Liver Disease & Cirrhosis Management
The complications of portal hypertension, managed one by one
Portal hypertension and prognosis
One driver, many complications. Cirrhosis (fibrosis with nodular regeneration) raises resistance to portal flow. The consequences are esophageal and gastric varices, ascites (from splanchnic vasodilation) with its risk of spontaneous bacterial peritonitis (SBP), splenomegaly with thrombocytopenia, and hepatic encephalopathy from shunting of gut-derived ammonia around the liver. A falling platelet count is often the first laboratory hint.
Decompensation. Ascites, variceal bleeding, encephalopathy, or jaundice marks decompensation and sharply worsens survival. Synthetic failure lowers albumin and prolongs the INR.
| Feature | MELD (MELD-Na) | Child-Pugh |
|---|---|---|
| Inputs | Bilirubin, INR, creatinine (plus sodium in MELD-Na) | Bilirubin, albumin, INR, ascites, encephalopathy |
| Output | Predicted 90-day mortality | Class A (5–6 points), B (7–9), C (10–15) |
| Main use | Allocates liver transplants: higher MELD, higher priority | Grades overall severity and operative risk |
Ascites and spontaneous bacterial peritonitis
Tap first. Perform diagnostic paracentesis for new ascites and in any cirrhotic with ascites who is admitted or deteriorates (fever, pain, encephalopathy, rising creatinine); send cell count, albumin, protein, and culture. Coagulopathy is not a contraindication.
| Feature | SAAG ≥1.1 g/dL | SAAG <1.1 g/dL |
|---|---|---|
| Meaning | Portal hypertension | Peritoneal process or hypoalbuminemia |
| Causes | Cirrhosis, alcoholic hepatitis, heart failure, Budd-Chiari, portal vein thrombosis | Peritoneal carcinomatosis, tuberculous peritonitis, nephrotic syndrome, pancreatitis |
Treating ascites. Restrict sodium (about 2 g/day) and give spironolactone plus furosemide in a 100:40 mg ratio, raising both together as needed (up to 400:160). Avoid NSAIDs. Tense or refractory ascites is drained by large-volume paracentesis with IV albumin, about 6–8 g per liter removed (when more than 5 L is taken off); TIPS or transplant follows if it keeps recurring.
SBP. Infection of ascites without a surgical source, usually a single enteric organism such as E. coli or Klebsiella. It can be nearly silent: low-grade fever, mild tenderness, new confusion, or AKI. An ascitic neutrophil (PMN) count ≥250 cells/mm3 makes the diagnosis. Treat empirically without waiting for culture: cefotaxime or ceftriaxone plus IV albumin (1.5 g/kg on day 1 and 1 g/kg on day 3), which lowers the rate of hepatorenal syndrome and death.
Prophylaxis. Long-term ciprofloxacin (or TMP-SMX; norfloxacin is no longer available in the US) follows a prior SBP episode or an ascitic protein <1.5 g/dL. Every cirrhotic with GI bleeding gets short-term ceftriaxone (up to 7 days).
Polymicrobial culture, very low ascitic glucose, or very high protein or LDH suggests secondary peritonitis from a perforation: image the abdomen and involve surgery.
Varices and variceal hemorrhage
Preventing the first bleed. Screen with upper endoscopy when cirrhosis is diagnosed, unless liver stiffness is below 20 kPa with platelets above 150,000/μL, when screening endoscopy can be skipped (Baveno VII). Primary prophylaxis is a nonselective beta-blocker (carvedilol preferred; propranolol or nadolol) titrated to a resting heart rate of about 55–60, or endoscopic band ligation. β1 blockade lowers cardiac output and β2 blockade leaves α-mediated splanchnic vasoconstriction unopposed, so metoprolol is not a substitute.
- ResuscitateTwo large-bore IVs; transfuse restrictively (hemoglobin about 7–8 g/dL), since over-transfusion raises portal pressure.
- Octreotide plus ceftriaxoneOctreotide (somatostatin analog) constricts the splanchnic bed; ceftriaxone prevents infection and lowers rebleeding and death.
- Endoscopy within 12 hBand ligation of the bleeding varices.
- Refractory or recurrent bleedingTIPS; balloon tamponade only as a temporary bridge.
- Secondary prophylaxisNonselective beta-blocker plus serial banding.
TIPS decompresses the portal system by routing blood past the liver, so it can precipitate or worsen hepatic encephalopathy.
Encephalopathy and hepatorenal syndrome
Hepatic encephalopathy. Ranges from sleep reversal and inattention to asterixis, confusion, and coma. It is a clinical diagnosis: blood ammonia correlates poorly with severity and is not needed. Precipitants are GI bleeding, infection (including SBP), constipation, hypokalemia, dehydration or overdiuresis, and sedatives or opioids.
Treatment. Correct the precipitant and give lactulose titrated to 2–3 soft stools daily; it acidifies the colon, trapping ammonia as ammonium, and speeds its elimination. Add rifaximin, a poorly absorbed antibiotic, for recurrence. Do not restrict protein long term.
In any confused cirrhotic, search hard for a precipitant, especially GI bleeding and infection: look for melena and tap the ascites.
Hepatorenal syndrome. Functional renal failure: splanchnic vasodilation lowers effective arterial volume and triggers intense renal vasoconstriction. It is a diagnosis of exclusion: bland urine, low urine sodium, normal kidneys on ultrasound, no shock or nephrotoxins, and no improvement after stopping diuretics and giving albumin. Treat with albumin plus a vasoconstrictor (terlipressin, or norepinephrine in the ICU; octreotide with midodrine only if neither is available); liver transplantation is definitive.
Chronic liver disease: viral, metabolic, alcohol
| Feature | Hepatitis C | Hepatitis B |
|---|---|---|
| Goal | Cure: sustained virologic response >95% | Suppression, not cure |
| Drugs | Oral direct-acting antivirals: sofosbuvir plus ledipasvir or velpatasvir | Entecavir or tenofovir |
| Duration | 8–12 weeks | Long term, often indefinite |
| Who is treated | Essentially every viremic patient | Cirrhosis, active hepatitis (high DNA, raised ALT), or before immunosuppression; not every carrier |
| Screening | All adults once (antibody, confirm with RNA) | HBsAg in pregnancy and at-risk groups |
NAFLD (MASLD). Nonalcoholic fatty liver disease, now metabolic dysfunction-associated steatotic liver disease, accompanies obesity, diabetes, and the metabolic syndrome and is the most common chronic liver disease, usually with mild ALT-predominant elevation. NASH can progress to fibrosis and cirrhosis. Weight loss of 7–10% is the primary treatment; cardiovascular disease is the leading cause of death.
Alcoholic hepatitis. Heavy drinking, then fever, jaundice, and tender hepatomegaly. AST:ALT exceeds 2:1 with both usually under 300–500 IU/L, favoring alcohol over viral hepatitis. The Maddrey discriminant function, 4.6 × (patient PT − control PT) + bilirubin, of 32 or more marks severe disease and prompts prednisolone once infection and GI bleeding are excluded; the Lille score at day 7 gauges response and whether to stop. Abstinence is essential.
HCC surveillance. Abdominal ultrasound, with or without AFP, every 6 months in all cirrhotics and in at-risk chronic hepatitis B carriers. A new nodule, a rising AFP, or new decompensation prompts multiphase CT or MRI; arterial enhancement with washout is diagnostic without biopsy.
Acetaminophen toxicity
Mechanism. Acetaminophen is the leading cause of acute liver failure in the US. In overdose, glucuronidation and sulfation saturate, CYP2E1 makes more of the toxic metabolite NAPQI, and once glutathione is depleted the result is centrilobular (zone 3) necrosis. Chronic alcohol use and fasting lower the toxic threshold.
- 0–24 hNausea or no symptoms; labs may be normal.
- 24–72 hRUQ pain, rising transaminases.
- 72–96 hPeak hepatotoxicity and acute liver failure.
- After day 4Recovery, or death without transplant.
Management. Draw a level 4 hours after ingestion (earlier levels cannot be interpreted) and plot it on the Rumack-Matthew nomogram (treatment line 150 μg/mL at 4 h). Give N-acetylcysteine, which replenishes glutathione, for a level above the line. NAC is effective, low-risk, and works best within 8 hours, so start it empirically when ingestion time is unknown or injury is already present. Normal early labs never justify discharge.
Acute liver failure is an INR ≥1.5 with encephalopathy within 26 weeks in a patient without prior liver disease; refer early to a transplant center.