Cirrohsis or scarring of liver appears as different types of liver cirrhosis and the patient may require liver transplantation as it is the end-stage disease.

Cirrhosis

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Ismail Munir

Overview

Histologically, cirrhosis is a diffuse hepatic process that is characterized by fibrosis. Additionally, the normal structure of the liver changes to abnormal nodules. The progression of liver injury to cirrhosis occurs over several weeks to years.

Cirrhosis is <a href="https://merisehat.pk/disease/fibroids">fibrosis</a> of the liver, which is a late stage of scarring caused by several forms of liver diseases or conditions e.g. hepatitis and chronic alcoholism respectively.

Whenever the liver is injured because of a disease, alcohol abuse, or any other reason, it works on repairing itself, and in the process, scar tissues are formed. More scar tissues form with the progression of cirrhosis, which makes it difficult for the liver to function. Moreover, advanced cirrhosis is fatal.

The liver damage is irreversible, but if liver cirrhosis is diagnosed during the early stages, it can be treated. In addition, it prevents further damage.

&nbsp;

Cirrhosis is classified through two methods: etiology and morphology. However, morphological classification is not currently recommended because it is an invasive procedure and provides little value to the diagnosis. Etiological classification is more acceptable. It may be obtained through lab testing, and the diagnostic value is also higher. 
&nbsp;

<h5>Classification Based On Etiology</h5>

&nbsp;

1. Alcoholic Cirrhosis

<ul>
	<li>Alcoholic cirrhosis is the most common type.</li>
	<li>It is caused by prolonged and continuous alcohol use.</li>
	<li>60-70% of cases of liver cirrhosis are because of alcohol abuse<a href="http://#accordion">[1]</a>. 
	&nbsp;</li>
</ul>

2. Post-Necrotic Cirrhosis

<ul>
	<li>Post-necrotic liver cirrhosis can lead to death&nbsp;and occurs because of a massive event.</li>
	<li>The most common cause is viral hepatitis.</li>
	<li>Some agents are toxic to the liver, which is a causative factor. 
	&nbsp;</li>
</ul>

3. Biliary Cirrhosis&nbsp;

<ul>
	<li>Biliary obstruction due to any disease is a common causative factor.</li>
	<li>It can be caused by inflammation or blockage in the bile duct.</li>
	<li>When there is excess bile in the liver, it can lead to tissue destruction and result in <a href="https://merisehat.pk/disease/jaundice-65">jaundice</a>. 
	&nbsp;</li>
</ul>

4. Cardiac Cirrhosis

<ul>
	<li><a href="https://merisehat.pk/disease/congenital-heart-diseases">Congestive heart failure</a> can lead to the inadequate circulation of oxygenated blood to the liver, which can cause cardiac cirrhosis.</li>
	<li>The result of poor circulation is cell death, and the dead cells are subsequently replaced by fibrous tissue. 
	&nbsp;</li>
</ul>

5. Genetic Disease Cirrhosis

It is caused by genetic disorders, which include, hemochromatosis, alpha-1 antitrypsin deficiency, and Wilson&rsquo;s disease<a href="http://#accordion">[2]</a>. 
&nbsp;

6. Malnutrition Cirrhosis

Several types of malnutrition, especially chronic starvation can cause cirrhosis.&nbsp; 
&nbsp;

<h5>Classification Based On Morphology</h5>

Cirrhosis is also classified based on nodular morphology. However, accurate assessment of the liver&rsquo;s morphology is only acquired through biopsy, autopsy, and surgery. Hence, non-invasive methods are preferred. 
&nbsp;

1. Micronodular

It is characterized by nodules that are less than 3mm. It is caused by alcoholism, hemochromatosis, hepatic venous outflow, cholestatic causes, and nutritional conditions. 
&nbsp;

2. Macronodular

The nodules in macronodular cirrhosis are more than 3mm in diameter. It is caused by viral <a href="https://merisehat.pk/disease/hepatitis-a&amp;e">hepatitis</a>, <a href="https://merisehat.pk/disease/wilsons-disease">Wilson&rsquo;s disease</a>, and hemochromatosis. 
&nbsp;

3. Mixed

Most often, micronodular cirrhosis progresses into macronodular cirrhosis and during this transformation, the mixed form can be seen. It is also seen in Indian childhood cirrhosis.

&nbsp;

Signs And Symptoms

Cirrhosis usually does not have any signs and symptoms till the damage becomes extensive. The signs and symptoms include the following:&nbsp;

<ul>
	<li>Fatigue</li>
	<li>Bleeding and bruising easily</li>
	<li>Nausea</li>
	<li>Loss of appetite</li>
	<li>Edema</li>
	<li>Weight loss</li>
	<li>Itchy skin</li>
	<li><a href="https://merisehat.pk/disease/jaundice-65">Jaundice</a></li>
	<li>Ascites</li>
	<li>The palms of the hands become red</li>
	<li>Loss or absence of a period in women - not linked with menopause</li>
	<li>Breast enlargement, loss of sex drive, and testicular atrophy in men</li>
	<li>Drowsiness, confusion, and slurred speech</li>
</ul>

&nbsp;

Causes

The most common causes of liver cirrhosis are:

<ul>
	<li>Chronic use of alcohol</li>
	<li><a href="https://merisehat.pk/disease/hepatitis-b-113">Hepatitis B</a> and <a href="https://merisehat.pk/disease/hepatitis-c-114">hepatitis C</a> &ndash; chronic viral infections of the liver.</li>
	<li>Fatty liver associated with diabetes and <a href="https://merisehat.pk/disease/obesity">obesity</a>. It is known as non-alcoholic steatohepatitis.</li>
</ul>

Anything that can cause damage to the liver can lead to cirrhosis. The other causes are:

&nbsp;

1. Inherited Diseases

<ul>
	<li>Alpha-1 antitrypsin deficiency</li>
	<li>Excess iron stored in the liver (hemochromatosis)</li>
	<li>Excess copper in the liver (Wilson&rsquo;s Disease)</li>
	<li><a href="https://merisehat.pk/disease/cystic-fibrosis">Cystic fibrosis</a></li>
	<li>Glycogen storage disease</li>
	<li>Born with less than normal bile ducts that cause jaundice and affect the flow of bile (Alagille syndrome) 
	&nbsp;</li>
</ul>

2. Autoimmune Hepatitis

<ul>
	<li>In this condition the body&rsquo;s immune system starts attacking the healthy liver tissues.&nbsp; 
	&nbsp;</li>
</ul>

3. Diseases That Block And Damage The Bile Ducts In The Liver

<ul>
	<li>The bile ducts become inflamed, injured, and damaged permanently (primary biliary cholangitis)</li>
	<li>Blockage in the bile duct</li>
	<li>Biliary atresia 
	&nbsp;</li>
</ul>

4. Chronic Heart Failure 

This causes fluid to back up in the liver, leading to swelling in other areas of the body. 
&nbsp;

5. Rare Diseases

Amyloidosis, for example, leads to abnormal deposits of amyloid protein in the liver, which disrupts the normal functioning of the liver.

&nbsp;

The liver changes that lead to cirrhosis are slow. If the liver cells are injured and if the injury continues, the liver cells start dying. Furthermore, as time passes, the scar tissue replaces the liver cells, preventing it from functioning properly. 
 
&nbsp;

Liver chemistries, also called a liver function test (LFT), determine the health of the liver by measuring the liver enzymes, proteins, and bilirubin in your blood. Moreover, it can also monitor whether the treatment for an existing disease is effective. 
&nbsp;

Diagnosis

Since cirrhosis is mostly asymptomatic till later stages, it is usually diagnosed during routine check-ups of other conditions or diseases.

If anyone has the following symptoms, they should consult their healthcare provider right away:

<ul>
	<li>Fever and shivers</li>
	<li>Shortness of breath</li>
	<li>Bloody vomiting</li>
	<li>Tarry or dark stools</li>
	<li>Drowsiness and confusion</li>
</ul>

&nbsp;

The healthcare provider physically examines the patient and feels the area around the liver to see if it is enlarged. The patient&rsquo;s medical history and lifestyle are also inquired about.&nbsp;

The following tests are used in the diagnosis of liver cirrhosis: 
&nbsp;

<h5>Blood Test</h5>

Blood tests measure the function of the liver. If ALT (alanine transaminase) and AST (aspartate transaminase) are abnormally high, hepatitis is suspected. 
&nbsp;

<h5>Imaging Tests</h5>

Ultrasound, CT scans, and MRI scans can be used to check the liver for enlargement and detect any nodules or scarring. 
&nbsp;

<h5>Biopsy</h5>

A sample of the liver cells is examined microscopically, which confirms the diagnosis of liver cirrhosis and its cause. 
&nbsp;

<h5>Endoscopy</h5>

A tube with a camera is passed through the esophagus into the stomach. Healthcare providers look for signs of swelling in the blood vessels (varices), which can be a sign of cirrhosis.

&nbsp;

Treatment

The treatment of cirrhosis is based on the cause and severity of the damage. Although it has no cure, treatment can stop or delay the progression of the disease. Prompt treatment can also help in reducing complications. 
&nbsp;

<h5>Alcohol-Related Liver Disease</h5>

If cirrhosis has developed because of alcohol abuse, stop consuming alcohol. Patients can contact their healthcare provider for help and recommendations for alcohol rehab programs.

<h5>Hepatitis B or C</h5>

Multiple antiviral medications are available for the treatment of hepatitis B and C.

Recombinant human interferon alfa-2b is used for the treatment of patients with chronic hepatitis and compensated liver disease. Patients who are eligible for this treatment are those who have elevated ALT and are HBsAg positive for six months with evidence of HBV replication.&nbsp;

Ribavirin is indicated in combination with interferon alfa-2b recombinant for the treatment of chronic hepatitis C. The combination is given to patients with compensated liver disease previously untreated with alpha interferon, or who have relapsed following alpha interferon therapy.&nbsp; 
&nbsp;

<h5>Nonalcoholic Fatty Liver Disease</h5>

The management includes losing weight by following a healthy diet and regular exercise. It is also helpful to reduce high blood sugar levels as part of the treatment plan.

&nbsp;

<h5>Inherited Liver Disease</h5>

The treatment of inherited liver disease depends on the specific disease. The treatment includes managing the complications or symptoms. For example, alpha 1 trypsin deficiency can be treated with antibiotics; in hemochromatosis, iron levels in the blood are reduced.

Another example is Wilson&rsquo;s disease. It is treated through medicines that remove copper from the body, preventing its absorption. Wilson&rsquo;s disease treatment plan also includes medications for clearing the mucus and improving lung functioning.&nbsp;

Glycogen storage disease is treated by keeping the glucose levels within a normal range.&nbsp;

&nbsp;

<h5>Autoimmune Hepatitis</h5>

Medications are used to suppress the immune system.

&nbsp;

<h5>Diseases That Damage And Block The Bile Duct</h5>

Ursodiol is used for medical treatment.&nbsp;

Surgical intervention may also be required to open the narrowed or blocked bile ducts. 
&nbsp;

<h5>Heart Failure</h5>

The treatment of heart failure is based on the cause and stage. Medications are used to treat high blood pressure, edema, and high cholesterol to improve the functioning of the heart.

Other treatments include implantation of devices that can monitor the rhythm of the heart, and maintain its function.&nbsp;

Surgical intervention may also be needed to unblock the arteries, and repair or replace damaged heart valves.&nbsp; 
&nbsp;

<h5>Medications That Contribute To Cirrhosis</h5>

Healthcare providers review all the medications that the patient is currently taking to determine if they are causing any problems. If the medications are damaging the liver, they are either stopped, or replaced, or the dosage is lowered depending on the case. 
&nbsp;

The complications of cirrhosis include the following: 
&nbsp;

Portal Hypertension

The normal blood flow slows down because of cirrhosis and increases the pressure in the portal vein, which brings blood from the intestines and spleen to the liver.&nbsp; 
&nbsp;

Swelling In The Abdomen And Legs

Fluid accumulates in the legs because of increased pressure in the portal vein and abdomen. Edema and ascites are also common when the liver is unable to make enough albumin, which is a blood protein. 
&nbsp;

Splenomegaly

Portal hypertension can lead to swelling or changes in the spleen. In addition, the white blood cells and platelets are trapped, which decreases their blood count. This is the first sign of cirrhosis. 
&nbsp;

Bleeding

Blood can be redirected to smaller veins in portal hypertension. Due to the extra pressure, these smaller veins can burst, causing severe bleeding. Portal hypertension can also cause varices (oesophageal&nbsp;and gastric varices), leading to life-threatening bleeding. Continued bleeding is also possible if the liver is unable to make enough clotting factors. 
&nbsp;

Infections

The body faces difficulties in fighting infections in cirrhosis. In addition, ascites can lead to bacterial peritonitis. 
&nbsp;

Malnutrition

The body does not process nutrients in cirrhosis, which can cause weight loss and weakness. 
&nbsp;

Hepatic Encephalopathy

Unlike a healthy liver, a damaged one does not clear toxins from the blood. These toxins build up in the brain, causing mental confusion and difficulty in concentration. This condition is called hepatic encephalopathy and can also progress to coma. 
&nbsp;

<a href="https://merisehat.pk/disease/jaundice-65">Jaundice</a>

When the liver does not remove enough bilirubin and blood waste, jaundice occurs. The skin and sclera of the eye become yellow, and the color of the urine darkens.&nbsp;

&nbsp;

Bone Disease

Bone strength is lost due to cirrhosis, which makes people prone to fractures. 
&nbsp;

Liver Cancer

People with pre-existing cirrhosis develop liver cancer<a href="#accordion">[3]</a>. 
&nbsp;

Acute-On-Chronic Cirrhosis

Multiorgan failure is possible in cirrhosis. However, the exact cause for this phenomenon is yet to be understood<a href="#accordion">[4]</a>.

&nbsp;

<ul>
	<li>Excessive alcohol consumption is a risk factor.</li>
	<li>When people are obese, it increases their risk of cirrhosis. For example, fatty liver disease and nonalcoholic steatohepatitis is often seen in obese patients.</li>
	<li>Chronic viral hepatitis develops into cirrhosis, and is one of the leading causes of death across the world<a href="#accordion">[5]</a>.&nbsp;Speak to your health care provider for hepatitis vaccinations.</li>
</ul>

&nbsp;

<ul>
	<li>Avoid drinking alcohol if you have cirrhosis or any other liver disease.</li>
	<li>Choose a healthy, plant-based diet. Whole grains are also a good source of protein. Also, reduce intake of fatty and fried foods.</li>
	<li>Excess fat can damage the liver. Consult a healthcare provider for obesity.</li>
	<li>Needle prick injury and using unsterilized&nbsp;sharps can increase the risk of hepatitis. 
	&nbsp;</li>
</ul>

Antiviral treatment and liver transplantation treatments have improved the outlook of hepatitis for patients with liver disease.&nbsp;

The new development is based on targeted treatments. In these treatments, patients will be treated with anti-inflammatory agents to lower portal pressure and fibrolytic agents. A panel of serum makers will be used to check the effectiveness of the treatment. In conclusion, it will change the treatment method and view of liver cirrhosis<a href="#accordion">[6]</a>. 
&nbsp;

Key Points

<ul>
	<li>Cirrhosis is a chronic liver disease.</li>
	<li>The healthy tissues of the liver are replaced by scar tissue, which stops it from functioning normally.</li>
	<li>The most common cause is hepatitis and excessive alcohol consumption.</li>
	<li>Liver cirrhosis is not reversible, but it can be managed to prevent further problems.</li>
	<li>A liver transplant is needed in severe cases.</li>
</ul>

&nbsp;

[1] Testino, G., Leone, S. and Borro, P., 2016. Treatment of alcohol use disorder patients affected by liver cirrhosis and/or hepatocellular carcinoma awaiting liver transplantation. Minerva Medica, 107(4), pp.223-238.

[2] Scorza, M., Elce, A., Zarrilli, F., Liguori, R., Amato, F. and Castaldo, G., 2014. Genetic diseases that predispose to early liver cirrhosis. International Journal of Hepatology, 2014.

[3] Tarao, K., Nozaki, A., Ikeda, T., Sato, A., Komatsu, H., Komatsu, T., Taguri, M. and Tanaka, K., 2019.

[4] Asrani, S.K., Simonetto, D.A. and Kamath, P.S., 2015. Acute-on-chronic liver failure. Clinical gastroenterology and hepatology, 13(12), pp.2128-2139.

[5] Sepanlou, S.G., Safiri, S., Bisignano, C., Ikuta, K.S., Merat, S., Saberifiroozi, M., Poustchi, H., Tsoi, D., Colombara, D.V., Abdoli, A. and Adedoyin, R.A., 2020.

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