Can cirrhosis be reversed?

First of all, I will like to tell you about the difference between treatment and cure. Treatment and cure are two different terms, cure means absolute remedy of a disease which will settle it and normalize the system to its original function as it was in the first place, but the treatment involves improving the condition and quality of the patient’s life.

Liver cirrhosis is not a curable but treatable disease. It cannot be reversed, but yes it can be treated and the survival of patients can be prolonged.

What is cirrhosis of the liver?

The liver is made up of a basic functional cell unit called hepatocyte which forms its main parenchymal tissue. Cirrhosis means scarring of tissues of the liver (1); morphologically it refers to the diffuse transformation of liver into regenerative parenchymal nodules surrounded by fibrous septa (A cluster of new cells surrounded by fibrous bands). Briefly, it means irreversible replacement of normal functional tissue with non-functional fibrous tissue. The liver has incredible potential to repair and regenerate itself, but whenever liver damage exceeds far from the certain limit as in chronic liver diseases like hepatitis B, C or Alcoholic liver disease it also forms fibrous tissue to repair itself apart from normal functional tissue, this is what we call fibrosis or scarring. When liver injury goes on and the causative factor is not removed, it leads to more scarring of tissue and declining of liver function and thus leading to cirrhosis. So basically, we can say cirrhosis is fibrosis or scarring of liver tissue with declining of liver function. As cirrhosis progresses, more and more normal tissue is converted into fibrous tissue and it leads to decompensated cirrhosis which is a life-threatening condition.

What causes liver cirrhosis?

               As discussed earlier, cirrhosis occurs in the background of chronic liver diseases with prolonged ongoing liver damage. Many diseases may lead to liver cirrhosis, but it is important to note that not all chronic liver diseases lead to cirrhosis, and not all cirrhosis leads to end-stage liver disease. The following are the most common causes of liver cirrhosis around the world (2)(3).

• Chronic Hepatitis C
• Alcoholic Liver Disease
• Non-Alcoholic fatty liver disease
• Chronic Hepatitis B

Apart from these there are less common conditions which also may lead to liver cirrhosis, these are:

• Hemochromatosis (Excessive iron accumulation in the body)
• Cystic fibrosis
• Wilson’s disease (excessive copper accumulation in the body)
• Biliary atresia (Poorly formed bile ducts)
• Alpha-1 antitrypsin deficiency
• Auto-immune hepatitis (Immune system of the body attacking its tissues)

What are the stages of liver cirrhosis?

               Cirrhosis itself in the late stage of chronic liver damage. In its early stages, liver tissue becomes inflamed and swells up but if causative factor/ organism is removed it will settle down with minimal structural and functional changes leading to the recovery of tissue completely, on the other hand, if this inflammation goes on it will lead to scarring and declining of liver function slowly. At this particular time, it can also be reversed with the removal of causative factors and appropriate treatment.

On clinical grounds liver cirrhosis is divided into 4 stages, mentioned below:

• Stage 1 cirrhosis involves minimal tissue injury with minimal scarring and few symptoms, also called compensated cirrhosis because there aren’t any complications.
• Stage 2 cirrhosis involves increasing pressure in the portal vein leading to portal hypertension and dilation of veins which are draining in the portal vein, for example, esophageal varices, caput medusae, hemorrhoids, etc.
• Stage 3 cirrhosis involves advanced liver scarring with compromised liver function leading to swelling of the abdomen and is also called decompensated cirrhosis. Serious complications like bleeding disorders develop in this stage which will manifest as haematemesis or Malena.
• Stage 4 cirrhosis involves end-stage stage liver disease, which is fatal until the liver is transplanted.

How cirrhosis manifests?

               Cirrhosis manifests differently in early and late stages. In early stages, the liver is damaged but its function is compensated and it is usually asymptomatic but can manifest mildly with:

• Anorexia
• Fatigue
• Weakness
• Jaundice (yellow discoloration of the skin)
• Nausea
• Weight loss

About 40% of patients are asymptomatic until the most advanced stage of the disease and even at last stages present with non-specific symptoms like anorexia, weight loss and weakness, and eventually signs of liver failure. In the rest of individuals when liver damage becomes extensive it manifests with the following features:

• Bleeding disorders (easy bruising, bleeding from GIT)
• Pruritus (itching of the skin)
• Spider angiomas (spider-like blood vessels on the skin) (4)
• Ascites (accumulation of fluid in the abdomen)
• Redness in palms
• Hyperesterogenemia (increase amount of estrogen leading to testicular atrophy, loss of libido and enlargement of breast in men and loss of periods in women) (5)
• Hepatic encephalopathy (confusion, slurred speech, and drowsiness)

Regeneration capacity of the liver:

               Before I tell you why cirrhosis is irreversible, let’s have a look at the regenerative potential of liver tissue. Liver repairs itself by two methods

• Either by the proliferation of remaining hepatocytes or,
• Regeneration by progenitor cells.

• The proliferation of remaining hepatocytes can make up for 90% of resected liver tissue; the process is driven by macrophages that produce Interleukin-6 (IL-6) and many other cell types that produce hepatocyte growth factor (HGF).
• Regeneration by progenitor cells is the second way of liver repair, it occurs when the proliferative activity of hepatocytes is impaired.
• Apart from these two methods, if liver injury goes beyond this repair process, fibroblasts move in and try to repair damaged cells by forming fibrous tissue, which is just a structural repair but a non-functional repair; gradually leading to declining function of the liver.

Why is cirrhosis irreversible?

               As mentioned above, when liver damage proceeds far beyond its repairing potential, it gradually proceeds toward fibrosis. As the disease progresses, more and more functional tissue is replaced by fibrous tissue leading to a decline in liver function. Once fibrous tissue is formed, it cannot be converted back into functional hepatocytes; hence it is an irreversible disease. If diagnosed in early stages, it can be cured by removing causative factors hence halting liver injury. In late stages, it may eventually end in End-Stage Liver Disease (ESLD).

References
1. "Cirrhosis". National Institute of Diabetes and Digestive and Kidney Diseases. April 23, 2014. Archived from the original on 9 June 2015. Retrieved 19 May 2015.
2. Friedman S, Schiano T. Cirrhosis and its sequelae. In: Goldman L, Ausiello D, eds. Cecil Textbook of Medicine. 22nd ed. Philadelphia, Pa.: Saunders, 2004:936–44.
3. Crawford JM. Liver and biliary tract. In: Kumar V, Abbas AK, Fausto N, eds. Robbins and Cotran Pathologic Basis of Disease. 7th ed. Philadelphia, Pa.: Elsevier Saunders, 2005:877–938.
4. Li CP, Lee FY, Hwang SJ, et al. (1999). "Spider angiomas in patients with liver cirrhosis: role of alcoholism and impaired liver function". Scand. J. Gastroenterol. 34 (5): 520–3.

5. van Thiel, DH; Gavaler, JS; Spero, JA; Egler, KM; Wright, C; Sanghvi, AT; Hasiba, U; Lewis, JH (Jan–Feb 1981). "Patterns of hypothalamic-pituitary-gonadal dysfunction in men with liver disease due to differing etiologies". Hepatology. 1 (1): 39–46.