HEPATIC CIRRHOSIS

1.- DEFINITION

Hepatic cirrhosis is a disease wich affects the liver tissue as a final consequence
of different chronic diseases.

The consequences of liver cirrhosis on the health of the individual depend

fundamentally on the degree of liver funcionallity can conserve despite the
histological alteration.

Cirrhosis is a chronic disease of the liver, which is characterized by being

progressive, diffuse, irreversible and of several reasons. This is identified by the
presence of fibrosis in the hepatic parenchyma, accompanied by regeneration
nodules. This results in an alteration of the vascular architecture of the liver.

CLASSIFICATION:
The classification of Liver Cirrhosis is based on morphological and etiological
criteria:
Alcoholic cirrhosis.
Postviral or postnecrotic and cryptogenetic cirrhosis (15%).
Biliary cirrhosis.
Primary biliary cirrhosis.
Secondary biliary cirrhosis.
Cardiac cirrhosis.
Metabolic, hereditary cirrhosis.
Hemochromatosis. Wilson's disease (rare).
Alpha-1 antitrypsin deficiency (rare).
Galactosemia (rare).
Others.
Cirrhosis produced by medications.
Cirrhosis of different causes.
2.- EPIDEMIOLOGY:

According to the WHO, about 27,000 people die each year from liver cirrhosis in
developed countries.

In Spain, affects 4 out of 10,000 people, of these the vast majority are caused by
excessive consumption of alcohol.

Hepatic cirrhosis is a frequent condition that occurs in all latitudes and human
groups, and is observed more often after the average age of life. It predominates
in men, except in the younger groups, because although cirrhosis occurs shortly
before age 20, when it does it is more common in women.

3.- PATHOGENY:

The main causes of cirrhosis in developed countries are:

 Excessive consumption of alcohol (Laennec's cirrhosis, alcoholic, ethylic

or enolic cirrhosis).
 Chronic hepatitis C virus (C virus cirrhosis).
 Other viruses, such as hepatitis B chronic hepatitis and mixed chronic
hepatitis B virus and hepatitis D virus infection.
 Primary biliary cirrhosis of immunological origin.
 Cryptogenic hepatic cirrhosis: of unknown origin.
 Chronic cholestatic diseases (affecting the production or exit of bile from
the liver), such as primary biliary cirrhosis or primary sclerosing
cholangitis.
 Congenital metabolic diseases of the liver such as primary
hemochromatosis (hepatic iron overload - quite frequent), Wilson's
disease (copper hepatic overload - very rare) and deficiency of alpha-1
antitrypsin (also quite rare); or acquired metabolic diseases such as
nonalcoholic steatohepatitis associated with diabetes or dyslipidemia.
  Other: autoimmune hepatitis. Hepatic toxicity by drugs or other
hepatotoxic chemicals. There are many more rare and some specific
causes of childhood that cause cirrhosis in children or adolescents.
 All of the above diseases usually require years of evolution to produce
cirrhosis.
 ETIOPATHOGENIA: Similar to what happens in other tissues, hepatic
inflammation is the basic process by which the liver responds to the
damage, whatever it may be. Through this process, the liver tissue is able
to recognize the damage and if possible repair it. If the repair is not
possible, then it will destroy the damaged tissue. Under normal conditions,
this type of response restores the original structure and function and
maintains tissue homeostasis, but sometimes the lesion is too intense or
persistent, and the inflammatory process itself compromises structural
integrity through processes such as fibrosis, posterior sclerosis, since
structures damaged by abnormal tissue are replaced.

The different etiologic agents of chronic liver diseases mentioned in the

previous section can cause tissue damage, inflammation and hepatocyte
necrosis, but the type of cellular repair that prevails (regeneration or
fibrosis) will determine whether the liver tissue recovers, or that fibrosis
progress and this abnormal tissue regeneration leads to cirrhosis.

The predominance of one type or another of response depends both on

the characteristics and persistence of the harmful agent, and on the
characteristics of the individual.

4.- CLINICAL MANIFESTATIONS:

In many cases, the diagnosis of cirrhosis is a casual one, since as it has been
said, in the compensated phase of the disease, its manifestations may be of little
consequence, presenting vague or non-specific symptoms such as dyspepsia,
asthenia or hyperpyrexia. Thus, it can be detected in the presence of
hepatomegaly on a routine physical examination, alterations in the liver function
tests, or in the positive tests in the study of viral hepatitis.
Among the manifestations that can be found are some cutaneous signs. None
are pathognomonic, but may be useful for diagnostic suspicion; Among these
"Stigmas de hepatopatía", spider veins or spiders, distributed in the territory of
the superior vena cava, are sometimes present. Occasionally, there is also a
reddening of the tenar and hypothenar eminences known as palmar erythema. In
cirrhosis of alcoholic origin, parotid hypertrophy and Dupuytren's contracture may
appear.

Occasionally xanthelasms appear on the eyelids, especially in cholestatic

diseases (primary sclerosing cholangitis and primary biliary cirrhosis), whereas
in Wilson's disease the Kayser-Fleischer ring (a brownish-brown ring appears on
the limbic border of the cornea, by deposition of copper in Descemet's
membrane).

When performing abdominal physical examination, an enlarged liver with

irregular surface and hard consistency is observed, although in the final stages
of the disease, it may be completely atrophic and withdrawn and not be palpable.

Since hepatomegaly is generally painless, the existence of abdominal pain

should suggest some intercurrent phenomena such as pancreatitis or biliary colic,
given the high incidence of biliary lithiasis in the cirrhotic patient.

Splenomegaly, together with the presence of collateral circulation (multiple

subcutaneous dilated veins in the abdominal wall), indicate portal hypertension.
When the collateral circulation is prominent around the umbilical vein in the navel
area it is classically called the "head of Medusa".

Portal hypertension can also condition the presence of ascites, which may
manifest as an increase in the abdominal perimeter, indicating the presence of
free intra-abdominal fluid. Abdominal wall hernias, especially umbilical are
common when there is ascites, as well as subcutaneous edema that appears in
the slope areas (usually legs)
 Endocrine alterations are common in cirrhosis, especially in those with alcoholic
etiology (Laennec cirrhosis of the liver); males may have testicular atrophy,
decreased libido, and erectile dysfunction. Gynecomastia is common. Women
often have menstrual abnormalities and even amenorrhea. These endocrine
alterations are called Silvestrini-Corda Syndrome

Jaundice is a sign that often accompanies decompensated cirrhosis and is

usually a sign of advanced disease.

In the decompensated cirrhosis, hemorrhagic lesions such as petechiae,

equidism, or hematomas may exist due to minimal trauma, epistaxis and
gingivororrhages, which may result in frequent coagulation alterations that may
occur in cirrhotic patients.

Hepatic Stink is a characteristic sweet smell that appears in these patients due
to the exhalation of substances derived from methionine (methylmercaptan), by
default in their demethylation.

To all the exposed findings a malnutrition state is usually added, with an evident
decrease in muscle mass and adipose panicle.

5.- MACROSCOPY:

HEPATIC CIRRHOSIS
Cirrhosis is diffuse, systematized liver fibrosis, inflammatory or triggered by
hepatocyte necrosis. The fibrosis delimits nodules of parenchyma remnant or
with similar atypical regeneration, in the form of septa, in all sectors of the organ.

The concept of cirrhosis is morphological, derived from an anatomical fact and

not a nosological entity; cirrhosis represents a terminal condition of various liver
diseases.

Major pathogenetic forms

1. Alcoholic.
2. Poshepatitis.
3. Secondary biliary (obstruction of the extrahepatic biliary tract).
4. Primary biliary.
5. Hemochromatosis.
6. Wilson's disease.
7. Deficiency of a-1-antitrypsin (on these last three forms see Manual of General
Pathology).

The cause can not always be deduced from the morphology of cirrhosis, because
the same noxa can produce different types of cirrhosis and different causes end
in the same morphological alteration.

Anatomical forms

Micronodular cirrhosis

It is also called portal, septal or monolobulillar.

Macroscopy: liver of normal or small size, increased consistency. It is diffuse

and homogeneously micronodular (1 to 3 mm) with pinkish-whitish, depressed,
firm or elastic connective septa, completely surrounding the nodules.

Histology: Lympho-histiocytic infiltration of varying degrees is observed in

fibrous septa. Partitions surround or dissect nodules of hepatocytes; these are of
trabecular or disorderly disposition with regenerative signs. Central lobules can
rarely be recognized. In the walls, a proliferation of bile ducts is present, and
especially in the periphery of the regenerative nodules, pseudoconducts
constituted by hepatocytes.
Micronodular cirrhosis is a frequent consequence of hepatic alcohol damage. It
may also be secondary to active chronic hepatitis, primary or secondary biliary
tract damage, or alpha-1-antitrypsin deficiency.
Macronodular cirrhosis
Also called postnecrotic, multilobulillar or postcolapso.

Macroscopy: the liver is observed of conserved size, less frequently small. The
nodules measure from 3 mm to 3 cm in diameter; including fibrous, grayish-
whitish or gray-red bands or partitions.

Histology: the walls are formed by collapse of the reticulum of necrotic areas
(passive partitions) to which active fibrosis is added. Portal spaces and central
veins are recognized. Some of the latter are communicated with portal spaces by
walls or are clearly included in the scars.

Macronodular cirrhosis is seen as a sequela of viral necrotizing hepatitis, Wilson's

disease, active chronic hepatitis with exacerbations, alpha-1-antitrypsin
deficiency, and in the late stages of alcohol damage with established
micronodular cirrhosis.

Secondary biliary cirrhosis

Also called cholangitic, is produced by an obstruction of the extrahepatic bile duct.

Cholangitis, which affects the ducts also in the portal spaces, progressively
damages perilobulillary hepatocytes. Portal inflammation leads to perilobulillar
fibrosis, which tends to dissect the lobules and alter liver architecture.

Macroscopy: the liver is micronodular, greenish-blackish, hard. The biliary tract

is dilated and there may be extensive perihiliary scars. Characteristic is the
appearance in garlands of the remaining parenchyma.

Primary biliary cirrhosis

Disease of unknown cause, of autoimmune pathogenesis, with circulating

antimitochondrial antibodies (see general pathology: immunopathology). It mainly
affects middle-aged women. Histology: lesion begins by degeneration of the bile
duct epithelium, followed by a chronic portal and periportal inflammatory reaction
 with necrosis in the saccharum, epithelial granulomas adjacent to the bile ducts,
disappearance of biliary ducts and signs of cholestasis. At a later stage there is
portal fibrosis with formation of bridges and further evolution to cirrhosis.

6.- DIAGNOSIS:

 For the diagnosis of liver cirrhosis, it is usually enough with non-invasive

procedures, such as the combination of imaging techniques such as
ultrasound, and laboratory findings.
 Hepatic biopsy is also used; however, this procedure is only used in
selected cases today.

LABORATORY ANALYSIS:
 Hepatic function. Blood is examined for excess bilirubin, which is a
breakdown product of red blood cells, in addition to certain enzymes that
may indicate liver damage.
 Renal function. The blood is checked for creatinine because liver function
may decrease in the late stages of cirrhosis (decompensated cirrhosis).
 Hepatitis B and C tests. Blood is tested for hepatitis viruses.
 Coagulation. The international normalized index is analyzed to check the
ability of the blood to clot.

IMAGES
 Magnetic resonance imaging or transitional elastography. These
noninvasive imaging tests detect hardening or stiffness of the liver and can
eliminate the need for a liver biopsy.
 Other imaging tests. MRI scans, CT scans, and ultrasound scans produce
images of the liver.
 Biopsy. A tissue sample (biopsy) is not needed to diagnose cirrhosis.
However, the doctor may use it to identify the severity, extent, and cause
of liver damage.nd further evolution to cirrhosis.

7.- TREATMENT:
Treatment for cirrhosis caused by hepatitis:
If cirrhosis was related to hepatitis, they are drugs recommended for the
treatment of the underlying disease. For example:
Peginterone (Pegasys ES, Pegintron) take 100 mcg of drug per week for 31
weeks; and subsequently continue the therapy assuming subcutaneous 50 mcg
/ week of 35-52 weeks.
Lamivudine / Zidovudine Lamivudine Teva Teva) may be taken for patients with
HIV and hepatitis B, in which case 100 mcg of peginterferon is recommended for
subcutaneous use for 31 weeks and continued treatment with 50 mcg per week
for 32-52 weeks. (For more information see the article on drugs against hepatitis)
Treatment to avoid complications of cirrhosis:
Increased pressure in small veins and portal vein can be prevented with the use
of medications that can control the pressure within the veins that carry blood to
the liver. These medicines can prevent severe bleeding. Particularly beta
blockers: Atenolol (eg Atenol.), Timolol maleate (Blocadren for example.),
Bosiprololo hemifumarate (eg Concor.). The dosage and mode of administration
of the medicines must be determined by your doctor.
Ascites (excess fluid in the abdomen) can be prevented by taking diuretics
(amiloride + hydrochlorothiazide for example: eg Moduretic: Take 1-2 tablets of 5
mg formulated with 50 mg of hydrochlorothiazide and amiloride O Esidrix,
formulated in tablets of 25 mg of hydrochlorothiazide be taken 1-2 times daily)
and correction of eating habits, such as taking foods low in salt. In some cases,
to remedy varices and ascites for cirrhosis of the liver, and recommended a
procedure called transjugular catheterization of the supra hepatic veins.
If cirrhosis was caused by bacterial infections, and so proceed to take antibiotics
directed against the responsible pathogen. For example: Amoxicillin (eg
amoxicillin, amoxicillin and Trimox, Zimox, Augmentin), ofloxacin (eg Exocin,
Oflocin, for E. coli and Klebsiella pneumoniae infections), Etc. Choosing an
antibiotic instead of another depends on the pathogen.
In the context of severe hepatic cirrhosis, the increase in toxins found in the blood
can be treated with drugs indicated for the treatment of hepatic encephalopathy
(severe complication of hepatic entities and advanced cirrhosis). In this case, the
drug most commonly used in therapy and lactulose (eg Normase, EPS Duphalac,
VERELAIT, Laevolac: initially assumes 30 ml of the drug orally or three times 300
ml of the substance in 700 ml of water or saline solution by enema, each dose 4-
6 hours of maintenance: 30-45 ml, orally 3 times daily). In such circumstances,
the patient must correct his or her power. Consult your doctor.
Because cirrhosis can develop into cancer, and a good rule of thumb to regular
blood tests and other specific tests, in order to fight against any type of cancer
from the early signs.
The best cure for liver cirrhosis and, without doubt, prevention:
 Do not drink alcohol
 Be careful with some medications
 Limit NSAID use in the case of chronic hepatitis
 Medications for heart failure
 Follow a balanced diet, being careful to limit the consumption of salty foods
 Assume probiotics to balance intestinal flora