Liver cirrhosis

BRIEF BACKGROUND OF THE DISEASE

Cirrhosis is an irreversible result of various disorders that damage liver cells

over time. Eventually, damage becomes so extensive that the normal structure of the
liver is distorted and its function is impaired. The disease process often takes the
following path:

Scarring. The main damage in cirrhosis is triggered by scarring (fibrosis) that occurs

from injuries due to alcohol, viruses, or other assaults. The scar tissue and other
changes in liver cells gradually replace healthy liver tissue and act like small dams to
alter the flow of blood and bile in and out of the liver.

Altered Blood and Bile Flow. The changes in blood and bile flow have significant
consequences, with both the liver and other organs responding to the altered flow:

 The spleen overproduces nitric oxide, a chemical that causes blood vessels in
the spleen to widen (dilate).
 The small blood vessels and bile ducts in the liver itself, however, narrow
( constrict ). (Blood vessels in other organs, including the kidney, also narrow.)
 Blood flow coming from the intestine into the liver is slowed by the narrow blood
vessels. It backs up through the portal vein and seeks other routes.
 Enlarged, abnormally twisted and swollen veins called varicesform in the
stomach and lower part of the esophagus in order to compensate for the backup blood.
 Bilirubin also builds up in the bloodstream, resulting in jaundice, a yellowish cast
in the skin and eyes, as well as dark-colored urine.
 Fluid buildup also occurs in the abdomen (called ascites ), and swelling in the
legs is common.

FUNCTIONS OF THE LIVER

The liver is the largest internal organ in the body. In the healthy adult, it weighs about 3
pounds. The liver is wedge-shaped, with the top part wider than the bottom. It is located
immediately below the diaphragm and occupies the entire upper right quadrant of the
abdomen.
 The liver performs over 500 vital functions. Damage to the liver can impair these and
many other processes. Among them are the following:

Processing Healthful Nutrients. The liver processes all of the nutrients the body
requires, including proteins, glucose, vitamins, and fats.

Bile Production. The liver produces bile , a green-colored fluid that helps the body
absorb fats and fat-soluble vitamins. Bile contains bilirubin, a yellow-green pigment
produced from the breakdown of hemoglobin, the oxygen-carrying component in red
blood cells. Bile contains bile salts, fatty acids, cholesterol, and other substances. Bile
travels from the liver to the gallbladder, where it is stored until after a meal. It is then
secreted into the intestines where it helps digest fat. Because bile can also travel
directly from the liver to the intestines, patients who have had their gallbladders
removed can still absorb fat normally.

Eliminating Toxins. One of the liver's major functions is to render harmless potentially

toxic substances, including alcohol, ammonia, drugs, and harmful by-products of
digestion.

STRUCTURE OF THE LIVER

The vital processes the liver performs rely on well-organized liver architecture.

The basic building blocks of the liver are the following structures:

 Bile ducts
 Blood vessels
 Working liver tissue (called the parenchyma)
 Supportive (connective) tissue
The liver is a built on a framework of lobes:

 Lobes . The liver is divided into two major lobes, a right and a smaller left, which
are separated by tough, fibrous connective tissue.
 Lobules . The liver's two major lobes contain about 100,000 smaller lobes, called
lobules. Each lobule contains microscopic columns of liver cells and blood vessels.
Bracing the corners of each lobule column are an artery and a vein that carry blood and
a bile duct that drains bile.
 Bile ducts . The bile ducts in the column corners collect bile draining from tiny
canals around the liver cells. These ducts eventually join to form the large common bile
duct that leads from the liver to the gallbladder.
 Arteries and veins . The arteries bring oxygen-rich blood to nourish the liver cells.
The veins supply the liver cells with blood containing the nutrients and toxins that the
liver cells process. A central vein runs through each column and collects the processed
blood from both sources. These veins join to form the hepatic vein.
The Liver's Blood Supply. The liver is rich in blood. It holds about a pint, or 13% of the
body's supply. It is furnished with blood from two large vessels, the hepatic
artery and the portal vein , and is drained of blood by the hepatic vein . (The word
"hepatic" derives from the Latin word for liver.)

The hepatic artery. This artery supplies blood from the heart directly to the liver. This
blood nourishes the liver.

The portal vein. The portal vein carries to the liver blood that has been circulating
through the stomach, spleen, and intestine. The liver processes this blood, extracting
nutrients and toxins.

The hepatic vein. This vein carries blood from the liver and connects to the inferior vena
cava , a large vein that carries blood back to the heart.

ETIOLOGIC FACTOR/AGENT

Alcoholic liver disease once was considered to be the predominant cause of cirrhosis in
the United States. Hepatitis C has emerged as the nation's leading cause of both
chronic hepatitis and cirrhosis.

Many cases of cryptogenic cirrhosis appear to have resulted from nonalcoholic fatty
liver disease (NAFLD). When cases of cryptogenic cirrhosis are reviewed, many
patients have one or more of the classical risk factors for NAFLD: obesity, diabetes, and
hypertriglyceridemia.1 It is postulated that steatosis may regress in some patients as
hepatic fibrosis progresses, making the histologic diagnosis of NAFLD difficult.
Up to one third of Americans have NAFLD. About 2-3% of Americans have nonalcoholic
steatohepatitis (NASH), where fat deposition in the hepatocyte is complicated by liver
inflammation and fibrosis. It is estimated that 10% of patients with NASH will ultimately
develop cirrhosis. NAFLD and NASH are anticipated to have a major impact on the
United States' public health infrastructure over the next decade.

Most common causes of cirrhosis in the United States 

 Hepatitis C (26%)
 Alcoholic liver disease (21%)
 Hepatitis C plus alcoholic liver disease (15%)
 Cryptogenic causes (18%)
 Hepatitis B, which may be coincident with hepatitis D (15%)
 Miscellaneous (5%)

Miscellaneous causes of chronic liver disease and cirrhosis 

 Autoimmune hepatitis
 Primary biliary cirrhosis
 Secondary biliary cirrhosis (associated with chronic extrahepatic bile duct
obstruction)
 Primary sclerosing cholangitis
 Hemochromatosis
 Wilson disease
 Alpha-1 antitrypsin deficiency
 Granulomatous disease (eg, sarcoidosis)
 Type IV glycogen storage disease
 Drug-induced liver disease (eg, methotrexate, alpha methyldopa, amiodarone)
 Venous outflow obstruction (eg, Budd-Chiari syndrome, veno-occlusive disease)
 Chronic right-sided heart failure
 Tricuspid regurgitation
 . MODE OF TRANSMISSION
Common modes of transmission in developing countries are:
 perinatal (from mother to baby at birth)
 early childhood infections (inapparent infection through close interpersonal
contact with infected household contacts)
 unsafe injections practices
 blood transfusions
 sexual contact
In many developed countries (e.g. those in western Europe and North America),
patterns of transmission are different than those mentioned above. Today, the majority
of infections in these countries are transmitted during young adulthood by sexual activity
and injecting drug use. HBV is a major infectious occupational hazard of health workers.
HBV is not spread by contaminated food or water, and cannot be spread casually in the
workplace.
The virus incubation period is 90 days on average, but can vary from about 30 to 180
days. HBV may be detected 30 to 60 days after infection and persist for widely variable
periods of time.

MEDICAL MANAGEMENT
Generally, liver damage from cirrhosis cannot be reversed, but treatment could stop or
delay further progression and reduce complications. A healthy diet is encouraged, as
cirrhosis may be an energy-consuming process. Close follow-up is often necessary.
Antibiotics will be prescribed for infections, and various medications can help with
itching. Laxatives, such aslactulose, decrease risk of constipation; their role in
preventing encephalopathy is limited.

Treating underlying causes

Alcoholic cirrhosis caused by alcohol abuse is treated by abstaining from alcohol.

Treatment for hepatitis-related cirrhosis involves medications used to treat the different
types of hepatitis, such as interferon for viral hepatitis and corticosteroids for
autoimmune hepatitis. Cirrhosis caused by Wilson's disease, in which copper builds up
in organs, is treated withchelation therapy (e.g., penicillamine) to remove the copper.
Preventing further liver damage

Regardless of underlying cause of cirrhosis, alcohol and paracetamol, as well as other

potentially damaging substances, are discouraged. Vaccination of susceptible patients
should be considered for Hepatitis A and Hepatitis B.

Preventing complications

]Ascites

Salt restriction is often necessary, as cirrhosis leads to accumulation of salt (sodium

retention). Diuretics may be necessary to suppress ascites.

Esophageal variceal bleeding

For portal hypertension, propranolol is a commonly used agent to lower blood pressure

over the portal system. In severe complications from portal hypertension, transjugular
intrahepatic portosystemic shunting is occasionally indicated to relieve pressure on the
portal vein. As this can worsen encephalopathy, it is reserved for those at low risk of
encephalopathy, and is generally regarded only as a bridge to liver transplantation or as
a palliative measure.

Hepatic encephalopathy

High-protein food increases the nitrogen balance, and would theoretically

increase encephalopathy; in the past, this was therefore eliminated as much as possible
from the diet. Recent studies show that this assumption was incorrect, and high-protein
foods are even encouraged to maintain adequate nutrition.[18]

Hepatorenal syndrome

The hepatorenal syndrome is defined as a urine sodium less than 10 mmol/L and

a serum creatinine > 1.5 mg/dl (or 24 hour creatinine clearance less than 40 ml/min)
after a trial of volume expansion without diuretics. [19]

Spontaneous bacterial peritonitis

Cirrhotic patients with ascites are at risk of spontaneous bacterial peritonitis.

Transplantation
If complications cannot be controlled or when the liver ceases functioning, liver
transplantation is necessary. Survival from liver transplantation has been improving over
the 1990s, and the five-year survival rate is now around 80%, depending largely on the
severity of disease and other medical problems in the recipient. [20] In the United States,
the MELD score is used to prioritize patients for transplantation. [21] Transplantation
necessitates the use of immune suppressants (cyclosporine or tacrolimus).

Decompensated cirrhosis

In patients with previously stable cirrhosis, decompensation may occur due to various
causes, such as constipation, infection (of any source), increased alcohol
intake, medication, bleeding from esophageal varices or dehydration. It may take the
form of any of the complications of cirrhosis listed above.

Patients with decompensated cirrhosis generally require admission to hospital, with

close monitoring of the fluid balance, mental status, and emphasis on adequate nutrition
and medical treatment - often
with diuretics, antibiotics, laxatives and/or enemas, thiamine and
occasionally steroids, acetylcysteine and pentoxifylline. Administration of saline is
generally avoided as it would add to the already high total body sodium content that
typically occurs in cirrhosis.