Clarifying Chronic Cirrhosis

A Case Study Presented to

Mr. Franklin Espinosa
First Asia Institute of Technology and Humanities,
Tanauan City

In partial fulfillment of the requirements in

BYCHEM9 - Biochemistry

By:
Coro, Jasmine Aizel M.
Galos, Mheil Francis Ivan S.
Nacilla, Michael Cedrick A.
Platon, Emilio E.

November 2023
Background and Description

Cirrhosis is a chronic and degenerative liver disease wherein the healthy liver tissues are replaced
with scar tissues impairing the liver’s functions such as metabolism, protein production, and the
detoxification of drugs and toxins, among others. This condition contributes to the morbidity and
mortality rate among individuals with chronic liver disease.

I. Epidemiology

Global Populace

The epidemiological dissemination of Cirrhosis shows a variance across the globe, due to factors
such as socioeconomic development and the application of antiviral therapies. Mostly in developed
countries, Cirrhosis is linked to people’s lifestyle and routines, including excessive consumption of
alcohol and unhealthy diet. The Global Burden of Disease (GBD) serves as an instrument on how
impactful Cirrhosis is to society. GBD studies show an overview of the morbidity and mortality rates
linked to liver-related disorders.

In 2017, a GBD study estimated 112 million people with compensated Cirrhosis worldwide,
corresponding to the 1,395 cases per 100,000 individuals (Huang, D.Q., Terrault, N.A., Tacke, F. et al,
2023). Globally, the mortality rate of Cirrhosis was 47.15% from 1990 to 2017. Particularly, India had the
highest number of deaths in 2017, and the United Arab Emirates showed the highest growth of
mortalities, followed by Qatar and the Philippines. (Ye, F., Zhai, M., Long, J. et al, 2022).

Local Populace

According to Fundación Clínica Médica Sur, A.C. (2023), cirrhosis cases in the Philippines
contribute 27.3 cases per 1000 deaths. In 2019, the country accounted for the impact of liver Cirrhosis,
with 7076 cases responsible for 1.05% of the reported deaths, which shifted the rate of mortality at 8.65%
per population of 100,000 individuals. Liver Cirrhosis is, therefore, positioned as the 19 th leading cause of
mortality in the Philippines.

II. Etiology

Origin of the Disease

René Laennec was the first to use the term Cirrhosis, located in a brief footnote in his paper about
auscultation in 1819. Because Mr. Laennec has more expertise regarding chest conditions -as he is the
inventor of the stethoscope- his term for Cirrhosis was overlooked; not until William Osler, a Canadian
physician, mentioned the term in the cirrhosis of Laennec in Principles and Practice of Medicine (Elsevier
Ltd. 2019).

Cirrhosis is a disease that takes place in the Liver, which functions as a storage for glycogen and
nutrients, such as vitamins and minerals, as well as for detoxification and production of bile that is needed
for digestion. The development of the disease originates from the person's lifestyle and the excessive
consumption of alcohol. Additionally, Hepatitis B and Hepatitis C are contributory factors for Cirrhosis,
which can occur when a person makes contact with an infected person through sharing used injection
needles, equipment, or same-sex intercourse, which can happen among men (Centers for Disease Control
and Prevention n.d). Furthermore, non-alcoholic steatohepatitis (NASH), the severe form of non-alcoholic
fatty liver disease (NAFLD), which causes inflammation in the liver, can increase the risk of developing
cirrhosis (Stanford Health Care, 2018).
Types of Cirrhosis

There are classifications to determine what kind of Cirrhosis a person has. There are 3 types of it
and these are, Alcoholic Cirrhosis (Laennec's Cirrhosis), Postnecrotic Cirrhosis and lastly, Biliary
Cirrhosis. Here is a detailed explanation to the stated types:

(a) Alcoholic Cirrhosis (Laennec’s Cirrhosis)

It is a given name to Cirrhosis which is the most common out of the three that is caused
by the excessive consumption of alcohol. (Healthline, 2023).

(b) Postnecrotic Cirrhosis

In postnecrotic cirrhosis, the liver builds up nodules that are more than 3mm wide. This
irreversible disease also means that healthy tissues in the liver are being replaced with scar tissues
which will cause symptoms such as jaundice, fatigue, and anemia. (Medical News Today, n.d).

(c) Biliary Cirrhosis

It is a rare form of liver cirrhosis in which the bile ducts are malfunctioning. It is
cholestasis which is defined as the gathering of bile in the liver due to it being at risk of
increasing age, obesity, heredity, and some prescribed medications. Biliary Cirrhosis has two
classifications, namely Primary and Secondary Biliary Cirrhosis. To differentiate, Primary Biliary
Cirrhosis is total destruction of bile ducts in the liver, while Secondary Biliary Cirrhosis results
from the prolonged obstruction of the bile duct (Johns Hopkins Medicine, 2019).

Vulnerable Groups

Cirrhosis is an illness that results not only from one specific cause but rather arises from various
reasons and factors and is further influenced by risks and vulnerabilities. Although Cirrhosis of the liver
does not have distinct types, it can be identified, approached, and treated differently based on the root or
underlying cause. The following are some of the vulnerable groups that are more prone to develop this
disease:

(a) Chronic Drinkers or Alcoholics

Individuals who consume alcohol in excess, also known as alcoholics, are more prone to
contracting alcoholic liver disease and, eventually, cirrhosis. Too much alcohol can lead to
excessive fat buildup in the liver, inflammation, and the turning point of the normal living tissue
replacing it with scarred tissue. This occurs when the intake exceeds the normal capacity of the
liver to break down alcohol contents inside the body. Some complications linked to alcoholic
liver disease include internal bleeding, ascites, liver cancer, and hepatic encephalopathy (NHS
inform, n.d).

(b) Overweight and Obese People

People who are diagnosed with obesity are more likely to also get diagnosed with non-
alcoholic steatohepatitis (NASH) due to the abnormal increase of lipid peroxidation, which,
defined in simple terms, is the metabolic process of degrading lipids that can lead to cell damage
or death, a risk factor for cirrhosis (Gastroenterological Association, 2003). Eventually, if too
many calories are consumed it will accumulate and turn into fats and may result in fatty liver
 disease. Moreover, if left untreated, esophageal varices, hypersplenism, liver cancer, and end-
stage liver cancer are the expected complications (Mayo Clinic, 2023).

(c) Hepatitis Patients

Individuals with viral hepatitis have a span of 10-20 years for the transition from
Hepatitis B Virus and Hepatitis C Virus that causes inflammation to the liver, and lead to serious
complications such as extensive scarring of the liver or cirrhosis, which impairs the liver’s ability
to function normally. In addition, the inflammation that is caused by the infections, Hepatitis B
Virus and Hepatitis C in the liver plays a part in the progression through the inflammation-
necrosis-regeneration cycle, ultimately leading to cirrhosis (World J Gastroenterol, 2014).
Additionally, a detrimental complication of the disease is called fulminant hepatitis, which is a
syndrome of immediate massive necrosis of the liver. Worst case scenario, a liver transplant is
needed immediately for the patient diagnosed.

In conclusion, Cirrhosis is a serious threat to an individual’s well-being that should be given

special attention, as it affects people across the globe, and leads to several health and bodily malfunctions.
It is especially dangerous as it is asymptomatic in its early stages. Fortunately, cirrhosis is a preventable
and treatable -although irreversible- disease. Further discussion of Cirrhosis, its physiological process and
pathway, will be undertaken in pathophysiology. [BACKGROUND OF THE CASE STUDY]
Pathophysiology

I. Development Stages

According to the National Institute of Diabetes and Digestive and Kidney Diseases (n.d.),
Cirrhosis is a condition in which the liver becomes scarred and permanently damaged. The scar tissue
replaces healthy liver tissue and inhibits the liver from functioning correctly. Initially, its signs and
symptoms may not develop until the liver is severely damaged. However, the common causes of liver
cirrhosis include: alcoholic liver disease, nonalcoholic fatty liver disease, chronic hepatitis C, and chronic
hepatitis B, which result in multiple stages.

Clinical Stages of Cirrhosis:

Cirrhosis has two clinical stages: compensated cirrhosis and decompensated cirrhosis. However,
certain health professionals may refer to the four stages of liver disease. These include inflammation,
fibrosis, cirrhosis, and liver failure. (Dresden, 2023)

Clinical Stage 1: Compensated cirrhosis

When the liver can still perform most or all of its tasks, it is believed to be able to compensate for
the hepatitis C virus's damage. Cirrhosis, like fibrosis, can range in severity from mild to moderate to
severe damage. People with compensated cirrhosis have no symptoms and have a life expectancy of 9–12
years. Although 5–7% of people with the illness will develop symptoms every year, such as silent liver
damage leading to reduced liver function, a person can be asymptomatic for years because the body may
still rely on the healthy liver cells to meet its demands and make up for the damaged and scarred cells.
(Dresden, 2023)

Clinical Stage 2: Decompensated cirrhosis:

Decompensated cirrhosis occurs when the liver is no longer able to compensate for the damage
caused by inflammation and scarring produced by an HCV virus. The liver cannot function normally
during decompensation. This type of cirrhosis already has symptoms and problems. Their life expectancy
is significantly lower than the person with compensated cirrhosis, and Hepatologists advise referral for a
possible liver transplant in these circumstances. An individual with advanced-stage cirrhosis has a life
expectancy of roughly 2 years, which is predicted based on the observation due to the liver's inability to
operate properly, resulting in an increase in serious complications such as:

(a) Bleeding of Varices

Varices are dilated blood vessels in the esophagus or stomach. They appear when the
portal vein becomes blocked, stopping the blood supply to the liver. Varices bleeding is a medical
emergency since there is a high risk of blood loss. Treatment must begin in order to control this
illness and avoid fatal outcomes (Mbbs, 2022d).

(b) Hepatic encephalopathy

This is a condition that develops when the liver's capacity to eliminate poisons from the
blood is compromised. Consequently, toxic compounds build up in the body and impact brain
function. Hepatic encephalopathy is an uncomfortable side effect of cirrhosis that frequently
results in cognitive deficits including confusion and forgetfulness (Mbbs, 2022d).
 (c) Ascites

Cirrhosis may result in ascites, a condition in which fluid builds up inside the abdominal
cavity. This fluid, known as ascitic fluid, fills the peritoneal cavity and causes discomfort and
swelling in the abdomen. It has a high concentration in the ascitic fluid associated with cirrhosis,
which is albumin. Ascites can have a serious negative effect on a person's quality of life, which
will lead to limitations in daily activities and may need to be treated medically in order to treat
the underlying cause and relieve symptoms (Mbbs, 2022d).

(d) Jaundice

Yellowing of the skin and eyes is the primary sign of jaundice, which is an indication of
liver disease. It happens when bilirubin, a yellow pigment included in bile, cannot be processed
by the liver. The liver's capacity to function normally is compromised by cirrhosis-induced
scarring and damage, which causes bilirubin buildup and the onset of jaundice (Mbbs, 2022d).

(e) Gallstones

Cirrhosis may disrupt the balance of chemicals in the body, particularly bilirubin.
Bilirubin levels that are too high can contribute to the production of gallstones. Gallstones are
solid particles that can form in the gallbladder or bile ducts, causing abdominal pain and other
problems (Mbbs, 2022d).

Developmental Stages of Liver Disease:

Stage 1: Steatosis (Inflammation of the Bile Duct or Liver)

The first stage of liver disease is characterized by inflammation within the liver or bile ducts. This
inflammation is frequently caused by the body's attempts to resist sickness or infection. Abdominal
discomfort is one of the early warning symptoms at this stage, and it can be a sign of persistent
inflammation.

If left untreated, this inflammation has the potential to cause liver damage, aggravating the
underlying sickness. However, throughout Stage 1, both the symptoms and the inflammation are often
curable and reversible with good, appropriate, and efficient medical care. Effective therapy at this stage
can successfully prevent liver disease from progressing to more advanced stages. (Mbbs, 2022d)

Stage 2: Scarring (Fibrosis) of the Liver Due to Inflammation

Many people with liver disease may be unaware of their condition until it has progressed to Stage
2 or even Stage 3, due to the fact that the earliest symptoms frequently go unrecognized or unreported.
Repeated liver injury causes scarring by causing the deposition of tough fibrous tissue, whereas infections
or toxins cause inflammation, both of which decrease liver function and would have a negative impact on
the liver in Stage 2, creating a disruption in normal blood flow inside the liver.

This disruption has an effect on the liver's ability to operate properly. However, with the right
medical intervention and therapy, the liver can heal and avoid further damage. Effective management at
this stage can delay the progression of liver disease, allowing the liver to eventually recover and restore
functionality. (Mbbs, 2022d)
Stage 3: Cirrhosis

Cirrhosis, the third stage of liver disease, is a crucial stage in the development of liver damage. It
generally happens as a result of liver disease progressing, which is frequently attributed to a lack of
efficient treatment or intervention. The primary characteristic at this point is the irreversible scarring of
the liver caused by the replacement of healthy liver tissue with scar tissue.

Healthy liver cells are progressively killed over several years of fighting a progressive sickness or
infection, resulting in this harmful scarring. The liver becomes hard and lumpy, diminishing its capacity
to conduct important processes, including the detoxification of harmful substances from the blood and the
production of essential proteins required for blood clotting. Scar tissue forms a severe barrier to blood
flow through the portal vein, which transports blood into the liver. This obstruction causes blood to be
rerouted to the spleen, causing additional issues and disorders throughout the body. (Mbbs, 2022d)

Stage 4: End Stage Liver Failure or Advanced Liver Disease (Hepatic Failure)

The final stage of liver disease is indicated by liver failure, which indicates the end of normal
liver function. At this stage, quick medical attention is required to avoid fatalities. Liver failure is a
serious and life-threatening illness that requires immediate attention and treatment.

At this advanced stage, the liver can no longer sustain the body's critical activities since its ability
to carry out its vital responsibilities has dramatically declined. As this stage represents a major turning
point in the evolution of liver disease, prompt and specialized medical care is essential to address the
consequences arising from liver failure. Comprehensive medical management is required to provide the
best possible outcome for the patient's health. (Mbbs, 2022d)

To conclude, cirrhosis is a serious and progressive liver disease that causes the replacement of
healthy liver tissue with irreversible scar tissue, limiting the liver's key activities. This condition has
several clinical stages, with two primary categories: compensated cirrhosis, in which individuals may be
asymptomatic and have a relatively longer life expectancy, and decompensated cirrhosis, which is
characterized by symptoms and a significantly reduced life expectancy, often necessitating consideration
for a liver transplant. Also, cirrhosis is further classified into four stages: steatosis, scarring of the liver
caused by inflammation, cirrhosis, and, finally, liver failure or advanced liver disease. Each stage has its
own set of symptoms and problems, emphasizing the critical need for early discovery, medical
intervention, and management to improve patient outcomes as well as quality of life.
II. Correlation

Cirrhosis is a disease that causes a variety of health problems by actively impairing the
performance of organ systems and some organ functions. It is caused by a combination of risk factors.
Among the affected systems are the six listed below:

Figure 1. Visual Diagram for Affected Organs and Organ Systems

Nervous System

The nervous system is sensitive. It is vulnerable to injury and heals slowly, if at all. This impairs
the brain's communication with the muscles and sensory organs. Nervous system injuries can be
extremely painful, resulting in weakness, tingling, numbness, and even alterations in blood circulation.
Every neuron in the body begins and ends in the brain. The brain is part of the central nervous system,
which is what most people think of first. (MBBS, 2022)

(a) Brain

Chronic liver failure, especially in cirrhosis alcoholics, may result in hepatic

encephalopathy (HE), a brain condition that impairs cognitive, psychological, and motor
functions. Before toxins are eliminated, some of the blood is redirected around the liver in these
individuals, and the quantity of functioning liver cells is decreased. Toxins like manganese and
ammonia can build up in the circulation and reach the brain, where they can harm astrocytes,
including impaired cognitive, psychological, and motor functions, which are cells that support
nerve cells, as well as nerve cells themselves. (Butterworth, 2003)

Integumentary System

The body's integumentary system, which is the first layer that defends against bacteria, and
protects the body from infection and injuries. When a patient has Cirrhosis, skin changes may appear as
this is one of the major organs that get affected. Palmar erythema, also called "paper money" skin,
rosacea, and rhinophyma are some of the signs patients get when their liver is scarring. This may be one
of the results when a person is drinking too much alcohol. (Koulaouzidis et al., 2007)
 (a) Skin

Cirrhosis patients may develop palmar erythema, a reddish-purple rash with tiny spots or
larger splotches as a result of bleeding from small blood vessels in the skin. People who have had
their liver function impaired for a long period may develop pruritus, which causes itching all
over, as well as yellowing of the skin and eyes caused by an accumulation of bilirubin. (Lee,
2023b)

Respiratory System

Respiratory damage can develop slowly. When this happens, it is referred to as persistent
respiratory failure. Shortness of breath or feeling as if one cannot get enough air, excessive weariness,
inability to exercise as before, and sleepiness are all symptoms. One of the reasons is that drinking
increases one’s chances of overdosing. An alcohol overdose has an effect on the part of the lungs that
regulates breathing. During an overdose, breathing becomes slow and shallow, which might result in
acute respiratory failure and a lung issue. (NHLBI, NIH, 2022)

(a) Lungs

Cirrhosis can cause blood arteries to dilate, resulting in low blood pressure. When this
happens, blood cannot properly move through the lungs, resulting in hypoxia, or a shortage of
oxygen in the body. The reasons why some people with cirrhosis have high lung artery pressure,
while others have low pressure or remain normal are still a medical mystery. (Sussman, 2015)

Digestive System

The food one consumes travels in the body through the digestive system, from the top (mouth) to
the bottom (anus). Afterwards, the food's healthy qualities are absorbed, providing the body with nutrients
and energy. However, it will cause issues and more complications in the liver if one has an unhealthy
digestive system because of dietary deficiencies, harmful lifestyle choices like alcohol consumption, food
intolerance, or even infections. (Intal, A., 2023)

(a) Liver

The liver is incredibly strong and self-regenerating. A portion of the liver cells perish
with each alcohol the liver filters. Although the liver may regenerate new cells, years of chronic
alcohol abuse (drinking excessive amounts) can limit this regenerative capacity. The liver may
sustain severe and irreversible damage as a result of this. However, quitting consuming alcohol
right away can stop more harm from occurring and greatly lengthen life. If a person with alcohol-
related cirrhosis continues to drink, their chances of living for at least five more years are fewer
than half (NHS inform, 2023).

Circulatory or Cardiovascular System

Being physiologically connected with one another, the circulatory system pumps and circulates
the blood. The hepatic artery brings in oxygen-rich blood, coming from the heart. However, if the liver is
not healthy enough, it may cause damage to the heart as well, resulting in an acute heart failure. If the
liver fails, the circulatory system will most likely be affected, such as infections, inflammatory and
systemic diseases, and chronic alcoholism (Bernardi, 2013).
 (a) Heart

According to Wilson (2022), the liver receiving at least 25% of blood from the
circulatory system, made it a reason as to how Cirrhosis affects vice-versa. The circulation of the
blood is abnormally increased, with increased cardiac output, decreased peripheral vascular
resistance, and arterial pressure (Liu, et al., 2006). Cirrhosis may cause heart failure to a patient,
with their liver being congested or blocked by blood the heart cannot pump back again from the
atrium. It is called Cirrhotic cardiomyopathy for it presents chronic cardiac dysfunction (Pudil et
al., 2013).

Urinary System

The function of the urinary system is intimately related to the health of the liver, representing the
liver's status, which can be either excellent or bad. When the liver is harmed by conditions such as
excessive alcohol consumption, viral infections, or hepatitis, urinary system malfunction can occur (Ilyas,
2023). This link between liver health and urinary system health emphasizes the significance of having a
healthy liver to support overall physiological functions.

(a) Kidneys

According to Yeung et al. (2004), cirrhosis causes complications. Kidney is one of the
organs affected by it, in a way it develops acute injury to the kidney, and hepatorenal syndrome.
Hepatorenal syndrome (HRS) occurs from the last phase of cirrhosis after an extreme circulatory
dysfunction. Peripheral edema and ascites are a result of worsening sodium control. Unfiltered
sodium will result in an extremely low urinary sodium in HRS. Renal impairment is frequently
experienced by patients with cirrhosis with spontaneous bacterial peritonitis (SBP).

Reproductive System

Due to hormonal imbalances and changes in metabolism, liver diseases can have an impact on
male reproductive systems. Liver dysfunction may affect hormone balance, resulting in changes in
testosterone levels. Severe liver illness can cause consequences such as testicular atrophy (a reduction in
testicular size), which impairs sperm production and can affect fertility. (Levy et al., 2023)
Figure 2. Visual Diagram for Pathophysiology
 Fibrosis is a process mediated by special cells called stellate cells that sit between the sinusoid
and hepatocyte, known as the perisinusoidal space. The basic functional unit of the liver includes the
portal vein and hepatic artery that combine into a sinusoid, which goes into the central vein, and these are
all lined with hepatocytes. Along with these, there's also a bile duct, and these three make up a portal
triad.

Normally, in healthy tissue, the stellate cells' stores vitamin A and quiescent. When the
hepatocytes are injured, they secrete paracrine factors that activate the stellate cells. When the stellate
cells are activated, they will start secreting transforming growth factor beta1, or TGF-beta, that causes
them to produce collagen, which is a main ingredient in extracellular matrix, fibrosis, and scar tissue.

If the fibrotic tissue builds up, it starts to compress the central veins and sinusoids. In a healthy
state, these cells play a key role in a natural wound healing process, but when the liver cells are constantly
injured, stellate cells are constantly activated, producing collagen and causing fibrosis. This is when
problems related to cirrhosis start showing up.

If the central veins and sinusoids become compressed and push on the fluid inside, their pressure
starts to build up, leading to intrasinusoidal (or portal) hypertension, which is the higher pressure in the
portal veins. Higher portal vein pressure means that fluid in blood vessels is more likely to get pushed
into tissues and across tissues into large open spaces like the peritoneal cavity. That is why cirrhosis leads
to excess peritoneal fluid, a condition called ascites, and can result in other complications like congestive
splenomegaly and hypersplenism, where the spleen becomes enlarged because all this fluid and blood
can’t get into the liver and backs up into the spleen.

Additionally, because of high liver pressure, the circulatory system starts sending blood away
from the liver, creating a portosystemic shunt. Blood flow follows the path of least resistance and shunts
away from the portal system and towards the systemic system of circulation. Although not fully
understood, these changes in portal flow trigger renal vasoconstriction, increasing resistance in the renal
circulation. which decreases blood flow through the kidneys, leading to hepatorenal failure, where kidney
failure follows liver failure.

The fibrotic tissue, pressure buildup, and diversion of blood from the hepatic circulation
essentially reduce the number of functional sinusoidal veins and the number of operational portal triads.
As one has less and less basic liver units, the liver becomes less able to detoxify. When the liver is not
detoxifying the blood, these toxins can get into the brain and start inducing mental deficits, a condition
known as hepatic encephalopathy. Although several neurotoxins contribute to the development of these
changes, the best-understood factor is ammonia in the blood, which is produced mainly in the
gastrointestinal tract; usually, the liver plays a crucial role in removing ammonia and stopping it from
going into the systemic circulation. As more of these and other toxins reach the brain, patients might
develop asterixis, where they have tremors or jerky hands when outstretched. And as even more toxins
build up, eventually, patients can progress to a coma.

Also, since the liver plays a significant role in metabolizing estrogen into inactive metabolites
removed from the blood and excreted, patients can experience complications due to increased estrogen in
the blood, like gynecomastia, spider angiomata, and palmar erythema. And, since the liver usually
conjugates bilirubin, the yellow pigment found in bile, increased unconjugated bilirubin in the blood from
a less functional liver can lead to jaundice. Another important job of the liver is producing albumin. So, if
the liver is not functioning right, one can have a decreased amount of albumin in the blood or
hypoalbuminemia. Finally, the liver helps create clotting factors or proteins that help coagulate blood, so
when the body is not producing these coagulation factors, one can develop issues related to one's ability
to clot blood, which one needs to stop blood loss after an injury.
In conclusion, Cirrhosis is a complex and progressive liver disease with multiple developmental
phases, each with its own set of clinical signs and implications. The progression from compensated
cirrhosis, in which the liver may still operate despite damage, to decompensated cirrhosis, which is
characterized by considerable impairment and consequences, emphasizes the severity and effect of this
disorder. Steatosis, scarring, cirrhosis, and end-stage liver failure are the four stages of liver disease that
show the progressive progression of liver damage. Early identification and management, especially in the
early stages, provide an essential opportunity for successful medical care, preventing the disease from
progressing to irreversible and life-threatening levels. Cirrhosis complications such as variceal bleeding,
hepatic encephalopathy, ascites, jaundice, and gallstones emphasize the systemic consequences of liver
disease. Each issue affects a separate organ system, highlighting the interdependence of biological
functioning and the huge impact of liver health on overall well-being.

Cirrhosis is correlated with a variety of organ systems, including the nervous, integumentary,
respiratory, digestive, cardiovascular, urinary, and reproductive systems, emphasizing the disease's
extensive impact. Cirrhosis has a wide-ranging influence on the human body, ranging from reduced brain
function to changes in skin appearance, respiratory failure, digestive disorders, cardiovascular difficulties,
renal malfunction, and reproductive system abnormalities. It is essential for individuals and communities,
as well as healthcare professionals, to have a comprehensive understanding of cirrhosis. Preventive
actions can be aided by knowledge of risk factors, early symptoms, and the significance of lifestyle
decisions. Moreover, information on the relationship between liver health and general health might enable
people to make better educated decisions, which may lessen the occurrence and severity of cirrhosis.

Lastly, understanding the pathophysiology of cirrhosis gives a roadmap for medical intervention,
emphasizes the need for early identification, and illustrates the interdependence of body systems. This
understanding plays an important role in promoting a holistic approach to health, supporting preventive
actions, and eventually improving outcomes for patients with cirrhosis. [PATHOPHYSIOLOGY]
Laboratory Diagnosis

The liver is the primary organ for the metabolism of the three main biomolecules—protein, fat,
and carbohydrates. A persistent infection with the hepatitis C virus is the primary cause of chronic liver
damage. According to the World Health Organization (2023), this virus is known to be a bloodborne
virus, transmitted through transfusion of unscreened blood products and bodily fluids, and by reusing
and/or insufficient sanitation of medical equipment, particularly in syringes and needles. Hepatitis C virus
occurs and also happens when transmission occurs from an infected mother to her child, and through
sexual behaviors that exposes a person to blood, semen, and reused unsterilized syringes or needles.
Moreover, infection of Hepatitis C virus can also result in fibrosis or tissue scarring.

To elaborate, fibrosis is the final stage and a typical pathological result of numerous chronic
inflammatory illnesses. Though collagen deposition is an essential and usually reversible component of
wound healing, if the tissue damage is extensive or frequent, or if the wound-healing response itself
becomes dysfunctional, normal tissue repair can develop into a gradually permanent fibrotic response.
The excessive buildup of fibrous connective tissue (which includes collagen and fibronectin, components
of the extracellular matrix (ECM)) in and around inflamed or damaged tissue is known as fibrosis. This
condition can cause permanent scarring, organ failure, and, in the worst-case scenario, death. Examples of
this include end-stage liver disease, kidney disease, idiopathic pulmonary fibrosis (IPF), and heart failure.

In terms of diagnosis, clinical results have led to the recognition that liver cirrhosis is not a
singular disease entity, but rather an illness that can be classified into discrete clinical stages, namely
compensated and decompensated cirrhosis. With this, several noninvasive techniques for measuring liver
fibrosis have been discovered, and these techniques have been applied to the diagnosis for patients with
liver cirrhosis. Noninvasive imaging methods, including elastography and basic ultrasound imaging, both
of which are essential supplements to the clinical evaluation of cirrhosis, as they lessen the need for liver
biopsies. Furthermore, liver damage and synthetic function can be assessed using biomarkers and
validated serum tests.

Medical professionals can accurately detect liver cirrhosis with the tests indicated below. These
techniques will aid in assessing the factors that could make the disease's prognosis worse.

Tests Used to Determine Cirrhosis:

Laboratory Findings:

Laboratory Test Normal Ranges (serum) Values in Liver Disease

Aspartate Aminotransferase 10-30 U/L Elevated
Male: 10-40 U/L
Alanine Aminotransferase Elevated
Female: 7-35 U/L
Alkaline Phosphatase 25-100 U/L Elevated
Gamma-glutamyl Transferase 5-40 U/L Elevated

Table 1. Laboratory Tests for Evaluation of Cirrhosis-Liver Damage

(a) Biochemical Markers

In testing liver functionality, it is commonly used to group the biochemical parameters.

There are four (4) major enzymes to consider in determining Liver Cirrhosis:

● Aspartate aminotransferase
● Alanine aminotransferase
● Alkaline phosphatase
● Gamma-glutamyl transferase

Aspartate and Alanine Aminotransferase (AST and ALT) are normal in advanced
cirrhosis but can be elevated in chronic liver disease. Both enzymes are found mostly in the liver
and function as catalysts for breaking down amino acids. Alanine Aminotransferase is raised
when there is significant liver damage, such as hepatitis, congestive heart failure, liver or bile
duct injury, and myopathy. On the other hand, Aspartate Aminotransferase leaks into the
extracellular space when hepatocytes are injured, raising serum AST activity. A high AST/ALT
ratio suggests skeletal muscle injury, helping differentiate between liver and muscle injuries.

Alkaline Phosphatase is an enzyme involved in liver metabolism and skeletal

development, found in bones, liver, kidneys, intestines, and the placenta of pregnant women. It is
high in cirrhosis, often due to cholestatic disease, which results from destructed liver bile ducts
due to alcoholism, acute hepatitis, and scarring. Primary biliary cholangitis is inflammation of
bile ducts, blocking bile flow and causing inflammation. The liver typically repairs itself when
inflammation is not severe, but fibrosis forms over the liver as inflammation worsens, causing
distortion of the liver's interior structure. Cirrhosis occurs when deformity and scarring extend
extensively.

Gamma-glutamyl Transferase is a transport molecule, GGT aids in the movement of

other molecules throughout the body. It is essential for the liver's ability to process drugs and
other harmful substances; it is also elevated in cholestatic liver disease but less specific.
Alcoholic liver disease, which can result from recent to long-term alcohol ingestion, is also the
main confounding factor that greatly raises its concentration.

(b) Hematological Markers

A crucial part in determining cirrhosis is thrombocytopenia (low platelet counts in the

blood). This is secondary to splenic sequestration and congestive splenomegaly resulting from
portal hypertension. A platelet count of less than 150 x 190/L is frequently the initial indication of
cirrhosis.

Classification Platelet Count

Normal Platelet Level 150,000 - 450,000/mcL

High Platelet Level (Thrombocytosis) more than 450,000/mcL

Low Platelet Level (Thrombocytopenia) less than 150,000/mcL

Table 2. Guideline for Platelet Counts/Level

Gold Standard:

Liver Biopsy

Liver biopsy is rarely needed for the diagnosis of cirrhosis, but still, liver biopsies are useful in
making the final diagnosis of the underlying cause of liver disease. Once substantial coagulopathy
(Impaired clotting formation; abnormalities in the body's blood clotting regulation) has been ruled out, it
is carried out through the skin under ultrasound guidance. For patients who have a higher risk of bleeding,
a transjugular liver biopsy conducted in a tertiary referral center is a safer procedure. It also makes it
possible to assess the hepatic vein pressure gradient, which is the most reliable indicator of portal
hypertension but is primarily utilized in studies as opposed to clinical care.

Imaging Techniques Used to Determine Cirrhosis:

(a) Ultrasound

The first imaging technique that is typically advised when liver disease is suspected is
abdominal ultrasound. It is inexpensive, easily accessible, and sensitive enough to rule out biliary
blockage. A nodular liver edge, splenomegaly, portal vein dilatation, and recanalization of the
umbilical vein are ultrasonography features suggestive of cirrhosis. However, one of the
limitations is that moderate hepatic steatosis can be overlooked.

(b) Elastography

A relatively new yet extensively used imaging technique for non-invasively estimating
liver stiffness is elastography. More advanced fibrosis is correlated with increased liver stiffness.
Elastography can quantify hepatic stiffness by measuring the speed at which mechanical waves
propagate through the liver parenchyma, however it cannot identify the underlying etiology of
cirrhosis.

Based on MRI or ultrasound, there are two types of elastography procedures. Shear
waves produced by ultrasound pass through liver tissue at a pace that depends on how stiff the
tissue is. The degree of liver stiffness increases with speed. Mechanical vibration in the liver
generates waves that are translated into an MRI-based tissue stiffness map during elastography.

In conclusion, Cirrhosis is becoming increasingly common. An early diagnosis is likely to

improve the prognosis for the patient to be diagnosed. A clinical suspicion of liver disease is necessary to
make the diagnosis, especially in groups that are at risk. Imaging and biochemical testing are part of the
preliminary inquiry. Hepatic fibrosis can be predicted by combining serum indicators and clinical
characteristics. Using elastography to measure tissue stiffness, liver fibrosis can also be evaluated.
Cirrhosis is currently infrequently diagnosed via biopsy.
Treatment and Management

Cirrhosis, which is the scarring or fibrosis of the liver, arises and is a result of long-term damage
induced and done to liver cells and tissues. There are various causes of cirrhosis, and so, naturally, there
are different approaches regarding treatment to address the overall disease, factored and influenced by the
root cause and extent of liver damage. Moreover, since cirrhosis of the liver is irreversible, there is only
so much that can be done to slow down the progression of tissue scarring and, better yet, prevent and
avoid the development of cirrhosis or efficient treatment of early symptoms and complications (Mayo
Clinic, 2023).

Treatment for the Underlying Cause of Cirrhosis

In early cirrhosis, or in its initial clinical stage known as compensated cirrhosis, although
structural and biological changes have already begun, there is a possibility to minimize and reduce
damage to the liver by treating the underlying cause including, but not limited to, the following:

(a) Treatment for alcohol dependency

Individuals diagnosed with cirrhosis as a result of excessive alcohol consumption must

try and stop drinking any and all amounts of it to improve results and lessen further complication
developments. However, if there are issues concerning alcohol management, one’s health care
provider may suggest and refer to a treatment program for alcohol dependency or, simply,
substance (alcohol) addiction. With cirrhosis, it is vital that alcohol is avoided as it is toxic and a
contributor of damage to the liver (Mayo Clinic, 2023).

(b) Weight loss

The liver of a healthy person does not typically contain a lot of fat or lipids. However, it
can accumulate as weight increases, particularly in those considered to be overweight or obese
people or diabetics or people with high blood pressure. This condition is known as non-alcoholic
fatty liver disease (NAFLD). In particular patients with NAFLD, liver fat can be dangerous and
cause inflammation and build-up of scar tissues. This is called non-alcoholic steatohepatitis
(NASH). With the continuous accumulation of scar tissues, NASH can progress to cirrhosis. To
successfully and functionally treat NAFLD and NASH, it is necessary to lose weight by
recalibrating and modifying eating habits and increasing physical exercise. Reducing just 5-10%
of one’s measured weight significantly decreases the symptoms and severity of NASH and
NAFLD and ameliorates liver health.

(c) Hepatitis Medications

Hepatitis B and C are infections in the liver caused by a virus, which can contribute to
liver damage, thus, causing cirrhosis. To provide further elaboration, hepatitis B is spread by
means of blood and contact with bodily fluid, while hepatitis C is typically spread by blood.
Unprotected sex with infected persons or close contact with an infected individual’s blood and
fluids are some of the common ways through which it is proliferated. Fortunately, with the
appropriate vaccines and prescription and intake of antiviral medications such as adefovir
(Hepsera), entecavir (Baraclude), tenofovir (Vemlidy), sofosbuvir (Sovaldi), ribavirin (Copegus
Rebetol), and peginterferon alfa-2a (Pegasys), these chronic or long-term infections can be treated
or slow and stop the virus from further damaging the liver.
Treatment for Complications of Cirrhosis

The fibrotic tissue, pressure build-up, and diversion of blood from the hepatic circulation, all of
which are effects and processes of cirrhosis, essentially reduces the number of functional sinusoidal veins
and the various functional portal triads (portal vein, hepatic artery, bile duct). As these basic liver
functional units are constantly affected and decreased, the liver becomes less and less capable of its
fundamental functions, such as detoxification. With this, numerous complications form and develop, as
defined in the pathophysiology section, and is treated as following:

(a) Fluid Buildup (Ascites)

Pressure buildup in the portal vein and decreased liver function can cause fluid to
accumulate in the belly. This condition is known as ascites. A low-sodium diet and medicine
(diuretics) can help target and prevent or get rid of extra fluid in the body and regulate ascites and
swelling. Antibiotics may also be prescribed to prevent bacteria from growing in it and causing
an infection and further complications. In the case of more-severe fluid buildup, medical attention
and procedures may be required to drain and remove the fluid from the belly or surgery to relieve
pressure in the portal vein (WebMD, 2023).

(b) Intrasinusoidal/Portal Hypertension and Varices

Formation of scars and collagen buildup in the liver impede, compress, and even block
blood flow through the portal vein, the primary blood vessel to the liver. This backup of blood
escalates pressure within the portal vein, as well as in the system of veins that connect to it, such
as the sinusoidal and central vein. This increase in blood pressure causes these vessels to swell.
Fortunately, there are certain blood pressure medicines, such as beta-blockers, that help regulate
and lower pressure in the portal vein and other blood vessels so they do not swell to the point of
breaking and prevent severe bleeding. In addition, a regular upper endoscopy check-up may be
appointed in search of enlarged veins that may bleed, known as varices (WebMD, 2023).

According to Mayo Clinic (2023), with the development of varices, medicine, such as
terlipressin, somatostatin and octreotide, is required to lower the risk of bleeding. If there are
signs that the varices are bleeding or have the possibility to bleed, a non-surgical treatment
known as band ligation may be needed. This procedure can stop the bleeding or reduce the risk of
further bleeding. Additionally, in severe cases, a transjugular intrahepatic portosystemic shunt
may be carefully and systematically placed in the veins to reduce blood pressure in the liver.

(c) Increased liver cancer risk

Cirrhosis can be linked and does increase a person’s probability and likelihood for liver
cancer. Medical professionals will likely suggest regular blood tests and ultrasound exams every
six to twelve months (6 to 12) to look for signs of liver cancer. And in the chance that a person
does indeed have liver cancer, the primary treatments include surgery, radiation, or chemotherapy
(WebMD, 2023).

(d) Hepatic encephalopathy

With cirrhosis and heavy scarring, the liver’s functions are greatly reduced, including its
detoxification properties. Therefore, unfiltered toxins in the blood passing through the brain can
damage it and lead to memory loss, personality changes, and intellectual impairment–hepatic
 encephalopathy. Patients with this condition may be prescribed medicines, such as lactulose (an
osmotic laxative) and rifaximin (an antibiotic), to help significantly and effectively reduce the
buildup of toxins in the blood caused by poor and improper liver function (Mayo, 2023).

Liver transplant surgery

If left undiagnosed and untreated, cirrhosis cases can worsen and degrade the liver quicker. In an
attempt to save the patient with an advanced case of cirrhosis, which is when the liver stops functioning
properly, a liver transplant may be the sole viable option. It is a process of replacing the cirrhotic liver
with a healthy one from either a deceased donor or with part of a liver from a living donor. Notably,
cirrhosis is one of the most common reasons for a liver transplant. However, to become an appropriate
candidate for liver transplant, there is extensive testing and screening used to determine (1) whether the
patient is healthy enough to produce towardly or favorable results post-operation, (2) the person’s
capability to comply with the post-transplant medical regime, and (3) the candidate poses no risks of
future alcohol or drug abuse. (Mayo Clinic, 2023).

In this regard, in the past, those with alcoholic cirrhosis have not been ideal liver transplant
candidates because of the risk that they will return to old habits of harmful drinking after the procedure.
Recent studies, however, imply that meticulously selected candidates with severe alcoholic cirrhosis have
post-transplant survival rates similar to those of liver transplant recipients with other types of liver disease
(Mayo Clinic, 2023).

For transplant to be an option with alcoholic cirrhosis, the patient would need to:
(a) Search for a program that focuses on individuals who have alcoholic cirrhosis.
(b) Meet the requirements of the program, including lifelong commitment to alcohol
abstinence or sobriety, as well as other requisites necessitated by the transplant center.

In summary, scientists are always continuously working and looking to expand current treatments
for cirrhosis, but success has been limited. Because liver cirrhosis has a number of causes, as well as
complications, there are many potential perspectives and avenues of approach. A combination of
increased screening, lifestyle changes, and appropriate medicines may improve outcomes for people with
liver damage, if diagnosed and initiated early in its developmental stages. Moreover, researchers are
working on therapies that will specifically target liver cells, helping to slow or even reverse the fibrosis
that leads to cirrhosis. However, despite targeted therapy being not quite ready, the future is unlimited,
and the potential is endless, so never lose hope (Mayo Clinic, 2023). [TREATMENT
MANAGEMENT]
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