Digestive system III PEDIATRIC LIVER DISEASES

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Digestive system III PEDIATRIC LIVER DISEASES

• Professor shahenaz M. Hussien

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Manifestations of liver diseases

• Symptoms
• Jaundice with dark colored urine and pale stool.
• Abdominal distension due to hepatomegaly.
• Bleeding tendency e.g. hematemesis, melena and
  epistaxis.
• Purities.
• Failure to thrive and malaise.
• Abdominal pain, anorexia, fever and vomiting in
  cases of hepatitis.
• Metabolic consequence of liver diseases e.g.
  encephalopathy.
• Signs
• Enlarged or shrunken liver.
• Signs of portal hypertension splenomegaly,
  dilated abdominal wall veins. -Ascites.
  -Clubbing especially in chronic liver
  disease.

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• Investigations of liver diseases
•  
• Liver function tests
• I. evidence of cellular injury assessed by Serum
  transaminases
• Alanine aminotransferase (ALT) normal value is
  5-45U/L
• Aspartate transaminase (AST) normal value
  15-55U/L
• They are increased in liver necrosis marked in
  acute hepatitis. ALT is a more sensitive
  indicator of liver damage.
• II. Excretory function of the liver can be
  assessed by-
• Bilirubin level normally no bilirubin in urine.
  
• It is present in Obstructive and
  Hepatocellular jaundice
• Urobilinogen in urine is increased in
• -Hepatocelluar jaundice. -Hemolytic
  anemia.
• Serum 5 nucleotidase is raised in intrahepatic
  cholestasis.
• Increased S. gamma glutamyl transferase in
  obstructive jaundice.

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• Decreased serum albumin level in liver cirrhosis.
• Elevated Serum immunoglobulins in chronic liver
  diseases.
• Delayed prothrombin time and concentration
  (normal value 10-13 seconds and 85-100
  respectively).
• Imaging study of the liver-
• Liver ultrasound it shows
• Diffuse liver disease cirrhosis, metabolic
  disease, hepatic periportal bilharzial fibrosis
  and fatty liver.
• Biliary channel patency, choledocal cyst and
  gall stones.
• Focal lesions, liver abscess - Ascites and
  subphrenic abscess.
• Radioisotopic scanning it display liver size,
  morphology, focal lesions and biliary excretion.
• Computerized tomography (CT) it demonstrates the
  presence of focal lesion, and cyst.
• Magnetic resonance imaging (MRI) it can shows
  patency of biliary tree and focal lesion.
• Liver biopsy and histopathological examination,
  it is the key for diagnosis of most liver disease.

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HEPATOMEGALY

• Definition- It is an inflammatory process of
  the hapatocytes characterized by degeneration and
  regeneration with loss of hepatic architecture.  
• Types-
• Acute less than six months duration
• Chronic more than six months
• Etiology
• I- Infections, which may be-
• Viral
• Hepatotropic viruses e.g A, B, C, D, E, F, G, H
  viruses
• Non -hepatotropic infect the liver in the course
  of other systemic illness
• - Epstein-Barr virus (EBV). -Cytomegalovirus
  (CMV).
• - Coxsakie, -ECHO, -rubella, -varicella and
  measles viruses.

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• Bacterial
• - As a part of generalized septicemia.
• - Isolated pyaemic liver abscess. -
  Leptospirosis.
• Protozoal e.g amoebic hepatitis.
• II- Drugs and Toxins
• Anti T.B. e.g Isoniozid - antimetabolites -
  anticonvulsant- valporic acid
• Irradiation - chloropromazin - total parenteral
  nutrition Carbontetrachloride - halothane
• III- Immunological Disorders
• -As apart of S.L.E and J.R.A
• - Isolated auto immune hepatitis
• IV- Metabolic Causes
• Alpha antitrypsine deficiency - galactosemia -
  tyrosenemia
• Haemosidrosis - Wilson disease
• V- Vascular Causes
• - Hepatic vein thrombosis. - Hepatic artery
  thrombosis
• VI- Tumors
• - Primary hepatoma or hepatoblastoma
• - Secondary- neuroblastoma, lymphoma, leukemia

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HEPATITIS -A

• Mode of transmission fecal-oral route
• Incubation period 15-45 days (average 4
  week). The virus is excreted in stool during
  the first few weeks of infection, prior to the
  onset of symptoms.
• Clinical manifestations Acute Viral
  Hepatitis
• 1- Prodromal stage (1-2 weeks)(pre-Icteric)
• Headache, anorexia, malaise.
• Nausea, vomiting, lethargy. This phase can be
  passed un-noticed by the parents.
• 2- Icteric phase (2-3 weeks) Characterized by
• jaundice - dark urine.
• Abdominal pain soft enlarged, and tender liver.
• 3- Convalescence phase (1-2 weeks) - After
  which the child become nearly normal.
• In endemic areas 30-80 of children acquire
  subclinical or anicteric infection in the first
  few years of life. -Anorexia - Nausea
  Vomiting -Fever - Abdominal discomfort
• -Irregular bowel motions for a few days -
  Dark urine and mild scleral jaundice.

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• Laboratory diagnosis
• Liver function tests shows-
• Raised serum level of .direct and indirect
  bilirubin Urine contains both bilirubin ( dark
  color) and Urobilinogen.
• Marked elevation of serum transaminases (ALT and
  AST).
• Increase in serum levels of alkaline phosphatase
  and 5 nucleotidase.
• IgM Anti- HAV is detected at
  the onset of the symptoms and disappears within
  4 weeks while IgG anti-HAV persists for life
• Complication
• Acute fulminant hepatitis.
• It is a rare condition with massive destruction
  of the liver cells.
• It is presented clinically by persistent
  vomiting, disorientation, encephalopathy,
  bleeding tendency, edema and ascites.
• Aplastic anemia
• Is a very rare complication it is transient but
  may be fatal.
• It is due to bone marrow depression.
• Death is usually due to serious infection due
  to depressed immunity
• Cholestassis
• The patient becomes intensely pruritic and
  jaundiced
• It is due to hepatocyte edema which may cause
  element of obstruction

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• Treatment
• There is no specific therapy for acute viral
  hepatitis,
• Most children are managed at home except if liver
  cell failure is suspected.
• Balanced diet with low fat intake should be
  given.
• Prevention
• Period of infectivity Contagious for about 7
  days before and 7 days after the onset of
  jaundice.
• Period of isolation from school From the
  appearance of dark color urine and appearance of
  jaundice till 7 days after disappearance of
  jaundice.
• Careful hand washing after changing diapers and
  before preparation of food. -Fly
  control.
• Intramuscular immunoglobulin may be indicated in
  pre and post exposure.
• Hepatitis A vaccine is now available to be given
  to children. Contacts are immunized with
  immunoglobulin or the vaccine.

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HEPATITIS -B

• Mode of transmission
• Perinatal transmission (vertical transmission).
• -Infection appears to be due to contact with
  a mother's infected blood at the time of
  delivery. -Transplacental transmission is
  rare.
• Parenteral In patient receiving blood
  transfusion or blood products, renal dialysis,
  dental care, and through contaminated syringe and
  needles.
• Child to child transmission It may occur
  through biting of insects, drooling and shared
  chewing gums.
• Although HBV was detected in breast milk of
  infected mother there is no role of breast milk
  in transmission the infection.
• Incubation periodHBV has long incubation period
  (45-160 days). 

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• Clinical manifestation Asymptomatic carrier
  is more common.
• Acute infection presented with
• Jaundice, dark color urine, anorexia, nausea,
  malaise.
• Hepatomegaly splenomegaly.
• Exctrahepatic manifestations as
• Papular skin eruption - Arthralgia
  Glomerulonephritis. -Aplastic anemia
  Polyarthritis.
• Chronic hepatitis may present with - Chronic
  active hepatitis. - Cirrhosis.
• Hepatocellar carcinoma in adult.
• Laboratory diagnosis
• Liver function tests The first evidence of
  infection is elevation of ALT. which begin to
  rise before the prodromal symptoms appears.
• Hepatitis markers
• The serological pattern of HBV is differ
  depending on either the patient is a carrier or
  acute or chronic case .
• Routine screening for HBV requires at least two
  serological markers
• -HBsAg which indicate infection and HBeAg which
  indicate infectivity.
• -HBcAb (IgM and IgG) is detected early in the
  disease and is important because it
  differentiates between the carrier and acute and
  chronic patient.

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• Complications
• Persistent infection
• Following acute infection, approximately 5 of
  infected individuals fail to eliminate the virus
  completely and become persistently infected.
• Those who are at particular risk include
• -Babies and young children.
  -Immunocompromised patients
  - Males gt females.
• Chronic hepatitis which can leads to cirrhosis
• Acute fulminant hepatitis with encephalopathy,
  coagulopathy and cerebral edema (Rare).
• Aplastic anemia .
• Hepatocelluar carcinoma on top of cirrhosis.

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• Treatment
• Supportive treatment.
• Interferon a 2b and lamivudine are used in
  chronic HBV in adult.
• Liver transplantation is used in end stage HBV
  infection
• Prevention
• Hepatitis B vaccine is now included in the first
  year compulsory vaccination program worldwide.
• Hepatitis B immunoglobulins (0.5 ml) should be
  given soon after delivery to babies whom mothers
  are HBsAg positive together with HB vaccine
• Proper screening of blood and blood products to
  eliminate all blood-borne viruses.
• Prognosis
• Recovery may be complete.
• The child may remain as an a symptomatic carrier
  ,0r chronic patient for months or years.

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HEPATITIS -C

• Etiology
• HCV was previously known as non-A non-B
  hepatitis.
• There are many genotypes(1,2,3,4) and
  phenotypes(a,b,c,d,e,) of each genotype.
• Mode of transmission
• Post-transfusion with repeated transfusion of
  blood and blood products.
• Intravenous drug, needle prick exposure,
  hemodialysis, organ transplant.
• Perinatal transmission is uncommon
  transplacental transmission not proved until now.
• Incubation period
• The incubation period is 7-9 weeks.
• Clinical picture
• The clinical pattern of the acute infection is
  usually similar to that of other hepatitis.
• Acute HCV infection is usually mild and may be
  asymptomatic but fulminant liver failure may
  occur leading to poor prognosis.
• HCV is the most likely hepatitis virus to cause
  chronic infection (in about 25 of the patients).
  
• Chronic HCV infection may be associated with
  exctrahepatic manifestation include
• -Cutaneous Vasculitis - Peripheral
  neuropathy - Cerebritis
• -Membrano-prolifrative glomerulonephritis
  - Nephrotic syndrome

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• Laboratory Diagnosis
• Liver function tests Fluctuating pattern of
  elevation of the levels of transaminases.
• Serologic assays
• Diagnosis of HCV infection is based on detection
  of antibodies to HCV antigens.
• This assay is used for detection of chronic
  hepatitis C because they remain negative for at
  least 1-3 months after the onset of illness.
• Detection of HCV antigens is done by polymerase
  chain reaction (PCR).
• Complications
• Fulminant hepatitis . - Chronic hepatitis.
• Hepatocelluar carcinoma is lower than HBV.

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• Treatment
• The effective therapy is under trial are
• -Monotherapy with Interferone a 2b
• -Combination therapy with Interferone a 2b and
  Ribavirine results in higher frequency of
  sustained response and in histologic improvement.
• Prevention
• There is no available vaccine against HCV.
• Proper screening of blood and blood products to
  eliminate all blood-borne viruses.
• Hygienic care in -
• Dentistry ( sterilization of all equipment ,
  using disposable instrument to every person)
• Using disposable syringe for injection
• Careful hygienic measure during shaving.
• Delivery by caesarian section for mothers with
  hepatitis C.
•  

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LIVER CIRRHOSIS

• What is Cirrhosis?
• It is defined as fibrosis (scarring) plus nodule
  formation (regeneration). Thus cirrhosis is a
  pattern, not a disease or a specific phenomenon.
• Cirrhosis can happen after any disease that
  causes liver cell death. Exactly why the
  regenerating nodules are not able to replace the
  function of the liver is not clear, although it
  may be the scarring itself that prevents
  recovery.
• Other organs like the kidneys, heart, and lungs
  are not able to regenerate. They can hypertrophy,
  (cells get larger) but they do not have cellular
  division that results in significant "regrowth"
  (more cells) like the liver does. This regrowth
  is what happens when a living donor gives part of
  their liver to be transplanted.

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• Etiology
• Several liver diseases can cause cirrhosis,
  including Hepatitis B and C, nonalcoholic fatty
  liver disease, biliary atresia, Alpha-1
  antitrypsin deficiency, primary sclerosing
  cholangitis, Wilson's disease, autoimmune
  hepatitis, and bile duct diseases.
• Autoimmune hepatitis is one of the major
  etiologies of chronic hepatitis in children.
  Chronic hepatitis may present with numerous
  hepatic clinical manifestations, associated with
  extrahepatic disorders.
• The etiology is unknown and the disease is
  characterized by the auto-antibody pattern and
  the positive response to immunosuppressive
  treatment.

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• Diagnosis
• -Cirrhosis may occur early, irrespective of the
  cause.
• -A combination of laparoscopy and biopsy is more
  reliable than biopsy alone for the diagnosis of
  cirrhosis in children with chronic hepatitis.
• -Changes in hepatic architecture in cirrhosis and
  chronic active hepatitis affect liver vascular
  haemodynamics. Portal vein velocity,
  arterio-portal vein ratio and hepatic artery
  visualisation together were reliable in diagnosis
  of cirrhosis in the paediatric age group.
• -Blood tests, CT scans, liver biopsies, and MRI
  and ultrasonography studies help confirm the
  cause of the cirrhosis, and the extent of liver
  damage.

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• Clinical manifestations
• Two problems happen in patients with cirrhosis --
  liver failure and portal hypertension.
• The liver failure causes fatigue, jaundice
  (yellow skin), and encephalopathy (a state of
  confusion that progresses to coma).
• The portal hypertension causes bleeding and
  ascites. These things happen in many forms of
  liver disease, not just in cirrhosis.
• The scarring never goes away, but the liver has
  "reserve," meaning it can do all the body
  requires even though it is not working at 100
  percent.

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• Treatment Options
• Even though cirrhosis can cause significant liver
  damage, the disease usually progresses slowly in
  children and most symptoms can be controlled.
• Treatment options vary based on the underlying
  cause or type of cirrhosis.
• Liver damage is irreversible however, when
  diagnosed early, it can be managed as a chronic
  condition. Treatment focuses on managing the
  specific liver dysfunctions and preventing
  further complications.
• If cirrhosis is undetected before severe liver
  damage occurs, a liver transplant may be the
  patient's only option.