24.CHRONIC HEPATITIS. LIVER CIRRHOSIS.

Question 1

Extra-hepatic manifestations of HBV infection:

Answer 1

• extra-hepatic manifestations include rash, arthralgia, glomerulonephritis, polyarteritis nodosa

Question 2

Peri-natal HBV infection:

Answer 2

-Perinatal HBV infection may manifests as neonatal hepatitis between 18 days and 6 months of age with jaundice, cholestasis with urobilinogen in the urine and hypocholic stool.
Hepatomegaly with splenomegaly and occasionally coagulopathy are found.
-Perinatal HBV infection usually progress to chronic B hepatitis. Many infected children are asymptomatic and develop normally.

Question 3

HBV treatment:

Answer 3

Treatment is directed toward interruption of the viral replication (HBsAg- and HBV DNA-negative tests) and prevention of severe liver damage. Interferon-alpha, pegylated interferon, nucleoside/nucleotide analogues and DNA vaccines are used in clinical practice.
- Interferon has an immunomodulatory eftect by destroying infected hepatocytes and inducing resistance to the virus in unintected cells.
- Nucleoside/nucleotide analogues block HBV DNA synthesis, bring transaminases levels to normal and Improve liver function.
Entecavir (0.5 mg daily in children over 2 years), Tenofovir (245 mg daily in children over 12 years), Lamivudine (3 mg/kg daily) are medicaments of choice. Lamivudine treatment
has an increased risk of resistance.

Question 4

HDV needs ________ to repliate

Answer 4

HBsAg

Question 5

HDV diagnosis and treatment:
Leads to cirrhosis in _____ of cases.

Answer 5

HDV RNA PCR
Can give interferon treatment
25%

Question 6

HCV diagnosis, treatment:

Answer 6

anti-HCV antibodies
HCV RNA PCR

Direct antiviral drugs
Glecaprivir + pibrentasvir

Question 7

Which virus is most closely associated with HCC?

Answer 7

HCV

Question 8

HCV extrahepatic manifestations:

Answer 8

Mixed cryoglobulinemia
B-cell Non-hodgkin lymphoma
ITP
Autoimmune hemolytic anemia
Membranoproliferative glomerulonephritis
Porphyria cutanea tarda
Lichen planus
Diabetes mellitus
Autoimmune thyroiditis
Leukocytoclastic vasculitis

Question 9

Type 1 vs 2 Autoimmune Hepatitis:

Answer 9

-Type 1 = common in females >8 yrs old – presence of antinuclear antibodies, antibodies to soluble liver antigen, anti-smooth muscle antibodies
- Type 2 = common in infants – presence of anti-liver/kidney microsomal antibodies (anti-LKM1)more aggressive and can progress to cirrhosis

Question 10

Autoimmune hepatitis overview:

Answer 10

• Autoimmune hepatitis is a chronic progressive inflammatory process mani-
  tested by liver-associated autoantibodies, hypergammaglobulinemia and histological findings of hepatitis

Question 11

Lab findings in autoimmune hepatitis:

Answer 11

-Include elevated levels of transaminases
-direct bilirubin
-moderate to highly elevated level of alkaline phosphatase and y-glutamyl transpeptidase, - often elevated gammaglobulins
- autoantibodies (ANA and/or SMA in type 1 and liver kidney microsomal antibodies (LKMA) in type 2).
- It is important that other types of chronic hepatitis, drug- and alcohol-induced hepatitis are excluded.

Question 12

Autoimmune hepatitis treatment:

Answer 12

-Is given in two stages - induction stage with prednisone at a starting dose of 1-2 mg/kg/24 h
and a second stage of gradual reduction over the next 2-4 months until the minimum dose of 0.1 mg/kg/24 h is reached.
-Immunomodulators are indicated in cases with poor response or side effects, most often azathioprine 1-2 mg/kg/24 h.
Good response to therapy leads to normal levels of transaminases within 1-3 months. In fulminant hepatitis and liver failure liver transplantation is indicated.

Question 13

Drugs with direct toxic effects are:

Answer 13

Salicylates, paracetamol, isoniazid, rifampicin, halothane, a-melhy/dopa, macrolides, sulfonamides, anticonvulsants, sedatives, antimetabolites, cylostatic agents, anabolic hormones and estrogens, Treatment consists of ayoiding the offending agent and supportive measures. Prednisone is given in immune-mediated disease.

Question 14

Non-alcoholic fatty liver disease:

Answer 14

-Non-alcoholic fatty llver disease is characterized by chronic liver steatosis, which is primary and not a consequence ot infections, use of steatogenic drug, alcohol consumption, malnutrition or other genetic/metabolic disorders.
-This disorder is associated with insulin resistance, central or generalized fat accumulation
and dyslipidemia.

Question 15

Wilson’s disease overview:

Answer 15

Wilson’ disease is a rare autosomal recessive disease associated with accumulation of copper in the liver, brain, kidneys, cornea, bones and other organs. It is progressive and potentially fatal if untreated. Abnormal gene for the disease is found on the long arm of chromosome 13 , encoding ATP7B - a copper transporting adenosine triphosphatase (ATPase), which is critical for biliary copper excretion.

Question 16

Easiest way to distinguish Wilson’s disease:

Answer 16

Neurological symptoms usually develop gradually and affect the motor functions - intention tremor, dysarthria, dystonia, loss of motor coordination presenting with difficult everyday activities like dressing and writing, masked facial expressions, hypersalivation, difficult swallowing. Psychiatric symptoms are also present. Kayser-Fleischer ring is deposition of copper in the cornea. It is detected by Slit-lamp examination. It is always present in patients with neurological involvement.

First manifestation of the disease may be a Coombs-negative hemolytic anemia. Kidneys involvement in Wilson disease presents with proximal or distal tubular dysfunction and nephrolithiasis. Arthritis, cardiomyopathy, hypoparathyroidism, bone changes are rare manifestations. Screening tests include assessment of serum ceruloplasmin level and copper excretion in the urine after D-penicillamine challenge (excretion exceeds 25 umol/24 h). Liver biopsy is to determine the severity of liver disease and the copper concentration in the liver that is significantly elevated.

Question 17

Treatment of Wilson’s disease:

Answer 17

copper-chelating agents, which leads to rapid excretion of large amounts of copper, for example D-penicillamine in a dose of 20 mg/kg/24 h. In response to treatment, urinary copper excretion reaches the normal levels, marked improve- ment in hepatic function occur. Liver transplantation is considered for patients with fulminant liver failure, decompensated cirrhosis, and progressive neurological disease.

Question 18

alpha-1-antitryspin deficiency:

Answer 18

a1-Antitrypsin deficiency is an autosomal recessive disorder caused by mu- tation in the SERPINA1 gene. a1-Antitrypsin - a protease inhibitor synthesized by the liver, protects lung alveolar tissues from destruction. Clinical manifestations are neonatal cholestasis, intermittent elevation of transaminases or progressive liver dysfunction to cirrhosis and liver transplantation. Treatment is supportive, liver transplantation is considered in end-stage liver disease.

Question 19

Liver cirrhosis overview:

Answer 19

Liver cirrhosis is an irreversible condition and the and stage of progressive liver
disease. when hepatocytes are injured, they form regenerative nodules (micronodular or macronodular) separated by fibrous septa, and there is loss of normal liver architecture with diffuse fibrosis

Question 20

Causes for chronic liver disease in children:

Answer 20

-Congenital disorders such as biliary atresia, tyrosinaemia, untreated galactosaemia,1-antitrypsin deficiency
-Hepatitis B and C, autoimmune hepatitis
-Wilson disease, hemochromatosis
-Cystic fibrosis
-Primary sclerosing cholangitis

Question 21

Clinical features of chronic liver disease:

Answer 21

-In many cases it is asymptomatic for long time with only manifestation of hepatosplenomegaly
-Growth retardation
-Weight loss, malaise, anorexia
-Hepatomegaly, jaundice, dull pain in right upper quadrant
-Bleeding and easy bruising (due to decreased clotting factors produced)
-Gynaecomastia, spider angiomas (dilated blood vessels beneath skin surface), palmar erythema, telangiectasia, xanthomas are observed
-Testicular atrophy
-Hypoalbuminemiaperipheral oedema

Question 22

Complications of liver cirrhosis:

Answer 22

Complications– portal hypertension is due to build-up of fibrotic tissue in perisinusoidal space, which compresses the sinusoids and causes a higher portal venous pressurecan result in collateral channels opening to divert blood away from the liver due to higher pressure, and so can lead to complications such as the following:
Portosystemic shunts –collateral channels between portal circulation & systemic circulation so blood follows a path of lower resistance, and results in:
-Haemorrhoids –collateral channel between inferior and internal iliac veins
-Caput medusae –dilated veins around umbilicus region as foetal umbilical vein forms channel with anterior abdominal wall
-Oesophageal varices– dilated submucosal veins in the oesophagus – susceptible to rupture and haemorrhage, resulting in hematemesis or melena
-Ascites =abnormal fluid accumulation in peritoneal cavity (increased pressure in sinusoids causes fluid in blood vessels to be pushed out into tissues and peritoneal cavity)presents with abdominal distension and discomfort
management is by fluid and dietary sodium restriction and spironolactone can be given
Spontaneous bacterial peritonitis is a complication of ascites, where there is infection of the peritoneal fluid in ascitic patientsInfecting organism (e.g.E. coli, Klebsiella)gain access to peritoneum by haematogenous spread
-Presents with fever, abdominal pain & tenderness, altered mental status
-positive ascitic fluid bacterial culture and elevated neutrophil count in ascitic fluid are diagnostic
-3rd gen cephalosporins e.g. cefotaxime or ceftazidime used
Splenomegaly/hypersplenism– spleen progressively enlarges due to shunting of blood into splenic vein increased removal of blood elements resulting in anaemia, leukopenia, thrombocytopenia
Hepatic encephalopathy results from accumulation of neurotoxins in the blood e.g. ammonia, due to loss of detoxifying capacity of the liver
- Symptoms include fetor hepaticus (sweet smell to breath), asterixis (tremor of the hands when outstretched – flapping tremor), changes in personality, mood & intellect, disorientation, irritability  can progress to coma
- Management includes removing possible precipitating causes, and enemas such as lactulose to empty the bowels of nitrogenous substances
Hepatorenal syndrome = acute renal failure occurring in patients with advanced cirrhosis, portal hypertension with jaundice and ascites
 characterised by oliguria, low urinary sodium concentration, rise in plasma creatinine concentration