Cirrhosis natural history, complications and prognosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Shankar Kumar, M.B.B.S. [2] Aditya Govindavarjhulla, M.B.B.S. [3]

Overview

Cirrhosis is an irreversible process, the course of which is highly variable from patient to patient. The natural history progresses so that there is a lengthy stage of compensation, followed by development of complications and sequelae as a result of the cirrhosis. The devastating complications include complete liver failure or the development of hepatocellular carcinoma. Other complications are portal hypertension, ascites, jaundice, itching, esophageal varices, spontaneous bacterial peritonitis, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome and cardiomyopathy. Prognosis depends on the causes, existing complications and a variety of factors which make prediction of life expectancy questionable. There are scores by which to classify severity and to determine suitability for liver transplant.

Natural History

• The symptoms of (disease name) usually develop in the first/ second/ third decade of life, and start with symptoms such as ___.
• The symptoms of (disease name) typically develop ___ years after exposure to ___.
• If left untreated, patients with cirrhosis may progress to develop ascites, esophageal varices, hepatic encephalopathy, spontaneous bacterial peritonitis, hepatopulmonary and hepatorenal syndrome.
• The general course of cirrhosis is characterized by a long stage of compensation, which may be followed by deterioration and development of specific complications.
• Life threatening complications may develop in almost any patient. Once the first complication in a patient with cirrhosis is seen, it is soon followed by numerous other complications that significantly decrease life expectancy.
• Prediction of the exact course of the disease and generalization to the entire population is difficult.
• Several factors play a key role in determining the course of the disease:
  • existing hepatic function
  • the etiology of cirrhosis
  • progression of the disease
  • development of hepatocellular carcinoma
  • ability of the patient to withstand a chosen therapeutic intervention
  • ability of the intervention to significantly improve the outcome

Decompensated Cirrhosis

In patients with previously stable cirrhosis, decompensation may occur due to various causes, such as constipation, infection (of any source), increased alcohol intake, medication, bleeding from esophageal varices or dehydration. It may take the form of any of the complications of cirrhosis listed above.

Patients with decompensated cirrhosis generally require admission to the hospital, with close monitoring of the fluid balance, mental status, and emphasis on adequate nutrition and medical treatment - often with diuretics, antibiotics, laxatives and/or enemas, thiamine and occasionally steroids, acetylcysteine and pentoxifylline. Administration of saline is generally avoided as it would add to the already high total body sodium content that typically occurs in cirrhosis.

Complications

• The high mortality rate associated with cirrhosis is primarily due to complications.
• Common complications of cirrhosis include:
  • Complications due to portal hypertension include:
    • Ascites : Ascites is the most common complication of cirrhosis
      • Due to increased pressure, fluid leaks through the vasculature into the abdominal cavity
    • Esophageal varices: Increased pressure in the portal vein leads to collateral portal blood flow through vessels in the stomach and esophagus
    • Portal vein thrombosis
    • Easy bruising and bleeding - due to the decreased production of coagulation factors
    • Jaundice
    • Itching (pruritus)
    • Hepatic encephalopathy : due to inability of the liver to clear ammonia and related nitrogenous substances from the blood, which are carried to the brain
      • The features of hepatic encephalopathy are as follows:
        • Changes in sleep pattern (insomnia and hypersomnia)
        • Unresponsiveness
        • Forgetfulness
        • Poor concentration
        • asterixis
        • Coma
    • Sensitivity to drugs due to decreased metabolism in the liver
  • Hepatocellular carcinoma is primary liver cancer and is most commonly seen in cirrhotic patients with:
    • Hepatitis B or C
    • Non-alcoholic steatohepatitis
    • hemochromatosis
  • Infection: due to immune system dysfunction
    • Non specific signs and symptoms
  • Spontaneous bacterial peritonitis:
    • Infection of the fluid in the abdomen due to ascites with intestinal bacteria
    • Symptoms and signs include pain, tenderness and altered mental status
    • Patient may be asymptomatic in early stages
    • Findings on diagnostic paracentesis such as a positive culture and/or absolute neutrophil count >250/mm3 are confirmatory
  • Hepatorenal syndrome:
    • has a very high mortality of over 50%
    • arises due to decreased perfusion to the kidneys, leading to acute renal failure
    • may be masked clinically due to decreased muscle mass and hepatic urea synthesis in cirrhotic patients leading to only a small elevation of BUN and creatinine
    • diagnosis of exclusion as causes of renal dysfunction need to be excluded first
    • bears poor patient prognosis
  • Pulmonary diseases associated with cirrhosis include:
    • Hepatopulmonary syndrome:
      • presents as a triad comprising of the following:
        • existing liver disease
        • increased alveolar-arterial gradient
        • intra-pulmonary vascular dilations
      • mild hypoxemia may be present due to ascites causing increased intra-abdominal fluid pressure on the diaphragm
    • Hepatic hydrothorax:
      • intra-abdominal fluid may seep in through the diaphragm into the pleural space leading to a pleural effusion
    • Portopulmonary hypertension:
      • due to increased blood pressure over the lungs as a consequence of portal hypertension
  • Cardiomyopathy:
    • presents with normal or increased cardiac output at rest but notably decreases in stress conditions
  • Muscle cramps:
    • occur due to reduction in circulating plasma volume

Prognosis

• Prognosis is generally excellent/good/poor, and the 1/5/10-year mortality/survival rate of patients with [disease name] is approximately [#]%.
• Depending on the extent of the [tumor/disease progression/etc.] at the time of diagnosis, the prognosis may vary. However, the prognosis is generally regarded as poor/good/excellent.
• The presence of [characteristic of disease] is associated with a particularly [good/poor] prognosis among patients with [disease/malignancy].
• [Subtype of disease/malignancy] is associated with the most favorable prognosis.
• The prognosis varies with the [characteristic] of tumor; [subtype of disease/malignancy] have the most favorable prognosis.

Well-Compensated, no alcohol	35% mortality at 2 years
Onset of Ascites	50% mortality at 2 years
Variceal bleeding	65% mortality at 1 year (35% short-term mortality)

Scoring Systems

• Model for End-Stage Liver Disease
• Pediatric End-Stage Liver Disease
• Child-Pugh score
• Child-Turcotte classification

• The severity of cirrhosis is commonly classified with the Child-Turcotte and Child-Pugh scores. It was devised in 1964 by Child and Turcotte and modified in 1973 by Pugh et al.
• The Child-Pugh score uses bilirubin, albumin, INR, presence and severity of ascites and encephalopathy to classify patients in class A, B or C types.
• Class A type has a favorable prognosis, while class C is at a high risk of death.

• Modern scores, used in the allocation of liver transplants are the Model for End-Stage Liver Disease (MELD) score and its pediatric counterpart, the Pediatric End-Stage Liver Disease (PELD) score.