Decompensated Liver Disease

Introduction

What is Decompensated Liver Disease?

Decompensated liver disease, also known as decompensated cirrhosis, is the acute wearing and weakening of liver function in patients diagnosed with cirrhosis. Commonly observed presentations in patients include ascites, hepatic encephalopathy, hepatorenal syndrome and jaundice. These signs are often instigated by the association of high alcohol intake, drug or toxin-induced liver damage, gastrointestinal bleeding and pathogenic infections.^[1] People with decompensated cirrhosis are approaching end-stage liver failure, hence why many patients undergo liver transplants. 

Cirrhosis can be categorized into two forms, compensated or decompensated. In compensated cirrhosis, the liver can tolerate liver damage and can maintain sufficient levels of vital hepatic functions. On the other hand, in decompensated cirrhosis, the patient’s liver cannot achieve all the essential functions effectively.^[2]

What is Cirrhosis?

Liver cirrhosis is a major worldwide cause of mortality. Around 40% to 60% of cases within the North American and European regions are understood to be directly caused by extensive alcohol abuse. Cirrhosis is the final manifestation of advanced fibrotic scarring within the liver initiated by damage caused by chronic liver disease. Additionally, it can include the accumulation of fatty deposits and hepatitis which is the inflammation of the liver. The progression of the liver disease involves the loss of hepatocytes in the liver parenchyma, the formation of additional connective tissue called fibrous septa, and manifestations of irregular nodule structures. Liver fibrosis results from the propagation of the wound healing mechanism causing an abnormal prolongation of connective tissue generation and deposition. The main clinical effects of cirrhosis are increased intrahepatic portal hypertension, compromised function of hepatocytes, and progression to develop hepatocellular carcinoma. Collectively, cirrhosis will result in the alteration of the normal and healthy hepatic vasculature.^[3] This contributes to the shunting of the blood supply associated with the portal and arterial blood vessels that control the hepatic outflow. The space of Disse is a site in the liver between a hepatocyte and a sinusoid, containing blood plasma, hepatic stellate cells, and mononuclear cells. It is elemental in maintaining the parenchymal cell function to conduct metabolic exchange between the blood flow and hepatocytes. However, in cirrhosis, the space of Disse occupied by fibrotic scar tissue directly causes termed sinusoidal capillarization– which is the loss of the particular phenotype of the liver sinusoidal endothelial cells – and the gaining of normal features of capillaries.^[4]

Causes and Risk factors

Viral hepatitis patients and overweight and obese individuals are also at risk. Alcohol is potentially toxic depending on its concentration, and given that it is detoxified by the liver, inappropriate abuse of drinking is directly related to the chances of developing decompensated cirrhosis. Chronic Hepatitis B or Hepatitis C, in which viruses invade the liver and cause sustained inflammation for many months, damage all parts of the liver. Hepatitis B is highly infectious and is transmitted through bodily fluids, whereas Hepatitis C is transmitted mainly by blood-borne routes.

Usually, patients with acute decompensated liver disease obtain it within a cascade of pathogenic mechanisms. However, in around 40% of cases there is no initial disease-causing event that has been acknowledged, as it is a chronic and progressive disease. Any sort of liver injury can induce fibrosis and scarring, contributing to the development of decompensated cirrhosis. In the long term, excessive alcohol consumption  and the build-up of fatty deposits within the liver are major drives to the development of liver disease.

In addition to this, there are other possible causes of decompensated liver disease. One cause is  the build-up of excess iron or copper in the liver. Having other chronic diseases decreases the body’s immunity overall, increasing susceptibility  of acquiring  liver disease. Autoimmune diseases also increase the risk of decompensated cirrhosis, as well as being associated with cystic fibrosis patients.

Symptoms

During the earliest stages of cirrhosis and liver disease, symptoms are difficult to observe, as the disease is generally silent. Eventually, when the patient progresses onto the stage of decompensated cirrhosis a wide range of clinical manifestations can be observed.^[2] 

One of the main signs of liver injury is the appearance of yellow discolouration of the skin or other membranes, known as jaundice. This occurs because the damaged liver cannot sufficiently clear enough bilirubin pigment, which is a blood waste product, from the blood of the patient. 

Another important sign of decompensated liver injury is the manifestation of spider angiomas, which are also known as spider veins. An abnormal collection of blood vessels near the surface of the skin, spider veins often appear most on the face, upper torso, neck, arms, or fingers. 

Ascites are a condition in which proteinaceous fluid builds up in the abdominal cavity, causing it to bloat and swell. This condition is severe and extremely painful. The main cause of this in advanced liver disease is because of the build-up of high pressure within the liver, and the low production of albumin by the damaged liver. If left untreated, the fluid can further accumulate and potentially become infected, putting the patient’s life at risk. 

Palmar erythema is a skin condition that makes the palms of your hands flush and turn red in color; this is also a common symptom of liver disease. This occurs due to some modifications in the process of estrogen metabolism by the patient’s cirrhotic liver. Another way estrogen is modified in male patients is that their bodies enhance the conversion of androstenedione to estrone and oestradiol. The relatively decreased oestradiol degradation in the liver leads to swelling and enlargement of glandular male breast tissue, this condition is called Gynecomastia.^[4] Hepatic encephalopathy is a nervous system disorder caused by advanced liver disease, it includes slurred speech, drowsiness and confusion. Additionally, general symptoms such as swollen legs, fatigue, weight loss and nausea are also exhibited, as it occurs in over 50% of cirrhotic liver patients.

Diagnosis

Clinical presentations of patients with decompensated liver disease are generally characterized by incidences of life-threatening complications. Usually, clinicians will start to investigate a patient when cirrhosis symptoms have manifested, such as jaundice or mental confusion. Physicians confirm the decompensated liver disease diagnosis by performing blood tests to study liver function.

A key diagnostic indicator of active liver damage is elevated serum levels of aminotransferases, with the concentration of ALT (alanine transaminase) levels higher than AST (aspartate transaminase) in viral cirrhosis, but higher levels of AST compared to ALT in alcoholic cirrhosis.^[3] This occurs due to aminotransferase leakage from damaged hepatocytes within the liver. Additionally, elevated levels of Alkaline phosphatase and Gamma-glutamyl Transferase can also be detected in cirrhotic patients. Another important laboratory test is for serum bilirubin, decreased hepatocyte and renal excretory function causes elevated serum levels, however, the incline is much later as the bilirubin concentration remains normal for a long time. Both albumin and prothrombin time are decreased in advanced cirrhosis, this is associated with decreased hepatic production and correlated malnutrition of specific vitamin levels.^[4] The concentration of ammonia within serum would also appear relatively high in patients with advanced liver failure, and this is generally supplemented by modifications in the normal amino acid pattern. Most cirrhosis patients have hyperglobulinemia, a sign of nonspecific activation of the humoral immune system caused by shunting of the portal vein. Elevated IgG levels indicate cirrhosis of viral origin and elevated IgA indicates the presence of alcoholic cirrhosis, whereas predominating IgM concentrations are a sign of biliary cirrhosis.^[3]

Most of the time, laboratory tests alone are not enough to successfully diagnose the stage and cause of cirrhosis. Therefore, other methods are also used in conjugation. Imaging techniques are another useful diagnostic tool to visualize the size and shape modifications of the cirrhotic liver. Although they are not sensitive enough to solely diagnose cirrhosis, they still can present images that indicate whether there is an abnormal visualization of the hepatic surface or texture, and radiography is used to detect any associated complications of advanced liver disease. Ultrasonography provides clinicians with imperative information on the hepatic architecture involving any atrophy of the lobes or observed fibrosis. Furthermore, MRI can also aid in effectively quantifying the fatty deposits and iron accumulation within the liver. Obtaining a liver biopsy is considered the best histological method to diagnose cirrhosis in patients, as it can properly assess the level of inflammation as fibrosis within the liver to categorize the stage of the liver disease. The biopsy usually is taken from at least one parenchymal nodule with its connective tissue surrounding the sample. A biopsy confirmation would not be necessary if the patient exhibits very direct signs of cirrhosis, these include signs of ascites, coagulopathy, and shrunken nodular appearing livers.^[4]

Management

Decompensated liver disease is an advanced and complex disorder which affects various systems within the body physiology, hence why its management requires a systematic approach to treat the direct cause as well as the associated symptoms or side effects. It is imperative to govern the fundamental cause of hepatic decompensation by going over the patient’s medical history and clinical examinations to implement suitable future treatments. Currently, the main and most effective treatment of decompensated liver disease is a liver transplant. However, due to organ donor availability and priority lists generated, patients are constantly treated via various methods to lessen the symptoms or slow the progression of the disease. Those who do not get a liver transplant due to such advanced stages or fail to respond to treatments are usually treated with palliative care. If the chronic liver disease is associated with the hepatitis virus, viral eradication methods are very successful at lowering the risk of further hepatic decompensation and development of hepatocellular carcinoma. There are worldwide approved antiviral treatments currently in use to treat both types of Hepatitis B and C.

Cirrhosis patients exhibit various degrees of hepatic encephalopathy. In order to treat these symptoms the accumulated toxins within the liver must be cleared. The main way to eliminate the toxins is using lactulose, a non-absorbable sugar that induces more stools to the laxatives. Ascites are one of the most enduring and life-threatening consequences of liver disease, so their treatment is vital. Patients with mild ascites would be managed by implementing a no-salt diet along with diuretic medication as a therapy to reduce the fluid accumulation. In some cases a paracentesis procedure can be done where a needle is inserted into the abdomen to remove the fluid; it is usually done when the fluid is relatively a very large volume.^[1]

Cirrhosis patients are relatively very immunocompromised, therefore they are very susceptible to acquiring infections, such as pneumonia and urinary tract infections. Therefore, these patients should be regularly screened for any pathogenic diseases so that if acquired, they can be treated at the beginning of the infection before it has the chance to spread. Ensuring that any malabsorption experienced by the patient is also very important as other conditions like sarcopenia and refeeding syndrome are common in decompensated liver disease patients. Regular blood tests are administered as well as nutritional supplements in many forms are given to the patients.

Gastrointestinal bleeding is prevalent in cirrhotic patients, and it is a very dangerous consequence that can lead to the death of the patient. Esophageal varices are often the most likely form of bleeding in decompensated liver disease, it is when enlarged veins in the esophagus are obstructed. Blood transfusions are a very common method to treat such bleeding, to prevent the hemoglobin levels from dangerously declining (below 7.0 g/L). For gastric varices, an injection of cyanoacrylate is administered to act as a “glue” endoscopically reducing the variceal bleeding. Post-bleeding antibiotics are also given to the patients to lessen the chances of external infections.^[1]

How long can you live with decompensated liver disease?

Countless patients who live with cirrhosis go on to live many normal years without the need for severe medical assistance or liver transplant, as their livers can adequately function even if it is damaged. However, reaching the decompensated cirrhosis stage can significantly reduce life expectancy as it is a very extreme threat to a patient’s life. Generally, patients who have been diagnosed with advanced decompensated cirrhosis have an estimated life expectancy of around 1 to 3 years.

A Model For End-Stage Liver Disease (MELD) score has been authenticated as a good predicted estimation of survival in patients with acute liver failure, cirrhosis, and acute hepatitis. It calculates the patient’s likelihood of surviving their liver disease during the next three months. The higher the calculated MELD score, the lower the patient’s chances of surviving another three months. However, in terminally sick patients, the number of extra-hepatic organ failures is a more accurate measure of mortality. Having a MELD score lower or equal to 15 corroborates with having a 95% chance of surviving for at least the next three months, for a score of 30 the survival rate is 65%. Therefore, the MELD score is used for categorizing who is most vulnerable and at a higher priority to have a liver transplant on the organ donor list.^[2]

Can you recover from decompensated liver disease?

Patients with advanced liver disease who receive a liver transplant tremendously extend their life expectancy as it is currently the most effective treatment to manage end-stage liver disease. Many patients go on to live their normally functioning lives with a mean survival rate of 75% for the next 5 years. With current revelations in the treatment of Hepatitis B and C, scientists believe that there is hope for novel drugs that can tackle scarring of the liver. However more research and clinical trials are being done to properly study potential new treatments.

When should I contact my doctor?

If a person is having many symptoms of cirrhosis that are more severe than mild signs then the person must contact their doctor and get some clinical investigations done as soon as possible. Especially if they have been previously diagnosed with cirrhosis or other liver diseases, the unusual manifestation of specific signs is very important. These signs would include but are not limited to: vomiting blood, shortness of breath, drowsiness, fever, shivering and mental confusion.^[2]

Summary

Decompensated liver disease is a very prevalent chronic condition that appears within acute medical units and it contributes to many liver disease-associated fatalities. Patients would present with severe scarring of the liver and would be at the final stages of chronic liver disease. Therefore, it is imperative to develop a systemic method to ensure patients are fully informed about the progress of this disease as well as how to properly manage it. It is established that high alcohol consumption, hepatitis viruses and obesity are the major driving forces that contribute to the disease; and people with these risks must be treated early on to prevent sufficient liver injury. If not properly treated, decompensated cirrhosis can go on and induce more life-threatening clinical problems that reduce the quality of life as well as accelerate kidney failure and liver cancer in patients.