Liver

Alcoholic liver disease, fatty liver disease, Hepatitis, Cirrhosis

protein synthesis (clotting factors), gluconeogenesis, hemolysis, processing and storing nutrients, Detox

Functions of the liver

RBCs are broken down into heme, heme is converted to unconjugated bilirubin by macrophages, hepatocytes conjugated bilirubin with glucuronic acid (makes it water soluble), Conjugated bili is secreted into the bile – some is taken by the kidneys (urobilin) or the intestines (stercobilin)

Describe the normal bilirubin processing

jaundice

Most obvious symptom of liver dysfunction

Pre-hepatic

What type of jaundice is characterized by more bilirubin is being produce than the liver can process (hemolytic anemia) leading to increased unconjugated bili

Hepatic

What type of jaundice is characterized by the liver being unable to keep up with normal levels of bilirubin production due to dysfunction/damage AND not being able to get conjugated bilirubin out of the liver leading to increased direct and indirect bili (liver disease)

Post-hepatic

What type of jaundice is characterized by bile not being able to be excreted from the body due to obstruction or liver dysfunction leading to increased conjugated bilirubin (liver or biliary disorder)

increased indirect, increased total bili

What do the labs look like for Pre-hepatic jaundice

increased total bili, increased direct, increased indirect, dark urine, increased ALT/AST

What do the labs look like for hepatic jaundice

Increased total bili, increased direct, dark urine, pale stools, increased ALP, increased ALT/AST

What do the labs look like for post-hepatic jaundice

Swelling leads to bile duct obstruction

Why can hepatitis lead to post-hepatic jaundice as well as hepatic jaundice?

Tylenol, EtOH, niacin, tetracyclines, valproic acids, statins

Which drugs cause DIRECT hepatotoxicity?

Amio, ASA, carbamazepine, Fluoroquinolones, isoniazid, phenytoin

Which drugs have idiosyncratic reactions that lead to liver damage?

Alcohol-related liver disease

Acute/chronic inflammation and parenchymal necrosis of the liver due to EtOH toxicity that can lead to fatty liver disease and cirrhosis

Fatty streaks occur with heavy drinking but is reversible with cessation, inflammation (EtOH hepatitis) and early fibrosis, Irreversible fibrosis and cirrhosis

Run me through the stages of Alcohol-related liver disease

50g+ of EtOH daily for 10yr+, chronic viral hepatitis, obesity, other hepatic toxic agents

Risk factors for Alcohol-related liver disease

LFT, CBC, U/S

55 y/o male presents to the clinic for weight loss. He states that he “just hasn’t felt like eating,” he also notes nausea and abdominal fullness. Hx is positive for a 1/5 of Titos DAILY. On a physical exam you note jaundice, hepatomegaly, and RUQ tenderness. What diagnostics you want?

quit dranking, no hepatoxic drugs, supportive/symptomatic care

55 y/o male presents to the clinic for weight loss. He states that he “just hasn’t felt like eating,” he also notes nausea and abdominal fullness. Hx is positive for a 1/5 of Titos DAILY. On a physical exam you note jaundice, hepatomegaly, and RUQ tenderness. Labs are as follows elevated AST/ALT (ratio is over 2), leukopenia, thrombocytopenia, elevated direct and indirect bilirubin. Abdominal U/S shows echogenicity. What is your treatment plan (let’s say its mild-moderate)

quit dranking, corticosteroids, Pentoxifylline (increased O2), N-actelycysteine, Supplemental nutrition (if necessary)

55 y/o male presents to the clinic for weight loss. He states that he “just hasn’t felt like eating,” he also notes nausea and abdominal fullness. Hx is positive for a 1/5 of Titos DAILY. On a physical exam you note jaundice, hepatomegaly, and RUQ tenderness. Labs are as follows elevated AST/ALT (ratio is over 2), leukopenia, thrombocytopenia, elevated direct and indirect bilirubin. Abdominal U/S shows echogenicity. What is your treatment plan (let’s say its severe)

progress to cirrhosis (40%), increased risk of hepatocellular carcinoma

What is the prognosis of Alcohol-related liver disease

viral hepatitis, NASH, Biliary tract disease, pancreatitis, Viral syndrome

Alcohol-related liver disease DDX

Fatty liver disease

What type of liver disease is associated with excess fat accumulation due to impaired lipid metabolism, insulin resistance, and oxidative stress

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH)

What are the types of fatty liver disease

obesity, DM type II, metabolic syndrome, hyperlipidemia, HTN, excessive alcohol consumption

Risk factors for Fatty liver disease

LFTS, lipids, fasting glucose, HbA1c, U/S (1^st line), MRI or CT, Liver biopsy (gold standard but rarely needed)

57 y/o male presents to the clinic for fatigue and malaise. PMHx is positive for hyperlipidemia. On a physical exam you note jaundice, hepatomegaly, and RUQ tenderness. What diagnostics you want?

Lose some weight and exercise, Vitamin E, Pioglitazone (for NASH), GLP-1/SGLT-2 (if DM or obese), NO drugs or alcohol

57 y/o male presents to the clinic for fatigue and malaise. PMHx is positive for hyperlipidemia. On a physical exam you note jaundice, hepatomegaly, and RUQ tenderness. Labs are as follows elevated ALT/AST, U/s reveals liver echogenicity. What’s the plan team?

liver fibrosis, cirrhosis, hepatocellular carcinoma, CVD (NAFLD), end-stage liver disease

Complications of fatty liver disease

Hepatitis A

Which type of hepatitis is characterized by fecal-oral transmission, 30 day incubation period BUT present in feces 2 weeks before clinical illness and tends to resolve with low issue?

international travel (40%), exposure to world traveler, contaminated food/water, crowded areas with poor sanitation

Risk factors for hepatitis A

CBC, LFTs, UA, Hepatitis serology

48 y/o male presents to the ER for flu-like symptoms of fatigue, loss of appetite, N/V/D, pale stools, and muscle aches. Vitals are stable except for a fever of 103.9. On a physical exam you note RUQ pain, hepatomegaly and jaundice. What diagnostics you want?

Thug it out (supportive care with rest)

48 y/o male presents to the ER for flu-like symptoms of fatigue, loss of appetite, N/V/D, pale stools, and muscle aches. Vitals are stable except for a fever of 103.9. On a physical exam you note RUQ pain, hepatomegaly and jaundice. Labs are as follows WBCs low with large atypical lymphocytes, ALT/AST elevated, Bilirubin and ALP are slightly elevated, UA shows proteinuria and bilirubinuria. Anti HAV IgM and IgG are both positive. What is your treatment plan?

prior HAV vax or infection

If only Anti-HAV IgG is positive this means…

encephalopathy (ammonia UP), coagulopathy (INR UP)

Which hepatitis patients require hospitalization or in some cases a liver transplant?

recover in 3 months, fulminant is uncommon unless chronic hep C

Prognosis for Acute Hep A

Inactivated (no immunosuppressed peeps), can use as post-exposure prophylaxis if 1-40 y/o (if older 40 add Ig)

Tell me about the Hep A Vax

Hep E

Which type of hepatitis is characterized by fecal-oral, blood and perinatal transmission and is self-limited (15-60 days) and uncommon in the US?

Acute Hep B

Which type of hepatitis is characterized by blood, saliva, semen, vaginal, and vertical transmission, incubates for 6 weeks to 6 months, and has decreased due to a subunit vaccine?

Sex, IV drug use, healthcare workers, incarceration, STDs

Risk factors for Hep B

Hospitalization, antiviral therapy (tenofovir/entecavir if elevated INR, jaundice for 4 weeks, acute liver failure - stop when HBsAG is negative 2× 4weeks apart),

37 y/o male presents to the ER for flu like symptoms of fatigue, loss of appetite, and Nausea. Social Hx is positive for heroin use. On a physical exam you note jaundice, hepatomegaly, and RUQ pain. WBCs are normal except for lymphocytes which are elevated, AST and ALT are markedly elevated, PT is prolonged, Anti-HBc IgM and HBsAG are positive. What is your treatment plan?

HBsAG

Which Hep B serology am I describing - found on the virus’ outer shell and is an early sign of infection (acute or chronic HBV)

Anti-HBs

Which Hep B antibody am I describing - antibody on the outer shell of the virus shows immunity from vax or previous exposure

Anti-HBc

Which Hep B antibody am I describing - Antibody to the protein found INSIDE the virus, active infection or previous exposure (not vax - subunit vax aren’t taken into the cell for processing)

HBeAg

Which Hep B antibody am I describing - virus is actively replicating and may not be present in early infection

Anti-HBe

Which Hep B antibody am I describing - antibody to the e antigen that differentiates early from diminishing/sub-acute infection

Elevated AST/ALT for 6+ months, persistence of HBsAG for 6+ months

What indicate the progression of acute hep B to chronic?

Depends on presence of cirrhosis, ALT and HBV levels, some patients may get immediate anti-virals

Game plan for Chronic Hep B

cirrhosis, liver failure, hepatocellular carcinoma

Complications of chronic hep B

Hep B Ig followed by vaccine series (vaccine protection wanes after 20 years - check titer)

Tell me about HBV post-exposure prophylaxis

Test all pregnant women for HBsAG, start anti-virals in 3rd trimester, C-section + Hep B Ig

Prevention of Hep B vertical transmission

Hepatitis C

Which type of hepatitis is transmitted via blood and incubates for 6-7 weeks

IV drug use (50%), body piercing, tattoos, hemodialysis, incarceration, HIV

Risk factors for Hep C

Enzyme Immunoassay (1st line), HCV RNA Assay (confirmatory), LFTs (ALT and AST 7x normal is CDC diagnostic criteria)

28 y/o male presents to the clinic for a regular check up. While collecting a hx he notes that he recently got a stick and poke tattoo and has been feeling “kinda icky” since then. On physical exam you note RUQ tenderness and hepatomegaly. What labs you want queen?

DAAs (antivirals based on viral genotype)

What is the treatment plan for hep C?

Peeps who have done IV drugs, long term hemodialysis, chronic liver disease, HIV, born between 1945-1965 (1 time only - less screening in blood transfusion)

Who gets screened for Hep C?

Men, EtOH/tobacco users, acute HCV at under 40 y/o, concurrent fatty liver (steatosis)

Which patients which chronic Hep C have an increased risk of progression to cirrhosis?

hepatitis D

Which hepatitis requires an associated with hep B and is primary seen in patient from Africa, Europe, Asia, Brazil?

Fulminant hepatitis with rapid progression to cirrhosis

Chronic Hep B + acute Hep D =

hepatocellular carcinoma

Hep D patients have an increased risk of

Mono, HSV, drug-induced liver disease, flue, parasitic liver infection, biliary disease

DDX for acute hepatitis

Cirrhosis

The result of hepatocellular injury with fibrosis and regenerative nodules that is the 12th leading cause of death in the US

Chronic viral hepatitis, Alcohol (female 4 drinks/day, male 6 drinks/day), drug toxicity, autoimmune disorders, metabolic liver disease (type II DM, obesity)

Risk factors for Cirrhosis

Compensated, Compensated with varices, Decompensated (ascites, encephalopathy, jaundice, etc)

Stages of Cirrhosis

Hepatocyte dysfunction, fibrosis, portal HTN, portsystemic dysfunction

What is the pathogenesis of cirrhosis?

Fatigue, disturbed sleep, muscle cramps, weight loss

What are the early signs of cirrhosis?

Spider angiomas, easy bruising, glossitis, cheilitis, jaundice, hepatomegaly with nodular edge, splenomegaly, fever due to infection, hematemesis, Ascites, pleural effusions, peripheral edema, asterixis (flapping tremor), delirium, coma

What might you find in a physical exam for cirrhosis?

AST/ALT UP (unless in the endstage), ALP UP, Bili UP, Albumin decreased, PT/INR prolonged, macrocytic anemia, leukopenia, thrombocytopenia

What do the labs look like for cirrhosis?

Abdominal U/S

What is the 1st line imaging study for cirrhosis?

Liver biopsy

What is the gold standard for Cirrhosis diagnosis - (rarely used if we have lab and u/s data that correlates)

NO EtOH or hepatotoxins, adequate nutrients (low protein diet), Vaccines, Propranolol, manage complications (diuretics and sodium restriction), transplant is curative

Treatment plan for Cirrhosis

portal HTN, hepatorenal syndrome, hepatic encephalopathy, Upper/lower GI bleed, portal vein thrombosis, systemic infections, osteoporosis, hepatocellular carcinoma

Complications of Cirrhosis

Distal 1/3 esophagus, umbilical region, rectum, retroperitoneal space, outside of liver

What are the sites for collateral circulation in portal HTN?

caput medusae, hemorrhoids, varices, hepatic encephalopathy, ascites, splenomegaly

Complications of portal HTN

Activation of the RAAS leads to renal vasoconstriction leading to AKI or worsening chronic kidney dysfunction

What is hepatorenal syndrome

discontinue diuretics, IV albumin, 7-14 days of peripheral vasconstriction

Treatment for hepatorenal syndrome

Hepatic encephalopahy

Impaired CNS function due to high levels of ammonia and commonly caused by increased protein in the diet or K+ deficiency

Elevated ammonia + Clinical symptoms (confusion, drowsiness, stupor, coma, asterixis)

Diagnostic criteria for hepatic encephalopathy

Lactulose, rifaxamin

Treatment plan for Hepatic encephalopathy

Hepatitis, alcoholism, NAFLD, hemochromatosis, Wilson’s, celiac disease, primary biliary cirrhosis, heart failure

DDX for cirrhosis