4.4 Hepatobiliary Disease, Cirrhosis & Acute Pancreatitis

Hepatobiliary Disease, Cirrhosis & Acute Pancreatitis

Hepatobiliary and pancreatic conditions constitute a major segment of acute medical admissions in the United Kingdom. Rapid differentiation between medical and surgical jaundice, prompt identification of biliary sepsis, and systematic severity stratification of acute pancreatitis are essential to prevent catastrophic deterioration.

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1. Differential Diagnosis of Jaundice

Jaundice (icterus) is the yellow pigmentation of sclerae, skin, and mucous membranes caused by hyperbilirubinaemia (clinically detectable when serum total bilirubin exceeds >35–50 umol/L; normal <21 umol/L). Pathophysiological classification depends on bilirubin fractionation and associated liver function test (LFT) derangements.

2. Gallstone Disease Spectrum (Cholelithiasis)

Gallstones affect ~15% of the adult UK population. Pathophysiology involves supersaturation of bile with cholesterol (80%) or bilirubin (pigment stones in haemolysis). The clinical spectrum spans asymptomatic carriage to life-threatening ascending cholangitis:

                              [ Gallstone Disease Spectrum ]
                                             │
             ┌───────────────────────────────┼───────────────────────────────┐
             ▼                               ▼                               ▼
     [ Biliary Colic ]             [ Acute Cholecystitis ]         [ Ascending Cholangitis ]
     • Transient cystic duct        • Persistent cystic duct        • Choledocholithiasis + 
       obstruction                    obstruction + infection         bacterial superinfection
     • Colicky RUQ pain < 6h        • Constant RUQ pain > 6h        • Charcot's Triad:
     • Provoked by fatty foods      • Fever, leukocytosis, CRP        - RUQ pain
     • Normal LFTs, no fever        • Positive Murphy's Sign          - Jaundice
     • Elective laparoscopic        • Thickened wall (>3 mm)          - Fever / Rigors
       cholecystectomy              • Laparoscopic Cholecystectomy  • Reynolds' Pentad (add Shock & Confusion)
                                      within 1 week of admission    • Emergency Resuscitation + IV Abx
                                                                    • Urgent ERCP Biliary Decompression

Acute Cholecystitis

• Clinical Presentation: Persistent, severe right upper quadrant (RUQ) or epigastric pain lasting >6 hours, radiating to the right infrascapular area (via phrenic nerve C3–C5 irritation). Accompanied by fever, anorexia, nausea, and vomiting.
• Physical Examination: Positive Murphy's Sign (palpation of the RUQ while the patient takes a deep breath produces sudden arrest of inspiration due to sharp pain when the inflamed gallbladder descends onto the examining hand).
• Diagnostic Imaging: Transabdominal Ultrasound is the initial investigation of choice; demonstrates gallstones, gallbladder wall thickening >3 mm, pericholecystic fluid, and sonographic Murphy's sign.
• Management: Nil-by-mouth, IV balanced crystalloids, adequate analgesia (NSAIDs or opioids), intravenous broad-spectrum antibiotics (e.g. IV co-amoxiclav), and early laparoscopic cholecystectomy within 1 week of presentation (ideally within 72 hours). NICE guidelines confirm that early index-admission surgery significantly reduces recurrent admissions and total hospital stay compared to delayed elective surgery.

Ascending Cholangitis

Ascending cholangitis occurs when choledocholithiasis or a biliary stricture causes complete biliary outflow obstruction, leading to bacterial stasis and purulent infection ascending into the intrahepatic biliary tree (predominantly Escherichia coli, Klebsiella pneumoniae, and Enterococcus species).

• Charcot's Triad:
  1. Right Upper Quadrant Pain
  2. Jaundice
  3. High Fever with Shaking Rigors / Chills
• Reynolds' Pentad: Charcot's triad PLUS hypotension (septic shock) and altered mental status (confusion/delirium). Signifies acute toxic suppurative cholangitis with catastrophic mortality.
• Emergency Management Protocol:
  1. Immediate aggressive fluid resuscitation according to Sepsis Six protocols.
  2. Intravenous broad-spectrum antimicrobials with high biliary penetration (e.g. IV piperacillin-tazobactam or cefotaxime + metronidazole).
  3. Urgent biliary decompression via Endoscopic Retrograde Cholangiopancreatography (ERCP) within 24 to 48 hours (or emergency ERCP within <12 hours if the patient is in septic shock or failing conservative medical therapy). Percutaneous transhepatic cholangiography (PTC) is the alternative if ERCP is anatomically unachievable.

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3. Cirrhosis & Complications of End-Stage Liver Disease

Cirrhosis represents end-stage hepatic fibrosis characterized by distortion of hepatic parenchymal architecture into regenerative nodules.

Ascites & Diagnostic Paracentesis

Diagnostic paracentesis is mandatory in all patients presenting with new-onset ascites or hospital admission for decompensated cirrhosis.

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

• High SAAG (≥ 11 g/L): Diagnostic of portal hypertension (transudative fluid driven by elevated hydrostatic pressure: cirrhosis, congestive cardiac failure, Budd-Chiari syndrome, constrictive pericarditis).
• Low SAAG (< 11 g/L): Excludes portal hypertension; indicates peritoneal disease or altered permeability (peritoneal carcinomatosis, tuberculous peritonitis, nephrotic syndrome, pancreatitis).
• Medical Management: Dietary sodium restriction (<2 g/day / 80 mmol/day), aldosterone antagonist spironolactone (100–400 mg once daily), and loop diuretic furosemide (40–160 mg daily). Large-volume paracentesis (LVP) for tense refractory ascites must be accompanied by intravenous human albumin solution (HAS, 20% solution) infusion at a dose of 8 g of albumin per litre of ascites removed over 5 litres, preventing post-paracentesis circulatory dysfunction.

Spontaneous Bacterial Peritonitis (SBP)

SBP is spontaneous infection of ascitic fluid without an identifiable surgically treatable source of intra-abdominal infection. It occurs in up to 20% of hospitalized cirrhotics with ascites.

• Diagnostic Hallmark: Ascitic fluid neutrophil (polymorphonuclear leukocyte [PMN]) count > 250 cells/mm³ (or >0.25 × 10⁹/L). Neutrophil count is calculated by multiplying total ascitic WCC by the percentage of neutrophils.
• Clinical Presentation: Can be remarkably insidious; low-grade fever, mild abdominal discomfort, worsening encephalopathy, or unexplained acute kidney injury.
• Treatment: Immediate empirical intravenous cefotaxime 2 g TDS (or ceftriaxone) PLUS intravenous human albumin solution (1.5 g/kg at diagnosis, followed by 1.0 g/kg on Day 3; albumin significantly reduces the incidence of hepatorenal syndrome from 30% to 10% and cuts mortality by two-thirds).
• Lifelong Secondary Prophylaxis: Following recovery, initiate lifelong oral ciprofloxacin (500 mg daily) or rifaximin to prevent recurrent SBP.

Hepatic Encephalopathy (HE)

Hepatic encephalopathy is a reversible neurocognitive syndrome resulting from failure of the cirrhotic liver to detoxify gut-derived nitrogenous waste products (primarily ammonia), compounded by portosystemic shunting.

• Clinical Features: Early reversal of sleep-wake cycle, apathy, personality change, progressing to confusion, lethargy, asterixis (bilateral flapping tremor), and coma.
• Precipitating Triggers: Constipation, infection (SBP, UTI), upper GI bleeding, electrolyte imbalance (hypokalaemia, hyponatraemia), dehydration (over-diuresis), and sedative medications.
• First-Line Pharmacological Management:
  1. Lactulose: Synthetic disaccharide titrated to produce 2 to 3 soft bowel movements per day. It is fermented by colonic bacteria into lactic and acetic acids; luminal acidification converts diffusible ammonia ($NH_3$) into non-absorbable ammonium ions ($NH_4^+$), trapping it in the bowel lumen for excretion.
  2. Rifaximin: Non-absorbable oral antibiotic (550 mg BD) added to lactulose for secondary prevention or refractory cases; suppresses ammonia-producing colonic bacteria.

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4. Acute Pancreatitis: Aetiology, Diagnosis & Severity Stratification

Acute pancreatitis is acute inflammatory necrosis of the pancreatic parenchyma induced by premature intracellular activation of digestive zymogens (trypsinogen to trypsin).

Aetiology: "I GET SMASHED"

• I – Idiopathic
• G – Gallstones (#1 cause in UK, ~45–50%)
• E – Ethanol (#2 cause in UK, ~30–35%)
• T – Trauma (blunt abdominal trauma, handle-bar injury in children)
• S – Steroids
• M – Mumps and other viruses (Coxsackie B, CMV, Epstein-Barr)
• A – Autoimmune pancreatitis (IgG4-associated pancreatitis)
• S – Scorpion venom (Tityus trinitatis)
• H – Hyperlipidaemia (serum triglycerides >11 mmol/L) / Hypercalcaemia (hyperparathyroidism)
• E – ERCP (post-procedure pancreatitis in 3–5%)
• D – Drugs (Azathioprine, 6-mercaptopurine, thiazide diuretics, sodium valproate, didanosine)

Diagnostic Criteria (The Atlanta Consensus)

Diagnosis requires at least 2 of the following 3 criteria:

1. Severe, acute-onset, persistent epigastric pain radiating directly through to the back, often relieved by leaning forward.
2. Serum amylase or lipase ≥ 3 times the upper limit of normal. (Serum lipase is more sensitive and specific than amylase; lipase remains elevated for 8–14 days, whereas amylase may normalize within 48–72 hours).
3. Characteristic cross-sectional imaging features of acute pancreatitis on contrast-enhanced CT, MRI, or transabdominal ultrasound.

Severity Stratification: The Modified Glasgow-Imrie Criteria

Assessed within the first 48 hours of hospital admission using the mnemonic PANCREAS:

Acute Management Principles

• Goal-Directed Fluid Resuscitation: Vigorous IV balanced crystalloids (Hartmann's solution), titrating to maintain a urine output >0.5 mL/kg/h and normalise haematocrit and lactate. Avoid excessive fluid overload.
• Adequate Analgesia: Intravenous opioids (morphine or fentanyl) titrated to pain score.
• Early Enteral Nutrition: Nil-by-mouth is outdated. Early oral feeding or enteral tube feeding (nasogastric or nasojejunal) commenced within 24 to 48 hours preserves the gut mucosal barrier, decreases bacterial translocation, and reduces septic complications compared to parenteral nutrition.
• Prophylactic Antibiotics: Routine prophylactic intravenous antibiotics are not recommended for either mild or severe sterile pancreatitis; antibiotics are reserved only for proven infected pancreatic necrosis (guided by CT-guided fine needle aspiration) or systemic sepsis.
• Gallstone Pancreatitis Management: In patients with concurrent cholangitis or persistent biliary obstruction, perform urgent ERCP with sphincterotomy within 72 hours. All patients with gallstone pancreatitis must undergo definitive cholecystectomy during the index admission (or within 2 weeks) to eliminate the high risk of recurrent, potentially fatal pancreatitis.

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Liver Abscess

• Pyogenic abscess: usually from biliary infection (cholangitis) or portal spread from bowel sepsis (appendicitis, diverticulitis); organisms include Klebsiella, E. coli and anaerobes. Fever, rigors and right upper quadrant pain with raised inflammatory markers; diagnose with ultrasound or CT and treat with percutaneous drainage plus IV antibiotics, looking for the source.
• Amoebic abscess (Entamoeba histolytica): after travel to endemic areas, often without preceding dysentery; diagnosed with serology and imaging and treated with metronidazole followed by a luminal agent.