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Explain the case and give the correct answer

Reading File

Finding Sources

Reading File

Finding Sources

I have enough foundational information from the library and my training knowledge to give comprehensive answers to both case studies. Let me now provide the full detailed responses.

Case Study 1: Ulcerative Colitis with Infliximab

The Clinical Picture

A 30-year-old woman with known ulcerative colitis (UC) presents with:

Bloody diarrhoea, pyrexia
CRP = 54 mg/L (elevated, normal <5)
Platelets = 545 x 10⁹/L (reactive thrombocytosis - a feature of active inflammation)
Hb = 10.5 g/dL (anaemia - likely from GI blood loss)

She is admitted for intensive medical management with:

IV and rectal steroids
Fluid and electrolyte replacement
Subcutaneous heparin

Question 1: Rationale for IV Steroids + Biochemical Monitoring

Why IV steroids?

This is Acute Severe Ulcerative Colitis (ASUC), defined by the Truelove & Witts criteria:

6 bloody stools/day
Pyrexia (>37.8°C)
Raised inflammatory markers (CRP >45 is key)
Anaemia (Hb <10.5 g/dL in women)
Tachycardia / raised ESR / low albumin

IV corticosteroids (hydrocortisone 100 mg four times daily, or methylprednisolone 60 mg/day) are first-line for ASUC because:

Oral steroids have inadequate/unreliable bioavailability when the bowel is severely inflamed
IV route ensures rapid and consistent therapeutic plasma levels
Rectal steroids (suppositories/enemas) are added for topical anti-inflammatory action in the rectosigmoid

Heparin (subcutaneous): UC is a hypercoagulable state due to thrombocytosis, inflammation, and bed rest. VTE prophylaxis is mandatory.

Biochemical monitoring during IV steroids:

Parameter	Reason
U&E (electrolytes, creatinine)	Steroids cause Na+ retention, K+ wasting; diarrhoea causes further electrolyte loss
Blood glucose	Steroids cause hyperglycaemia (steroid-induced diabetes)
Magnesium	Depletion common; must be corrected to prevent hypokalaemia refractory to replacement
LFTs	Baseline before any rescue therapy; albumin reflects disease severity
FBC (daily)	Track Hb, WBC (steroids cause leukocytosis masking infection), platelets
CRP / ESR	Daily CRP - predictor of steroid response and need for rescue therapy
Blood cultures / stool cultures	Exclude infection (especially C. difficile, CMV in refractory cases)

Question 2: Codeine Phosphate or Diclofenac for Abdominal Pain?

Advice: Both should be AVOIDED or used with extreme caution.

Codeine phosphate:

Opioids reduce intestinal motility and mask symptoms, increasing the risk of toxic megacolon (life-threatening dilatation of the colon) in ASUC
Codeine is contraindicated in acute severe colitis for this reason
If analgesia is needed, paracetamol is the safest option

Diclofenac (NSAID):

NSAIDs are also contraindicated in IBD
They inhibit prostaglandin synthesis which is protective for the gut mucosa
NSAIDs can precipitate or worsen a flare of UC and increase the risk of colonic complications
They also carry risk of GI bleeding, which is already a concern here

Recommendation: Prescribe paracetamol PRN for pain. Avoid opioids and NSAIDs. Consider antispasmodics with great caution only after ruling out megacolon.

Question 3: Assessments Before Starting Infliximab

By Day 3, she is failing IV steroids (still >6 stools/day, CRP >45 mg/L). This meets criteria for rescue therapy with infliximab 5 mg/kg (weight = 65 kg → dose = 325 mg IV).

Mandatory pre-infliximab assessments:

Infections to screen and exclude:

Tuberculosis (TB): Chest X-ray + Mantoux test (tuberculin skin test) or IGRA (QuantiFERON-TB Gold). Infliximab is a TNF-alpha inhibitor - TNF is critical for containing latent TB granulomas. If latent TB is found, prophylactic isoniazid must be given for at least 4 weeks before starting infliximab
Hepatitis B: HBsAg, anti-HBc, anti-HBs. Active or occult HBV can reactivate catastrophically on anti-TNF therapy
Hepatitis C: Anti-HCV antibody
HIV: Baseline HIV status
CMV colitis: Sigmoidoscopy + biopsies/blood CMV PCR - CMV superinfection can mimic steroid-refractory UC and must be excluded before rescue immunosuppression

General baseline:

Full blood count, LFTs, renal function
Exclude sepsis / intra-abdominal abscess (CT abdomen/pelvis or AXR) - abscesses are a contraindication to infliximab
Check for bowel perforation or obstruction (AXR)
Pregnancy test in women of childbearing age
Check vaccination status - live vaccines should not be given within 3 months of anti-TNF therapy

Question 4: Dose and Nursing Staff Advice for Infliximab Administration

Dose:

5 mg/kg IV infusion
Patient weighs 65 kg → 325 mg
In acute severe UC, some centres use accelerated induction (weeks 0, 2, 6) and some use a single dose as rescue
It is given as an IV infusion over 2 hours, diluted in 250 mL 0.9% NaCl

Nursing advice for administration:

Pre-medication: Administer hydrocortisone 100 mg IV, paracetamol 1 g oral/IV, and chlorphenamine 10 mg IV 30 minutes beforehand to reduce risk of infusion reactions
Infusion rate: Start slowly (e.g., 10 mL/hr for first 15 minutes), then increase gradually. Never give as a bolus
Monitoring during infusion:
- Vital signs (BP, HR, temp, SpO₂) every 15 minutes for first hour, then every 30 minutes
- Observe for infusion reactions: flushing, urticaria, dyspnoea, chest tightness, hypotension
Anaphylaxis kit at bedside: Adrenaline (epinephrine) 1:1000, antihistamine, corticosteroids, and resuscitation equipment must be immediately available
If infusion reaction occurs: STOP the infusion, call the doctor, treat per anaphylaxis protocol
Documentation: Record lot number, expiry date, and time of infusion in notes (pharmacovigilance requirement)
Post-infusion observation: Observe patient for at least 1-2 hours after completion before discharge (though in this inpatient case, she is already admitted)

Case Study 2: Hepatitis C Diagnosis - 40-Year-Old Woman

The Clinical Picture

A 40-year-old woman discovers her donated blood is unusable because:

Elevated aminotransferases
Positive hepatitis C test

Specialist findings:

ALT = 871 IU/L (normal 3-39) - markedly elevated
AST = 103 IU/L (normal 8-42) - elevated
Bilirubin = 0.3 mg/dL - normal
Liver biopsy: chronic active hepatitis

She was placed on interferon + ribavirin for 3 months - but aminotransferases NOT responding.

Then: RT-PCR was NEGATIVE for HCV - so it is NOT hepatitis C!

Hidden history: 6 months ago she had a positive skin test for TB after discovering her partner is HIV+. She was treated in another city with isoniazid and completed the prescription but never returned.

The Real Diagnosis

The most likely diagnosis here is isoniazid-induced drug-induced liver injury (DILI), presenting as chronic active hepatitis. Isoniazid is one of the most common causes of drug-induced hepatitis.

Clues:

Anti-HCV positive (false positive is possible, or resolved acute HCV with residual antibody) but PCR negative = not active HCV infection
Started on isoniazid - a well-known hepatotoxin
Elevated transaminases, biopsy showing chronic active hepatitis

Question 1: Roles of 2nd and 3rd Generation Tests in HCV Diagnosis + Other Non-Viral Causes of Chronic Hepatitis

2nd and 3rd Generation HCV Tests

The testing hierarchy for Hepatitis C:

Test	Generation	What it detects	Notes
ELISA (enzyme immunoassay)	1st → 2nd → 3rd gen	Anti-HCV antibodies	Increasingly sensitive with each generation; 3rd gen detects antibody earlier (window period ~8 weeks)
RIBA (recombinant immunoblot assay)	2nd/3rd gen	Confirmatory antibody	Used to confirm positive ELISA; can distinguish true positive from false positive
HCV RNA (RT-PCR)	Molecular	Actual viral RNA	Gold standard - detects active infection; positive before antibodies appear; can be qualitative or quantitative

2nd generation ELISA:

Uses antigens from NS3, NS4, core regions
More sensitive than 1st gen
Still has false positive rate, especially in low-prevalence populations

3rd generation ELISA:

Adds NS5 antigen
Sensitivity >99%, but specificity still imperfect
Window period reduced to ~8-10 weeks

Role of RT-PCR (confirmatory / gold standard):

Detects HCV RNA directly
Confirms active infection - antibodies alone can persist after cleared infection
This is exactly what happened here: anti-HCV was positive (from possible past exposure or false positive), but RT-PCR was negative = no active HCV replication
Quantitative PCR (viral load) is used to guide and monitor treatment response

Practical algorithm:

Screen with 3rd gen anti-HCV ELISA
If positive → confirm with HCV RNA RT-PCR
If RNA positive → active infection, genotype and treat
If RNA negative → resolved infection or false positive antibody

Other Non-Viral (Other) Forms of Chronic Hepatitis

These are conditions that can mimic viral hepatitis clinically and histologically:

Cause	Key Features	Diagnosis
Autoimmune hepatitis (AIH)	Young women; elevated IgG; ANA/ASMA/anti-LKM positive; responds to steroids	Anti-smooth muscle antibody, ANA, liver biopsy
Drug-induced liver injury (DILI)	History of drug exposure (INH, methotrexate, minocycline, nitrofurantoin, methyldopa); resolves on withdrawal	Drug history, RUCAM score
Isoniazid hepatitis	Occurs in ~1% of patients on INH; dose-related; N-acetylhydrazine is toxic metabolite	Most relevant here
Alcoholic hepatitis	AST:ALT ratio >2:1; history of alcohol; fatty change on biopsy	History, AST/ALT ratio
Non-alcoholic steatohepatitis (NASH)	Metabolic syndrome; insulin resistance; steatosis on biopsy	Imaging, biopsy, exclude alcohol
Wilson's disease	Young patients; Kayser-Fleischer rings; neuropsychiatric features; low ceruloplasmin	Serum ceruloplasmin, 24h urine copper, slit-lamp exam
Haemochromatosis	Middle-aged men; elevated ferritin, transferrin saturation; "bronze diabetes"	Serum iron studies, HFE gene mutation
Alpha-1 antitrypsin deficiency	Associated with emphysema; PAS-positive globules in hepatocytes	Alpha-1 antitrypsin level, PiZZ phenotype
Primary biliary cholangitis (PBC)	Middle-aged women; pruritus; anti-mitochondrial antibody (AMA); elevated ALP	AMA, ALP, liver biopsy
Primary sclerosing cholangitis (PSC)	Often associated with IBD; bile duct strictures; pANCA positive	MRCP, ERCP, biopsy

In this case specifically: The most likely explanation is isoniazid-induced DILI masquerading as chronic active hepatitis. She should have isoniazid discontinued (she may have already finished it), be monitored for LFT recovery, and be evaluated for alternative TB prophylaxis if still at risk (given HIV-positive contact).

Summary of the two cases:

Case 1 tests knowledge of ASUC management - steroids, rescue therapy with infliximab (anti-TNF), pre-treatment screening, and safe administration
Case 2 tests knowledge of HCV diagnostic testing, the difference between antibody positivity and active viral infection (PCR-confirmed), and the broad differential of non-viral causes of chronic hepatitis, with isoniazid-induced hepatitis being the answer hiding in the history

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