Chronic Hepatitis and Hepatocellular Cancer

Question 1

chronic hepatitis

Answer 1

-Chronic necrosis and inflammation of the liver for more than 3-6 months duration
-Abnormal LFTs
-Histologic findings
-Categorization:
-Etiology**- MC
-Grade of portal, periportal or lobular inflammation- Mild, moderate or severe
-Stage of fibrosis- None, mild, moderate, severe, cirrhosis

Question 2

causes of chronic hepatitis

Answer 2

-Viral: HBV, HCV, HDV
-Autoimmune hepatitis
-Medications (INH, nitrofurantoin, others)
-Wilson’s disease
-Alpha 1 antitrypsin disease- associated with emphysema
-Hemochromatosis- iron metabolism
-Primary Biliary Cirrhosis/Cholangitis

Question 3

chronic hepatitis B

Answer 3

-Chronic HBV- 8 genotypes and 4 subtypes
-257 mill people worldwide and estimated 2.2 mill in US
-Risk of progression to cirrhosis-
-Risk of hepatocellular cancer in those with cirrhosis
-Prognosis depends on histology/replication- HBeAg +

Question 4

initial evaluation for HBV

Answer 4

-family history- important for vertical transmission
-test for HBV replication
-hepatocellular carcinoma screenings- US
-rule out coinfections - HDV
-fibrosis screenings- vibration controlled transient elastography (density), liver bx, serum fibrosis panel

Question 5

chronic hepatitis B variations in presentation

Answer 5

-Asymptomatic (unless have decompensated cirrhosis or have extrahepatic manifestations)
-Nonspecific symptoms ie. fatigue
-Exacerbations of infection which may be asymptomatic, mimic acute hepatitis, or manifest as hepatic failure
-wide variation in presentation- asymptomatic to failure
-Physical examination:
-Normal
-Stigmata of chronic liver disease- caput medusa, varices
-Decompensated cirrhosis-jaundice, splenomegaly, ascites, peripheral edema, and encephalopathy
-liver flap- hands flap

Question 6

extrahepatic complications of chronic HBV

Answer 6

-Due to circulating hepatitis B antigen–antibody immune complexes**
-Two major extrahepatic complications of chronic HBV are:
-1. Polyarteritis nodosa- inflammation of medium sized vessels -> Fever, fatigue, night sweats, loss of appetite, weight loss, and generalized weakness, myalgias and arthralgias
-2. Glomerular disease- membranous nephropathy and less often, membranoproliferative glomerulonephritis- Proteinuria, edema

Question 7

identifying chronic hep B

Answer 7

-Persistence of HBeAg (for a variable period), HBsAg, and HBV DNA in the circulation; anti-HBs is not seen
-Persistence of HBsAg > 6 months after acute infection is indicative of chronic infection
-after 6 months - chronic

Question 8

treatment of chronic HBV (dont need to know drugs names)

Answer 8

-**Who to treat based on circulating virus, HBeAg, LFTs, if have cirrhosis
-Nucleoside or nucleotide analog (entecavir; tenofovir alafenamide; tenofovir disoproxil fumarate) OR Pegylated interferon
-Nontreated patients: follow up varies based on HBeAg, HBV DNA, ALT level
-If have cirrhosis, monitor for HCC and sequela of cirrhosis- US, AFP q 6 mos , EGD
-AFP- liver tumor marker

Question 9

chronic hepatitis D

Answer 9

-Co-infection can increase the severity of acute hepatitis B
-Does not increase risk of chronic hepatitis B
-Superinfection in pt with chronic hep B -Long-term HDV infection is the rule also Worsening of the liver disease
-Treatment: Interferon alpha 2a-relapse common (dont need to know)

Question 10

chronic hepatitis C

Answer 10

-2.4 million in US
-Majority remain asymptomatic and well compensated with no clinical sequelae of chronic liver disease!
-1/3 serum aminotransferases normal
-5 to 30 percent develop cirrhosis over a 20- to 30-year period of time
-Increased risk of hepatocellular ca

Question 11

increased likelihood of progression of liver disease in chronic HCV

Answer 11

-Older age
-Longer duration of infection (most important)
-Advanced histologic stage and grade
-Genotype 1
-Concomitant other liver disorders (alcoholic liver disease, chronic hepatitis B, hemochromatosis, alpha 1-antitrypsin deficiency, steatohepatitis)
-HIV infection
-Obesity (fat in liver aggravates), DM
-Etoh intake >50g

Question 12

clinical findings and extrahepatic complications with HCV

Answer 12

-Similar as chronic hepatitis B
-Fatigue and sleep disturbances mc symptoms
-Jaundice rare
-Extrahepatic complications:
-Hematologic diseases- essential mixed cryoglobulinemia and lymphoma
-Renal disease- membranoproliferative glomerulonephritis
-Autoimmune disorders- thyroiditis
-Dermatologic conditions- porphyria cutanea tarda and lichen planus
-Diabetes mellitus

Question 13

initial evaluation of chronic hep c

Answer 13

-Evaluation of patients with Chronic Hep C is the same as Hep B
-H&P
-FH
-Routine Labs
-Tests for HCV replication and genotype
-Tests to r/o other viral coinfections
-Tests to screen for HCC
-Tests to screen for fibrosis

Question 14

ALT

Answer 14

-not a marker for liver disease

Question 15

treatment of chronic HCV

Answer 15

-F/u monthly
-Quantitative HCV RNA test at week 4 of therapy
-Virologic response to treatment- viral load at 12 weeks following the cessation of therapy
-HCC screening for all with h/o Chronic Hep C with advanced fibrosis:
-LFTs, U/S, AFP q 6 mos
-EGD

Question 16

autoimmune hepatitis

Answer 16

-Chronic hepatitis of unknown etiology
-Characterized by immunologic and autoimmunologic features
-Autoantibodies and a high serum globulin concentration
-Any sex/any age- commonly in middle aged women
-Can follow viral illness
-Onset is insidious in most

Question 17

autoimmune hepatitis presentation varies

Answer 17

-Asymptomatic patients vs debilitating symptoms
-Physical findings range:
-Normal
-Hepatomegaly, splenomegaly
-Stigmata of chronic liver disease- guy in the photo
-+/- jaundice
-Signs associated with other autoimmune disorders

Question 18

autoimmune hepatitis diff dx

Answer 18

-Chronic viral hepatitis
-Primary biliary cirrhosis/cholangitis
-Primary sclerosing cholangitis
-Wilson disease
-Hemochromatosis
-Drug-induced liver disease
-α1-Antiprotease (antitrypsin) deficiency

Question 19

autoimmune hepatitis: for adults with compatible clinical or lab features obtain serum…(just focus on ANA and ASMA)

Answer 19

-antinuclear antibodies (ANA)*
-anti-smooth muscle antibodies (ASMA)*
-anti-mitochondrial antibodies (AMA)
-anti-liver/kidney microsomal-1 antibodies (anti-LKM-1)
-either an immunoglobulin G (IgG) or gamma globulin level
-For patients who are negative for above, obtain:
-anti-soluble liver antigen/liver pancreas antibody (anti-SLA/LP)
-anti-actin antibodies
-typical perinuclear anti-neutrophil cytoplasmic antibodies

Question 20

autoimmune hepatitis labs

Answer 20

-High Bili
-High AST and ALT
-Classic Type 1:
-***ANA and/or Anti Sm Muscle +
-Increased serum Gamma Globulin
-Anti-HCV can be false +

Question 21

autoimmune hepatitis dx and tx

Answer 21

-DX: Liver bx to establish dx/severity
-Treatment: (can be self limiting) Prednisone +/- azathioprine
-Vaccinate for Hep A and B
-If cirrhosis is monitored for HCC:
-LFTs
-US, AFP q 6 mos if cirrhosis
-EGD

Question 22

primary biliary cholangitis

Answer 22

-Rare
-Formally known as primary biliary cirrhosis
-An autoimmune disease -> environmental trigger
-90 to 95% female, and most patients 30-65 yo (often in 40s-50s)
-Usually incidental finding of elevated LFTS

Question 23

GGT

Answer 23

-differentiate if its bone are liver pathology -> high = liver

Question 24

findings with primary biliary cholangitis

Answer 24

-Symptoms: 50-60% asymptomatic -> If any-pruritis, fatigue mc
-cholesterol deposits
-PE:-depends on stage
-Labs:
-High Alk Phos* (fractionate) >1.5 nl
-** High AMA ≥1:40
- +/- high LFTS,bili
-Imaging: MRCP-shows hepatic biliary duct disease

Question 25

primary biliary cholangitis dx and tx

Answer 25

-Dx: High AMA, high Alk Phos, Bx -Treatment: Ursodeoxycholic acid and Replacement of fat-soluble vitamins if deficient -Monitor: LFTs, Bone density (associated), TFTs -If cirrhosis: -US, AFP q 6 mos -EGD

Question 26

primary sclerosing cholangitis

Answer 26

-intra AND EXTRAHEPATIC BILE DUCT -large ducts- youre able to stent these -males>females -associated with- inflammatory bowel disease (ulcerative colitis)

Question 27

primary biliary cholangitis vs primary sclerosing cholangitis

Answer 27

primary biliary cholangitis -female > male -intrahepatic bile ducts -small ducts -associated with sjogrens syndrome primary sclerosing cholangitis -intra AND EXTRAHEPATIC BILE DUCT -large ducts- youre able to stent these -males>females -associated with- inflammatory bowel disease (ulcerative colitis)

Question 28

hemochromatosis

Answer 28

-Increased accumulation of iron as hemosiderin in organs especially liver -Autosomal recessive disorder- Homozygous for C282Y2 mutation mc -*Not all who are homozygous for HFE C282Y variant develop iron overload and clinical HH. Other genetic and/or environmental factors, medical conditions, dietary iron intake, and blood loss play a role.

Question 29

signs and symptoms of hemochromatosis

Answer 29

-Nonspecific symptoms-fatigue, lethargy, apathy -Often asymptomatic or nonspecific symptoms until >40yo in males and after menopause in females (periods balance females out up until menopause) -Symptoms attributable to iron overload: -Heart failure, arrhythmias, type 2 diabetes, hypogonadism, cognitive changes, arthropathy, bronze-colored skin -Untreated, can develop cirrhosis, hepatocellular cancer (HCC)

Question 30

hemochromatosis labs

Answer 30

-Mildly elevated LFTs -High Ferritin/iron/transferrin saturation -HFE gene mutation -high iron -> HFE gene mutation+ -> phlebotomy

Question 31

alcoholic liver disease

Answer 31

-Excessive alcohol can cause steatosis (fat deposition in liver), steatohepatitis (irritation due to fat in liver) and cirrhosis -One of the most common causes of cirrhosis in the US -Often reversible -Acute or chronic inflammation and parenchymal necrosis -Typically drink 100g/day for > 20 years - Risk increases if obese or liver ds -Rule out other causes of liver disease-acute and chronic -viral, medication-induced, biliary obstruction, Wilson’s ds, autoimmune hepatitis, alpha 1 antitrypsin, NAFLD, etc

Question 32

alcoholic liver disease signs and symptoms

Answer 32

-Varies: -asymptomatic hepatomegaly (common) to rapidly fatal acute illness or end stage cirrhosis - +/- : -Anorexia -Nausea -Hepatomegaly -Jaundice -Severe ds: Abdominal pain/tenderness, splenomegaly, ascites, fever, encephalopathy

Question 33

alcoholic liver disease labs

Answer 33

-AST>ALT** usually by 2x rarely >300 -> only time this happens (SLOSHED) -High alk phos, GGT, bilirubin -Can have: -Anemia - damaged bone marrow, poor diet (B12, folate), varices -Thrombocytpenia in 10% -Prolonged PT -Decreased albumin

Question 34

alcoholic liver disease imaging and dx

Answer 34

-Imaging: -US/CT/MRI: -Detects steatosis, cirrhosis, ascites and Can r/o biliary obstruction, mass -Transient elastography Liver Biopsy-often not necessary: -Steatosis: micro- or macrovesicular steatosis -Hepatocellular ballooning with cytoplasmic rarefaction -Infiltration by neutrophils or lymphocytes -Mallory-Denk bodies -Fibrosis -Cholestasis -Bile duct proliferation

Question 35

alcoholic liver disease tx

Answer 35

-ABSTINENCE!!...Fatty liver quickly resolves with abstinence -Nutritional support -Adequate calories and protein -Vitamins/herbs (careful) -> limit -Vaccinate -Meds: Severe ds: -Methyprednisone -Pentoxifylline -Screen for comp if have cirrhosis-HCC, varices -Liver transplantation-controversial

Question 36

nonalcoholic fatty liver disease (NAFLD)

Answer 36

-Hepatic steatosis, with or without inflammation and fibrosis. -Subdivision: nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). -Most common liver disorder in western world -Risk factors: -Obesity >40%** -Diabetes >20% -High TG >20% -Meds: Steroids, amioderone, diltiazem, tamoxifen, antiretroviral therapy, endocrinopathies, starvation and refeeding, TPN

Question 37

nonalcoholic fatty liver disease signs and symptoms / labs

Answer 37

-Most asymptomatic or mild RUQ pain -Labs: -NL in up to 80% in NAFL (steatosis) -Mildly elevated aminotransferases (NASH) and alk phos -ALT>AST -R/o other causes: -Anti-hepatitis C -Hepatitis B surface antigen, surface antibody, and core antibody -Plasma iron, ferritin, and total iron binding capacity -Serum gammaglobulin level (IgG), AMA, ASMA, ANA, ceruloplasmin, alpha 1 antitrypsin

Question 38

nonalcoholic fatty liver disease dx

Answer 38

-Diagnosis of NAFL requires all of the following: -Hepatic steatosis by imaging or biopsy- US, CT, MRI -Exclusion of significant alcohol consumption -Exclusion of other causes of hepatic steatosis -Absence of coexisting chronic liver disease -Normal LFTS*** -Monitoring for fibrosis and Inflammation -Elastography (vibration-controlled transient elastography, ultrasound shear wave or magnetic resonance elastography) OR -Serum fibrosis markers -LFTS

Question 39

nonalcoholic fatty liver disease tx and referral

Answer 39

-Weight loss-5-7% body wt -Diabetes tx -Hyperlipidemia tx -Vaccinate -Vitamin E if NASH -Referral: -LFTS remain elevated despite loss of ≥5 percent of body weight -Clinical features of advanced liver disease (eg, ascites, splenomegaly, jaundice) -Advanced Inflammation/fibrosis on liver biopsy -Advanced fibrosis on a noninvasive liver assessment -MELD> 10-refer for transplant

Question 40

cirrhosis

Answer 40

-14th leading cause of death worldwide -End result of hepatocellular injury from chronic inflammation or cholestasis -Fibrosis and nodular regeneration -Most Common Causes in US (80%): Chronic Hep C, alcohol, NASH (can be anything tho)

Question 41

classification of cirrhosis

Answer 41

-histologic is MC -Micronodular -Macronodular -Mixed forms -Descriptive terms rather than separate diseases -Each form may be seen in the same patient at different stages of the disease

Question 42

determining etiology of cirrhosis

Answer 42

-Influences treatment decisions, counseling of family, predicts prognosis. -Initial evaluation: history, physical and obtaining routine blood tests -Findings from the initial evaluation are used to guide additional testing-bloodwork, imaging, bx -Referred to liver specialist

Question 43

common causes of cirrhosis

Answer 43

-Alcohol and Viral hepatitis (Hepatitis B, C, D) -Steatohepatitis -Metabolic and/or genetic: Hemochromatosis, Wilson's disease, a1-antitrypsin deficiency -Cholestatic and/or autoimmune- Primary sclerosing cholangitis, Primary biliary cirrhosis/cholangitis -Drug-induced

Question 44

clinical features of cirrhosis result from

Answer 44

-Hepatic cell dysfunction -Portal hypertension -Portosystemic shunting

Question 45

routine lab findings in cirrhosis

Answer 45

-Absent or minimal in early or compensated cirrhosis -Elevated LFTs, Bili -Low albumin -Prolonged prothrombin time -Anemia -Low vs high WBC -Thrombocytopenia

Question 46

cirrhosis dx and complications

Answer 46

-Suggestive on US -Liver Bx (gold std but not always necessary) -Elastography vs fibrosure -Complications: -UGI bleeding -Varices, portal hypertensive gastropathy, or gastroduodenal ulcer Ascites -Spontaneous bacterial peritonitis -Hepatorenal syndrome -Hepatic encephalopathy -Carcinoma of the liver

Question 47

cirrhosis tx

Answer 47

-Treat the underlying disorder and complications -Healthy diet, no alcohol -Vaccinate -Regular surveillance and early detection of hepatocellular failure- Check US and AFP q 6 mos, EGD -Periodic MR Elastography -End stage liver ds MELD >10: transplant evaluation

Question 48

cirrhosis: prevent decompensation

Answer 48

-Control of ascites: -Low Na, restrict fluid, diuretics, TIPS -Avoid ace inhibitor, NSAIDS -Avoidance drugs poorly metabolized by the liver -Avoid ASA and NSADIS (bleeding) -Prompt treatment of infection (SBP)- E. coli and pneumococci most common -> IV cefotaxime -Prompt variceal hemorrhage treatment- prophylaxes prior

Question 49

hepatic encephalopathy

Answer 49

-Disordered CNS function -Stages: -Mild confusion -Drowsiness -Stupor -Coma -Amonia is most measurable toxin but not solely responsible -Diagnosis is based on characteristic symptoms and signs including asterixis -Tx: Daily protein intake is 1.2 to 1.5 g/kg IBW -Lactulose (causes diarrhea, poop it out), neomycin

Question 50

hepatocellular carcinoma

Answer 50

-Arise from parenchymal cells -85% associated with cirrhosis -Chronic hepatitis B and C infections, ETOH, NASH** hemochromatosis -Men > women

Question 51

hepatocellular carcinoma S&S, labs, dx, staging

Answer 51

-S&S- Clinical recognition may be difficult -> Deterioration of the known cirrhotic -Labs: +/-High LFTS, INR, labs suggestive of cirrhosis etiology High AFP (alpha-fetoprotein) sensitivity 66%,specificity 80% -Diagnosis: -Mass/nodules on US -CT and MRI with contrast used -Liver bx -Staging: PET Scan

Question 52

staging of hepatocellular carcinoma

Answer 52

-TNM -PLUS -Child-Pugh score: -5 factors, first 3 are blood tests: -Bilirubin -Albumin -Prothrombin time -Ascites -Encephalopathy -Determines severity of liver disease

Question 53

hepatocellular carcinoma tx

Answer 53

-depend on the following: -Size, number, and location of tumors -Presence or absence of cirrhosis -Operative risk based on extent of cirrhosis and comorbid ds -Overall performance status -Portal vein patency -Presence or absence of metastatic disease -United States 5-year survival rate is 20% (33% if localized) -Screening and Prevention: -AFP and US every 6 mos if have chronic liver disease/cirrhosis -Risk is 3-5% year with cirrhosis

Question 54

anti HBc positive and anti HBs positive

Answer 54

-prior infection -not just vaccinated bc the core is positive -anti-HBc neg and anti HBs positive- vaccine

Question 55

HBsAg positive, anti-HBc positive, IgM anti-HBc positive

Answer 55

-IgM- means acute

Question 56

HBsAg positive, anti-HBc positive, IgM anti-HBc neg, anti-HBs negative

Answer 56

-surface antigen positive- active -IgM neg- chronic