End Stage Liver Disease Symptoms Before Death

Introduction

An estimated 1.5 billion people worldwide live with some form of chronic liver disease. Liver diseases are therefore a very important topic. In this article we will discuss liver diseases, ‘end-stage liver disease, and the management necessary for these conditions.1

What is Liver Disease?

The liver is the organ found in the upper right part of the abdomen with functions including:

  • processing digested food from the intestine for storage or utilization
  • controlling blood concentration of glucose, fats, and amino acids
  • manufacturing components of the blood clotting system
  • fighting infections
  • metabolizing various drugs to useful or less harmful forms
  • metabolizing toxins to less harmful forms
  • combating infections
  • clearing the blood of particles and infections, including bacteria
  • manufacturing bile to aid in digestion
  • storing iron
  • manufacturing and regulating the concentration of hormones

Liver diseases occur when there is a disorder that causes a harmful deviation from the normal structural or functional state of the liver. This can be very serious as the liver plays many vital roles in the body.2

Types and causes of liver disease

1. Alcohol abuse-related liver disease: This is a liver disease caused by excess alcohol intake. Initially, the consumption of alcohol causes fats to build up in the liver and then causes inflammation of the liver tissue.

2. Nonalcoholic fatty liver disease (NAFLD): Describes the build-up of fat in the liver which is unrelated to alcohol consumption. This extra fat can cause inflammation of the liver and liver disease.

3. Liver disease from infections: This type of liver disease arises from infection from viruses. These viruses are either transmitted through contaminated food, water, and blood and are sometimes sexually transmitted. Hepatitis A and Hepatitis E are transmitted through contaminated food. Hepatitis B is transmitted through contaminated blood or unprotected sex with an infected person. Hepatitis C is transmitted through infected blood.

4. Liver disease from toxic substances and abuse of prescription medication: The liver can develop inflammation from exposure to a toxic substance or during a drug overdose. A very common drug overdose that can cause liver damage is paracetamol or acetaminophen overdose. Other prescription medications that may cause liver damage if used incorrectly include the combination drug amoxicillin-clavulanate, phenytoin, azathioprine, certain antivirals, and anabolic steroids. 

5. Immune System Disorders: Sometimes the body’s immune system can incorrectly attack the liver, resulting in liver damage. Such disorders are primary biliary cholangitis and primary sclerosing cholangitis which is characterised by the immune system attacking tiny tubes in the liver called bile ducts. The damage to the bile ducts causes the bile produced in the liver to back up inside the liver and eventually scars it. It may even predispose the liver to cancer.

6. Cancer - The liver is one of the most common sites for the spread of cancers from other parts of the body such as the breasts and colon. This is referred to as secondary cancers of the liver. Cancers can also arise primarily in the liver because of liver diseases such as Hepatitis C and primary sclerosing cholangitis. Primary liver cancer is the 6th most common cancer worldwide.3

7. Inherited liver diseases: Some liver diseases run in families. The first example is hemochromatosis a condition that makes your body store up too much ingested iron and builds up the iron in your liver, heart, or other organs. In another condition called Wilson's disease, there is copper build-up in your liver and other organs. Finally, Alpha-1 Antitrypsin Deficiency can lead to liver disease and is the most common genetic cause of liver disease in children.4,5 

Symptoms

In the early stages, most types of liver disease do not cause many symptoms beyond yellowish discoloration of skin and eyes (jaundice), loss of appetite, generally feeling unwell and fatigued, loss of appetite, weight loss, nausea and vomiting, diarrhea, and abdominal pain in the liver area.

Once the liver disease progresses and affects the liver over a long period of time it may lead to fibrosis and cause the liver to be permanently scarred (a situation known as cirrhosis). When liver cirrhosis is described as compensated cirrhosis, it means the liver still functions well enough to only have a few symptoms of liver disease. Marked symptoms of liver disease are however seen in people with decompensated liver cirrhosis.

Management and Treatment of liver disease

The management and treatment of liver disease largely depend on the cause of the disease. In liver disease caused by alcohol consumption, the major step is to stop drinking alcohol.  Hepatitis A and E are usually dealt with by the body’s immune system with some supportive treatment such as adequate fluid intake and bed rest. Hepatitis B and C are managed with antiviral drugs and immune system modulators. Treatment of immune-related liver diseases typically revolves around the use of steroids.

What is End-Stage Liver Disease (ESLD)?

End-stage liver disease (ESLD) is said to occur when the liver is damaged beyond repair with severe symptoms of liver disease. End-stage liver disease is also known as liver failure.

What is the Difference Between Liver Cirrhosis and End-Stage Liver Disease?

While liver cirrhosis is scarring of the liver due to chronic liver disease, End-Stage Liver Disease (ESLD) can either be because of chronic liver disease (chronic ESLD) or an acute liver injury (acute ESLD). In fact, decompensated liver cirrhosis can be the immediate cause of chronic ESLD.

Causes of ESLD

It includes all liver diseases such as viral hepatitis and alcoholic liver that lead to decompensated liver cirrhosis, liver cancer (hepatocellular cancer), and causes of acute liver failure.

Acute liver failure is rarer and usually occurs right after a large overdose of paracetamol or poisoning. Less commonly, acute liver failure can occur from viral hepatitis and autoimmune conditions. 

Symptoms of ESLD

The symptoms of ESLD include: 

  • itchy skin
  • dark urine
  • pale stool
  • swelling of lower limbs
  • abdominal swelling (ascites)
  • severe abdominal pain
  • enlarged spleen
  • tendency to bruise easily with purplish rashes
  • signs of brain injury/encephalopathy such as poor concentration, slurred speech, disordered sleep rhythm, lethargy, drowsiness, confusion, coma
  • bleeding in the throat (variceal bleeding)
  • web-like markings on abdomen (spider naevi)
  • painful defecation from hemorrhoids
  • poor blood sugar control
  • susceptibility to infections

Clinical Course of End-Stage Liver Disease

The severity of ESLDand the need for a liver replacement via transplant surgery is commonly assessed using one of MELD-Na scores or Child-Pugh scores. 

MELD stands for ‘model for end-stage liver disease’ and has a score that ranges from 6 to 40 based on lab tests. The higher the MELD score, the more severe or urgent the case of ESLD is. The components of the MELD score include 

  • Serum creatinine level, which is related to kidneys function
  • Serum Bilirubin level, which is related to how well the liver clears bile
  • INR (international normalized ratio), which reflects how well your liver makes coagulation factors
  • Blood sodium level.

On the other hand, the Child-Pugh score uses five measures of liver disease with each measure getting a score of one, two, or three. The total Child-Pugh score ranges from 5 to 15. The 5 parameters considered are:

  • Total serum bilirubin
  • Serum Albumin
  • Prothrombin time, which relates to how long it takes your blood to clot
  • Ascites
  • Encephalopathy

A score less than 7 is grade A and is considered mild. A score of 7-9 is grade B and is considered moderate. A score of 10-15 is grade C and is considered severe and most urgently needs a liver transplant. The one-year survival rates for patients with Child-Pugh grades A, B, and C are approximately 100, 80, and 45 percent, respectively.

Management

Though the term "end-stage liver disease" sounds dreary, liver transplantation can be a definitive and potentially curative treatment for liver failure. Despite this many individuals with ESLD are not candidates for transplantation because of clinical and/or social factors. Furthermore, the demand for healthy donor livers for transplantation far outnumbers the number of patients who qualify for transplantation. Because of these complexities, it is considered best to initiate palliative care even for patients considered for transplantation.

The primary goal of palliative care is to improve the quality of life for patients with ESLD and their family through the relief of emotional distress and physical symptoms. This palliative care should ideally be provided throughout the trajectory of illness. The provision of palliative care for ESLD  is interdisciplinary and requires the efforts of primary care physicians and gastrointestinal or hepatology specialists. This provision of palliative care is termed primary palliative care and is different from secondary or subspecialty palliative care provided by medical personnel trained specifically to provide an advanced level of palliative care. The timing of subspecialty palliative care consultation for each patient is unique and depends on local resources and patient needs. 

Difference between palliative care and hospice — Hospice is a term closely related to palliative care and shares the same principles of providing support and comfort for patients and their families. Hospice however differs from palliative care in that while hospice is care that is offered when curative or life-prolonging therapy is no longer the focus of treatment for patients with a terminal disease who generally have an estimated life expectancy of six months or less, palliative care is offered to patients at any time along the disease projection trajectory, even concurrent with restorative, life-prolonging therapies. That is to say, while all care that is delivered by hospice programs can be considered palliative care, not all palliative care is considered to be hospice care.

Components of palliative care in ESLD 

The essential components of palliative care include:

  • assessing and managing physical symptoms
  • exploring the patient's understanding of their condition and prognosis
  • soliciting and discussing care goals, coordinating care, and helping to plan end-of-life care, including determining the need for and timing of hospice care if necessary.
  • the treatment approach in ESLD should be guided by care goals in the context of the current prognosis and available treatment options.
  • Ascites management: Involves salt restriction and diuretic therapy. In refractory cases, albumin infusion, paracentesis, or the creation of a shunt to drain the ascites may be considered.
  • Encephalopathy: General supportive care for patients with hepatic encephalopathy in ESLD include the provision of nutritional support, avoiding dehydration and electrolyte abnormalities, and providing a safe environment such as precautions to prevent falls for disoriented patients.
  • Pain: Pain is challenging to treat in patients with ESLD since paracetamol may be toxic to the liver and NSAIDs may be damaging to patients with co-existing chronic kidney disease. Opioids are considered the best option for pain management here but should be used with caution in patients with ESLD due to challenges with metabolism. Lower doses of opioids are started first to monitor response before increasing doses. Where possible, nonpharmacologic management for pain such as massage, acupuncture, and cognitive behavioral therapy should be considered.
  • Variceal hemorrhage/ Bleeding in the throat: In patients who are yet to experience variceal bleeding, beta-blocker drugs can be used for primary prophylaxis. Treatment mainly involves endoscopic therapy.
  • Itching:  For patients with itching, topical emollients, avoidance of hot baths, and cool humidified air may help alleviate symptoms. Bile sequestrants that reduce bile levels may also be tried.6,7

Summary

ESLD is synonymous with liver failure. The severity of ESLD and the need for a liver replacement via transplant surgery is commonly assessed using one of MELD-Na score or Child-Pugh score. 

Though the term "end-stage liver disease" sounds dreary, liver transplantation can be a definitive and potentially curative treatment for liver failure. Despite this many individuals with end-stage liver disease are not appropriate transplant candidates due to clinical and/or social factors. Furthermore, the demand for healthy donor livers for transplantation far outnumbers the number of patients who qualify for transplantation. Because of these complexities, it is considered best to initiate palliative care even for patients considered for transplantation.

The primary goal of palliative care is to improve the quality of life for patients with ESLD and their family through the relief of emotional distress and physical symptoms.

The essential components of palliative care include assessing and managing physical symptoms, exploring the patient's understanding of their condition and prognosis, soliciting and discussing care goals, coordinating care, and helping to plan end-of-life care, including determining the need for and timing of hospice care if necessary.

References

  1. Moon AM, Singal AG, Tapper EB. Contemporary Epidemiology of Chronic Liver Disease and Cirrhosis. Clin Gastroenterol Hepatol. 2020 Nov 1;18(12):2650–66. 
  2. Kalra A, Yetiskul E, Wehrle CJ, Tuma F. Physiology, Liver. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 [cited 2022 Apr 4]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK535438/
  3. Ananthakrishnan A, Gogineni V, Saeian K. Epidemiology of primary and secondary liver cancers. Semin Interv Radiol. 2006 Mar;23(1):47–63. 
  4. Kumar A, Riely CA. Inherited liver diseases in adults. West J Med. 1995 Oct;163(4):382–6. 
  5. Alpha-1 Antitrypsin Deficiency [Internet]. American Liver Foundation. [cited 2022 Apr 3]. Available from: https://liverfoundation.org/for-patients/about-the-liver/diseases-of-the-liver/alpha-1-antitrypsin-deficiency/
  6. Scottish Palliative Care Guidelines - End Stage Liver Disease [Internet]. Scottish Palliative Care Guidelines. [cited 2022 Apr 4]. Available from: http://www.palliativecareguidelines.scot.nhs.uk
  7. Walling AM, Wenger NS. Palliative Care and End Stage Liver Disease. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2014 Apr;12(4):699–700. 
This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

Get our health newsletter

Get daily health and wellness advice from our medical team.
Your privacy is important to us. Any information you provide to this website may be placed by us on our servers. If you do not agree do not provide the information.

Samuel Oninku

Masters of Science in Operational Management, University of Warwick, Coventry, England
He is a young doctor, public health, and health management professional with a passion for health promotion and education. He believes quality health information should be accessible in an understandable form to all persons.

Leave a Reply

Your email address will not be published. Required fields are marked *

my.klarity.health presents all health information in line with our terms and conditions. It is essential to understand that the medical information available on our platform is not intended to substitute the relationship between a patient and their physician or doctor, as well as any medical guidance they offer. Always consult with a healthcare professional before making any decisions based on the information found on our website.
Klarity is a citizen-centric health data management platform that enables citizens to securely access, control and share their own health data. Klarity Health Library aims to provide clear and evidence-based health and wellness related informative articles. 
Email:
Klarity / Managed Self Ltd
Alum House
5 Alum Chine Road
Westbourne Bournemouth BH4 8DT
VAT Number: 362 5758 74
Company Number: 10696687

Phone Number:

 +44 20 3239 9818