Diseases of the Liver

Autoimmune Hepatitis: Extrahepatic manifestations are common: -Arthritis -Sjogren syndrome -Thyroiditis -Nephritis -Ulcerative colitis -Coombs-positive hemolytic anemia What is there an increased risk for? (2)

cirrhosis and CA

Acute Hepatitis C: What is the modes of infection? (4) Co-infection in HIV positive patients is common. No vaccination available. High risk of conversion to chronic state. Significantly increased risk of what 2 liver diseases?

50% by IV drug use; transfusion of infected blood, body piercing/tattoos/hemodialysis, STI and maternal transmission possible (low risk) cirrhosis and carcinoma

Acute Hepatitis C: The incubation period is ___-___ weeks. Clinical illness is mild or often totally asymptomatic. Waxing/waning elevations of what 2 liver lab values? Natural history is either spontaneous clearance of the virus or progression to chronic disease. Lab findings: Hepatic Panel (LFTs) similar to HAV & HBV -Order Anti-HCV EIA, if result if positive/equivocal, obtain HCV RNA test (PCR). Presence of HCV RNA is confirmatory. If HCV is confirmed ---> obtain renal panel and UA ---> to observe for proteinuria, hematuria, and/or reduction in GFR

6-7 weeks AST/ALT

Acute Liver Failure: By definition, patients with acute liver failure have severe acute liver injury due to hepatic encephalopathy and prolonged prothrombin time (INR >________). Other symptoms: fatigue, malaise, lethargy, anorexia, N/V, RUQ, Pruritis, Jaundice, ABD distenstion from ascities Laboratory Findings: -INR >_______ -Markedly elevated aminotransferase levels -Elevated bilirubin and ALP -_________ platelet count (<150k) -Elevated ammonia -Elevated amylase and lipase -Elevated BUN and creatinine

>1.5 >1.5 low

Jaundice AKA Icterus is the result of the accumulation of bilirubin in body tissues. Not clinically apparent until serum bilirubin is >______ mg/dL. Where does jaundice appear first? Jaundice Characterization: Plasma elevation of predominantly unconjugated (indirect) bilirubin due to what three processes?

>2 conjunctiva (scleral icterus) overproduction of bilirubin, impaired bilibrubin uptake by the liver, abnormalities of bilirubin conjugation

Hepatitis E: Major cause of acute hepatitis throughout what 4 geographic regions? ---> consider in patients who traveled to endemic areas. What is the transmission? What type of outbreaks? Mild-moderate clinical illness. Who is this severe in and common to progress to fulminant hepatitis?

Central and SE Asia, Middle East, and North Africa Fecal-Oral ---> waterborne outbreaks from contaminated water pregnant patients

Chronic Viral Hepatitis: Infection with HBV (+/- HDV) or HCV for greater than ______ months. -What lab value will be persistently elevated? (2) -Persistent presence of HBsAg and anti-HBc, anti-HCV -Or histologic findings on liver biopsy In the absence of concomitant cirrhosis, patients may be asymptomatic.

3 months AST/ALT

Hepatits A S&S: Occurs ~____ weeks post exposure. -Malaise, myalgia, arthralgia, easy fatigability, Upper respiratory symptoms, N/V, Anorexia ---> smokers develop distaste for cigarettes, Low grade fever ---> fever breaks and onset of jaundice after 5-10 days. Presentation may initially be mistaken for what 2 viral diseases?

4 weeks viral gastroenteritis or a viral URI

Jaundice Clinical Findings: Conjugated Cholestatic syndromes: Jaundice will be present. How is the stool? What other unique symptom? Conjugated Biliary obstruction Clinical Findings: Jaundice is present: RUQ pain. If they have weight loss, suspect what? What unique symptom does this share with Conjugated Cholestatic syndrome? How is the urine? How is the stool?

light colored stool; pruritis carcinoma; pruritus; dark urine; light colored stools (acholic stools)

LFT Patterns: Cholestatic Pattern: Disproportionate elevation inthe ALP compared with serum aminotransferases. ALP is an enzyme that transports metabolites across cell membranes. What 2 diseases are the most common cause of pathological elevation of ALP? Hepatic ALP is present on the surface of _________ epithelium -----> Cholestasis enhances the synthesis and release of ALP, and accumulating bile salts increase its release from the cell surface.

liver and bone diseases bile duct epithelium

Acute Liver Failure: Admission for inpatient management: -IV fluid and electrolyte replacement -Dietary monitoring -Gastroprotective measures (prevention of stress gastropathy) ----> what 2 drugs can we give? -Other treatments as indicated based on etiology

IV PPI or H2

Bile: Each day ~800-1000 mL of bile is secreted by hepatocytes. Bile is yellow, brownish, or olive-green liquid. A pH of 7-6-8.6 Consists of: Bile solids (bile salts, phospholipids, cholesterol, bilirubin), water, and electrolytes. What does the gallbladder do to bile?

store and concentrate it

Liver Functions: Metabolism of drugs and hormones: -Detoxification of substances such as alcohol and excretion of drugs such as penicillin, erythromycin, and sulfonamides into bile. -Chemically alters or excretes thyroid and steroid hormones, such as what 4 hormones? Excretion of bilirubin: Bilirubin is reabsorbed from broken down RBCs and excreted in bile. Most bilirubin is metabolized in the small intestine by bacteria and eliminated in feces.

T3/T4, estrogen, aldosterone

Acute Hepatitis C: Treatment: Medical Treatment typically initiated after sufficient time to evaluate for spontaneous clearance. Recheck HCV RNA ____ weeks after exposure or after diagnosis if exposure is uncertain. Treatment decisions for acute HCV infection are made by a Hepatologist and are based on patient risk factors. Pharmacotherapy (typical course): What drug for 12-24 weeks (depending on viral genotype)? Prognosis: Clinical recovery typical in ___-___ months. Up to 80% conversion to chronic disease. 30% develop cirrhosis ---> which increases risk for what?

12 weeks Peginterferon weekly for 12-24 weeks 3-6 months hepatocellular carcinoma

Liver Functions: Storage: -What 5 vitamins? -Glycogen -What 2 minerals? Phagocytosis: _______ cells phagocytize aged RBCs, WBCs, and some bacteria

A,D,E,K, B12 Iron and copper Kuppfer

Where is ALT primarily found? Where is AST found? Which one is more specific for hepatic injury? Transaminitis: Elevation in the serum transaminases ---> often found on routine labs in otherwise asymptomatic patients. DDx of etiologies is VAST! Get a thorough history, physical exam to evaluate for hepatic abnormality, repeat labs, hepatitis panel, hepatic US, referral to GI. What ratio of AST:ALT often indicated alcohol related liver disease?

ALT is primarily found in the liver AST is also found in skeletal muscles and erythrocytes ALT elevations are more specific for hepatic injury 2:1 (particularly in light of an elevated GGT)

Acute Hepatitis B: S&S: Acute clinical syndrome is similiar in presentation to HAV infection. Lab findings: Also similiar to HAV but there are greater elevations in what two lab values? Serology: _______________: serologic hallmark of HBV infection ____________: appears in most individuals after clearance of HBsAg and after successful vaccination against hepatitis B. __________: intracellular antigen expressed in infected hepatocytes. not detectable in serum. ___________: appears shortly after HBsAg is detected. During acute infection, anti-HBc is predominantly of IgM class. Detection of IgM anti-HBc usually regarded as an indication of acute HBV infection. IgG anti-HBc persists in patients who recover from acute HBC and those who progress to chronic HBV. _______________: a secretory protein that is processed fromthe pre-core protein. Indicates viral replication and infectivity. Persistance beyond 3 months indicates increased likelihood of chronic HBV. ___________: parallels the presence of HBeAg

AST & ALT Hepatitis B surface antigen (HBsAg) anti-HBs (antibody to HBsAg) Hepatitis B core antigen (HBcAg) Anti-HBc Hepatitis B e antigen (HBeAg) HBV DNA

AST and ALT are enzymes that catalyze the transfer of a-amino groups from aspartate and alanine to the a-keto group of ketoglutaric acid to generate oxyalacetic and pyruvic acids respectively. Both enzymes require Vitamin B6 in order to carry out this reaction, although the effect of Vitamin B6 is greater on ALT activity than that of AST. This has clinical prevelance with what type of liver disease, in whom Vitamin B6 deficiency may decrease ALT serum activity and contribute to the increase in the AST/ALT ratio that is observed in these patients?

Alcoholic Liver disease

Acute Hepatitis A: Significant decrease with HAV vaccination. What is the transmission? What is it associated with? (2) Incubation of _____ days. Viral shedding in feces of infected host for up to ______ weeks prior to onset of clinical syndrome. Low mortality; progression to fulminant disease is rare, unless there is a co-infection with what other hepatitis?

Fecal Oral; Assocaited w/localized outbreaks from contaminated food or water, travel to endemic areas 30 days 2 weeks HCV

Jaundice Treatment Approach: Treatment aimd at underlying etiology. After initial lab testing, patients with jaundice should be referred to who for further testing and evaluation?

GI

Hepatitis D: Defective RNA virus. Causes hepatitis only associated with what hepatitis virus? Usual route of infection is what? Test for in patients who have what hepatitis infection?

HBV ---> specifically only in the presence of HBsAg IV drug use and other routes similar to HBV HBV infection

Acute Hepatitis B: Treatment: -Supportive (as in acute HAV) -Antiviral therapy reserved for patients who develop severe disease -____________ and __________ indicate severe disease requiring inpatient mangement. Prognosis: Clinical illness lasts ____-____ weeks. Complete recovery by ______ weeks. Prevention: Screening of donated blood Sereologic testing in pregnancy Safe sex practices Safe handling of blood and body fluids or contaminated material Vaccination Wash your hands Hepatitis B Immune Globulin: Administered for known exposure; Followed by vacinnation series

Hepatic encephalopathyor coagulopathy 2-3 weeks 16 weeks

Jaundice Lab Work Up: Lab studies: What 4? Radiographs: what modality? ERCP to evaluate bile ducts if you suspect what? What is ERCP and when is it indicated?

Hepatic labs, CBC, CMP, UA Hepatic US Obstruction Endoscopic Retrograde Cholangiopancreatography: An endoscopic technique in which a specialized side-viewing upper endoscope is guided into the duodenum, allowing for instruments to be passed into the bile and pancreatic ducts. Indicated in jaundiced patient suspected of having biliary obstruction.

Jaundice Characterization: Unconjugated hyperbilirubinemia: This is due to what? (hemolytic anemias, hemolytic reactions, hematoma, pulmonary infarction) What is the problem with posthepatitis hyperbilirubemia, Gilbert syndrome, Crigler-Najjar syndrome, Drug reactions)?

Increased bilirubin production Impaired bilirubin uptake and storage

Acute Hepatitis B: What is the mode of transmission? (3) Variable presentation (mild ---> fulminant) risk of conversion to chronic hepatitis. High Risk Groups: Healthcare workers (including staff at hemodialysis centers), IV drug users, Prisoners Screening recommened for high risk groups. The incuabation period is _____ weeks to ______ months. Chronic hepatitis B patients: Have a substantial risk for cirrhosis and hepatocellular carcinoma. Men >>women

Inoculation of infected blood or blood products, sexual contact (virus present in salvia, semen, and vaginal secretions), HBsAg positive mothers may transmit to newborn during delivery. 6 weeks to 6 months

Chronic HCV Antiviral Treatment: Direct-acting and host-targeting antiviral agents. Regimens are based upon virus genotype. What drug can we treat with that has a sustained virologic response rates well above 90%? The problem with this drug is that it is super expensive and medicaid won't cover it.

Ledipasvir + Sofosbuvir (Harvoni)

What is the blood flow entering the liver to the right atrium of the heart? (6)

Oxygenated blood from hepatic artery/nutrient-rich deoxygenated blood from hepatic portal vein ---> hepatic sinusoids --> central vein --> hepatic vein --> inferior vena cava --> right atrium of heart

Liver functions: __________ metabolism: -Hepatocytes deaminate amino acids (remove the amino group) so that the amino group can be used for ATP production or converted to carbohydrates or fat. -An __________ ion is left after amino group is removed. -Also synthesizes most plasma proteins like alpha and beta globulins, albumin, prothrombin, and fibrinogen. Synthesis of bile salts/acids Activation of what vitamin?

Protein metabolism; ammonia (NH3) --> this is converted to urea and then excreted in the urine. Vitamin D (skin, liver, and kidneys participate in synthesizing the active form of Vitamin D)

Acute Hepatitis A: When jaundice develops: Dark urine ---> _______ stools. Clinical symptoms worsen initially followed by progressive improvement. Course of illness is typically ____-___ weeks. Self-limiting and there is no chronic carrier state. Lab Findings: How will AST, ALT, ALP, Bilirubin present on labs? Anti-HAV antibodies appear and the presence of IgM anti-HAV is diagnostic of actue illness. Treatment: Bed rest if needed. Avoid what? (4) Symptomatic care: antiemetic, antidiarrheal, fluids, regular meals

acholic stools; 2-3 weeks elevated ALT, AST, ALP, bilirubin avoid strenuous exercise, work, alcohol, or hepatotoxic meds

Liver Functions: ____________ metabolism: maintenance of blood glucose. -If plasma glucose if low=_____________ -If plasma glucose if high=____________ _________ metabolism: -stores some triglycerides -break down fatty acids to generate ATP -Synthesize lipoproteins (transporters of fatty acids, triglycerides, and cholesterol to and from cells) -Synthesizes cholesterol -Uses cholesterol to make bile salts

carbohydrate metabolism low= liver breaks down glycogen to glucose and release it (glycogenolysis) high= liver converts glucose to glycogen and triglycerides as storage (glycogenesis) Lipid metabolism

Acute Liver Failure: Development of severe acute liver injury without cirrhosis or preexisting liver disease ---> patient does have _________ and impaired synthetic function INR >/=_________. This occurs within _______ weeks of disease. What drug toxicity is the most common cause (45%)? What disease process increases the risk of liver failure?

hepatic encephalopathy; >1.5 8 weeks Acetaminophen; DM

Jaundice Characterization: Plasma elevation of both unconjugated and conjugated bilirubin due to: _____________: i.e. hepatitis, cirrhosis ____________: i.e. choledocholithiasis, biliary atresia, carcinoma. What imaging modality would we order to start the workup with this? Hereditary cholestatic syndromes Often referred to as conjugated hyperbilirubinemia, even though both fractions of bilirubin are elevated.

hepatocellular disease/dysfunction Biliary obstruction; US

Liver Function Tests: This is not actually representative of the function of the liver but instead are actually markers of what 2 things? Commonly included in LFTs are what 6 components? What other 4 markers can elevate the liver?

hepatocellular injury or cholestatic disease Serum aminotransferases (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)); Alkaline Phosphatase; Total Protein; Bilirubin; Albumin Gamma-glutamyl transpeptidase (GGT); Lactate dehydrogenase; Prothrombin Time/INR; Platelets

y-Glutamyl Transpeptidase (GGT) Where is the GGT enzyme present in? (5) The mechanisms of alteration are similar to those with Alkaline phosphatase. Elevated GGT levels can be observed in a variety of nonhepatic diseases, including what 2? The whole spectrum of liver diseases, regardless of cause, may be responsible for altered GGT serum levels. Because of its lack of specificity but high sensitivity for liver disease, GGT can be useful for identifying causes of altered _______ levels. Elevated levels, together with other biochemical abnormalities (AST/ALT ratio >2), may support the diagnosis of what liver disease?

hepatocytes, biliary epithelial cells, renal tubules, pancreas, and intestine COPD and renal failure ALP alcoholic liver disease

Bilirubin is the principal bile pigment. What is bilirubin made from? Bilirubin gets secreted in the bile from the liver. Bilirubin becomes a good measure of liver function (conjugated vs. unconjugated). Bilirubin Steps: 1) RBCs broken down, bilirubin deposited in the bloodstream from hemoglobin. At this point it is considered what? 2) Bilirubin binds to albumin (protein), transported to the liver. What is it at this point? 3) Once in the liver, it is rendered soluble by the conjugation with what enzyme? What is it called now? 4) Transported into bile ducts, then into the intestines. What happens in the intestines?

made from phagocytosis of aged RBCs ---> releases iron and globin that is recycled, and bilirubin 1) free or pre-hepatic bilirubin 2) Insoluble, indirect, hepatic, or unconjugated bilirubin 3) glucuronide; direct, post-hepatic, or conjugated bilirubin 4) bacterial enzymes convert bilirubin to urobilinogen

Jaundice Clinical Findings: Unconjugated Clinical Findings: -How is the jaundice? -Stool color and urine color? -If you have splenomegaly, what is the etiology? Conjugated Hepatocellular Disease Clinical Findings: How will the urine look? How will jaundice be compared to Unconjugated? What other 8 symptoms?

mild jaundice; normal stool and urine color (no bilirubin in urine); hemolytic disorder Urine is dark; jaundice worse than unconjugated malaise, anorexia, low-grade fever, RUQ discomfort, amenorrhea, enlarged tender liver, spider telangiectasias, palmar erythema, ascites, gynecomastia

Hepatic Portal System: What are the 2 functions of the hepatic portal system? Portal HTN: How does this develop? Pathologic increase in portal pressure is a pressure gradient between the portal vein and IVC >________ mmHg. What is the most common cause of portal HTN?

supplies the liver with metabolites; ensures that ingested substances are processed in the liver before reaching the systemic circulation Develops when there is resistance to portal blood flow and is aggravated by increased portal collateral blood flow >10mmHg Cirrhosis (cirrhosis --> increased intrahepatic vascular resistance --> increased capillary pressure --> increased hepatic lymph formation --> ascities)

Chronic HBV and HDV: Antiviral treatment: Patients with active viral replication should receive a Nucleoside or Nucleoside Analog.....what 5 drugs? T2EAL OR What other drug?

tenofovir, telbivudine, entecavir, adefovir, lamivudine pegylated interferon

Phases of Viral Hepatits: Phase 1 (________________): Patients are asymptomatic during this phase. Lab studies demonstrate serologic and enzyme markers of hepatitis. Phase 2 (_____________): Anorexia, N/V Arthralgias, malaise, fatigue, urticaria, pruritus, and what unique symptom? (1) Phase 3 (_____________): Predominanat GI symptoms, Jaundice, Dark urine, followed by ________ stools. Malaise, May develop RUQ pain with hepatomegaly. Phase 4 (________________): Symptoms and jaundice resolve. Liver enzymes return to normal.

viral replication phase prodromal phase; alterations in taste (development of an aversion to cigarette smoke) Icteric phase; pale-colored stools Convalescent phase

Autoimmune Hepatitis: Is this more common in men or women? This is a form of chronic hepatitis due to autoantibodies. There is a varying clinical presentation and in some patients, this is discovered incidentally. S&S vary widely: -Transaminitis found incidentally during routine screening labs. -Mild, non specific findings: fatigue, lethargy, malaise, anorexia, nausea, ABD pain, and itching. What type of joints are affected with arthralgias? -Acute presentation of hepatits and liver failure with: profound jaundice, elevated PT, marked AST/ALT elevation >1000

women small joints