Literature Review on Medical Fibrosis

Running head: MEDICAL
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Author Note:

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Literature Review:
1.0: Introduction:
Literature review can be explained as the segment of a dissertation or a thesis that
comprises of an exhaustive review of literatures that has already been done and closely relate
to the research topic (Aveyard 2014). This section would include an exhaustive review of
scholarly literatures that are aligned to the research objectives. Typically the scholarly
literatures included in the review were published in between 2010 to 2018. The rationale for
the inclusion of papers published over 9 years include a detailed overview about what has
already been done in the research area of interest.
1.1: Review of literatures:
Research studies mention that fibrosis includes the formation of a large amount of
scar tissue in the liver (Sumida et al. 2014). The condition arises when the liver repairs and
regenerates its damages cells. It should be noted in this context that a number of conditions
can damage the liver. Further, as stated by Zeybel and Idilman (2018), fibrosis does not
typically trigger any symptoms but excessive scarring can result in cirrhosis which can
worsen the intensity of the symptoms. Fibrosis can be detected on the basis of blood and
imaging tests, however on certain occasions liver biopsy can help in detecting fibrosis
(Fallatah 2014). The condition can be treated with the implementation of a number of
medical treatment.
Fibrosis manifests when the liver gets continuously damaged. It should be noted in
this context that a single event of injury does not lead to fibrosis. Liver fibrosis manifests
itself when the injury is repetitive and results in the formation of a scar tissue (Castera and
Pinzani 2010). In cases where the injury is repetitive and continuous the hepatic cells or the
liver cells attempt to recover the damaged tissue but the attempt to repair and recover the

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damaged tissue leads to the formation of a scarred tissue (Hernandez-Gea and Friedman
2011). Fibrosis is generally formed when a blockage is formed within the bile ducts
(Friedrich-Rust et al. 2008). The scar tissues that are formed replace the hepatic cells and do
not perform any important metabolic function. Also, scarring leads to distortion of the
internal structure of the liver. It should be crucially noted in this context that widespread and
controlled scarring and distortion lead to cirrhosis. In other words, it can be said that fibrosis
and cirrhosis are not specific disorder but are other primary causes that lead to liver damage
(Wallace et al. 2008). The scar tissues that are formed interfere with the blood flow to the
liver and limits the blood supply to the hepatic tissues (Friedrich-Rust et al. 2008). On
account of lack of appropriate blood supply, more scar tissues are formed and the condition
elevates the blood pressure in the hepatic portal vein that is responsible for carrying the blood
from the intestine to the liver. This condition is also known as portal hypertension. Research
studies suggest that the condition of Fibrosis can be reversed only if the condition is
diagnosed early and appropriate treatment regimen is followed so as to ensure recovery
(Zeybel and Idilman 2018; Castera and Pinzani 2010)).
The condition is triggered by a broad spectrum of drugs that continuously damage the
liver and cause liver fibrosis. These drugs mostly include Alcohol Amiodarone,
Chlorpromazine, Corticosteriods, Isoniazid, Methotrexate, Methyldopa, Oxyphenisatin and
Tolbutamide (Wallace et al. 2008). The mentioned drugs are mainly processed in the liver
and therefore can interfere with the normal functioning of the liver. In addition to this, a
number of other factors such as congenital disorders including congenital hepatic fibrosis and
Non-alcoholic fatty liver can also elevate the risk of suffering from Liver Fibrosis. Research
studies reveal that congenital hepatic fibrosis typically damage the kidneys, gallbladder and
the liver (Schuppan and Kim 2013; Tacke and Zimmermann 2014). The disorder is present at
birth and also leads to the manifestation of a number of symptoms. In case of the second most

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common disorder, or the Non-alcoholic fatty liver, the fat accumulates within the liver which
leads to the development of fibrosis (Lee et al. 2015). The disorder is more common in
people who suffer from metabolic syndrome. A number of other physiological problems can
enhance the probability of suffering from Liver fibrosis. Scholarly literature suggests that a
number of genetic metabolic disorders can increase the risk of suffering from Liver Fibrosis
(Tacke and Zimmermann 2014). Patients that suffer from Alpha-1 antitrypsin deficiency OR
Iron Overload hemochromatosis or Wilson disease are twice more likely to suffer from Liver
Fibrosis. These genetic disorders typically manipulate the manner in which nutrients are
broken down, metabolised or assimilated within the body (Puche et al. 2011). In cases where
the nutrients are not metabolized in a synchronised manner, there could be a possibility that
the substances would accumulated within soft tissue organs such as the liver which could lead
to scarring. Further, the evidence base also suggests that viral infections like chronic hepatitis
B or C can adversely affect the liver which could give rise to scarring of hepatic tissues (Shah
et al. 2009). Also, the risk of suffering from liver fibrosis increases in patients who suffers
from autoimmune disorders. These autoimmune disorders include problems such as Auto-
immune hepatitis Primary biliary, Cholangitis and Primary Sclerosing Cholangitis (Iwaisako
et al. 2012). On being affected with these autoimmune disorders, the body has a tendency to
act against its own immune system. This increases the probability of scarring the hepatic
tissues. In the mentioned autoimmune disorders, the bile duct is inflamed with scarring of
tissues and blockage. Further, liver fibrosis also manifests in cases where the hepatic blood
flow is interrupted. In case of Budd-Chiari syndrome, a blood clot interrupts the blood flow
out of the liver (Parkes et al. 2010). Further, in case of Heart failure or Portal Vein
thrombosis, the main vein that supplies blood to the liver is blocked by a blood clot. In case
of Veno-occlusive disease of the liver, the small veins of the liver are blocked by the
presence of blood clot and this leads top scarring of the hepatic tissues (Bejarano et al. 2009).

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It should be noted in this context that in conditions where the blood is unable to leave the
liver, the liver gets inflamed and the size of the liver enlarges. Also, due to lack of sufficient
blood supply, the hepatic cells die and are continuously replaced with the scar tissues. Also,
scarring can be caused due to Sinusoidal obstruction syndrome. The Sinusoidal obstruction
syndrome is caused by the accumulation of pyrrolizidine alkaloids (Cales et al. 2009). These
alkaloids are present in a number of herbal products which include supplements and herbal
tea extracts which are considered beneficial for the physical health of individuals (Mallet et
al. 2009).
The evidence base further enlist the most common causes to be alcohol abuse, viral
hepatitis C and Nonalcoholic fatty liver which lead to Liver fibrosis within the U.S
population base (Poynard et al. 2012). In this regard, it is important to note that Non-
alcoholic fatty liver in generally occur in individuals who are obese, are either pre-diabetic or
are diagnosed with Diabetes (Mallet et al. 2009). Further, increase in level of cholesterol or
lipid within the blood serve as high risk factors that lead to Liver Fibrosis.
According to Cales et al. (2009), it has been mentioned that scarring forms the first
stage of Liver fibrosis. If the scarring of the hepatic tissue is uncontrolled then liver Fibrosis
can assume a more serious forms which is also known as Liver Cirrhosis. It is important to
note in this context that research done on a number of animal trials have successfully proven
that the damaged liver has the capability to regenerate itself (Bejarano et al. 2009). However,
unfortunately, the same has not been researched in human models. As a matter of fact, the
research conducted on humans show that once there is scarring within the liver tissue, the
hepatic tissue do not reveal or regenerate at an accelerated pace (Parkes et al. 2010).
However, a number of lifestyle modifications can help in preventing the fibrosis from getting
worse and ensure proper symptom management. It is on the basis of staging that the
physician estimates the percentage of liver damage (Bejarano et al. 2009). It is important to

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acknowledge in this context that staging is subjective and every scale has its own set of
limitations. The most prevalent scoring system is the METAVIR scoring scale. The system
helps in predicting the degree at which the scarring of the tissues or fibrosis is spreading.
Physicians generally assign the score after performing the biopsy on a tissue sample. Also,
the activity grades range invariably in between the scores A0 to A3. A0 suggests no activity, A1
suggests mild activity, A2 suggests moderate activity and As suggests severe activity
(Iwaisako et al. 2012). The fibrosis stages are marked in between the range of F0 to F4. F0
suggests no fibrosis, while F1 suggests portal fibrosis without septa. F2 suggests portal fibrosis
with few septa, F3 suggests a number of septa without the indication of Cirrhosis and F4
suggests Cirrhosis (Mallet et al. 2009). Therefore, on the basis of grading discussed, a patient
that suffers from the most severe form of the disease would be scored A3, F4 METAVIR
score.
The scoring system propounded by Batts and Ludwig is one of the other scoring
system that marks Liver Fibrosis in a range of grade 1 to grade 4. Grade 4 marks the most
severe form of Liver Cirrhosis. Some of the most common symptoms of Liver Fibrosis
include, loss of appetite, distortion of thoughts, fluid accumulation within stomach or legs,
nausea, weight loss, weakness and Nausea. A research study conducted by Shah et al. (2009),
reported that almost 6% to 7% of the World population suffers from Liver Fibrosis but is not
aware of the same.
The most common treatment options comprise of implantation of pharmacological
interventions such as using ACE inhibitors like Lisinopril, Ramipril and Benazepril. In
addition to this treating with a Tocopherol or interferon-alpha and PPAR-alpha agonist can
also help in treating Liver Fibrosis (Puche et al. 2011).