A 29-year-old man with jaundice

• Jaundice is the yellowish staining of the skin, sclerae, and mucous membrane by excess plasma bilirubin

Jaundice occurs when there is a marked increase in production, decreased uptake, or decreased excretion of bilirubin.

Bilirubin stains all tissues but jaundice is most intense in the face, trunk, and sclerae

The deep yellow staining of jaundice can acquire a green hue if is long-standing

Jaundice is visible when the concentration of bilirubin exceeds 3mg/dL (60umol/L)

• Scleral icterus

Can also present first under the tongue as these two regions have very superficial blood vessels

The sclerae also have a high affinity for bilirubin due to their high elastin content. Its white colour also makes it easy to appreciate the yellow tinge

• Mucous membranes
• Palms
• Soles
• The skin of the chest, abdomen, and legs

The sclerae, mucous membranes, palms, and soles have more bilirubin since they are less exposed to sunlight and hence have less photodegradation of bilirubin

Jaundice spreads down the body starting with the face (including the eyes and mucous membranes) then the chest, abdomen, and legs

• Yellow skin can also be caused by carotene and other rare chemical toxins

However, carotene does not stain the sclera. It accumulates in the skin of the forehead, around the alae nase, and in the palms and soles.

Thyroid hormone is required to convert carotene into Vitamin A. Hypothyroid individuals can get carotinemia (yellow skin) and nyctalopia

• Hemoglobin is degraded into unconjugated bilirubin, iron, and globin
• Unconjugated bilirubin circulates bound to albumin (hence cannot be filtered by the kidneys)
• Unconjugated bilirubin is taken up by the liver and combined with glucuronic acid to form water-soluble conjugated bilirubin
• Conjugated bilirubin is excreted into the intestines with bile
• Bacterial enzymes convert conjugated bilirubin into urobilinogen
• Most urobilinogen is lost in feces as stercobilin
• Small amounts are reabsorbed by the intestines and re-excreted in bile (enterohepatic circulation) and some in urine
• Excess amounts of water-soluble conjugated bilirubin in blood is filtered by the kidneys and excreted in urine

• By the site of the problem
  • Pre-hepatic jaundice
  • Hepatocellular jaundice
  • Cholestatic/obstructive jaundice
• By the type of circulating bilirubin
  • Conjugated hyperbilirubinemia
  • Unconjugated hyperbilirubinemia

• Hemolysis: Malaria, DIC, Sickle Cell Disease, Antimalarials
• Ineffective erythropoiesis:
• Impaired hepatic uptake: Drugs (Paracetamol, Rifampicin), Ischemic hepatitis
• Impaired conjugation: Gilbert’s, Criggler-Najjar
• Physiological neonatal jaundice
• Overproduction of unconjugated bilirubin: Hemolysis e.g. Malaria/DIC, ineffective erythropoiesis

Stool and urine are normal in color since unconjugated bilirubin is bound to albumin and is water-insoluble.

• Hepatocellular dysfunction: hepatitis, drugs, alcohol, cirrhosis, metastasis, abscess, hemochromatosis, etc.
• Cholestasis: gallstones in the common bile duct, pancreatic cancer, primary biliary cholangitis, primary sclerosing cholangitis, Mirrizi’s syndrome, drugs, etc.

Pale stool + dark urine = conjugated bilirubin

Conjugated bilirubin is water-soluble and is excreted in urine making it dark-yellow to brown. Shaking the specimen produces yellow foam because bile salts lower the surface tension of water

Feces become pale as less conjugated bilirubin enters the gut

Can result in intractable pruritus when severe which is best treated by relieving the obstruction

• Biliary obstruction: dark yellow-brown urine with jaundice, pale stools, and RUQ pain
• Hemolysis: dark urine accompanying fatigue, jaundice, and back/abdominal pain
• Hematuria
  • Blood at the start of voiding that clears = urethral source
  • Blood at the end of voiding = bladder or prostate source
  • Blood throughout voiding = upper urinary tract source
  • Hematuria + H/O smoking = bladder cancer
• Rhabdomyolysis: dark urine following crush injury or physical exertion
• Dehydration
• Drugs e.g. Rifampin, Metronidazole and B complex vitamins

Differentials according to colour

• Hepatitis
• Carcinoma of the liver and stomach
• Pulmonary tuberculosis
• Chronic renal failure
• Drugs such as Chloroquine, Metronidazole and Antibiotics

• Liver: hepatitis, amoebic liver abscess, budd-chiari syndrome, congestive heart failure
• Gall bladder: acute cholecystitis
• Duodenum: duodenal ulcer
• Diaphragm: pleuritis, right lower lobe pneumonia or pneumonitis, subdiaphragmatic abscess

Non-colicky right hypochondriac pain can be caused by gall stones, urolithiasis, or intestinal colic due to duodenal ulcer or amoebic colitis

• Hepatic failure: H/O altered consciousness, drowsiness, tremors
• Bleeding disorder or Leukemia: H/O abnormal bleeding, purpura, petechiae
• Hepatorenal syndrome: H/O oliguria
• Ascites: H/O abdominal distension
• Portal hypertension: H/O hematemesis, melaena
• Spontaneous bacterial peritonitis; H/O sudden abdominal pain, high fever, abdominal distension

• Blood transfusions
• Travel history
• Sexual activity
• Contacts with jaundice
• Family history of jaundice
• Alcohol use
• Recreational drug use
• Intravenous drug use (IDU)
• All medications

Where have you been?… Where are you going?… Who are you with?… What are you taking?…

• Acute onset of prodromal symptoms (fever, anorexia, nausea, and vomiting) followed by jaundice and right upper quadrant abdominal pain
• Prior History of IDU
• Illicit drug use (predisposes to infection and the possibility of hepatotoxic agents)
• Unprotected sexual contact

Prodromal symptoms usually precede jaundice by a few days to 2 weeks

Once jaundice develops the prodromal symptoms often regress

Ecstasy is a RARE cause of acute (toxic) hepatitis

• Hepatitis B virus
• A – Acute only
• B – Both acute and chronic
• C = Chronic only
• D = chronic only, but requires HBV
• E = acute only

• There are various possible reasons including tattoos, history of injection drug use, anemia from other causes etc.
• This patient may have tested positive for infectious disease including either one of the following:
  • Positive HIV test
  • Hepatitis B surface antigen
  • Hepatitis B core antibody
  • Hepatitis C virus antibody
  • HBV DNA
  • HCV RNA
  • Syphilis serology
  • Antibodies for Trypanosoma cruzi

• Hepatitis A
• Malaria
• Typhoid fever
• Gastroenteritis
• Traveler’s diarrhea
• Amoebiasis
• Giardiasis

Hepatitis A is endemic in Africa and South America

• Hepatitis B and C
• HIV

Other infections include skin and soft-tissue infections, septic pulmonary emboli, infected deep venous thromboses, and endocarditis

• Viral causes
• Toxic causes
• Autoimmune causes
• Exposures e.g. Alcohol
• Ischemia
• Pregnancy

Serum bilirubin between 1-2mg, however no scleral icterus is seen

• Jaundice
• Gynaecomastia
• Spider naevi
• Palmar erythema
• Loss of pubic and axillary hair
• Testicular atrophy
• Flapping tremors
• Altered consciousness
• Dupuytren’s contracture

• Inflammation causes stretching of Glisson’s capsule which causes pain in the right upper quadrant

Glisson’s capsule is AKA the liver capsule

• Hepatitis
• Amoebic liver abscess
• Bacterial abscess
• Cholangitis
• Congestive Heart Failure
• Fast growing hepatoma

Non-tender hepatomegaly can be caused by malaria, schistosomiasis, typhoid, tuberculosis, hydatid cyst, fatty liver, malignancy, lymphoma, leukemia, hydatid cysts etc.

• The liver span is the distance between the upper and lower border of the liver (anterior hepatic projection) in the mid-clavicular line (MCL)
• It is measured by percussion downwards from the 2nd rib in the MCL. The upper border is detected as dullness and the lower border is detected as a shift from dullness to normal abdominal tympani, and confirmed by palpation.
• The normal liver span is 8 – 12 cm

• Hepatitis
• Liver abscess
• Obstructive jaundice
• Hemolytic anemia
• Storage disorder
• Liver malignancy

• Liver Function Testing and Coagulation Panel
• Viral Hepatitis Serology to confirm etiology
• Complete Blood Count for leucocytosis
• Electrolytes
• HIV testing given his risk factors

• This patient most likely has acute viral hepatitis with notable liver injury and disruption of synthetic function
  • There is significantly elevated AST and ALP
  • His ALP > AST with an AST:ALP ratio is 0.79 which points towards acute viral hepatitis
  • His total bilirubin and direct bilirubin are elevated with a major fraction of the elevated bilirubin being direct (conjugated) bilirubin
  • He also has an elevated INR and aPTT.

• AST (SGOT)
• ALT (SGPT)

• Total serum bilirubin
• Direct bilirubin
• Indirect bilirubin

• ALP
• 5’ nucleotidase
• GGT

• Albumin
• Total Protein
• Prothrombin Time or INR

0.7-1.4

• Alcoholic Hepatitis: AST:ALT > 2.0
• Acute Viral Hepatitis: AST: ALT <1

Persistently elevated ALT and AST beyond 6 months

Prolongation of the Prothrombin Time or INR

Acute Hepatitis A

Acute Hepatitis C

• Chronic Hepatitis C

HBsAg

• HBeAg

It reflects the activity of HBV DNA Polymerase, hence represents viral load

• Recent infection (Anti-HBc is also positive)
• Previous vaccination (Anti-HBc is negative)

Chronic infection

HBV Serology is complex

HBV + Liver function tests

• This patient has Acute Hepatitis B
  • This illness is of acute onset with prodromal symptoms (fatigue, anorexia, nausea, and vomiting) preceding the onset of jaundice by 1-2 weeks
  • This patient has risk factors for infection with HBV including IDU and unprotected sexual contact
  • There is obvious icterus with, an enlarged and tender liver
  • ALT and AST are elevated (peak levels usually between 400-4000 IU/L). ALP is increased to a lesser degree
  • There is hyperbilirubinemia with primarily an increase in conjugated bilirubin
  • The core IgM, surface antigen, and e-antigen for Hepatitis B are all elevated indicating acute infection

• He has a positive Hepatitis C antibody
• There is a possibility he might have a chronic infection with HCV given the history of being previously rejected to donate blood
• He also has a history of IDU and unprotected sex which are risk factors for Hepatitis C

85% of individuals develop silent chronic infection with HCV

• Hepatitis A IgM is not elevated

Hepatitis A IgM is elevated in acute infection with hepatitis A

Note that this patient has also not been vaccinated against hepatitis A since Hepatitis A IgG is negative

• EBV
• CMV
• Leptospirosis
• Malaria
• Q fever
• Syphilis
• Yellow Fever

Liver Biopsy or Elastography

• Only supportive treatment is recommended in the acute phase
  • Support liver function and monitor for liver failure (occurs in <1%)
  • Advise the patient to avoid alcohol
  • Avoid elective surgery as it can lead to post-operative liver failure
  • Immunize sexual contacts
• Long-term monitoring of Liver Function based on ALT and AST
• Monitor for Hepatocellular carcinoma via ultrasound
• Start Monotherapy at 6 months if surface antigen remains positive

There is no specific treatment in the acute phase since 99% recover without any assistance

• Chronic hepatitis B
• Chronic liver inflammation (ALT ≥ 30 IU/L)
• Cirrhosis
• HBV DNA> 2000 IU/mL

• Agents for monotherapy include Tenofovir, Lamivudine, Adefovir or Entecavir

Pegylated (PEG) is falling out of favor since it is less tolerated by patients

• In patients with low viral load and elevated transaminases

To augment the immune system

• Cirrhosis

It may precipitate liver failure

• In patients co-infected with HIV

To prevent HIV antiviral drug resistance

Specialist treatment with a combination of antivirals is recommended

• Genotyping
• Combination therapy with Sofosbuvir/velpatasvir or glecaprevir/pibrentasvir or Ledispavir/sofosbuvir
• Long-term monitoring of HCV RNA (indicates response to treatment)
• Avoid alcohol

In case of Acute Hepatitis C infection, viral Load (HCV RNA) is monitored from diagnosis and continued for 12 weeks.

Treatment can be discontinued at 12 weeks if the patient recovers. If the infection turns chronic treatment is continued indefinitely.

Recovery is uncommon in acute hepatitis C (10-15%). Progression to chronic hepatitis is the rule.

Genotype 1 is much easier to treat than Genotype 2 and 3.

Genotype 4, 5 and 6 are more common in lower income countries

Liver transplant

• Only supportive (however, the vaccine can help)
• Avoid alcohol

Hepatitis A is self-limiting

Rarely, Interferon alpha can be used for fulminant hepatitis

• Hygiene
• Safe sex practices
• Vaccination against Hepatitis A and B
• Precautions in handling bodily fluids and lab equipments

• Hepatitis A Virus vaccine (given to individuals with risk factors e.g. travelers, crowded areas, oral-anal sexual contact)
• Hepatitis B Virus Vaccine (given to everyone)

• Once the newborn weighs ≥ 2 kg

This is the only exception to the rule that preterm infants should receive vaccine according to their chronological age

In Kenya it is routinely given as part of the pentavalent vaccine (Penta) at 6, 10, and 14 works

• 2 doses for Hepatitis A
• 3 doses for Hepatitis B

• No, they should pick up from where they left off

2 doses for Hepatitis A

3 doses for Hepatitis B

Hepatitis B immune globulin followed by Hepatitis B vaccine at birth

• Yes

As long as there is no active bleeding from the nipples

• Drink only boiled water or bottled mineral water
• Pre-exposure prophylaxis given 2 weeks before travel to an endemic area
  • Booster dose
  • For patients who are previously unvaccinated the vaccine can be given as soon as travel is considered and the 2 dose series completed according to routine

• Hepatitis A Virus Immune Globulin + Hepatitis A Virus Vaccine within 2 weeks of exposure
• Hepatitis A Virus Immune Globulin if they are immunocompromised or have chronic liver disease

• Hepatitis B Virus immune globulin and Hepatitis B Virus Vaccine

This is what is typically given to children who are born to mothers with chronic Hepatitis B

• Fulminant hepatic failure
• Cirrhosis
• Hepatocellular cardinoma
• Cholangiocarcinoma
• Cryoglobulinemia
• Membranous nephropathy
• Polyarteritis nodosa

• Glomerulonephritis
• Cryoglobulinemia
• Thyroiditis
• Autoimmune hepatitis
• Polyarteritis nodosa
• Polymoyositis
• Porphyria cutaenea tarda

• t accelerates the progression to cirrhosis

HDV requires a protein coded by the HBV genome for its assembly

It is transmitted the same was as HBV

It increases the risk