(a) A 45-year-old hepatitis-C positive patient presents with icterus, oliguria, abdominal distention and blood in stools. Discuss…

(a) A 45-year-old hepatitis-C-positive patient with jaundice, oliguria, abdominal distension and blood in the stools (25 marks)

Working diagnosis. This is decompensated cirrhosis due to hepatitis C with jaundice, ascites, gastrointestinal bleeding (most likely from ruptured oesophageal or gastric varices) and acute kidney injury (oliguria), which is most likely hepatorenal syndrome (HRS-AKI) or pre-renal injury from bleeding or infection. Precipitating causes to look for are variceal haemorrhage, spontaneous bacterial peritonitis (SBP), sepsis, hepatocellular carcinoma with portal vein thrombosis, alcohol, and drugs (NSAIDs, diuretics).

Investigations.

• Bedside first: vital signs, mental state (encephalopathy grade), urine output, and rectal examination to confirm melaena or fresh blood.
• Blood tests: complete blood count (anaemia, thrombocytopenia from hypersplenism), prothrombin time/INR, liver function (bilirubin, AST, ALT, albumin), urea, creatinine, electrolytes (dilutional hyponatraemia), glucose, arterial blood gas and lactate, blood group and cross-match, and blood cultures.
• Aetiology and virology: HCV RNA (viral load) and genotype, anti-HCV, HBsAg and anti-HIV, and alpha-fetoprotein.
• Diagnostic paracentesis (in every patient with ascites): cell count (neutrophils of 250/mm³ or more mean SBP), total protein, albumin (a serum-ascites albumin gradient of 1.1 g/dL or more indicates portal hypertension), and culture inoculated in blood-culture bottles at the bedside.
• Kidney assessment: urine microscopy and protein (to exclude glomerular disease and acute tubular necrosis), urine sodium (below 10 mmol/L in HRS), and kidney ultrasound.
• Imaging: ultrasound of the abdomen with Doppler (a nodular liver, splenomegaly, ascites, portal vein thrombosis, a hepatic mass), with CT or MRI if HCC is suspected; a chest X-ray.
• Upper gastrointestinal endoscopy within 12 hours of resuscitation to find and treat the bleeding source (oesophageal or gastric varices, portal hypertensive gastropathy, ulcer).
• Severity scoring: Child-Pugh and MELD-Na scores (prognosis and transplant listing). The diagnostic criteria for HRS-AKI are cirrhosis with ascites; a rise of serum creatinine of 0.3 mg/dL or more within 48 hours, or 50% or more from baseline; no response after 2 days of diuretic withdrawal and albumin (1 g/kg/day); no shock; no nephrotoxic drugs; and no structural kidney disease (proteinuria below 500 mg/day, fewer than 50 red cells per high-power field, and a normal ultrasound).

Management. The patient should be treated in an intensive care or high-dependency unit.

• Resuscitation and the variceal bleed.
• Airway protection, two large-bore intravenous lines, and cautious volume replacement. Transfuse red cells only to keep haemoglobin at about 7–8 g/dL (a restrictive policy, since over-transfusion raises portal pressure); do not correct the INR routinely with plasma.
• Start a vasoactive drug at once, before endoscopy: terlipressin (2 mg IV, then 1–2 mg every 4–6 hours) or octreotide (50 µg bolus, then 50 µg/hour), for 2–5 days.
• Give prophylactic antibiotics (ceftriaxone 1 g daily for up to 7 days), which reduce infection, rebleeding and mortality.
• Endoscopic therapy: band ligation for oesophageal varices, and cyanoacrylate glue for gastric varices. If bleeding is uncontrolled, use a Sengstaken-Blakemore balloon tube as a bridge to TIPS (transjugular intrahepatic portosystemic shunt); pre-emptive TIPS within 72 hours is considered in high-risk patients (Child-Pugh C, or B with active bleeding).
• Give lactulose to prevent hepatic encephalopathy.
• Ascites and SBP. Restrict sodium (about 2 g/day). Stop diuretics while there is AKI. If SBP is present, give ceftriaxone or cefotaxime (2 g daily for 5–7 days) with intravenous albumin (1.5 g/kg on day 1 and 1 g/kg on day 3) to prevent renal failure. Large-volume paracentesis is done with albumin (8 g per litre removed above 5 litres). Long-term SBP prophylaxis (norfloxacin or ciprofloxacin) after an episode.
• Hepatorenal syndrome. Stop diuretics, NSAIDs, nephrotoxins and beta-blockers, then give albumin 1 g/kg (maximum 100 g) for 2 days. If AKI persists, start a vasoconstrictor with albumin: terlipressin (0.85 mg IV every 6 hours, or a continuous infusion) plus albumin 20–40 g/day, or noradrenaline in the ICU (or midodrine with octreotide when terlipressin is not available). Monitor for pulmonary oedema and ischaemic effects. Renal replacement therapy is a bridge for those who are transplant candidates.
• Hepatic encephalopathy (if present): lactulose (20–30 mL two or three times a day, to 2–3 soft stools) with rifaximin 550 mg twice a day, and treat precipitants (bleeding, infection, sedatives).
• Antiviral treatment (after stabilisation). Direct-acting antivirals, for example sofosbuvir-velpatasvir with ribavirin for 12 weeks (or sofosbuvir-daclatasvir under the National Viral Hepatitis Control Programme), guided by a transplant centre; protease-inhibitor regimens are contraindicated in decompensated disease, and interferon is not used.
• Supportive and long-term: nutrition (35 kcal/kg/day, protein 1.2–1.5 g/kg, a late-evening snack), abstinence from alcohol, avoidance of NSAIDs and sedatives, hepatitis A and B vaccination, screening for HCC every 6 months (ultrasound with AFP), secondary prophylaxis of variceal bleeding (non-selective β-blocker such as carvedilol or propranolol with repeated band ligation every 2–4 weeks until eradication), and referral for liver transplantation evaluation.

(b) A 12-year-old girl unimmunised since 1 year of age, for catch-up vaccination (5 + 5 + 5 = 15 marks)

(b)(i) Vaccination plan (5 marks)

Principles of catch-up. First check the vaccination card and the records, and count every dose already given as valid. Do not restart a series, only complete it. Several vaccines can be given at the same visit at different sites. Live vaccines are given on the same day or at least 4 weeks apart. Minimum intervals between doses must be respected, and there is no upper age limit for the doses listed below. It is assumed here that she completed the primary series in the first year (BCG, OPV, DTP/pentavalent, hepatitis B and measles), and missed the boosters.

Vaccines to give (as per the IAP recommendations).

• Tdap (tetanus, reduced-dose diphtheria and acellular pertussis) one dose, then Td every 10 years. If she has had no primary series, give three doses: Tdap, then Td at 1–2 months and Td at 6–12 months.
• MMR two doses at least 4 weeks apart (if she has not received two doses of a measles-containing vaccine).
• Varicella two doses at least 3 months apart (as she is under 13 years).
• HPV (for girls aged 9–14 years): two doses, 6 months apart.
• Typhoid conjugate vaccine: one dose.
• Hepatitis A two doses, 6 months apart; hepatitis B three doses (0, 1 and 6 months) only if she was not vaccinated.
• IPV (inactivated polio) one dose if there are no polio boosters; annual influenza vaccine; and the Japanese encephalitis, meningococcal or cholera vaccine only in endemic areas or for risk.

A practical schedule. Visit 1 (day 0): Tdap, MMR-1, varicella-1, hepatitis A-1, HPV-1 and typhoid conjugate. Visit 2 (4 weeks): MMR-2 (and the second Td if unvaccinated). Visit 3 (3 months): varicella-2. Visit 4 (6 months): HPV-2 and hepatitis A-2.

(b)(ii) Adverse events following immunisation (5 marks)

An adverse event following immunisation (AEFI) is any untoward medical event after vaccination that does not necessarily have a causal relation to the vaccine. The WHO classifies AEFIs by cause:

• Vaccine product-related reactions: local (pain, redness, swelling, induration, and BCG lymphadenitis or abscess), and systemic (fever, malaise, headache, irritability; the mild measles-like fever and rash 7–12 days after MMR). Severe reactions include anaphylaxis, febrile convulsions, hypotonic-hyporesponsive episodes, persistent inconsolable crying, thrombocytopenia (MMR), Guillain-Barré syndrome, intussusception (rotavirus), vaccine-associated paralytic poliomyelitis (OPV) and disseminated BCG disease in immunodeficiency.
• Vaccine quality defect-related reactions: a defect in the product, such as a faulty manufacturing batch.
• Immunisation error-related reactions (programme errors): a contaminated multi-dose vial causing an infected abscess or toxic shock syndrome, a wrong site or wrong dose, a wrong diluent, or an unsterile injection.
• Immunisation anxiety-related reactions: fainting (vasovagal syncope, common in adolescents) and hyperventilation.
• Coincidental events: an illness that happens to occur after vaccination without a causal relation.

Serious AEFIs must be reported and investigated.

(b)(iii) Anaphylaxis after vaccination (5 marks)

Clinical manifestations. Anaphylaxis is a severe, generalised, immediate hypersensitivity reaction, usually starting within minutes (up to 4 hours) of the injection. It is diagnosed on acute onset of skin or mucosal involvement together with respiratory compromise or hypotension (or involvement of two organ systems).

• Skin and mucosa: generalised flushing, urticaria and angio-oedema of the lips, face and tongue, itching.
• Respiratory: hoarseness, stridor, wheeze, cough and breathlessness, with cyanosis.
• Cardiovascular: tachycardia, hypotension, weak pulse, pallor and collapse (shock).
• Gastrointestinal: abdominal cramps, vomiting and diarrhoea; neurological: anxiety, dizziness and loss of consciousness.

Management. It is a medical emergency, and adrenaline is the first-line drug.

• Call for help, lay the patient flat with the legs raised (sit her up if breathless), and note the time.
• Give adrenaline (1 mg/mL, 1 in 1000) intramuscularly into the mid-outer thigh, 0.01 mg/kg (0.01 mL/kg), at once; for this girl about 0.3–0.5 mL (maximum 0.5 mg). Repeat every 5–15 minutes if there is no response.
• Give high-flow oxygen, and intravenous normal saline (20 mL/kg boluses) for hypotension. Establish an airway if there is upper-airway obstruction.
• Adjuncts (second line and not a substitute for adrenaline): nebulised salbutamol for bronchospasm, an antihistamine (chlorpheniramine or cetirizine) for itching and urticaria, and hydrocortisone.
• Observe for at least 4–6 hours (longer after a severe reaction) for a biphasic reaction, and hospitalise if severe. Report the event as a serious AEFI, and record the vaccine as contraindicated (with allergy referral) for the future. Prevention: observe every recipient for 30 minutes after vaccination, and keep an adrenaline kit ready at every session.

(c) Management of the microvascular complications of diabetes mellitus (10 marks)

Measures common to all. Optimise glycaemic control (an individualised HbA1c goal, usually below 7%), which delays the onset and progression of all microvascular complications (DCCT and UKPDS), control blood pressure to below 130/80 mmHg, a statin for lipids, stopping smoking, weight reduction and exercise, and regular screening: a dilated retinal examination at diagnosis of type 2 diabetes (5 years after diagnosis in type 1, or at puberty) and then every 1–2 years (yearly when there is retinopathy), urine albumin-creatinine ratio and eGFR every year, and a foot examination at every visit.

• Retinopathy. Mild to moderate non-proliferative disease needs only tighter control of glucose, blood pressure and lipids, with follow-up. For severe non-proliferative or proliferative retinopathy, give panretinal laser photocoagulation. For diabetic macular oedema, first-line treatment is intravitreal anti-VEGF injections (ranibizumab, aflibercept or bevacizumab), with focal or grid laser or steroid implants as alternatives. Vitrectomy is used for non-clearing vitreous haemorrhage and tractional retinal detachment. Fenofibrate may slow progression.
• Nephropathy (albuminuria of 30 mg/g or more, or a falling eGFR). Give an ACE inhibitor or an angiotensin receptor blocker at the maximum tolerated dose when there is albuminuria and hypertension, add an SGLT2 inhibitor (empagliflozin or dapagliflozin) to slow the decline in eGFR, and consider finerenone or a GLP-1 receptor agonist. Restrict dietary protein to 0.8 g/kg/day, avoid nephrotoxins (NSAIDs), adjust drug doses (metformin) to the eGFR, and manage anaemia and bone-mineral disorder. Refer to a nephrologist at eGFR below 30 mL/min, and plan dialysis or transplantation for end-stage disease.
• Neuropathy. For painful neuropathy, use pregabalin or gabapentin, duloxetine or amitriptyline, with topical capsaicin or lidocaine. Autonomic neuropathy is treated by symptom: postural hypotension (fluids, fludrocortisone), gastroparesis (small meals, metoclopramide), erectile dysfunction (sildenafil) and bladder dysfunction.
• Diabetic foot. Prevention is the aim: patient education, daily foot inspection, protective footwear, callus care and screening with a 10-g monofilament. An ulcer needs off-loading (a total-contact cast), debridement, culture-guided antibiotics, vascular assessment and revascularisation if needed, and a multidisciplinary foot team to avoid amputation; Charcot foot needs immobilisation.