Decompensation, viral hepatitis and surveillance

Complications of Decompensated Cirrhosis

1. Ascites & Serum-Ascites Albumin Gradient (SAAG)

Ascites is the pathological accumulation of fluid within the peritoneal cavity. Diagnostic paracentesis is mandatory for every patient with newly detected ascites or any cirrhotic inpatient undergoing clinical deterioration.

The SAAG Calculation

$$\text{SAAG} = \text{Serum Albumin Concentration} - \text{Ascitic Fluid Albumin Concentration}$$

Both samples should be drawn simultaneously.

• High SAAG: SAAG Value: $\ge 11\text{ g/L}$; Pathophysiological Mechanism: Portal Hypertension; increased hydrostatic pressure in hepatic sinusoidal and splanchnic capillaries.; Common Causes: Cirrhosis ($> 80\%$); congestive cardiac failure (Ascitic protein $\ge 25\text{ g/L}$); Budd-Chiari syndrome (hepatic vein thrombosis); constrictive pericarditis
• Low SAAG: SAAG Value: $< 11\text{ g/L}$; Pathophysiological Mechanism: Normal Portal Pressure; increased peritoneal capillary permeability or decreased plasma oncotic pressure.; Common Causes: Peritoneal carcinomatosis; peritoneal tuberculosis; nephrotic syndrome; acute pancreatitis; biliary ascites

Medical Management of Cirrhotic Ascites

1. Dietary Sodium Restriction: Limit daily sodium intake to $2000\text{ mg/day}$ ($88\text{ mmol/day}$). Fluid restriction is NOT indicated unless profound hypervolaemic hyponatraemia develops (serum sodium $< 120-125\text{ mmol/L}$).
2. Diuretic Therapy: Dual therapy targeting secondary hyperaldosteronism and distal nephron sodium reabsorption:
   • Spironolactone: Aldosterone antagonist; starting dose $100\text{ mg}$ once daily, titrated every 3-5 days up to a maximum of $400\text{ mg}$ daily.
   • Frusemide: Loop diuretic; starting dose $40\text{ mg}$ once daily, titrated up to $160\text{ mg}$ daily.
   • Maintain the 100 mg : 40 mg ratio to preserve serum potassium balance. Target weight loss: $0.5\text{ kg/day}$ without peripheral oedema, or $1.0\text{ kg/day}$ with peripheral oedema.

• Large-volume paracentesis: When more than 5 L is removed, albumin replacement is usually calculated against the total volume removed, often 8 g/L under local guidance. For 6 L, 8 × 6 = 48 g, not 8 g for only the litre above 5. Assess renal risk and protocol indications for smaller-volume taps.

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2. Spontaneous Bacterial Peritonitis (SBP)

SBP is an acute bacterial infection of ascitic fluid occurring in the absence of an identifiable surgically treatable intra-abdominal source. It arises from bacterial translocation of enteric organisms (predominantly Escherichia coli, Klebsiella pneumoniae, and Streptococcus pneumoniae) across an oedematous gut wall into mesenteric lymph nodes and ascitic fluid.

Diagnostic Criteria

• Mandatory bedside paracentesis prior to antibiotic administration.
• Diagnostic Threshold: Ascitic fluid polymorphonuclear (PMN) neutrophil count $\ge 250\text{ cells/}\mu\text{L}$ ($0.25 \times 10^9\text{/L}$).
• Fluid should be directly inoculated into blood culture bottles at the bedside to maximize microbiological yield.

Therapeutic Management

1. Empirical Antibiotic Therapy: Initiate promptly upon finding PMN $\ge 250/\mu\text{L}$:
   • Intravenous Ceftriaxone 1 to 2 g daily (or intravenous cefotaxime 2 g 8-hourly) for 5 days.
2. Intravenous Human Albumin Infusion: Mandatory adjunctive therapy to prevent hepatorenal syndrome and reduce mortality:
   • 1.5 g/kg body weight within 6 hours of diagnosis
   • 1.0 g/kg body weight on Day 3
   • Albumin therapy reduces the incidence of hepatorenal syndrome from $30\%$ to $10\%$ and cuts hospital mortality from $29\%$ to $10\%$.
3. Secondary Prophylaxis: Following recovery from a single episode of SBP, the 1-year recurrence rate reaches $70\%$. Indefinite oral antibiotic prophylaxis is mandatory (e.g. norfloxacin 400 mg daily or ciprofloxacin 500 mg daily) until liver transplantation or complete resolution of ascites.

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3. Hepatic Encephalopathy (HE)

Hepatic encephalopathy is a reversible neuropsychiatric disturbance caused by gut-derived neurotoxins (predominantly ammonia) bypassing hepatic metabolic clearance via intrahepatic shunting or portosystemic collaterals.

West Haven Staging

• Grade 1: Subtle attention, personality or sleep changes; clear asterixis is more typical of grade 2. Exclude infection, medicines, glucose/electrolyte disturbance and intracranial disease.
• Grade 2: Lethargy, marked apathy, slurred speech, obvious asterixis ('flapping tremor'), inappropriate behaviour.
• Grade 3: Somnolence, stupor, gross disorientation, incoherent speech, but responsive to voice.
• Grade 4: Comatose state, unresponsive to verbal stimuli; decerebrate or decorticate posturing.

Common Precipitating Factors (Must Be Actively Screened)

• Infections: SBP, urinary tract infection, pneumonia.
• Gastrointestinal Haemorrhage: Digestion of blood proteins delivers a massive ammonia load to the portal circulation.
• Constipation: Prolonged colonic transit enhances enteric ammonia generation and mucosal absorption.
• Electrolyte Derangements: Hypokalaemia and metabolic alkalosis (frequently caused by over-diuresis) promote the conversion of charged ammonium ($NH_4^+$) to uncharged, lipophilic ammonia ($NH_3$), which readily crosses the blood-brain barrier.
• Dehydration / Prerenal Azotaemia: Reduces renal clearance of urea.
• Sedating Medications: Benzodiazepines, opioids, z-drugs.

Management Algorithm

1. Identify and Correct the Underlying Trigger: Treat infection, stop diuretics, correct hypokalaemia, and control GI bleeding.
2. Lactulose (First-Line Therapy): Synthetic non-absorbable disaccharide fermented by colonic bacteria into lactic and acetic acid:
   • Luminal acidification ($pH < 5.0$) protonates ammonia ($NH_3$) into non-absorbable ammonium ($NH_4^+$), trapping it for faecal evacuation (ammonia trapping).
   • Induces an osmotic cathartic effect.
   • Dosing: $20-30\text{ mL}$ orally two to four times daily, titrated to achieve 2 to 3 soft bowel motions per day.
3. Rifaximin (Second-Line / Add-on): Non-absorbable oral rifamycin antibiotic (550 mg twice daily). Eradicates ammonia-producing gut bacteria. Indicated as adjunctive maintenance therapy following a second episode of hepatic encephalopathy to prevent recurrences.

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Hepatorenal syndrome and AKI

In cirrhosis with ascites and AKI, assess infection, bleeding, nephrotoxins, volume status, urine findings and obstruction. ADQI–ICA 2024 no longer requires an automatic 48-hour albumin challenge. When clinically indicated volume resuscitation has failed to improve renal function within 24 hours and no stronger alternative explanation exists, assess HRS-AKI with hepatology. Give vasoconstrictor/albumin therapy with careful fluid and respiratory monitoring and consider transplantation. Treat triggers concurrently; albumin in an already overloaded patient can cause harm.

Hepatocellular Carcinoma (HCC) Surveillance

HCC accounts for $> 90\%$ of primary liver cancers in Australia, arising predominantly on a background of established cirrhosis.

High-Risk Target Populations

1. All patients with established cirrhosis (Child-Pugh Class A or B; transplant-eligible Class C) regardless of aetiology.
2. Non-cirrhotic chronic Hepatitis B carriers with high-risk features:
   • Asian males $> 40\text{ years}$; Asian females $> 50\text{ years}$
   • African ethnicity $> 20\text{ years}$
   • Family history of hepatocellular carcinoma
   • High persistent HBV DNA viral load ($> 2000\text{ IU/mL}$) with active inflammation

Surveillance Protocol

• Modality: Transabdominal Liver Ultrasonography every 6 months $\pm$ serum alpha-fetoprotein (AFP).
• Six-month intervals reflect tumor doubling time, enabling detection of small, asymptomatic nodules ($< 2-3\text{ cm}$) amenable to curative therapies:
  • Surgical resection (single lesion in well-preserved Child-Pugh A liver without portal hypertension)
  • Orthotopic liver transplantation (meeting Milan Criteria: single lesion $\le 5\text{ cm}$ or up to 3 lesions each $\le 3\text{ cm}$ without macrovascular invasion or extrahepatic spread)
  • Radiofrequency ablation (RFA) or microwave ablation

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Viral Hepatitis Serology Interpretation

Accurate interpretation of viral hepatitis panels is a high-yield AMC examination skill.

Hepatitis B Serology Matrix

• Acute Hepatitis B: HBsAg: Positive; Anti-HBs: Negative; Total Anti-HBc: Positive; IgM Anti-HBc: Positive; HBeAg: Positive; Anti-HBe: Negative

• Chronic Hepatitis B (High replication): HBsAg: Positive ($> 6\text{ mo}$); Anti-HBs: Negative; Total Anti-HBc: Positive; IgM Anti-HBc: Negative; HBeAg: Positive; Anti-HBe: Negative

• Chronic Hepatitis B (Low replication): HBsAg: Positive ($> 6\text{ mo}$); Anti-HBs: Negative; Total Anti-HBc: Positive; IgM Anti-HBc: Negative; HBeAg: Negative; Anti-HBe: Positive

• Natural Immunity (Resolved infection): HBsAg: Negative; Anti-HBs: Positive; Total Anti-HBc: Positive; IgM Anti-HBc: Negative; HBeAg: Negative; Anti-HBe: Positive/Neg

• Vaccine-Induced Immunity: HBsAg: Negative; Anti-HBs: Positive; Total Anti-HBc: Negative; IgM Anti-HBc: Negative; HBeAg: Negative; Anti-HBe: Negative

• Window Period: HBsAg: Negative; Anti-HBs: Negative; Total Anti-HBc: Positive; IgM Anti-HBc: Positive; HBeAg: Variable; Anti-HBe: Variable

• HBsAg (Surface Antigen): Hallmark of active infection (acute or chronic).

• Anti-HBs (Surface Antibody): Marker of immunity and viral clearance. Protective titer is $\ge 10\text{ mIU/mL}$.

• Anti-HBc Total (Core Antibody): Marker of natural viral exposure; positive in anyone who has ever contracted HBV. Crucially negative in individuals with vaccine-induced immunity.

• IgM Anti-HBc: Indicates acute infection (present during the initial 6 months) or an acute severe flare of chronic hepatitis B.

• Hepatitis B: Interpret HBsAg, anti-HBc, anti-HBs and HBV DNA together. HBeAg negativity does not guarantee inactive infection: precore/core-promoter variants may replicate actively. Treatment and monitoring depend on DNA, ALT, fibrosis and clinical context.

• HBV DNA PCR: Quantifies viral load; guides initiation of nucleoside/nucleotide reverse transcriptase inhibitors (entecavir, tenofovir disoproxil, or tenofovir alafenamide).

Hepatitis C Diagnosis & Direct-Acting Antivirals (DAAs)

1. Screening Test: Anti-HCV Antibody. Indicates exposure to HCV at any time in the past.
2. Confirmatory Test: HCV RNA PCR. Detects active, viraemic infection.
   • Anti-HCV Positive + HCV RNA Positive: Confirms active hepatitis C infection. Treat with oral DAAs.
   • Anti-HCV Positive + HCV RNA Negative: Indicates past resolved infection (spontaneous clearance occurs in $15-25\%$) or successfully treated prior infection.
3. Treatment: Pan-genotypic direct-acting antivirals (e.g. sofosbuvir/velpatasvir for 12 weeks, or glecaprevir/pibrentasvir for 8 weeks) achieve Sustained Virological Response (SVR12) with cure rates $> 95\%$.
4. Critical Rule for Cirrhotics: Patients with cirrhosis who achieve SVR remain at persistent, lifelong risk of developing hepatocellular carcinoma and must continue 6-monthly ultrasound surveillance indefinitely.

Primary references (checked 7 October 2026): ADQI–ICA cirrhosis/AKI consensus.