Hepatobiliary Quiz (Answers)—15 (2015)

• 1.Answer A

  Vitamin deficiencies in chronic liver disease are due to diminished hepatic reserves, poor dietary intake, or malabsorption. Fat-soluble vitamin deficiencies are commonly seen.¹ Vitamin A is principally stored in hepatic stellate cells. As quiescent stellate cells become activated, they lose their vitamin A stores.² Vitamin A deficiency is seen in 50% of patients with alcoholic cirrhosis. Patients with chronic alcoholism have been shown to have very low concentrations of hepatic vitamin A at all stages of their disease.^{3, 4} Chronic liver disease commonly results in vitamin D deficiency. Decreased hepatic production of vitamin D binding protein seems to be a key mechanism responsible for the low serum vitamin D levels in patients with liver disease.^{1, 6, 7} Vitamin E deficiency has been well documented in alcoholic liver disease. However, supplementation has not been shown to cause clinical improvement or reduction in mortality.^{1, 8, 9} Acute and chronic hemorrhagic lesions in thalamus and mammillary bodies that are typical of Wernicke's encephalopathy are seen in thiamine deficiency.²

• 2.Answer A, B, C, D and E

  Magnesium deficiency is common in chronic liver disease, and is associated with peripheral insulin resistance as well. Supplementation has been shown to improve hepatic enzyme levels.¹⁰ Selenium is a co-factor for multiple seleno-proteins which have antioxidant functions. Chronic liver disease is associated with decreases in serum, whole blood, and hepatic selenium content.¹¹ Total body manganese stores are increased in cirrhosis, and accumulation of manganese in basal ganglia is common.¹² Copper and copper-associated protein accumulation may be observed in chronic biliary obstructive processes and cirrhosis.²

• 3.Answer A, B and E

  Patients with cirrhosis are usually malnourished and require careful nutritional management to prevent energy and nutrient depletion and correction of macro- and micronutrient deficiencies. Carbohydrate content should constitute 45–75% of caloric intake divided in 4–6 carbohydrate rich meals. A late evening or nighttime snack prevents gluconeogenesis, reduce protein utilization and favor a positive nitrogen balance. Protein intake of 1.2–1.5 g/kg should be maintained even in patients with hepatic encephalopathy. Vegetable and dairy protein is preferable.² Branched chain amino acid supplementation may be considered as they are not metabolized by the liver, providing an alternative source of proteins.¹³ Total body manganese stores are increased in patients with liver disease and its supplementation is not recommended.¹⁴

• 4.Answers A and D

  The spectrum of nonalcoholic fatty liver disease (NAFLD) ranges from simple steatosis to nonalcoholic steatohepatitis (NASH). The physiological level of fat in the hepatocytes is <5%, and accumulation of fat more than this is required for development of NASH. NAFLD is a polygenic disease with involvement of multiple loci, environmental and nutrient interactions. The major locus among these is 22q13.31, which harbors the PNPLA3 gene.¹⁵ Single nucleotide polymorphisms in the PNPLA 3 gene are strongly associated with progression of NAFLD to NASH. Polyunsaturated fatty acids (PUFAs) are of 2 types – n3 and n6. n-6 PUFAs which includes linoleic acid and arachadonic acid and have the capability of producing proinflammatory eicosanoids, thereby aggrevating the lipotoxicity in NASH.¹⁶ Although raised aspartate aminotransferase and alanine aminotransferase levels are very common, they may even be normal in biopsy proven NASH.¹⁷

• 5.Answers A, C, D and E

  Hepatitis may be commonly seen with coeliac disease. Upto 10% patients with unexplained transaminitis have been found to have coeliac disease.¹⁸ Transaminitis may be seen in 50% of coeliac disease at presentation.¹⁹ Although usually subclinical, the liver injury can occasionally progress to cirrhosis and liver failure. Thus, it is recommended to screen coeliac disease patients for liver disease at presentation, and follow-up with periodic liver function tests.²⁰

  Three fourths of patients with raised transaminases in coeliac disease do not have a separate disorder and these individuals respond well to gluten withdrawal.²¹ Patients with coeliac disease have higher likelihood of developing autoimmune hepatitis and primary biliary cirrhosis.²²

• 6.Answer A,C and D

  Dengue is a common arthropod-borne viral fever in South-East Asia. It is a non-hepatotropic virus, however, liver dysfunction is common. Hepatitis is common and can be found in 60–90% of dengue-infected patients.^{23, 24} Most of the cases with hepatitis have mild disease. Usually the AST levels are more than ALT levels probably due to skeletal muscle injury.²⁵ Severe dengue can even manifest with acute liver failure. Other gastrointestinal manifestations include acalculous cholecystitis, acute pancreatitis, acute parotitis and diarrhea. 80% of the cases develop hepatomegaly, and jaundice is seen in 60%. Both these symptoms are more common in severe dengue (93% and 94.5% respectively); thus being important predictors of severe dengue.²⁶ The presence of dengue virus antigens and nucleic acid has been shown in liver tissue using immunohistochemistry, in situ hybridization and in situ polymerase chain reaction techniques.²⁷

• 7.Answer C, D and E

  Jaundice leading to encephalopathy in infants has been called bilirubin encephalopathy or kernicterus. It occurs due to staining of the basal ganglia of infants by unconjugated bilirubin.^{23, 28} The most common cause is any type of hemolytic anemia, usually due to Rh or ABO incompatibility. Other causes include congenital or acquired disorders of bilirubin metabolism. Low birth weight, hypothermia, anoxia, acidosis, sepsis, hypoalbuminemia, and meningitis are risk factors.²⁹ In the first few days, infants were present with somnolence, hypotonia, and loss of the Moro reflex. They later develop irreversible changes leading to hypertonia of the extensor muscle groups. Patients who survive develop choreoathetosis, sensorineural hearing loss, dental dysplasia, gaze abnormalities and mild mental retardation.³⁰

• 8.Answers B and D

  High-dose corticosteroids are usually first-line therapy for acute cellular rejection. Methylprednisolone is the most commonly used agent. 80% episodes of acute cellular rejection resolve. In most of those who do not respond, a repeat course is effective. Improvement in biochemical parameters and histology occurs within 3–5 days of successful therapy. Cytomegalovirus and pneumocystis prophylaxis for three to six months is indicated in these patients.^{31, 32} Anti-interleukin antibodies like basiliximab and daclizumab are effective and may lead to resolution of steroid-resistant rejection in up to 75% cases.³³

• 9.Answers A, B and C

  The main pathway for ethanol metabolism is by oxidation to acetaldehyde. Alcohol dehydrogenase plays the most important role. Other pathways include microsomal oxidation, mainly via cytochrome P 2E1(CYP2E1) (∼10%) and catalase pathway. CYP2E1 is mainly concentrated in the perivenular zone 3 hepatocytes.^{34, 35} Less than 10% of ethanol is excreted unchanged.³⁶ Reduced glutathione and hemeoxygenase-1 protect the liver against oxidative damage.³⁷

• 10.Answers A, B and C

  HCC is commonly associated with portal vein thrombosis (PVT). It is associated with worse survival and indicates advanced disease. PVT is more commonly seen in patients with low serum albumin and high AFP levels.³⁸ HCC patients with PVT have a higher frequency of MTHFR and prothrombin gene G20210A mutations.^{39, 40} Contrast enhanced ultrasound can detect tumor invasion in 100% and correctly characterize it in 98% of patients, thus making it superior for detection than color Doppler sonography and computed tomography.⁴¹ Both radio frequency ablation and transarterial radioembolization with yttrium-90 glass microspheres appear to be safe and well tolerated in patients with portal vein obstruction without cavernous transformation.⁴²

  Radiation therapy is considered to be treatment of choice for selected patients with HCC and PV invasion especially for those with a favorable performance status.⁴³

Conflicts of interest

The authors have none to declare.

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