The term progressive familial intrahepatic cholestasis summarizes three cholestasis that are very similar in appearance and can be distinguished from one another by different genetic defects. The diseases are inherited in an autosomal recessive manner and lead to a build-up of bile in the body due to incorrectly encoded membrane transport proteins in the bile capillary membranes. A cure for the disease requires a liver transplant, otherwise the prognosis for all three forms of the disease is unfavorable.
What is progressive familial intrahepatic cholestasis?
The rare progressive intrahepatic cholestasis (PFIC) is an autosomal recessive inherited disease of the liver. There are three different forms of the disease known, PFIC type 1 to type 3 (PFIC1, PFIC2, PFIC3), which clinically differ only slightly. Their main distinguishing feature consists of different gene defects, each of which incorrectly encodes a specific membrane transport protein in the liver cells. See healthknowing for What is the Definition of Radiculopathy.
This leads to a disturbed excretion of bile acids and causes a build-up of bile acids that has a toxic effect on the liver cells (hepatocytes) as well as a build-up of bile in the body (cholestasis). PFIC type 1 is also known as Byler’s disease or Byler syndrome because the causative genetic defect was first identified in a Byler family.
All three forms of the disease lead to the development of liver cirrhosis at an early age, which can only be delayed with medication and diet, but cannot be prevented. The only possible cure is a liver transplant in childhood.
Progressive familial intrahepatic cholestasis is caused exclusively by certain gene defects that are inherited in an autosomal recessive manner. This means that the disease is not gender specific and only comes into play when both parents have the same genetic defect. PFIC1 derives from the mutated ATP8B1 gene ATP on chromosome 18.
The gene mutation disrupts the phosphoglyceride phosphatidylserine, which is important for the function of a particular aminophospholipid transporter. This leads to intrahepatic cholestasis. Since the same cell type is also present in the pancreas, similar symptoms appear there as well. This explains the extrahepatic symptoms also observed with PFIC1.
The disease variant PFICB2 can be traced back to a gene mutation of the ABCB11 gene on chromosome 2. The defective gene is involved in the functioning of a bile acid transporter and also leads to cholestasis. A gene mutation in the ABCB4 gene on chromosome 7 leads to reduced excretion of lecithin, resulting in reduced protection of the hepatocytes.
The effects of the gene defect, which is responsible for the development of PFICB3, are expressed in chronic cholangitis, which is ultimately the trigger for the development of liver cirrhosis.
Symptoms, Ailments & Signs
The symptoms of all three forms of PFIC differ only slightly and often occur in newborns. All three manifestations are accompanied by severe itching, which is only milder in PFIC3. Byler syndrome is characterized soon after birth by chronic jaundice, diarrhea, pancreatitis, growth disorders and hearing loss.
The occurrence of liver tumors and the formation of gallstones in the first or second year of life are typical signs of PFIC2. Although the course of the disease appears to be slower and milder in PFIC3 compared to the other two forms, liver cirrhosis develops later.
Diagnosis & course of disease
In newborns who show symptoms of cholestasis without obstruction of the bile ducts, this indicates the hereditary disease PFIC. A chemical laboratory test provides information about the liver enzyme levels and bile acid in the blood. Further diagnostic options consist of a liver biopsy with subsequent histological examination and checking for the presence of defective transport proteins.
In principle, a molecular genetic examination is helpful, especially to differentiate between the three forms of PFIC. However, the results of such an investigation are not always reliable. The additional designation progressive already indicates that the disease takes a progressive course if left untreated. The prognosis for survival is unfavorable for all three manifestations of the disease. The average life expectancy is less than ten years if left untreated.
This disease is fatal in most cases if left untreated. Those affected are usually dependent on liver transplantation in order to survive. Self-healing does not occur in this case. The symptoms already appear in childhood and can lead to very severe itching on the skin.
Jaundice also occurs and reduces the patient’s quality of life enormously. Those affected also suffer from hearing loss and growth and development disorders. Furthermore, the disease also leads to annoying diarrhea or flatulence. The parents and relatives of the patients often suffer from depression or other mental disorders as a result of the disease.
If left untreated, this disease usually leads to cirrhosis of the liver, which eventually leads to the death of the affected person. This disease is treated with medication. However, in most cases, patients need a liver transplant to increase life expectancy.
When should you go to the doctor?
The first signs of an irregularity appear shortly after the birth of the patient. Itching, changes and abnormalities in the appearance of the skin and discoloration of the skin must be examined and treated. In many cases, the peculiarities are noticed immediately after birth by members of the nursing and support team. Midwives and doctors carry out the initial examinations of newborns. If there are any irregularities at this point, they are documented and followed up. In these cases, parents and relatives should maintain close contact with the doctor treating them.
If growth disorders become apparent in the further development process, it is advisable to clarify the observations. If the child is short in stature in direct comparison to peers, a doctor should be consulted. Hearing impairments, reduced hearing and irregularities in speech must also be examined and treated.
Pimples, ulcers, and growths on the skin indicate liver dysfunction. A doctor’s visit is advisable so that the symptoms can be clarified. Disorders of digestion, diarrhea and abdominal pain should be presented to a doctor. An increased body temperature, inner restlessness as well as nausea and vomiting should be examined by a doctor. If you feel weak and lethargic, a doctor is needed to clarify the cause.
Treatment & Therapy
Due to its genetic origin, PFIC cannot be cured, so therapies focus on treating the symptoms in order to delay the progressive course of the disease. A high-quality diet with high-calorie elements is important in order to compensate for the reduced absorption capacity of the intestine caused by diarrhea.
With regard to nutrition, a sufficient supply of fat-soluble vitamins and an enrichment with medium-chain fats (MCT diet) should also be ensured. Itching is usually treated with antihistamines, although not all patients respond. Any side effects of these mildly sedating drugs must be considered.
Some patients respond to ursodeoxycholic acid, which may stop or at least greatly slow down the fibrous remodeling of the liver. In the case of PFIC1 and 2 in particular, partial external bile diversion can stop the course of the disease. A stoma, an artificial outlet for the gallbladder, is created by means of a loop in the small intestine, so that around 30 to 50 percent of the bile can bypass the outside.
Alternatively, about 15 to 20 percent of the small intestine can be bridged with a bypass, so that the reabsorption of the bile salts is reduced. The advantage is that no artificial exit needs to be created. As a last resort, the only way to cure the disease is liver transplantation.
Due to the genetic cause of PFIC, there are no preventive measures that would have an impact on preventing the disease. It is advisable to research within one’s own family whether cases of diagnosed PFIC are known.
Follow-up care for progressive familial intrahepatic cholestasis is only provided if the patient has had a new liver transplant. After the operation, regular follow-up examinations are scheduled for the first few months. The doctor checks whether the new organ has been well accepted by the body and whether the patient’s blood values have improved.
Since the patients are mostly young children, the operation can entail complications. The immunosuppressants administered carry the risk of pathogens establishing themselves in the patient’s body. A simple cold can turn into a severe flu. For this reason, patients are also given broad-spectrum antibiotics.
The risk of organ rejection is comparatively low. Nevertheless, the doctor checks whether the new organ is capable of functioning or whether there are rejection reactions. In the majority of cases, adjusting the medication dosage is sufficient for the patient’s body to adjust to the new liver.
However, if the performance of the liver decreases too much, rejection of the liver can no longer be prevented. In such cases, care is taken to alleviate the patient’s suffering and to keep him as pain-free as possible. A cure for progressive familial intrahepatic cholestasis or a new transplant is no longer possible.
You can do that yourself
The disease is associated with many different severe lifestyle restrictions. Therefore, as part of self-help, care should be taken to ensure that everyday life is optimally structured.
The well-being and zest for life are to be promoted so that the adversities and circumstances of the illness can be handled well. The patient should be informed comprehensively by doctors and relatives about the course of the disease and the further development steps. In addition, doing your own research can be helpful to get open questions answered. Information about the disease is exchanged in self-help groups. Communicating with others affected can be perceived as emotionally supportive.
According to the current state of scientific knowledge, the only way to cure or improve the situation is to find a liver transplant. In order to be able to survive this procedure well, a healthy lifestyle should take place. The immune system can be stabilized with a balanced diet rich in vitamins. In addition, the consumption of harmful substances such as nicotine and especially alcohol should be avoided completely.
Mental techniques or relaxation methods can be used to stabilize the psyche. These serve the inner balance in the reduction of existing stressors and strengths. A healthy self-confidence is necessary in order to be able to overcome possible teasing of growth disorders in everyday life.