1DDX: LECTURE 29 – JANUARY 24TH 2007

GASTROINTESTINAL DISORDERS: LIVER

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• First slide: these are the most important/common pathologies
• In healthy person, Hepatitis A may go unnoticed.
• Flu-like symptoms, RAPID WEIGHT LOSS: consider cancer.
• Arthralgias? Always consider Hepatitis B.

• Jaundice with fever, chills? Always consider viral hepatitis

• Questions you must always ask: alcohol use, occupational exposure, drug use, see other questions.

Accumulation of lipids: the most common response of the liver to injury.

Fatty infiltration in chemotherapy: it is very hard on the liver, and this is how it will respond (usually focal response).

Pathogenesis: skipped : read on our own.

FATTY LIVER DISEASE

Can present without hepatomegaly. May be asymptomatic.
Best diagnosis is made by biopsy. Ultrasound will show fatty infiltration, but can’t dx for sure without biopsy.

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Good prognosis for some types: Dr. W. mentioned a patient that reversed it after cancer surgery.

ALCOHOLIC LIVER DISEASE

“spectrum” of clinical syndromes: a wide range of different presentations.
Most important factors: quantity consumed, period of time over which alcohol consumed, nutritional status, genetic, metabolic traits.
Binge drinking: greater damage than smaller amounts over a short period: more acute damage to the liver.

Women: drinking more than 1 drink a day will increase chance of breast cancer by 60-70% (recent research) Alcohol increases estrogen.
(Example below is from PubMed for reference: extra info)

1: Am J Epidemiol. 2007 Jan 4; [Epub ahead of print]

Alcohol Consumption and Breast Cancer Risk in the Women's Health Study.
,
Zhang SM Lee IM, Manson JE, Cook NR, Willett WC, Buring JE.
Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
The authors assessed the association between moderate alcohol consumption and breast cancer risk in the Women's Health Study (United
States, 1992-2004). During an average of 10 years of follow-up, 1,484 cases of total breast cancer (1,190 invasive and 294 in situ) were
documented among 38,454 women who, at baseline, were free of cancer and cardiovascular disease and provided detailed dietary
information, including alcohol consumption, for the preceding 12 months. Higher alcohol consumption was associated with a modest
increase in breast cancer risk; the multivariable relative risks for >/=30 g/day of alcohol vs. none were 1.32 (95% confidence interval (CI):
0.96, 1.82) for total breast cancer and 1.43 (95% CI: 1.02, 2.02) for invasive breast cancer. An increased risk was limited to estrogen
receptor (ER)- and progesterone receptor (PR)-positive tumors; the multivariable relative risks for an increment of 10 g/day of alcohol were
1.11 (95% CI: 1.03, 1.20) for ER+PR+ tumors (804 cases), 1.00 (95% CI: 0.81, 1.24) for ER+PR- tumors (125 cases), and 0.99 (95% CI:
0.82, 1.20) for ER-PR- tumors (167 cases). The association also seemed strongest among those taking postmenopausal hormones
currently, but the test for interaction was not significant. The findings from this prospective study suggest that moderate alcohol
consumption increases breast cancer risk.
PMID: 17204515 [PubMed - as supplied by publisher]

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GGT: marker for alcohol consumption.

ALCOHOLIC HEPATITIS
This is a sign that the liver has had enough!
End stage: cirrhosis.

What can we do for patients? Like smoking, have to stop drinking! Most difficult problem is to make them stop drinking. If they continue to drink, the liver
cannot be recovered.
If their own health is not important to them, talk about socio-economic factors: impact on job, on family relationships, have to get to root of problem: why
are they drinking in the first place?
Research shows that there are a number of genes involved in smoking, drinking, drug use. There might be a genetic component to their behaviour.

Chart:
Chronic hepatitis (many etiologies): leads eventually to cirrhosis: has many consequences to the rest of the body.

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LIVER CIRRHOSIS
• Can have cirrhosis on only one part of the liver, and other parts will be healthy.
• Fibrosis happens anywhere in the body when there is injury. General response to injury and trauma.
• For liver, can be infection, storage diseases, alcohol, auto-immune…
DDX LECTURE 29, JANUARY 24TH, 2007 – PAGE 1
• Cirrhosis is last resort, after many years of damage.
• See list of reasons why you develop Liver Cirrhosis.
• Can have tendancy to produce fibroses (congenital)

• Due to trauma, Kupffer cells produce inflammatory cytokines  fibroblasts  increased collagen synthesis  permanent scarring of the liver!

• Signs and symptoms: patients can be asymptomatic for years.

• Xanthelasmas: cholesterol deposits around the eyes.

• Malnutrition is common: even if they are eating a normal diet, they are not able to absorb nutrients.
• May be able to palpate nodules in thin patients
• Pathognomonic: palmar erythema
• Dupuytren’s contractures: Dupuytren's contracture (also known as Morbus Dupuytren) is a fixed flexion contracture of the hand where the fingers
bend towards the palm and cannot be fully extended (straightened).
• Non-specific symptoms are all result of hormone problems, malnutrition.

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• People can have cirrhosis for years with NORMAL BLOOD TESTS: the normal parts of the liver will take over and maintain function. Biopsy is the
best diagnosis.
• Doppler Ultrasound: to hear sound of blood flow through artery. This checks for blood flow in the liver.

PRIMARY BILIARY CIRRHOSIS

Mainly in women, develops in stages over time.

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• Pruritis and fatigue are 2 signs that women will present with: may be asymptomatic apart from this.
• Pruritis can be a sign of many other conditions, but have to keep this in mind, especially in a female patient. DDX pruritis with no other signs:
Vitamin A deficiency, possibly with poor peripheral circulation, lymphomas, leukemias, EFA deficiencies, malnutrition in general…
•
• Only jaundice in 20% of patients.
• Osteoporosis develops early in life.
• Commonly associated with other auto-immune disorders. This may be an auto-immune disorder as well: we just don’t have the markers yet to
show this.
•
• See list of DDXs, slide 4.
• Steps: someone presents with itching and fatigue. Start with blood test. Simple, less invasive than other tests. Liver, kidney function, CBC, fasting
glucose. May send to dermatologist, check for fungal infection (skin scraping). Then send for abdominal and pelvic ultrasound (check abdominal
organs, but pelvic too: uterus, ovaries.) With ultrasound, may see obstruction, backflow causing inflammation, fibrotic response.
• Tongue and pulse diagnosis?

• Prognosis: better with slow progression of disease.

• Better prognosis if there are signs of reversal of the disease (pruritis disappears, reduced serum cholesterol, shrinking xanthomas)
• What is the mechanism for pruritis? Jaundice: accumulation in the skin, irritates nerve endings, get itching. It is generalized itching, and it is
extreme itching: can cause marks on the skin from scratching. May have to take meds to reduce sensation of itching. May have some itching
without jaundice because there are other mechanisms at work: low EFAs.

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• Hepatitis: can’t tell which one it is by looking.
• Lungs and urinary tract are the 2 most common sources of fever.

• See list of DDXs: slide 4.

• There are hundreds of coxsackievirus
• Herpes: look for skin involvement
• Any drug taken in large quantities can affect the liver and cause hepatitis: the ones that are listed have an increased chance.
• Syndrome called “Tylenol-alcohol syndrome” Tylenol affects LV and KI, even in small doses. In people who are drinking at the same time, the
quantity of alcohol reduces the amount of Tylenol needed to produce necrosis. Taking Tylenol for a hangover??? Probably better to just wash the
alcohol out with lots of water. The alcohol isn’t being processed at the same time, but there may still be some damage.

• Hepatic artery thrombosis: when would you have this? Coagulopathies, many cases.

HEPATITIS A
• May pass it unconsciously during asymptomatic period.
• Very important to wash hands, can reduce, stop spread.

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• Rare, but can progress to fulminant hepatic failure in a couple of weeks. Not as common now, treatment given.
• Hepatitis A in carrier state does not lead to cirrhosis: has to be another complication that causes cirrhosis.

DDX LECTURE 29, JANUARY 24TH, 2007 – PAGE 2

HEPATITIS B
• DNA virus
• As NDs, we can be exposed, especially if we are doing parenteral therapy

• Only jaundice in 35% of cases. Fatal in 2% of cases: rare now that treatment is possible. Other complications may accelerate progression to
hepatic failure.

• Hepatitis B and Hepatitis C: most related to hepatocellular carcinoma.

HEPATITIS C
• Patients may not know that they have it until they develop cancer, cirrhosis, chronically hepatitis.
• No known vaccine

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HEPATITIS D
• Only occurs with Hep B: doesn’t occur on its own. Symptoms are more severe because the patient now has 2 types of hepatitis.
• No vaccine against Hep D. Can immunize against Hep B.

HEPATITIS E
• See this in areas where there is flooding. Spread of disease through water (fecal-oral route)
• No specific serological tests, no known vaccine.

Chart comparing Hepatitis A, B, C.

CHRONIC HEPATITIS
• If it lasts more than 6-12 months, it is chronic hepatitis.
• Can be mild symptoms, or they can progress to hepatic failure: wide spectrum of presentation.
• Most important causes: Hepatitis B, Hepatitis C.
• Others: auto-immune, Wilson’s disease, 1-antitrypsin deficiency.

• The more symptoms present: the more advanced the disease. Symptoms are due to pathologies in pathways of liver function.

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• Conditions that cause secondary liver pathologies? Have to focus on the liver first: this organ is more important than thyroid (eg.). If the function of
the liver improves, the primary condition will probably improve more quickly.
• Biopsy for definitive diagnosis.
• Most instances: the specific cause cannot be discerned!
• On biopsy: will see more lymphocytes and plasma cells if this is an AI condition.

HEPATOCELLULAR CARCINOMA
• It is much less common than other cancers that metastasize to the liver as a secondary site.
• Link with Hep B, Hep C, and environmental carcinogens.
• We have a great toxic load, from birth: eg. Plastic pacifiers, plastic bottles, warmed in the microwave (phthalates). Just warming the bottle in water
will cause leaching of toxins, but microwaving is worse. Plastic toys, plastic teething rings…
• Since WWII: there has been an increase of Hep C cases, leading to an increase in hepatocellular carcinoma.

• May see cirrhosis deteriorate: it has become cancerous.

• First manifestation of condition may be from rupture of the tumour. Portal hypertension, rupture of esophageal varices, vomiting blood, taken to
hospital, diagnosed with cancer.
• Correction to Slide 5: last line is “bruit”.

Other types of liver cancers:

• Fibrolamellar carcinoma: no viral involvement: better prognosis than those with Hep B/C link.
• Cholangiocarcinoma: from liver flukes
• Hepatoblastoma: infants can be born with this, or develop soon after birth. Usually RUQ mass that leads to diagnosis.

DDX LECTURE 29, JANUARY 24TH, 2007 – PAGE 3