Introduction

This study is based on the Bioartificial liver that would state its importance, current market trends, and new design through which the functionality of the Bioartificial liver would be enhanced. Moreover, before the elaborate discussion on the Bioartificial liver, a background about the liver’s structure, functions, physiology, and malfunctions would be discussed. Afterward, the study would discuss the importance of Bioartificial and artificial liver, and then the study would turn towards the discussion on Bioartificial livers, their current market status, and improvement strategy.

Background and significance

Liver Functions

The liver which is the largest internal organ and second largest organ of the human body weighs 1.5 kg (approx.) that has a variety of functions (Rad, 2020). The different functions of the liver are discussed below.

  1. Function related to blood and circulation: during the foetal condition, it plays a role in RBC formation while within the adult, it plays a role in RBC destruction. Further, it manufactured prothrombin, fibrinogen, and heparin that are essential for clotting (Rad, 2020). Furthermore
  2. carbohydrate and protein and Ketone body formation. Moreover, it stores fat.
  3. Function related to the metabolism of protein: The liver is the main site for the formation of urea, uric acid formation, plasma protein, and nitrogen metabolism through the deamination process, urea synthesis, and so on.

Basic anatomy, physiology of Liver

The Liver is divided into the left and right lobes by the presence of falciform ligament. Further, from the right lobe, the other two accessory lobes arise which are called the caudate lobe and quadrate lobe.

The Caudate lobe is located on the upper portion of the Liver’s visceral surface between the inferior vena cava and fossa that is produced by the presence of ligamentum venosum. On the other hand, the Quadrate lobe is in the lower portion of the Liver’s visceral surface that lies in between the gallbladder and fossa that are produced by ligamentum teres. Moreover, caudate and quadrate lobes are separated by porta hepatis that transmit the nerves, ducts, and vessels into and out of the liver (May 2018).

Diseases/conditions due to Liver malfunction

Hepatitis: Liver gets inflated due to viruses such as Hepatitis A, B, and C. Though, it is non-infectious, it is also caused due to illicit drugs, allergic reactions, heavy consumption of alcohol, and obesity (Rad, 2020).

Cirrhosis: It is a condition in which, the regenerated hepatic cells aggregate and are separated by bands of scar tissues or deposition of collagen tissues causing damage and death of liver cells. Some of the cause of cirrhosis is due to prolonged hepatitis infection, chronic alcoholism, genetic metabolic disease. Besides, due to cirrhosis, the liver function stops completely

Liver failure: It occurs either due to liver disease or due to intoxication of the liver or chronic disease.

Jaundice: Bilirubin level along with bile pigments level raises, excessively. The causes of Jaundice are many, however, the two common cause diseases in the hepatic and biliary tract.

Hemochromatosis: deposition of iron into the liver causing liver failure

Primary sclerosing cholangitis: rare disease in which, scarring and inflammation occurs in the liver’s bile duct

Primary biliary cirrhosis: Bile duct is destroyed, and permanent liver scarring took place and develops.

Treatment: Is there a need?

(Rad, 2020) Liver failure or liver cirrhosis is one of the global problems. However, it is found to be highest in Egypt, Sierra Leone, Nigeria, Ethiopia, and so on (WHO, 2020).

Further from 2000-2015, it was found that only in the US, the death rates related to chronic liver disease along with cirrhosis increased by 31% especially among the people aged between 45-64 years (CDC, 2017). furthermore, it was found that the death rate among the aged group between 25-44 years was increased by 21% among which women become more prone to disease compared to men (CDC, 2017).

Therefore, due to the presence of a high death rate due to liver failure, it becomes crucial to enhance its treatment process. Orthotopic liver transplantation is one of the solutions if the liver fails to regenerate. However, to detoxify and mimic the function of the liver in case of liver failure artificial and Bioartificial liver exists to support patient health until the liver starts to regenerate or till the time donor organ is not available.

The significance of Bioartificial vs. artificial

Showing the difference between Artificial and Bioartificial liver support system

Hepatic function

Artificial; It performs the process of detoxification process with the efficient removal of the accumulated toxins. Thus, it allows the natural process of recovery of the liver whereas Bioartificial could perform different hepatic functions. It can perform both the synthetic and metabolic functions of the hepatocyte module.

Cost

Artificial; Less costly than Bioartificial liver support system whereas Bioartificial Designing, operating costs, and management costs are very high.

Efficacy

Artificial; Very limited efficacy whereas Bioartificial High-quality result obtained.

Use

Artificial is easy to use whereas Bioartificial complex to use and maintain.

Analysis of current designs and status of Bioartificial liver in market

Review current products

It has already been mentioned in the above sections that the bioartificial liver is the cell-based artificial liver that has been established and is still under process in some cases. It allows supporting the functioning of a liver in an individual whose liver has failed and has not undergone the replacement therapy. The current products of the bioartificial liver can be described as follows:

HepatAssist

It was the first biologically based artificial liver device. It was first developed with the approach of the FDA. A fibre extracorporeal bioreactor is present in the device. It is further loaded with porcine hepatocytes that have been cryopreserved (Wang, Jakus, & Baptista, 2016). The entire bioreactor is however not solid and is a hollow one. The research studies have however suggested the success rate of this device thereby being able to allow the survival rate for many.

Extracorporeal liver assist devices

This is another significant type of device that supports in case of any liver failure. This system allows blood to pass through the hollow fibre devices. These hollow fibre devices contain human hepatocytes that have been further derived from the hepatoblastoma cell line. The hepatoblastoma cell line is mainly derived from the dialysate side. The results and outcome of this system have also been significant as the patients have shown positive results for tolerating this system. Improvement has also been witnessed in the process of encephalopathy. This system has thus passed the efficacy rate of being used in patients who cannot be immediately involved in the process of liver transplantation.

Modular extracorporeal liver support

Hepatocytes are the main components of the bioartificial liver. These are collected from the cell lines of the humans to be incorporated into the system. This is due to the reason that most of the functions of the liver are carried out by hepatocytes (Damania, Kumar, & Teotia, 2018). These include metabolism, digestion, and storage. Similar to the above-mentioned two liver support systems with cell-based components, modular extracorporeal liver support also contains porcine hepatocytes. It is based on hollow fibres. The hepatocytes however incorporated as used as the cell base of the instrument need to be freshly prepared.

Bioartificial liver support system

The bioartificial liver support system is another significant liver support system that has been designed by Excorp medical in the USA. It further uses the porcine hepatocytes in a single fibre cartridge that is hollow and not solid. However, this device has not been successfully established and used in the technique of including bioartificial liver in case of liver failure. This is due to the reason that this device is still under study in phase 2 or 3 and thus not have established successful results significantly.

Comparison of pros and cons

The bioartificial liver being used among patients who suffer from liver failure and cannot be immediately provided with liver transplantation is associated with both advantages and disadvantages. The pros include the support system that is provided to the patients as it becomes tough for the health practitioners to establish the replacement therapy significantly after detection and diagnosis of liver failure. Hence this support system provides time for replacement therapy. Furthermore, it also allows normal functioning of the liver to a great extent as the hepatocytes are the main base of these devices. The bioartificial liver is more advantageous as compared to that of the artificial liver because these are completely based on cells and not any other materials. All the above-mentioned products of the bioartificial liver have proved to be significant in their outcomes. The bioartificial devices, furthermore, provide both synthetic functions and detoxification, unlike the artificial ones that only provide detoxification and not synthesis. The only cons that are associated with the bioartificial liver are the lack of clinical trials that can signify the safety of humans to a large extent. Although outcomes have been satisfying in some cases still the safety standards have not been ascertained due to the lack of a huge number of clinical trials.

Need for improving current designs/products

The bioartificial liver support systems are significant and can be used to provide the detoxification and synthesis processes of the liver in individuals who have reported having liver failure. The only improvements that are needed are the increased number of clinical trials to maintain safety and allow bile synthesis. The bioartificial livers have not undergone many clinical trials concerning the safety of individuals. Although some of the bioartificial liver products have provided successful results yet the clinical trials owing to their usage and implementation should be ascertained. Furthermore, another improvement that is needed in the structure and functioning of the device is to allow the excretion of bile. The bioartificial liver does not have any significant functioning in the system that can provide a source for excreting bile pigments. Thus, redesigning of the device is necessary to be carried out so that the excretion of bile pigments can be established (Chen, Joo, & Shaheen, 2019). This will then not interfere with the body functions of humans and maintain their safety


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