depending on the underlying cause, such as chronic alcohol abuse, viral hepatitis, or non-alcoholic fatty liver disease. Symptoms often develop gradually over many years. Early stages may be asymptomatic, with more obvious signs—such as jaundice, fatigue, and abdominal swelling—appearing as the disease progresses.
Prevalence: The worldwide prevalence of hepatic cirrhosis is not precisely documented, but it is estimated to affect millions globally. In the United States, it is estimated that around 1 in 400 adults have cirrhosis. The prevalence generally increases with age and is higher in males compared to females. Key risk factors include chronic alcohol consumption, hepatitis B and C infections, and non-alcoholic fatty liver disease (NAFLD).
Epidemiology: Each year, approximately one million deaths are due to complications of cirrhosis, making cirrhosis the 11th most common cause of death globally. Cirrhosis and chronic liver disease were the tenth leading cause of death for men and the twelfth for women in the United States in 2001, killing about 27,000 people each year.The cause of cirrhosis can vary; alcohol and non-alcoholic fatty liver disease are main causes in western and industrialized countries, whereas viral hepatitis is the predominant cause in low and middle-income countries. Cirrhosis is more common in men than in women. The cost of cirrhosis in terms of human suffering, hospital costs, and lost productivity is high.
Globally, age-standardized disability-adjusted life year (DALY) rates have decreased from 1990 to 2017, with the values going from 656.4 years per 100,000 people to 510.7 years per 100,000 people. In males DALY rates have decreased from 903.1 years per 100,000 population in 1990, to 719.3 years per 100,000 population in 2017; in females the DALY rates have decreased from 415.5 years per 100,000 population in 1990, to 307.6 years per 100,000 population in 2017. However, globally the total number of DALYs have increased by 10.9 million from 1990 to 2017, reaching the value of 41.4 million DALYs.
Intractability: Hepatic cirrhosis is considered intractable in the sense that it represents end-stage liver damage and cannot be reversed. While the progression of cirrhosis can sometimes be slowed or managed with appropriate treatment, such as lifestyle changes, medications, or addressing underlying causes, the damage already done to the liver is usually permanent. In advanced cases, a liver transplant may be the only definitive treatment option.
Disease Severity: Hepatic cirrhosis is a progressive liver disease characterized by the replacement of healthy liver tissue with scar tissue, leading to impaired liver function. The severity of hepatic cirrhosis is commonly evaluated using the Child-Pugh score, which assesses the prognosis based on several clinical parameters including bilirubin, serum albumin, prothrombin time, ascites, and hepatic encephalopathy. The disease can range from compensated (mild to moderate, where the liver retains some functional capacity) to decompensated (severe, marked by significant functional impairment and complications such as variceal bleeding, ascites, encephalopathy, and jaundice).
Healthcare Professionals: Disease Ontology ID - DOID:5082
Pathophysiology: The liver plays a vital role in the synthesis of proteins (for example, albumin, clotting factors and complement), detoxification, and storage (for example, of vitamin A and glycogen). In addition, it participates in the metabolism of lipids and carbohydrates.Cirrhosis is often preceded by hepatitis and fatty liver (steatosis), independent of the cause. If the cause is removed at this stage, the changes are fully reversible.The pathological hallmark of cirrhosis is the development of scar tissue that replaces normal tissue. This scar tissue blocks the portal flow of blood through the organ, raising the blood pressure and disturbing normal function. Research has shown the pivotal role of the stellate cell, that normally stores vitamin A, in the development of cirrhosis. Damage to the liver tissue from inflammation leads to the activation of stellate cells, which increases fibrosis through the production of myofibroblasts, and obstructs hepatic blood flow. In addition, stellate cells secrete TGF beta 1, which leads to a fibrotic response and proliferation of connective tissue. TGF-β1 have been implicated in the process of activating hepatic stellate cells (HSCs) with the magnitude of fibrosis being in proportion to increase in TGF β levels. ACTA2 is associated with TGF β pathway that enhances contractile properties of HSCs leading to fibrosis. Furthermore, HSCs secrete TIMP1 and TIMP2, naturally occurring inhibitors of matrix metalloproteinases (MMPs), which prevent MMPs from breaking down the fibrotic material in the extracellular matrix.As this cascade of processes continues, fibrous tissue bands (septa) separate hepatocyte nodules, which eventually replace the entire liver architecture, leading to decreased blood flow throughout. The spleen becomes congested, and enlarged, resulting in its retention of platelets, which are needed for normal blood clotting. Portal hypertension is responsible for the most severe complications of cirrhosis.
Carrier Status: Hepatic cirrhosis is a condition characterized by the irreversible scarring of the liver. It does not have a carrier status as it is not an infectious disease that can be transmitted from one person to another. Instead, it typically results from chronic liver damage due to factors like long-term alcohol abuse, hepatitis infections, or non-alcoholic fatty liver disease.
Mechanism: Hepatic cirrhosis is a chronic liver disease characterized by widespread fibrosis, altered liver architecture, and impaired liver function.

**Mechanism:**
1. **Injury and Inflammation**: Chronic liver injury (e.g., from hepatitis, alcohol, non-alcoholic fatty liver disease) initiates an inflammatory response.
2. **Fibrosis**: Sustained inflammation leads to activation of hepatic stellate cells (HSCs), which differentiate into myofibroblasts, producing extracellular matrix (ECM) components and collagen, resulting in fibrosis.
3. **Nodule Formation**: Fibrous tissue encapsulates regenerating liver cells, forming nodules. This architectural disruption impairs blood flow and liver function.
4. **Liver Dysfunction**: Progressive scarring and nodule formation lead to compromised liver functions like detoxification, production of vital proteins, and regulation of metabolism.

**Molecular Mechanisms:**
1. **Hepatic Stellate Cell Activation**: Various cytokines, such as TGF-β (Transforming Growth Factor Beta), promote the transformation of quiescent HSCs into collagen-producing myofibroblasts.
2. **Inflammatory Cytokines**: Elevated levels of pro-inflammatory cytokines like TNF-α (Tumor Necrosis Factor Alpha) and IL-1 (Interleukin-1) perpetuate hepatic inflammation and fibrogenesis.
3. **Oxidative Stress**: Reactive oxygen species (ROS) generated through liver injury induce cellular damage and activate HSCs.
4. **Matrix Metalloproteinases (MMPs) and Tissue Inhibitors (TIMPs)**: Imbalance between MMPs and TIMPs contributes to excessive ECM deposition.
5. **Growth Factors**: PDGF (Platelet-Derived Growth Factor) and VEGF (Vascular Endothelial Growth Factor) play roles in HSC proliferation and angiogenesis within the liver, respectively.

Understanding these mechanisms helps in developing targeted therapies aimed at halting or reversing the progression of hepatic cirrhosis.
Treatment: Generally, liver damage from cirrhosis cannot be reversed, but treatment can stop or delay further progression and reduce complications. A healthy diet is encouraged, as cirrhosis may be an energy-consuming process. A recommended diet consists of high-protein, high-fiber diet plus supplementation with branched-chain amino acids. Close follow-up is often necessary. Antibiotics are prescribed for infections, and various medications can help with itching. Laxatives, such as lactulose, decrease the risk of constipation. Carvedilol increases survival benefit for people with cirrhosis and portal hypertension.Alcoholic cirrhosis caused by alcohol use disorder is treated by abstaining from alcohol. Treatment for hepatitis-related cirrhosis involves medications used to treat the different types of hepatitis, such as interferon for viral hepatitis and corticosteroids for autoimmune hepatitis.Cirrhosis caused by Wilson's disease is treated by removing the copper which builds up in organs. This is carried out using chelation therapy such as penicillamine. When the cause is an iron overload, iron is removed using a chelation agent such as deferoxamine or by bloodletting.As of 2021, there are recent studies studying drugs to prevent cirrhosis caused by non-alcoholic fatty liver disease (NAFLD or NASH). A drug called semaglutide was shown to provide greater NASH resolution versus placebo. No improvement in fibrosis was observed. A combination of cilofexor/firsocostat was studied in people with bridging fibrosis and cirrhosis. It was observed to have led to improvements in NASH activity with a potential antifibrotic effect. Lanifibranor is also shown to prevent worsening fibrosis.
Compassionate Use Treatment: For hepatic cirrhosis, compassionate use treatment and off-label or experimental treatments can include:

1. **Antifibrotic Agents**: Some drugs initially developed for other fibrotic conditions are being studied for their potential use in treating liver fibrosis and cirrhosis.

2. **Stem Cell Therapy**: Experimental treatments using stem cells aim to regenerate damaged liver tissue and improve liver function.

3. **FXR Agonists**: Farnesoid X receptor (FXR) agonists are being studied for their potential to reduce liver fibrosis and improve liver function.

4. **Statins**: Although primarily used to lower cholesterol, some studies suggest that statins may have beneficial effects on liver fibrosis due to their anti-inflammatory and antifibrotic properties.

5. **Repurposing Antiviral Drugs**: For cirrhosis caused by viral hepatitis, antiviral drugs that effectively control or eliminate the viral infection may also help in reducing liver damage and improving liver function, although this use might be beyond their primary indication.

6. **Mesenchymal Stem Cell (MSC) Therapy**: This experimental treatment suggests that MSCs might help in reducing liver inflammation and fibrosis.

7. **Antioxidants and Anti-inflammatory Agents**: Experimental use of various antioxidants and anti-inflammatory compounds aims to reduce oxidative stress and inflammation in the liver.

These treatments are still under research and may not be widely available. It is essential for patients to consult with their healthcare providers to discuss potential participation in clinical trials or access to experimental therapies.
Lifestyle Recommendations: For hepatic cirrhosis, lifestyle recommendations include:

1. **Alcohol Abstinence**: Avoid all forms of alcohol to prevent further liver damage.
2. **Healthy Diet**: Focus on a balanced diet rich in fruits, vegetables, lean protein, and whole grains. Limit salt to reduce fluid retention.
3. **Regular Exercise**: Engage in moderate physical activity to maintain overall health and prevent muscle wasting.
4. **Avoid Hepatotoxic Substances**: Steer clear of medications and substances that can further harm the liver.
5. **Regular Monitoring**: Keep up with regular medical check-ups to monitor liver function and manage complications.
6. **Vaccinations**: Stay up-to-date with vaccines for hepatitis A and B, influenza, and pneumonia to prevent infections.
7. **Avoid Raw or Undercooked Shellfish**: These can contain bacteria harmful to people with liver disease.
8. **Weight Management**: Maintain a healthy weight to reduce the risk of fatty liver disease which can exacerbate cirrhosis.

These recommendations help manage symptoms and improve quality of life for those with hepatic cirrhosis.
Medication: For hepatic cirrhosis, medication options depend on the underlying cause and complications. Common treatments include:

1. Diuretics (e.g., furosemide, spironolactone) for managing fluid retention.
2. Beta-blockers (e.g., propranolol, nadolol) to reduce portal hypertension and the risk of variceal bleeding.
3. Lactulose or rifaximin to reduce ammonia levels and treat hepatic encephalopathy.
4. Antiviral medications if hepatitis B or C is an underlying cause.
5. Vitamin and mineral supplements, as deficiencies are common in cirrhosis patients.

It is important to note that medication should be tailored to the individual patient's needs and underlying conditions, under a healthcare provider's supervision.
Repurposable Drugs: For hepatic cirrhosis, several repurposable drugs have been studied and may offer therapeutic benefits. These include:

1. **Statins**: Commonly used for lowering cholesterol, statins have shown potential in improving liver function and reducing portal hypertension.
2. **Farnesoid X Receptor (FXR) Agonists**: Drugs like obeticholic acid, initially investigated for conditions like primary biliary cholangitis, have seen interest for their potential to improve liver fibrosis and cirrhosis.
3. **Angiotensin II Receptor Blockers (ARBs)**: These antihypertensive agents may benefit patients with cirrhosis by reducing portal hypertension.
4. **Proton Pump Inhibitors (PPIs)**: Though primarily used to treat acid-related gastrointestinal conditions, some research suggests that PPIs might help manage complications related to cirrhosis, such as gastrointestinal bleeding.

Always consult with healthcare professionals before considering any medication for off-label use.
Metabolites: The term "nan" appears unclear in this context. However, in the context of hepatic cirrhosis, some key metabolites often associated with the disease include:

1. **Bilirubin**: Elevated levels can indicate liver dysfunction.
2. **Ammonia**: Increased levels can be noted due to impaired liver function and urea cycle abnormalities.
3. **Albumin**: Typically decreased due to the liver's reduced capacity to synthesize this protein.
4. **Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST)**: Enzyme levels are often elevated in liver disease.
5. **Alkaline phosphatase (ALP)**: Levels may be elevated, indicating liver or bile duct issues.

Would you like more detailed information about any of these metabolites?
Nutraceuticals: Nutraceuticals for hepatic cirrhosis may include milk thistle (silymarin), curcumin, and vitamin E. These supplements are thought to have hepatoprotective properties, though their efficacy and safety can vary, so they should be used under medical supervision.

Nanotechnology is being explored for the treatment and diagnosis of hepatic cirrhosis. Nanoparticles can deliver drugs directly to the liver, increasing treatment efficacy while minimizing side effects. Research is ongoing to develop targeted therapies using nanomaterials to manage liver fibrosis and cirrhosis more effectively.
Peptides: Hepatic cirrhosis refers to the advanced scarring of the liver due to long-term damage. peptide-based approaches are being studied as potential treatments, for example, to reduce fibrosis or inflammation. Nanotechnology is also being explored to improve drug delivery and target specific cells in the liver to potentially treat or reverse cirrhosis. However, these are mostly in experimental stages and not yet standard treatments.