Liver Diseases

Question 0

Hepatitis B
Acute viral hepatitis
Liver

Answer 0

Epi/MOI: horizontal (IVDU, sex) in U.S.
Signs/Symptoms/Findings:
symptoms: fatigue, nausea, anorexia, fever arthralgia, myalgia, headache, RUQ pain
signs: jaundice, scleral icterus, coca-cola urine, hepatomegaly
labs: really increased ALT and AST, increased total bilirubin and alk phos, bilirubin in urine; increased IgM
biopsy: diffuse periportal lymphocytic inflammation, hepatocellular ballooning
Pathophysiology: the only enveloped, partially double-stranded DNA virus; 6-8 week incubation, 20% serum sickness prodrome
Treatment/Notes: progresses to chronic in 4%; treatment and vaccine (passive + active)

Question 1

Hepatitis A
Acute Viral Hepatitis
Liver

Answer 1

Epi/MOI: oral-fecal
Signs/Symptoms/Findings:
symptoms: fatigue, nausea, anorexia, fever, arthralgia, myalgia, headache, RUQ pain
signs: jaundice, scleral icterus, coca-cola urine, hepatomegaly
labs: really increased AST and ALT, somewhat increased total bilirubin and alk phos, bilirubin in urine; increased IgM
biopsy: diffuse periportal lymphocytic inflammation, hepatocellular ballooning
Pathophysiology: nonenveloped ssRNA virus: @2 weeks, excreted in stool; @4 weeks, increased ALT, symptoms benign; @8 weeks, resolution
Treatment/Notes: never chronic; no treatment but gamma globulin vaccine available (passive)

Question 2

Hepatitis D
Acute viral hepatitis
Liver

Answer 2

Epi/MOI: Hep B
Signs/Symptoms/Findings:
symptoms: fatigue, nausea, anorexia, fever, arthralgia, myalgia, headache, RUQ pain
signs: jaundice, scleral icterus, coca-cola urine, hepatomegaly
labs: really increased ALT and AST, increased total bilirubin and alk phos, bilirubin in urine, increased IgM
biopsy: diffuse periportal lymphocytic inflammation, hepatocellular ballooning
Pathophysiology: delta agent, uses HBsAg protein coat, HepB must be present
Treatment/Notes: superinfection worse than coinfection?

Question 3

Hepatitis E
Acute viral hepatitis
Liver

Answer 3

Epi/MOI: pigs
Signs/Symptoms/Findings:
symptoms: fatigue, nausea, anorexia, fever, arthralgia, myalgia, headache RUQ pain
signs: jaundice, scleral icterus, coca-cola urine, hepatomegaly
labs: really increased ALT and AST, increased total bilirubin and alk phos, bilirubin in urine, increased IgM
biopsy: diffuse periportal lymphocytic inflammation, hepatocellular ballooning
Pathophysiology: like HepA, waterborne, endemic in Asia, N. Africa, Mexico
Treatment/Notes:

Question 4

Chronic Hepatitis B
chronic hepatitis
Liver

Answer 4

Epi/MOI: 350 million; 1 million in US
Signs/Symptoms/Findings:
labs: increased ALT, AST > 6 months (+)HBsAg, (+)HBcAb IgG
biopsy: ground glass
Pathophysiology: vertical transmission predominant in most parts of world; can –> Hepatocellular carcinoma
Treatment/Notes: PEG-interferon, tenofovir/entecavir to decrease HBV DNA levels; not curative

Question 5

Chronic Hepatitis C
Chronic hepatitis
Liver

Answer 5

Epi/MOI: 170 million, 3 million in US
Signs/Symptoms/Findings:
labs: increased ALT and AST > 6 months, (+)anti-HCV, (+)HCV RNA
biopsy: portal lymphoid aggregates, interface hepatitis
Pathophysiology: unlike chronic HepB, anti-HCV doesn’t kill (neutralize) virus; but also unlike HBV, HepC can be cured (in about 75%), since no virus in nucleus
Treatment/Notes: PEG interferon, ribavarin, (+boceprevir/telaprevir in genotype 1); SNP encoding interferon = 2x change in response

Question 6

Alcoholic Hepatitis/ASH (Alcoholic Steatohepatitis)
Fatty Liver Disease
Liver

Answer 6

Epi/MOI: decades of alcohol use; “Make a toAST”
Signs/Symptoms/Findings: acute jaundice, liver failure, hepatomegaly, ascites, encephalopathy; increased AST+ALT, AST:ALT ratio >2:1; PMNs, ballooned hepatocytes, Mallory bodies, centrilobular macrosteatosis
Pathophysiology: acetaldehyde (toxic metabolite of alcohol) damages central hepatocytes, leads to production of triglycerides; some degree of fibrosis but generally not cirrhotic; can see portal HTN from hepatic swelling
Treatment/Notes: abstinence from alcohol, banana bag (electrolytes), steroids (esp if discriminant function > 32 which = poor prognosis), pentoxifylline (anti-TNF), need 6 month abstinence for transplant

Question 7

Non-Alcoholic Fatty Liver (NAFL)
Fatty liver disease
Liver

Answer 7

Epi/MOI: metabolic syndrome, M>F, 40-60 yo
Signs/Symptoms/Findings: same as alcoholic steatohepatitis (ASH) except mixed PMNs + lymphos, AST:ALT lipid peroxidation, cytokine release, damage to cell membranes + mitochondria
Treatment/Notes: less cirrhosis risk than ASH; treat with weight loss, exercise, glycemic/lipid control, pioglitazone, vitamin E

Question 8

Non-alcoholic steatohepatitis (similar to NAFL)

Answer 8

see NASH

Question 9

Hemachromatosis
Genetic dzs
Liver

Answer 9

Epi/MOI: M>F (due to periods), N.Europeans
Signs/Symptoms/Findings: “bronzing diabetes,” HCC, cirrhosis, cardiomyopathy; transferrin saturation (TIBC) > 50% in F, > 60% in M
Pathophysiology: HFE mutation (C282Y +/+ or H63D/C282Y) results in decreased hepcidin, which is usually inhibitor of absorption, recycling, storage
Treatment/Notes: phlebotomy, liver transplant if bad; can also see iron overload due to causes other than HFE mutation

Question 10

Wilson’s Disease
Genetic disease
LIver

Answer 10

Epi/MOI: AR, 1/30K, 2-40 yo
Signs/Symptoms/Findings: Kayser-Fleischer rings, decreased ceruloplasmin, increased urinary Cu, AST +ALT > 2.2, renal dz
Pathophysiology: ATP7B on chromosome 17 encode metal-transporting ATPase, mutation results in excessive copper in liver and brain
Treatment/Notes: chelation, penicillamine, zinc, transplant if bad

Question 11

Alpha-1-Antitrypsin deficiency
Genetic diseases
Liver

Answer 11

Epi/MOI:
Signs/Symptoms/Findings: biopsy: (+)PAS granules; Labs: decreased alpha1 antitrypsin
chronic hepatitis, cirrhosis
Pathophysiology: SERPINA/PI*Z +/+ leads to alpha1 antitrypsin getting trapped within ER of hepatocytes
Treatment/Notes: smoking cessation, pneumovax, alpha1 antitrypsin, manage chronic liver dz, transplant

Question 12

Autoimmune Hepatitis (AIH)
Autoimmune
Liver

Answer 12

Epi/MOI: F>M, 4:1
Signs/Symptoms/Findings: acute hepatitis (30%), occ fulminant, 34% asymptomatic; increased ALT + AST, IgG, gamma globulin; plasma cell infiltrate + interface hepatitis
Pathophysiology: 97% are Type 1: anti-smooth muscle Ab (SMA) and/or ANA; Type 2: anti-ILKM1, affects kids 2-14 yo
Treatment/Notes: prednisone + azathioprine, 10 year survival 90% but 3 year relapse 90%; long-termtreatment usually necessary, transplant

Question 13

Overlap syndromes
Autoimmune
LIver

Answer 13

Epi/MOI: F>M, 4:1
Signs/Symptoms/Findings: acute hepatitis (30%), occ fulminant, 34% asymptomatic, increased ALT + AST, IgG, gamma globulin; plasma cell infiltrate + interface hepatitis
Pathophysiology: autoimmune hepatitis + (primary biliary cirrhosis or primary sclerosing cholangitis)
Treatment/Notes: prednisone + azathioprine, 10 year survival 90% but 3 year relapse 90%; long-term treatment usually necessary, transplant

Question 14

Primary Biliary Cirrhosis (PBC)
Autoimmune
LIver

Answer 14

Epi/MOI: F>M, other autoimmune dzs
Signs/Symptoms/Findings: (+) AMA, fatigue, pruritus, cirrhotic symptoms, chronic cholangitis
Pathophysiology: AMA (anti-mitochondrial antibodies) vs. small intrahepatic bile ducts
Treatment/Notes: ursodeoxycholic acid; cholestyramine for pruritus

Question 15

Primary Sclerosing Cholangitis (PSC)
Autoimmune
Liver

Answer 15

Epi/MOI: M > F 3:1, 20s-30s, 80% IBD
Signs/Symptoms/Findings: really increased alk phos + total bilirubin, increased ALT + AST, (+)p-ANCA, ANA, SMA, (-) AMA; onion-skin fibrosis on biopsy; beads on a string ERCP
Pathophysiology: ANCA>ANA>SMA vs. both intrahepatic and extrahepatic bile ducts
Treatment/Notes: median survival 12 years; transplant is only way to improve; watch for colon cancer, cholangiocarcinoma