Lecture 23 Flashcards
What is one of the most common causes of chronic liver disease?
Chronic viral hepatitis
-can lead to potential progression to cirrhosis and other risks and other complications
When can acute liver failure occur
In someone who has acute liver injury
- e.g. acute hepatitis
- drug overdose
- chronic liver disease/cirrhosis –> then develops acute injury on top of that
Case 1:
68 year old lady
1973: operation for endometriosis
Complicated by peritonitis
Further laparotomy; given blood transfusion (due to bleeding during surgery)
8 wks later - nausea, anorexia, vomiting “looking yellow”
AST and ALT >1000 U/L (normal 0-40 U/L) for 2 weeks; elevated bilirubin for 1 week (jaundice)
Admitted to hospital for dehydration (anorexia and vomiting) - given intravenous fluids
Symptoms resolved completely after 1 month
Liver tests: Transaminases
Transaminases:
AST: aspartate Transaminase/aminotransferase
ALT: alanine transaminase/aminotransferase
When elevated:
- hepatic inflammation= hepatocellular injury
Liver tests: GGT and ALP
Cholestatic enzymes:
GGT: gamma-glutamyl transferase
ALP: alkaline phosphatase
When elevated- cholestasis i.e.
1. bile stasis (fat in liver causing bile to flow slowly) -bile flows slowly through liver
or
2. obstruction (tumour/stones) mechanical stopping bile flow
Liver tests: Bilirubin
When bilirubin elevated causes Jaundice (symptom/sign of hyperbiliaremia)
-yellow sclera, yellow skin
Liver diseases are the most common reason for an increased bilirubin count, but it isnt the only reason/cause
-Haemolysis (excessive breakdown of RBC, resulting elevated bilirubin)
Can be due to biliary obstruction (of bile flow. Bile cannot leave liver, accumulated and spills into circulation) or hepatocellular injury (damage to hepatocytes, inflammation of hepatocytes, results in hepatocytes undergoing Lysis, then bile/bilirubin into circulation)
Liver tests: Albumin and clotting factors
Produced by liver
-liver makes proteins such as Albumin and Clotting factors
When abnormal (in clotting factors/albumin), suggests impaired synthesis by liver i.e. liver not functioning properly
-not able to make normal amounts of albumin/clotting factors
When interpreting abnormal liver tests:
- Is the pattern of abnormality mostly: (hepato recognition to figure out underlying cuase)
- Hepatocellular (Transaminases significantly elevated re to other enzymes)
- Cholestatic (GGT or ALP predomianntly elevated- more tan transaminases)
- mixed (both Transaminases and Cholestatic enzymes equally or similarily elevated without preferance for one of the other) - Is there Jaundice?
- bilirubin
- depending on whether cholestasis problem or hepatocellular problem, may indicate underlying condition - Is Liver Synthetic function impaired?
- Albumin
- Prothrombin ratio (measure of clotting time)
Case 1:
Well until 1993; presented with tiredness
-abnormal AST and ALT 200-300 U/L; serum albumin and prothrombin ratio normal
-tested positive for hepatitis C active infection
Elevated Transaminases
-Not jaundice
-normal synthetic function
Elevated AST and ALT - think viral causes (more common Hep A B C)
-Hep C not recognised until 1989, therefore anyone who received blood transfusion prior to 1990’s was at risk of acquiring Hep C (non A non B transfusion related hepatitis)
Hepatitis in medical context
Hepatitis =”titis”- inflammation (of liver)
- doesn’t infer particular eateology
- most patients refer hepatitis to “infection”
- incorrect as doesn’t necessarily mean it is viral in eateology
Hepatitis B and C
(Hep A is self-limiting infection. most imunnosupressed/ elderly patients (not people who are healthy, therefore not a chronic infection/hepatitis))
-can cause acute and (subsequently) chronic viral hepatitis (if not cleared)
-acute infection -first 6 months
-if still infected after six months - chronic
Both are transmitted via blood (risk factors to vary)
Hepatitis B R.f.:
1. child hood/birth (mother with Hep B can transfer to baby)
2. Country with endemic of hep B. acquired as child via horizontal transmission.
3. Adult: most commonly acquired through sexual transmission
4. Adult: second common injecting drug use
Hep C R.f.:
1. Most common: injecting drug use
- for hep C sexual transmission not particularly high risk factor
2. Blood transfusion (contaminated blood -prior to 1990s (prior to Hep C awareness) or -acquired in a country which has no proper screening for Hep C)
Both Important causes of chronic liver disease and cirrhosis (due to potential for causing chronic infection)
- Majority of people infected with Hep C will develop chronic infection (wont be able to clear infection once infected with the disease)
Vaccine available for hepatitis B but not C
Risk factors for Hepatitis B
Hepatitis B R.f.:
- child hood/birth (mother with Hep B can transfer to baby)
- Country with endemic of hep B. acquired as child via horizontal transmission.
- Adult: most commonly acquired through sexual transmission
- Adult: second common injecting drug use
- vaccine available
Risk factors of Hepatitis C
Hep C R.f.:
- Most common: injecting drug use (~60^ of HCV cases)
- Sexual: Risk is extremely low in monogamous long-term relationships (even in partner has Hep C) and absence of HIV
- If person infected with Hep C was co-infected with HIV, increased risk of sexual transmission
- for hep C sexual transmission not particularly high risk factor - Blood transfusion
a) Recieved unscreened blood products/donated organs
- pre 1992 in Western countries
- In countries with no universal HCV screening
- contaminated blood -prior to 1990s (prior to Hep C awareness) or -acquired in a country which has no proper screening for Hep b) Vertical (mother to baby)
- risk (for baby) also low (unlike Hep B) but can be much higher if mother HIV positive - Occupational
- Medical treatments in countries with poor sterile practice (people who deal with needles/needle stickinjuries) (countries which dont sterilise medical equipment, or reuse certain needles or medical equipment
- Tattooing or body piercing with non-sterile equipment (not so much any more)
What is one of the particular issues and problems/risks of Hepatitis C?
- Majority of people infected with Hep C will develop chronic infection (wont be able to clear infection once infected with the disease)
- No vaccination
Acquiring Hepatitis B
- Sexual intercourse
- Injecting drug use
-most adults who are healthy will be able to clear Hep B acutely
-But if acquire Hep B as a child/baby, unlikely to clear infection acutely
Therefore most commonly seen Chronic Hep B cases, are people who have acquired Hep B: - During Childhood
- At birth
-Now Hep B vaccination to decrease rates
Hepatitis C (HCV)
Single-stranded RNA virus (different to hep B)
-discovered in 1989, diagnostic tests available soon after
-many cases of post-transfusional hepatitis, previously known as “non-A non-B hepatitis”, were due to HCV
Spread by blood
Exists as different strains known as genotypes
Majority of people infected are unable to eliminate the virus
-up to 85% of people acutely infected will end up with chronic infection
Case 1:
1995: decided to have treatment
- Interferon for 6 months
Many side effects
Treatment failed
Remained infected with Hepatitis C
Treatment for HCV
HCV treatment has evolved over the years
Regimens were Interferon based
Interferon:
*Cytokine produced by lymphocytes in response to viral infection (in natural immune response. physiological cytokine)
* Our body makes it “endogenous”
* In HCV treatment “exogenous” Interferon is used to increase interferon response (to increase immune response against virus)
* Causes “flu-like” symptoms (headache, fever, muscle aches, tiredness) - related to interferon release
Interferon treatment for HCV
Interferon has been the cornerstone of HCV treatment for almost 2 decades
- given as subcutaneous injection (like insulin)
- initially interferon alone i.e. mono-therapy
- moved on to interferon with Ribavirin (treatment combo)
- moved on to pegylated interferon with ribavirin
- -Pegylation - addition of polyethylene glycol (PEG) molecule to prolong half-life i.e. stays in body for longer (and concentration remains more stable)
Pegylation
addition of polyethylene glycol (PEG) molecule to prolong half-life i.e. stays in body for longer (and concentration remains more stable)
-e.g. PEgylation of interferon with Ribavirin
Problems with interferon
- Sub-optimal cure rates: with newer regimes, cure rates were better but still only 50-80% depending on genotype
- Problematic side-effects (flu like symptoms)
- Long duration - 6 to 12 months depending on genotype (longer treatment vs most viral infection treatments)
