S3 AG1 PBL 6 - Hepatitis
S3 AG1 PBL 6 - Hepatitis
S3 AG1 PBL 6 - Hepatitis
A 25-year-old junior nurse presents to a physician with a 2-3-week history of fatigue, loss of
appetite, and right upper quadrant discomfort. During the past week, she has noticed yellow
discoloration of her eyes. She was previously healthy and has no chronic medical problems.
She enjoys alcoholic drinks when meeting up with friends. Three months ago, she suffered a
needle-stick injury while attending to a trauma patient. She did not seek medical care
immediately due to the patient’s critical condition but suspected that the patient might be an IV
drug user
Discussion
1. What differential diagnoses should be considered for a young adult presenting with
fatigue, loss of appetite, and right upper quadrant discomfort?
1. Hepatitis
2. Jaundice
3. HIV
2. What are the risk factors/ causes/ factors leads to needle stick injury?
3. What are the potential implications of yellow discoloration of the eyes in the absence of other
chronic medical problems?
- Jaundice
- Hepatitis
- Gallstones
- Tumores
- Genetics - Gilbert’s Syndrome
- Alcoholic Drinks
- G6PD
4.How might social habits, such as alcohol consumption, contribute to her symptoms?
Vaccinations
Medications
6. Physical Examinations
7. Lab Examinations
Part 2
On physical examination, she has jaundice, right upper quadrant tenderness and hepatomegaly
Difficult Words
- Stigmata = scar, pain, wound (stigmata of chronic liver disease, which includes spider
nevi, palmar erythema, gynecomastia, caput medusae, Dupuytren contractures, parotid
gland enlargement, and testicular atrophy).
-
Antibodies Indicators
Vaccinations
Diagn
osis- Hepatitis C
c. Lymphatic drainage
i. Periportal lymphatic vessels: surround the portal triads and
hepatic lobules. They collect lymph fluid from the periportal space,
which is the area between the hepatocytes (liver cells) and the
sinusoids (capillaries).
ii. Sublobular lymphatic vessels: Located along the hepatic veins,
these vessels drain lymph from the central and sublobular regions
of the liver lobule.
d. Capsular lymphatic vessels: lie on the surface of the liver, beneath the
Glisson's capsule (connective tissue capsule surrounding the liver).
They drain lymph from the capsule itself and the upper zones of the liver
lobules.
Lymph Nodes
7.
LO2
The liver is a vital organ located in the upper right-hand portion of the abdominal cavity.
It performs over 500 essential functions, including the regulation of chemical levels in
the blood and the excretion of bile, which helps carry away waste products1. The liver
processes blood from the stomach and intestines, breaking down nutrients and
metabolizing drugs into forms that are easier for the body to use or that are
non-toxic1.
Bilirubin Metabolism: Bilirubin is a yellow bile pigment produced through the breakdown
of red blood cells in a process known as hemolysis. The metabolism of bilirubin
involves several steps:
1. Creation of Bilirubin: Reticuloendothelial cells (macrophages) in the blood take
up red blood cells and metabolize the hemoglobin into its components—heme
and globin. Heme is then broken down into iron and biliverdin, which is
subsequently reduced to create unconjugated bilirubin2.
2. Bilirubin Conjugation: Unconjugated bilirubin travels in the bloodstream bound to
3. albumin to the liver. In the liver, it is conjugated with glucuronic acid by the
enzyme glucuronyl transferase, forming water-soluble conjugated bilirubin2.
4. Bilirubin Excretion: Conjugated bilirubin is excreted into the duodenum in bile. In
the colon, bacteria deconjugate bilirubin and convert it into urobilinogen. Most
urobilinogen is further oxidized to stercobilin and excreted through feces, giving
them their color. A small portion is reabsorbed into the bloodstream and excreted
in the urine as urobilin2.
Jaundice can occur if there is an accumulation of bilirubin, leading to a yellow
discoloration of the skin and eyes. This can be due to various reasons, including
increased hemolysis or issues with liver function affecting bilirubin processing2.
https://www.hopkinsmedicine.org/health/conditions-and-diseases/liver-anatomy-and-functions
https://teachmephysiology.com/gastrointestinal-system/liver/bilirubin-metabolism/
Function and Physiology of the Liver: The liver, the largest internal organ, plays a crucial
role in numerous bodily functions. It is responsible for:
What is Jaundice?
· It is not a disease, but it is a clinical presentation characterised by yellow discoloration of skin, sclera
and mucous membrane
· Billirubin a yellow-orange pigment derived from the breakdown of heme, which is released during the
destruction of red blood cells.
Pathophysiology
Under normal circumstances, bilirubin undergoes conjugation within the liver, making
it water-soluble. It is then excreted via the bile into the GI tract, the majority of which
bloodstream and excreted through the kidneys. Jaundice occurs when this pathway
Aetiology of Hepatitis C
Hepatitis C infection is caused by the hepatitis C virus (HCV).
You can catch hepatitis C if the blood of someone who has HCV
enters your body. Exposure may occur:
● Inject street drugs or share a needle with someone who has HCV
● Have been on long-term kidney dialysis
● Have regular contact with blood at work (such as a health care worker)
● Have unprotected sexual contact with a person who has HCV
● Were born to a mother who had HCV
● Received a tattoo or acupuncture with needles that were not disinfected properly after
being used on another person (risk is very low with practitioners who have a tattoo
license or permit or an acupuncture license)
● Received an organ transplant from a donor who has HCV
● Share personal items, such as toothbrushes and razors, with someone who has HCV
(less common)
● Received a blood transfusion (rare in the United States since blood screening became
available in 1992)
Epidemiology of Hepatitis C
The hepatitis C virus (HCV) has a significant global impact, with 58 million people chronically
infected and about 1.5 million new infections occurring per year.2 There remains considerable
global variation within these figures. In high-income countries, the prevalence is generally below
2%, with people who inject drugs (PWID) being disproportionately affected, while countries with
low-middle incomes have the highest prevalence (see Table 1). WHO also estimated that in
2019 approximately 290,000 people died from hepatitis C, mostly from cirrhosis and
hepatocellular carcinoma.2
In England in 2020, around 81,000 people were living with chronic HCV infection.1 However,
this represents a significant reduction from earlier years, thanks to the introduction of very
effective treatments, which will be explored further in part 2 of this series. For example, by 2020,
the prevalence of HCV in England had fallen by 37% compared to the 2015 baseline (see
Figure 1) and HCV mortality decreased by 35%.1
Figure 1
Estimated prevalence of chronic hepatitis C virus (HCV) infection in England, 2010–2020 (with
95% credible intervals)1
Early diagnosis of HCV infection is essential for the most effective treatment and care. However,
from a global perspective, only 19% (13.1 million) of people living with hepatitis C know their
status. In England in 2020, 40.4% of PWID surveyed were aware of their HCV antibody-positive
status,1 but this does not necessarily link successfully to treatment services.
In malaysia:
We organized a cross-sectional study at the end of 2020 across Malaysia. We used a two-stage
stratified random sampling technique to select representative community dwelling individuals
aged ≥15 years. The optimum size sample required was 5000 based on the single proportion
sample size formula, adjusted for design effect and non-response. We obtained written
consents and assent (if ≤ 18 years) and conducted face-to-face interviews to collect
sociodemographic characteristics and HCV status. We collected blood samples and extracted
serum to test for HCV antibodies. A positive sample (denotes HCV infection) would be tested
further for HCV core antigen. Positive results on both tests denote chronic infection.4 We used
SPSS v26 to perform descriptive analysis and apply weights in complex sampling analysis to
obtain representative prevalence and their 95% Confidence Interval (CI)
Out of 5957 eligible individuals, test results were available for 4076 (response rate 68.4%).
Their mean age was 41.2 ± 17.3 years. The weighted prevalence of HCV infection in Malaysia
was 0.4% (95% CI 0.2–0.7) amounting to an estimated 90,119 infected “population age ≥15
years. More than half of them (≈51,675) are chronically infected with a prevalence of 0.2% (95%
CI 0.1 -- 0.4).
https://www.thelancet.com/journals/lanwpc/article/PIIS2666-6065(23)00120-7/fulltext#:~:text=Th
e%20weighted%20prevalence%20of%20HCV,population%20age%20%E2%89%A515%20year
s.
1. Viral Entry: Hepatitis C virus (HCV) enters hepatocytes via attachment and fusion to
the cell membrane.
2. Replication: Inside the hepatocytes, HCV RNA genome is released. Virus begins to
replicate using the host cell machinery.
3. Immune Response: Immune system recognizes the presence of the virus → initiates an
immune response. CD4+ and CD8+ T cells, as well as B cells are to control the infection.
4. Inflammation: The immune response results in inflammation of the liver, which can
cause liver damage and dysfunction.
Clinical Presentation
History
● Most people with hepatitis C are asymptomatic
● Acute hepatitis C symptoms, present in a minority of patients, subside after a few
weeks. These are usually nonspecific and include the following:
○ Fever
○ Fatigue, malaise, or weakness
○ Anorexia
○ Nausea or vomiting
○ Abdominal pain
○ Arthralgia or myalgia
● Manifestations of excess bilirubin occur in a small percentage of patients with
hepatitis C, and they suggest a diagnosis of hepatitis. The manifestations are:
○ Dark or concentrated urine
○ Clay-colored bowel movements
○ Jaundice
○ Pruritus
● Chronic hepatitis C is largely asymptomatic; symptoms associated with cirrhosis may
appear after years of silent infection
○ Abdominal distention
○ Peripheral edema
○ Bleeding or bruising easily
Physical examination
● Acute hepatitis C
○ Fever
○ Scleral icterus
○ Jaundice
○ Right upper quadrant tenderness
○ Palpable liver edge
● Chronic hepatitis C is undetectable by examination until there are signs of cirrhosis,
which are as follows:
○ Cachexia
○ Scleral icterus
○ Jaundice
○ Gynecomastia
○ Large, firm, nodular liver
○ Ascites
○ Peripheral edema
○ Ecchymoses
○ Spider angiomata
Additional evaluations
Laboratory studies
● Viral load determination: quantitative PCR for HCV RNA
● Routine studies
○ CBC, BMP (Basic metabolic panel)
○ Hepatocellular enzymes
■ Normal or ↑ transaminases (10–20 × ULN)
● Transaminases: Enzymes involved in amino acid metabolism,
e.g., alanine aminotransferase (ALT) and aspartate
aminotransferase (AST), which are used clinically as parameters
of hepatocellular injury.
■ Fluctuating ALT peaks indicate acute HCV infection
● (ALT) Alanine aminotransferase: An enzyme involved in amino
acid metabolism that catalyzes the transfer of an alpha-amino
group between glutamate and alanine. Primarily found in
hepatocytes; thus, serum concentrations are used to monitor for
hepatocellular damage.
○ Cholestasis parameters (The laboratory values that indicate that bile cannot flow
from the liver to the duodenum)
■ ↑ GGT
● Gamma-glutamyl transferase: A membrane-bound enzyme of
glutathione metabolism and amino acid transport. The most
sensitive parameter for diseases of the liver and/or biliary tract.
However, it is not very specific, as it is found in many tissues.
■ ↑ Alkaline phosphatase
● A group of enzymes found throughout the body but produced
predominantly in the liver, bones, placenta, and small intestine.
Common causes of elevated serum ALP include cholestasis, bone
disease (e.g., bone metastases, Paget's disease,
hyperparathyroidism), and pregnancy. The normal reference range
is 20–70 U/L.
■ ↑ Bilirubin
● A hemoglobin breakdown product and parameter of cholestasis.
Serum total bilirubin consists of unconjugated bilirubin and
conjugated bilirubin.
○ Liver synthetic function tests (alterations suggest cirrhosis)
■ ↓ Albumin
● A protein whose functions include maintenance of colloid osmotic
pressure and transportation of enzymes and degradation
products. Produced exclusively by the liver and comprises the
majority of total plasma proteins (~60%). Levels decrease with
decreased hepatic synthesis, urinary protein loss, and
malnutrition.
■ ↓ Total protein
■ ↑ PT/INR
● PT (prothrombin time): An assay that evaluates the extrinsic and
common pathways of the coagulation cascade (measures activity
of factors I, II, V, VII, and X). Used to evaluate coagulation
disorders and to monitor the effect of warfarin. Normal range is
11–15 seconds.
● INR: The ratio of an individual's prothrombin time (PT) relative to
the PT of a control sample. Common causes of elevation include
vitamin K deficiency and warfarin therapy. Used to monitor the
effectiveness of the latter.
● Evaluation of coinfection
○ HIV testing
○ Hepatitis B serology
○ Hepatitis A serology
● Serum pregnancy test (if applicable): ideally performed directly before initiating treatment
Liver biopsy
● Consider when:
○ Etiology of hepatitis is unknown
○ Accurate liver fibrosis staging would alter treatment
Treatment
Not all hepatitis infected individuals require therapy.
General principles
● The goal of treatment is sustained virologic response (SVR).
○ SVR: The absence of hepatitis C virus RNA after 12 weeks of therapy with
direct-acting antivirals. A patient in this state is considered to be cured of
hepatitis C virus infection.
● Refer patients with end-stage liver disease for liver transplantation evaluation.
Antiviral therapy
HCV infection is always treated with a multidrug approach (no antivirals are approved as
monotherapy).
● Direct-acting antivirals (DAAs)
○ Antivirals target and inhibit HCV-encoded proteins that are essential for the
HCV replication cycle.
○ Example regimens
■ Glecaprevir PLUS pibrentasvir (all 6 genotypes)
■ Sofosbuvir PLUS velpatasvir (all 6 genotypes)
■ Ledipasvir PLUS sofosbuvir (genotypes 1, 4, 5, and 6)
■ (genotypes refer to the different strains of HCV)
● Interferon PLUS ribavirin
○ Was the preferred treatment before the development of DAAs
○ Associated with severe adverse effects (e.g., arthralgias, thrombocytopenia,
leukopenia, depression, anemia) and teratogenicity
○ Contraindicated in patients with decompensated cirrhosis (high risk of worsening
cirrhosis decompensation)
DAAs have superior efficacy and safety profiles compared with interferon or ribavirin-based
regimens and are thus preferred.
Acute and chronic HCV are treated with the same antiviral regimens.
Prevention
● Currently, no effective vaccine or postexposure prophylaxis exists
● Public programs encourage safe needle disposal and discourage needle sharing
among people who inject drugs
● Avoidance of high-risk behaviors
○ Safe sexual practices, including use of barrier contraception, are imperative to
reduce transmission by sexual contact for patients with multiple sexual partners if
either partner is HIV positive or at risk for other sexually transmitted infections
○ Advise patients that transmission of hepatitis C occurs through contact with
blood, and therefore, they should avoid sharing razor blades, toothbrushes,
or nail clippers
○ Transmission between long-term monogamous but HCV-discordant couples is
uncommon
● Universal precautions by health care workers
● Sterilization of medical equipment
● Avoidance of breastfeeding by hepatitis C–infected adults with cracked or bleeding
nipples
Screening tests
● HCV-antibody testing with reflex HCV-RNA polymerase chain reaction testing is the
initial screening test
○ Quantitative HCV-RNA testing is performed for a positive anti-HCV test result;
document the baseline viremia before antiviral treatment
● Patients exposed to hepatitis C virus within the 6 months preceding a negative
HCV-antibody test are recommended to have HCV-RNA or repeat HCV-antibody testing
after 6 months or more have elapsed
● Health care workers with occupational exposure
○ Determine hepatitis C status of source patient; no further testing is required if
source patient is HCV negative
○ If source patient is positive for HCV or status is unknown, obtain baseline
anti-HCV antibody test within 48 hours of exposure
○ If baseline anti-HCV test result is negative, test for HCV-RNA 4 weeks after
exposure or test for anti-HCV 4 to 6 months after exposure
● Perinatally exposed children
○ Antibody-based testing is recommended at or after age 18 months; testing earlier
may detect maternal antibody
● Testing with an HCV-RNA assay can be considered as early as age 2 months