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Liver cirrhosis is the final stage of chronic liver disease. It is accompanied by a loss of hepatic function.

Liver cirrhosis is the final stage of a chronic liver process. It leads to nodular parenchymal remodeling with fibrous septa formation and infiltration of the tissue with inflammatory cells. Functionally, liver cirrhosis is characterized by hepatic insufficiency and portal hypertension. There is also the formation of intrahepatic porto-systemic shunts.

Epidemiology

The annual incidence in western industrialized countries (Europe and the USA) is 250 cases per 100,000 inhabitants. Men are more frequently affected by the disease (men:women; 2:1). Alcoholic liver cirrhosis causes around 8,600 deaths per year (as of 2009). It is one of the 20 most common causes of death in Germany.

Causes

The main causes of liver cirrhosis in Germany are alcoholic and non-alcoholic fatty liver disease (59%), but also chronic viral hepatitis (20-25%), especially hepatitis C. In Africa and Asia, viral hepatitis is the leading cause at around 90%. Smoking also promotes the development of liver cirrhosis.

Risk stratification for the development of liver cirrhosis from chronic liver disease

An individual risk stratification for the development of liver cirrhosis from chronic liver disease helps to determine the individual risk and adapt therapeutic measures.

Non-alcoholic fatty liver: In the case of non-alcoholic fatty liver, for example, the risk of fibrosis progression can be estimated with the help of the initial biopsy result. Signs of inflammation in the biopsy indicate rapid progression towards liver cirrhosis, while in the absence of inflammation the time to development of cirrhosis is over 13 years. If a biopsy is not available/desired/possible, the risk can also be estimated using non-invasive ultrasound procedures.

Genetic influences: Genetic influences can also favor the progression of chronic liver disease towards cirrhosis. For example, genetic polymorphisms in the patatin-like phospholipase domain-containing 3 gene (PNPLA3, adiponutrin) represent a risk factor in nutritive-toxic liver diseases (alcoholic and non-alcoholic fatty liver disease), which is associated with both progression and an increased risk of hepatocellular carcinoma (HCC).

Hepatitis B and hepatitis C: In the case of chronic hepatitis C, the development of liver cirrhosis depends on age and possible alcohol consumption. The progression to liver cirrhosis increases significantly from the age of 40. Furthermore, the risk of liver cirrhosis increases significantly with alcohol abuse.

In the case of hepatitis B, however, the viral load (HBV DNA in serum) is the main factor influencing possible progression. This value is therefore also a significant factor in the indication for initiating antiviral therapy.

Pathogenesis

During the development of liver cirrhosis, collagen fibers are deposited in the liver tissue. Ito cells (heptic stellate cells) in particular are involved in the formation of these fibers. This results in liver fibrosis. In addition, the hepatocytes of the liver lobule die (necrosis), which are then replaced by disorganized nodular regeneration.

The organ becomes scarred and shrinks. The reduction in compliance and obliteration of the hepatic capillary bed increases the resistance to perfusion in the liver and portal hypertension can develop. The function of the liver decreases and water retention occurs as a result: edema and ascites. Blood clotting disorders also occur. On the other hand, there is a backlog of blood in the portal vein system. Vascular collaterals form, e.g. to the oesophageal veins. So-called oesophageal varices can develop.

Symptoms

At the beginning, liver cirrhosis is usually asymptomatic. As it progresses, non-specific general symptoms such as fatigue, a feeling of pressure and fullness in the upper abdomen and pruritus come to the fore. In addition, jaundice and an increase in abdominal girth may occur as part of ascites.

Gynecomastia, abdominal baldness/breast baldness can also occur as part of the disease due to hormonal disorders (testosterone reduction and oestrogen increase). Patients may also complain of libido and potency disorders. Patients may also exhibit the so-called liver skin signs (see Diagnostics section).

Complications

Liver cirrhosis can lead to life-threatening complications. These include bleeding from collateral vessels, ascites, hepatocellular carcinoma, infection-related organ failure and the occurrence of encephalopathy and even coma hepaticum. Increased hemorrhagic diathesis is also observed in liver cirrhosis patients.

Diagnosis

The diagnosis of liver cirrhosis is made on the basis of appropriate clinical and laboratory findings in conjunction with instrumental procedures.

Physical examination

The physical examination reveals liver cirrhosis with signs of liver skin and palpation of a consistently enlarged liver:

  • Lacquer tongue
  • The appearance of spider naevi (telangiectasias, e.g. on the trunk)
  • Caput medusae (periumbilical dilation of the subcutaneous veins)
  • Palmar and plantar erythema
  • Milky glass nails/white nailsWhite glass nails
  • parchment-like skin atrophy

Suspicion of the presence of liver cirrhosis should be considered in certain risk constellations:

  • metabolic syndrome
  • increased alcohol consumption
  • Medication
  • Hepatotoxic substances

Diagnostic equipment

B-scan sonography can be used as an imaging procedure to diagnose liver cirrhosis. Here, liver cirrhosis can be seen as an irregular liver surface, inhomogeneity of the liver, enlargement of the caudate lobe and splenomegaly. Detection/exclusion of liver cirrhosis is possible in >90% of cases with the aid of ultrasound procedures. In addition, an oesophago-gastro-duodenoscopy (OGD), which can assess oesophageal varices and their risk of bleeding, is part of the diagnostic equipment.

Laboratory diagnostics

Liver synthesis parameters are reduced as a sign of liver insufficiency. In phases of inflammatory attacks, there is an increase in transaminases, gamma-GT and, in around two thirds of cases, hyperbilirubinemia. An increase in serum ammonia occurs when detoxification function is severely impaired.

Decreased in liver insufficiency are:

  • Cholinesterase
  • Vitamin K-dependent coagulation factors (II, VII, IX, X) and non-vitamin K-dependent coagulation factors (I, V, XII, XIII)
  • Quick value
  • AT III
  • Protein C
  • Protein S
  • Albumin

The following laboratory parameters are elevated during an inflammatory episode:

  • GOT/ ASAT
  • GPT/ALAT
  • Gamma-GT
  • Bilirubin
  • Ammonia

Liver biopsy:

A biopsy from the liver is only indicated if the aetiology of the liver disease is unclear and the resulting therapeutic consequences and if the stage cannot be clearly determined on the basis of other parameters.liver cirrhosis is represented pathologically and anatomically by fibrous septa between the portal fields. It is divided into a coarse (macronodular) and a fine-nodular (micronodular) form.

Fibrosis indices

Fibrosis indices can be formed from routine laboratory parameters associated with the liver. One example is the APRI test (AST to Platelet Ratio Index). This is calculated as a quotient of the GOT and platelets as a screening index for advanced fibrosis/cirrhosis, and liver stiffness can be measured during sonography using elastography and Acoustic Radiator Force Impulse (ARFI) technology, from which a relationship can be established with the extent of liver fibrosis. Fibrosis indices can be used for long-term assessment of the progression of fibrosis in patients with chronic liver disease.

Severity of liver cirrhosis

The extent of liver cirrhosis is classified into stages A-C using the Child-Pugh criteria. Patients in stage A have the highest survival rates, while stage C reflects advanced cirrhosis and has the worst prognosis. Serum albumin, bilirubin, the Quick or INR (international normalized ratio) are included in this score. The presence of ascites on sonography and the degree of hepatic encephalopathy are also taken into account, and the MELD score (model for end-stage liver disease) can be used to classify the severity of liver cirrhosis. The MELD score is calculated from the parameters total bilirubin, INR, serum creatinine and serum sodium. The score ranges from 6-40 points, with high values being associated with a poorer prognosis.

Therapy

General: The treatment of liver cirrhosis is based on the underlying chronic liver disease. In addition, risk factors that can contribute to the progression of liver cirrhosis should be avoided. These include, in particular, alcohol and liver-toxic drugs (e.g. paracetamol and some other non-steroidal anti-inflammatory drugs). 60-70% of patients with advanced liver cirrhosis often suffer from malnutrition due to a negative energy balance, so a high-energy diet is recommended. According to the guidelines, the patient's energy intake should be 30-35 kcal/kg body weight/day. If the desired weight gain or stabilization is not achieved, special products for calorie enrichment are available. Nutrition experts also recommend eating many small meals a day, and liver cirrhosis patients generally have an increased protein requirement. The diet should therefore be rich in protein. According to the guideline, the protein requirement of patients is 1.2-1.5 g/kg body weight/day. Branched-chain amino acids have proven effective in patients who have developed hepatic encephalopathy in the course of enteral nutrition. They do not cause the ammonia level to rise and thus counteract the development of hepatic encephalopathy. Patients with protein intolerance who require a protein-reduced diet are the exception; a deficiency of water-soluble vitamins, especially the B vitamins, is common in patients with liver cirrhosis, especially if it is caused by alcohol. Deficiencies in fat-soluble vitamins are particularly common in steatorrhea, bile salt deficiency and alcoholics.

Patients with liver cirrhosis also often suffer from a lack of potassium, magnesium, phosphate and other minerals, and their salt intake should be moderate. A low-salt diet is not recommended by the guideline, as it tastes bad and leads to reduced oral food intake. If ascites is present, a reduction in salt intake is recommended. Fluid intake should be based on the patient's clinical picture. For example, it should be limited in the presence of edema, ascites or low sodium levels, and in the presence of esophageal varices, food should be soft, thoroughly chewed and not too hot or cold. Acidic and spicy foods should also be avoided.

Liver transplantation: As a last resort, liver transplantation can be performed as the only causal, established therapy for irreversible chronic or acute liver failure. Timely registration is essential here, as waiting times of at least 1 to 2 years are to be expected for chronic liver diseases.

Prognosis

The life expectancy of patients with advanced liver cirrhosis is significantly shorter than that of healthy people. The extent of liver cirrhosis, which can be determined using the Child-Pugh or MELD score, provides an indication of the patient's prognosis.

The prognosis is particularly limited if ascites or portal hypertension occurs. 50% of patients die within 2 years. The most common causes of death in liver cirrhosis patients are liver failure, oesophageal variceal bleeding and heptatocellular carcinoma. Liver cirrhosis forms the basis for hepatocellular carcinoma. The prophylaxis of liver cirrhosis is therefore also a prophylaxis for the development of liver cancer.

Liver cirrhosis patients suffer from malnutrition, especially in the advanced stages. Their prognosis is negatively influenced by malnutrition. If patients require a liver transplant, malnutrition is associated with a poorer probability of survival.

Prophylaxis

Liver cirrhosis can be prevented by adequate screening for chronic liver disease so that timely treatment can be initiated.

As chronic liver disease is often asymptomatic, the determination of alanine aminotransferase (ALT) as a liver inflammation parameter and gamma-glutamyltransferase (GGT) as a cholestatic-metabolic parameter is also indicated in symptom-free patients. In addition, risk factors for chronic liver disease must be identified. These include, for example, metabolic syndrome as a trigger for non-alcoholic fatty liver disease, exogenous noxious substances such as alcohol and long-term use of hepatotoxic drugs.

In most cases, elevated transaminases are associated with relevant liver diseases. It is therefore not surprising that they are associated with a significant increase in mortality from liver disease. Elevated GGT values may indicate an increased risk of occupational disability. If possible, this laboratory screening test should be combined with sonography of the upper abdomen and possibly even elastography, and in the case of pathological values in the screening tests, a staged diagnosis should be carried out to clarify the etiology of the liver disease.In many cases, early treatment of the underlying disease can reduce further progression or, ideally, even achieve a regression of the cirrhosis:

  • antiviral therapy for cirrhosis induced by hepatitis B and C
  • therapy for hemochromatosis or Wilson's disease
  • immunosuppressive therapy for autoimmune hepatitis
  • alcohol abstinence for alcohol-toxic liver cirrhosis