Liver Cirrhosis:.

Cirrhosis represents a late stage of progressive hepatic fibrosis

characterized by distortion of the hepatic architecture and the formation of
regenerative nodules. It is generally considered to be irreversible in its
advanced stages at which point the only option may be liver transplantation.
Patients with cirrhosis are susceptible to a variety of complications and
their life expectancy is markedly reduced.

CLINICAL MANIFESTATIONS: Patients with cirrhosis may present in

a variety of ways. They may have stigmata of chronic liver disease
discovered on routine physical examination. They may have undergone
laboratory or radiologic testing or an unrelated surgical procedure that
incidentally uncovered the presence of cirrhosis. They may present with
decompensated cirrhosis, which is characterized by the presence of
dramatic and life-threatening complications, such as variceal hemorrhage,
ascites, spontaneous bacterial peritonitis (SBP), or hepatic
encephalopathy.Some patients never come to clinical attention. In older
reviews, cirrhosis was diagnosed at autopsy in up to 30 to 40 percent of
patients.

All patients with cirrhosis should undergo diagnostic endoscopy to

document the presence of varices and to determine their risk for variceal
hemorrhage. Patients at high risk for development of variceal hemorrhage
should be considered for primary prophylaxis. I like Variceal Banding.
Much to often Liver Cirrhosis is being related to excessive alcohol
ingestion. Even though alcoholism is a common cause of this entity, it is by
far not the only cause of this often deadly disease. Liver cirrhoses is not
curable, but it is definitely preventable in many instances, if one recognizes
and minimizes certain risk factors.
The liver, the largest of our organs, is a real laboratory. With many many
functions, essential for the human body. Within the liver cell carry out,
complex enzymatic processes take place and many essential nutrients as
well as glycogen, proteins, fat and vitamins are stored. Generally speaking,
it is a very resistant organ that rarely ever fails to perform, contrary to the
teachings and beliefs of many naturist, quacks and charlatans, who readily
blame the liver for many diverse symptoms, without any scientific basis. 

DIAGNOSIS 
Physical Examination: A physical examination may reveal the following
findings in a patient with cirrhosis:
A liver biopsy is the only definite method for diagnosing cirrhosis. It also
helps determine its cause, treatment possibilities, the extent of damage, and
the long-term outlook. For example, hepatitis C patients who show no
significant liver scarring when biopsied appear to have a low risk for
cirrhosis. 
Percutaneous Liver Biopsy: This approach uses a needle inserted through
the abdomen to obtain a tissue sample from the liver. Various forms of
needles are used, including those that use suction or those that cut out the
tissue. If cirrhosis is suspected, a cutting needle is the better tool. This
approach should not be used in patients with bleeding problems, and it
must be used with caution in patients with ascites or severe obesity.
Laparoscopy: This procedure employs small abdominal incision through
which the physician inserts a thin tube that contains small surgical
instruments and a tiny camera to view the surface of the liver. This is
generally reserved for staging cancer or for ascites with unknown causes.
Biopsies can be dangerous, so they cannot be performed on patients who
have test results that indicate clotting problems, on those who have had
previous liver biopsies, or who have ascites .
Imaging Tests. Ultrasound examination of the abdomen is useful to
confirm hepatosplenomegaly and may also reveal enlargement or venous
obstruction of the portal or splenic veins with portal hypertension.
Cavernous transformation of the portal vein can also be identified and the
presence of esophageal varices is suggested. New ultrasound modalities are
beginning to estimate portal vein flow.
Blood Tests .

Routine tests of liver function may be quite normal in cirrhosis. A

decreased serum albumin and a prolonged prothrombin time directly reflect
impaired hepatic function in the truest sense. An increased serum gamma
globulin accompanies many forms of chronic liver disease. AST and ALT
are often moderately elevated, while alkaline phosphatase may be normal
or increased, particularly with biliary obstruction. Bilirubin is usually
normal. Increased total serum globulin is common. A normochromic
normocytic (occasionally macrocytic) anemia, thrombocytopenia, and
leukopenia may be present. With alcohol-related liver disease, the anemia
is occasionally macrocytic.

COMPLICATIONS
Ascites is the accumulation of fluid within the peritoneal cavity. It is the
most common complication of cirrhosis. Nearly 60 percent of all patients
with compensated cirrhosis will develop ascites in 10 years . The two-year
survival of patients with ascites is approximately 50 percent .
Spontaneous bacterial peritonitis Spontaneous bacterial peritonitis (SBP) is
an infection of preexisting ascitic fluid without evidence for an
intraabdominal secondary source such as a perforated viscus . SBP is
almost always seen in the setting of end-stage liver disease . Manifestations
of SBP include fever, abdominal pain, abdominal tenderness, and altered
mental status. Some patients are asymptomatic and present with only mild
laboratory abnormalities.
Hepatorenal Syndrome: The hepatorenal syndrome refers to the
development of acute renal failure in a patient who usually has advanced
hepatic disease, due to cirrhosis or less often metastatic tumor or severe
alcoholic hepatitis. Rather than being a new disease, the hepatorenal
syndrome usually represents the end-stage of a sequence of reductions in
renal perfusion induced by increasingly severe hepatic injury. The initial
reductions in glomerular filtration rate are often masked clinically since
associated decreases in muscle mass and hepatic urea production minimize
elevations in the plasma creatinine concentration and blood urea nitrogen.
Hepatorenal syndrome (HRS) is the development of renal failure in patients
with advanced chronic liver disease, occasionally fulminant hepatitis, who
have portal hypertension and ascites. Estimates indicate that at least 40% of
patients with cirrhosis and ascites will develop HRS during the natural
history of their disease.
Causes: Risk factors for developing HRS have been reported based on a
large series of patients with cirrhosis and ascites. Patients with marked
sodium and water retention, characterized by a low urinary sodium
excretion (<5 mEq/L) and dilutional hyponatremia, have a higher
probability of developing HRS compared to patients with less sodium and
water retention. Another important risk factor is the presence of severe
disturbances in the systemic circulation (mean arterial pressure <80 mm
Hg) associated with marked activation of the RAAS and SRS. Surprisingly,
patients with advanced liver disease, defined by a high Child-Pugh score or
worsening albumin, bilirubin, and prothrombin levels, are not at higher risk
of developing HRS. 
Mortality/Morbidity: Importantly, be aware that 2 different forms of HRS
are described. Although their pathophysiology is similar, their
manifestations and outcomes are quite different.

Type 1 HRS is characterized by rapid and progressive renal impairment

and is precipitated most commonly by SBP. Type 1 HRS occurs in
approximately 25% of patients with SBP, despite rapid resolution of the
infection with antibiotics. Without treatment, median survival of patients
with type 1 HRS is less than 2 weeks and virtually all patients die within 10
weeks after the onset of renal failure. 
Type 2 HRS is characterized by a moderate and stable reduction in the
GFR and commonly occurs in patients with relatively preserved hepatic
function. Median survival is 3-6 months. Although this is markedly longer
than type 1 HRS, it is still shorter compared to patients with cirrhosis and
ascites who do not have renal failure.
The following is a list of risk factors associated with the development of
HRS in patients with cirrhosis who are nonazotemic. All measurements
Hepatopulmonary Syndrome The hepatopulmonary syndrome (HPS) is
considered to be present in patients with the following triad: 
1. Liver disease.
2 .Increased alveolar-arterial gradient while breathing room air
3.Evidence for intrapulmonary vascular abnormalities, referred to as
intrapulmonary vascular dilatations (IPVDs). Estimates of the prevalence
of HPS among patients with chronic liver disease range from 4 to 47
percent, depending upon the diagnostic criteria and methods used. Even in
cirrhotic patients lacking HPS, mild hypoxemia is common and is
presumably caused by ascites, with resulting diaphragmatic elevation and
ventilation/perfusion mismatch. 
Hypoxemia is seen in one-third of decompensated cirrhotic patients.
Hepatopulmonary syndrome (HPS) is the triad of chronic liver disease,
increased alveolar-arterial oxygen gradient on room air, and
intrapulmonary arteriovenous shunting (due to subpleural arteriovenous
microshunts that resemble spider angiomas . Patients present with the
gradual onset of hypoxemia that is commonly more severe in the upright
position. Laboratory abnormalities include hypoxemia, and decreased
diffusing capacity for CO2. The majority of patients with HPS demonstrate
marked improvement in symptoms when given 100% oxygen. HPS is a
relative contraindication to liver transplant surgery, however, some patients
with HPS may actually improve following transplant. 
Chest radiograph abnormalities are detected in 46-100% of patients with
HPS . Medium sized (1.5 to 3 mm), bilateral, basilar, nodular or
reticulonodular opacities, with normal lung volumes, are characteristic of
HPS and represent dilated subpleural lung vessels.
Hepatic Encephalopathy Hepatic encephalopathy describes the spectrum
of potentially reversible neuropsychiatric abnormalities seen in patients
with liver dysfunction. Disturbance in the diurnal sleep pattern (insomnia
and hypersomnia) is a common early feature that typically precedes overt
neurologic signs. More advanced neurologic features include the presence
of asterixis, hyperactive deep tendon reflexes, and less commonly,
transient decerebrate posturing. 
year . Patients with most forms of chronic hepatitis are not at an increased
risk until cirrhosis develops. Exceptions to this rule are patients with
chronic hepatitis B virus infection who can develop HCC in the absence of
cirrhosis Certain causes of cirrhosis appear to have a relatively increased
risk for HCC. Patients with cirrhosis from hepatitis B, hepatitis C, and
hemochromatosis are at the highest risk, while those with cirrhosis from
autoimmune hepatitis, nonalcoholic steatohepatitis, and Wilson's disease
appear to have a lower risk.
 
Ascites is the accumulation of fluid in the peritoneal cavity.

Grading — A grading system for ascites has been proposed by the

International Ascites Club.

Grade 1 — mild ascites detectable only by ultrasound examination

Grade 2 — moderate ascites manifested by moderate symmetrical

distension of the abdomen

Grade 3 — large or gross asites with marked abdominal distension.

Alcoholic hepatitis regularly causes ascites with or without cirrhosis. 

Causes of Cirrhosis
Although most often associated with alcohol abuse, cirrhosis of the liver
can result from many causes. Almost any chronic liver disease can lead to
cirrhosis. This list gives some of the many causes: 
Alcoholic liver disease most common cause.
Chronic viral hepatitis B, C and D Postnecrotic cirrhosis: Hepatitis, a viral
infection of the liver, usually causes this disease, although poisonous
substances may also cause it. Two types of hepatitis, hepatitis B or hepatitis
C, cause 25-75% of these cases. Large areas of scar tissue mix with large
areas of healing nodules. 
Chronic autoimmune hepatitis 
Non-alcoholic Steatohepatitis, Malnutrition and Diabetes: Steatohepatitis
is the medical term for an enlarged, fatty liver. The condition is usually
caused by alcoholism, but can also be the result of malnutrition, obesity
and diabetes. Nonalcoholic steatohepatitis (liver inflammation that can be
caused by fatty liver)
Inherited metabolic diseases (e. g. hemochromatosis, Wilson disease,
Galactosemia) 
Chronic bile duct diseases (e. g. primary biliary cirrhosis) When small
tubes that help you digest food become blocked, your body mistakenly
turns on itself and reacts against these bile tubes. Gallstones often block
tubes and cause this type of cirrhosis. The disease usually affects women
aged 35-60 years
Chronic congestive heart failure Your heart is a pump that pushes blood
throughout your body. When your heart doesn't pump well, blood "backs
up" into the liver. This congestion causes damage to your liver. It may
become swollen and painful. Later it becomes hard and less painful. The
cause of the heart failure may be from heart valve problems, smoking, or
infection of the heart muscle or the sac around the heart
Parasitic infections (e. g. schistosomiasis) 
Long term exposure to toxins or drugs.
Alpha-1-antitrypsin Deficiency: This is a hereditary disorder that prevents
the body from properly utilizing the alpha-1-antitrypsin protein. In some
cases, alpha-1-antitrypsin builds up in the liver, where excess amounts can
lead to tissue scarring.
Liver Cirrhosis is a disease of this noble organ, which is not easily
understood by the lay person. This disease comprises the destruction
(necrosis) of the individual liver cells and its substitution for scar tissue, a
process which is irreversible. Often this is consequence of chronic alcohol
abuse, but may also be the result of previous infection with hepatitis
B,C,D . Specially hepatitis C which can develop in chronic viral hepatitis is
frequently related to liver cirrhosis.

Other causes of liver cirrhosis are diseases of metabolic origin. Metabolic

defects may cause the deposition of cirrhosis inducing substances into the
liver cells. Wilson´s disease as well as Galactosemia are such entities. In
Wilson´s disease, a specific enzyme deficiency causes the deposition of
copper particles in liver tissue. In Galactosemia , the deficiency of the
enzyme Galactose 1 Uridiltransferase , necessary for metabolism of
galactose, is responsible for the abnormal deposition of galactose in the
tissues, leading to mental retardation, cataracts and liver cirrhosis.Liver
injury that results in cirrhosis also may be caused by a number of inherited
diseases such as cystic fibrosis, alpha-1 antitrypsin deficiency,
hemochromatosis and glycogen storage diseases others causes of liver
cirrhosis are prolonged exposure to environmental toxins, and repeated
bouts of heart failure with liver congestion.

Prescription Drug abuse or even the prolonged or simultaneous ingestion of

some Over the Counter remedies, may cause liver cirrhosis. Special
attention should be given to the abuse of acetaminophen and paracetamol,
which is widespread here in El Salvador as well as in many other countries,
and is being self-medicated for a diverse variety of symptoms including
"hangovers", since liver cirrhosis may be a consequence of this abuse.
Specially the ingestion of acetaminophen during "hangovers" should be
avoided since the alcohol toxicity and the acetaminophen liver toxicity are a
dangerous combination for the liver. In normal persons large doses of
acetaminophen are needed to damage liver cells while patients with chronic
alcoholism may suffer massive liver damage when exposed to small
therapeutic doses of this drug. For this reason acetaminophen should be
avoided in chronic alcoholic patients. 

Symptoms of Cirrhosis 
People with cirrhosis often have few symptoms at first. At the beginning
The person may experience fatigue, weakness, and exhaustion. Loss of
appetite is usual, often with nausea and weight loss. As liver function
declines, less protein is made by the organ. For example, less of the protein
albumin is made, which results in water accumulating in the legs (edema)
or abdomen (ascites). A decrease in proteins needed for blood clotting
makes it easy for the person to bruise or to bleed.
With respect to the clinical signs and symptoms of liver cirrhosis In the
later stages this entity may present with uncharacteristic clinical features
over a long period of time and go undiagnosed over many years. Symptoms
and observable symptoms may appear late in the disease and may include
loss of libido, nausea, anorexia, vomiting, ocular or total body jaundice,
itching, reddening (erythema) of the palms, spider naevi on the chest,
gynaecomastia, abdominal swelling, hepatomegaly, splenomegaly, pubic
and axillary hair loss, swelling of ankles, abdominal pain, or mores severe
manifestations such as encephalopathy, upper G.I. Tract bleeding due to
esophageal varices or gastric ulcers or patient may even fall into a comatose
state. Due to this diversity of manifestations, special classifications exist
that classify a patient according to his or hers clinical features, which range
from an asymptomatic state to an advanced life threatening condition.

The definite diagnosis of liver cirrhosis can only be obtained through liver
biopsy. Other diagnostic methods such as ultrasound, CT Scan, MRI can
detect certain morphologic abnormalities associated with cirrhosis,
although these changes are usually seen in advanced disease only.

Liver cirrhosis in its initial stages can most often not be diagnosed by
diagnostic imaging methods. Endoscopy is useful to document the presence
of esophageal varices, as well as gastric or duodenal ulcers, often associated
with cirrhosis. 

Treatments for Cirrhosis 

As Liver cirrhoses is not curable the Treatment of cirrhosis is aimed at
stopping or delaying its progress, minimizing the damage to liver cells, and
reducing complications. 
The major goals of treating the cirrhotic patient include:
1. Slowing or reversing the progression of liver disease.
2. Preventing superimposed insults to the liver.
3. Preventing and treating the complications
4. Determining the appropriateness and optimal timing for liver
transplantation

Slowing or reversing the progression of liver disease. Although cirrhosis is

generally considered to be irreversible in its advanced stages, the exact
point at which it becomes irreversible is unclear . Some chronic liver
diseases respond to treatment even when the liver disease has progressed to
cirrhosis. Thus, specific therapies directed against the underlying cause of
the cirrhosis should be instituted. As examples:
The 10-year survival rate in patients with cirrhosis from autoimmune
hepatitis who are treated with steroids or immunosuppressive agents
approaches 90 percent. This number is similar to survival rates of treated
patients with autoimmune hepatitis who do not have cirrhosis.
Abstinence from alcohol improves survival in alcoholic cirrhosis.
Interferon therapy slows the progression of cirrhosis in patients with
chronic hepatitis C virus infection, and may also decrease fibrosis and the