Cirrhosis

Cirrhosis is the histologic end point of chronic liver injury of any cause: bridging fibrosis and regenerative nodules replace the normal hepatic lobular architecture, distorting intrahepatic blood flow (driving portal hypertension) and progressively impairing the liver's synthetic, detoxifying, and immune functions. Cirrhosis exists on a spectrum, not as a single fixed state.

Compensated cirrhosis is often clinically silent or produces only nonspecific fatigue — patients can look and feel well for years while fibrosis and portal hypertension quietly progress. Decompensated cirrhosis is defined by the onset of one of the major complications this chapter is built around: ascites, variceal hemorrhage, hepatic encephalopathy, or jaundice from hepatic synthetic failure. Each decompensating event roughly doubles mortality risk relative to the stage before it, which is why a first decompensation event is itself one of the two triggers (alongside a MELD score of 15 or higher) for transplant-centre referral, not a routine finding to simply treat and move on from.^[1]

Severity and prognosis are tracked with two complementary tools covered in Assessment & Diagnosis: the Child-Pugh score (bilirubin, albumin, INR, ascites, encephalopathy), which is simple, bedside, and still widely used for baseline staging and drug-dosing decisions, and the Model for End-Stage Liver Disease (MELD / MELD-Na), a purely laboratory-based score that better predicts short-term mortality and is what actually drives transplant waitlist priority.^[2][3]

Massive ascites — abdominal distension from fluid accumulation driven by portal hypertension — in a patient with decompensated cirrhosis. Tense ascites of this degree is generally managed with large-volume paracentesis rather than diuretics alone. (James Heilman, MD, CC BY-SA 3.0, Wikimedia Commons)

Compensated cirrhosis — often subtle

Many patients with compensated cirrhosis have no symptoms at all, or only nonspecific fatigue, mild right-upper-quadrant discomfort, or reduced appetite. Physical exam findings — stigmata of chronic liver disease — are the main clue in this stage, and none of them alone is diagnostic:

Decompensated cirrhosis — the defining complications

• Ascites — abdominal distension, new or accelerating weight gain, early satiety, dyspnea if tense enough to limit diaphragmatic excursion.
• Variceal hemorrhage — hematemesis or melena; a medical emergency (see Red Flags & Refer) rather than something managed in the ambulatory setting.
• Hepatic encephalopathy — ranges from subtle personality change and reversed sleep-wake pattern through confusion, asterixis, and coma; often precipitated by a specific trigger (infection, GI bleeding, dehydration, constipation, a new sedative, or electrolyte disturbance) that should always be sought (see Treatment Failure / Next Step).
• Jaundice — yellowing of the skin and sclera from failing hepatic bilirubin clearance; a marker of advancing synthetic failure, not merely a cosmetic finding.

Underlying causes of cirrhosis

• Alcohol-associated liver disease — risk rises with the quantity and duration of alcohol use; complete cessation is the single most important intervention regardless of how advanced the fibrosis already is.
• Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) — the updated nomenclature for what was previously called NAFLD/NASH; strongly linked to obesity, type 2 diabetes, and metabolic syndrome, and now one of the leading causes of cirrhosis in North America.
• Chronic hepatitis B or hepatitis C infection — antiviral suppression/cure reduces but does not eliminate the risk of progression once cirrhosis is established, and does not remove the need for ongoing hepatocellular carcinoma surveillance.
• Autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis.
• Hereditary hemochromatosis, Wilson disease, and alpha-1 antitrypsin deficiency.
• Cardiac/vascular causes — chronic right heart failure or constrictive pericarditis ("cardiac cirrhosis"), and Budd-Chiari syndrome (hepatic venous outflow obstruction).
• Chronic drug- or toxin-induced liver injury, and, in a meaningful minority, cryptogenic cirrhosis with no cause identified despite full work-up.

Risk factors for decompensation once cirrhosis is established

• Ongoing alcohol use, or poorly controlled metabolic risk factors (obesity, diabetes) in MASLD-related cirrhosis.
• Nonadherence to diuretic or lactulose/rifaximin therapy.
• Intercurrent infection of any kind, including spontaneous bacterial peritonitis.
• Use of a nephrotoxic drug (NSAID, aminoglycoside) or a drug that lowers effective renal perfusion (ACE inhibitor, ARB) — see Drug Tables.
• Large- or medium-caliber esophageal varices without primary prophylaxis in place.
• Dehydration from any cause, including over-aggressive diuresis or an unrelated GI illness.

Child-Pugh score

A simple, bedside severity score combining 2 laboratory values, 1 coagulation value, and 2 clinical findings. Score each parameter 1-3 points and sum for a total of 5-15.^[2]

Class A (5-6 points): well-compensated, best prognosis. Class B (7-9 points): significant functional compromise. Class C (10-15 points): decompensated, worst prognosis — this classification also drives several dosing decisions in Drug Tables.

MELD / MELD-Na

A purely objective, laboratory-based score originally developed to predict 3-month mortality and now the basis for liver-transplant waitlist priority in North America.^[3]

A pharmacist does not need to calculate MELD by hand day to day, but recognizing that a MELD ≥15, or any first decompensation event, is itself the transplant-referral trigger — not a number to simply note and move past — is directly relevant to catching a patient who needs escalation (see Red Flags & Refer).^[1]

Confirming the diagnosis and staging portal hypertension

• Cirrhosis is usually diagnosed from a combination of clinical findings, laboratory pattern (thrombocytopenia from splenic sequestration is often the earliest clue, together with a falling albumin and rising INR), and imaging or elastography rather than routine biopsy.
• Transient elastography (e.g., FibroScan) or other non-invasive fibrosis markers (FIB-4, APRI) are used to stage fibrosis and, increasingly, to risk-stratify for clinically significant portal hypertension without requiring endoscopy in every patient.^[5]
• Screening upper endoscopy for esophageal/gastric varices is performed at the time cirrhosis is diagnosed (or non-invasively risk-stratified first in compensated patients) to determine whether primary variceal-bleed prophylaxis is needed — see Choose Initial Treatment.
• Routine ongoing labs: CBC (thrombocytopenia tracks portal hypertension severity), INR, comprehensive metabolic panel (renal function and electrolytes are critical given diuretic therapy), and liver enzymes/bilirubin/albumin to recalculate Child-Pugh/MELD at each significant change in status.
• Hepatocellular carcinoma surveillance (ultrasound, with or without alpha-fetoprotein, every 6 months) continues indefinitely once cirrhosis is established, regardless of the underlying cause or how stable the patient currently appears.

• Prevent the first decompensation event, and prevent further decompensation once it has occurred.
• Control ascites to a comfortable, non-tense level without over-diuresis, hyponatremia, or renal injury.
• Prevent first (and recurrent) variceal hemorrhage through appropriate primary (and secondary) prophylaxis.
• Keep hepatic encephalopathy controlled at baseline and identify precipitants promptly when it worsens.
• Avoid or dose-adjust medications that are hepatotoxic, nephrotoxic, or that precipitate encephalopathy.
• Maintain adequate nutrition and prevent sarcopenia — never restrict protein.
• Complete alcohol cessation and appropriate immunization.
• Maintain hepatocellular carcinoma and variceal surveillance on schedule.
• Refer for transplant evaluation at the correct trigger point — a first decompensation event or MELD ≥15 — rather than waiting for further deterioration.

• Complete alcohol cessation — regardless of the underlying cause of cirrhosis, not only when alcohol is the primary etiology; continued use accelerates progression and worsens every complication in this chapter.
• Sodium-restricted diet — 2 g/day (about 88 mmol/day) once ascites is present; routine fluid restriction is not needed unless sodium falls below about 125 mmol/L.
• Adequate protein intake, not restriction — target 1.2-1.5 g/kg/day; a late-evening snack (roughly 50 g complex carbohydrate plus 25 g protein) helps offset the overnight catabolic state that develops faster in cirrhosis than in health. Protein restriction was once used to "protect" against hepatic encephalopathy — this is now recognized as outdated: it does not reliably improve encephalopathy and instead worsens the sarcopenia and malnutrition that independently predict poor outcomes.^[7]
• Avoid raw or undercooked shellfish — a real risk of severe, sometimes fatal Vibrio vulnificus infection in a cirrhotic patient, out of proportion to the risk in the general population.
• Maintain physical activity where possible to counter sarcopenia; refer to physiotherapy or a structured exercise program if frailty is present.
• Vaccination: hepatitis A and hepatitis B (if non-immune), annual influenza, pneumococcal vaccine, COVID-19 per current recommendations, and herpes zoster/RSV per standard age-based adult schedules — cirrhosis itself is an indication to keep these current, not a reason to defer them.
• Screening upper endoscopy for varices at diagnosis, repeated at an interval determined by findings and NSBB use (see Monitoring & Follow-Up).
• Hepatocellular carcinoma surveillance — ultrasound, with or without alpha-fetoprotein, every 6 months, continued indefinitely.
• Smoking cessation, and avoidance of unregulated herbal/dietary supplement products, which carry a disproportionate hepatotoxicity risk in an already-compromised liver.

Renal impairment and hepatorenal syndrome

Rising creatinine in a patient with ascites needs urgent evaluation — pre-renal azotemia, acute tubular necrosis, and hepatorenal syndrome (HRS-AKI) all need to be distinguished, and HRS-AKI is a diagnosis of exclusion made after volume expansion and stopping diuretics/nephrotoxic drugs fails to improve renal function.^[4] Treatment of confirmed HRS-AKI (terlipressin plus albumin where available, or midodrine plus octreotide plus albumin as an alternative) is specialist-directed and typically inpatient — this is not an ambulatory pharmacotherapy decision, but recognizing the picture and referring urgently is well within the pharmacist's role.

Coagulopathy and thrombocytopenia — "rebalanced hemostasis"

An elevated INR and a low platelet count are both common in cirrhosis, but current AASLD guidance is explicit that neither reliably predicts bleeding risk in this population — cirrhosis reduces both pro- and anti-coagulant factors in parallel, producing a fragile but often net-neutral ("rebalanced") hemostatic state rather than a simple bleeding tendency.^[8] Do not routinely correct INR with fresh frozen plasma or vitamin K, and do not routinely transfuse platelets, before a low-risk procedure based on the lab numbers alone.^[8] Anticoagulation itself is not categorically avoided in cirrhosis — current guidance supports treating symptomatic or extensive portal vein thrombosis, particularly in transplant candidates, despite a baseline elevated INR, because the same rebalanced-hemostasis principle applies; this decision requires specialist input rather than a reflex avoidance based on INR alone.^[8]

Pregnancy

Decompensated cirrhosis is uncommon in pregnancy (amenorrhea and reduced fertility often accompany advanced disease) but compensated cirrhosis with portal hypertension can and does occur; the physiologic plasma volume expansion of pregnancy increases variceal bleeding risk, so pre-conception variceal screening and prophylaxis are ideal when a pregnancy is planned. Propranolol is the preferred NSBB in pregnancy based on the broader obstetric safety experience with it; ACE inhibitors and ARBs (already avoided in ascites generally) are specifically contraindicated in pregnancy. Manage jointly with maternal-fetal medicine and hepatology.

Older adults / frailty

Diuretic-related hypotension and falls, and lactulose-related dehydration from diarrhea, carry disproportionate consequences in a frail older patient — titrate more conservatively and monitor more closely. Sarcopenia is often more advanced at presentation, reinforcing the nutrition guidance in Non-Pharmacologic Treatment.

MASLD-related cirrhosis / obesity

Weight loss and metabolic risk-factor control (glycemic control, lipid management) remain appropriate and beneficial even after cirrhosis is established, though rapid or aggressive weight loss should be avoided given sarcopenia risk — coordinate with hepatology on pace and target.

• Weight, symptom review, and renal function/electrolytes roughly every 1-2 weeks during active diuretic titration; space out once a stable maintenance dose is reached.
• Serum sodium and potassium at every diuretic dose change — both hyponatremia and hyperkalemia/hypokalemia are common triggers for dose reduction.
• INR, albumin, and bilirubin periodically to recalculate Child-Pugh/MELD, particularly around any change in clinical status or before a transplant-centre visit.
• Heart rate and blood pressure at every visit for a patient on an NSBB, confirming the resting-HR target (55-60 bpm) is being met without symptomatic hypotension.
• Surveillance upper endoscopy interval is determined by baseline findings and whether an NSBB or EVL was chosen — follow the treating gastroenterology/hepatology team's specific interval rather than a fixed platform-wide schedule.
• Hepatocellular carcinoma surveillance (ultrasound ± AFP) every 6 months, indefinitely, regardless of how stable the patient appears.
• Medication reconciliation at every encounter specifically for NSAIDs, ACE inhibitors/ARBs, new sedative-hypnotics, and uncapped acetaminophen use — these are easy to miss when prescribed by an unrelated provider (see Common Errors to Avoid and Drug Tables).
• Reassess adherence to sodium restriction, lactulose titration, and alcohol abstinence at every visit — nonadherence is one of the most common drivers of preventable decompensation.

1. Ascites not responding to standard diuretic titration — confirm dietary sodium adherence first (a surprisingly common cause of apparent "diuretic failure"), then confirm the 100:40 spironolactone:furosemide ratio is being maintained at the current dose before assuming refractoriness.
2. True refractory ascites (diuretic-resistant or diuretic-intractable, as defined in Choose Initial Treatment) — refer for transjugular intrahepatic portosystemic shunt (TIPS) evaluation or transplant assessment; continuing to push diuretics past the maximum tolerated dose does not help and increases the risk of renal injury.^[4]
3. Breakthrough or first variceal bleed despite adequate NSBB dosing (resting HR already at target) — this is an emergency requiring immediate hospital assessment, not an outpatient dose increase; secondary prophylaxis after the acute event typically combines an NSBB with EVL, unlike primary prophylaxis.^[5]
4. Recurrent overt hepatic encephalopathy despite lactulose plus rifaximin — actively search for and correct a precipitant (infection/SBP, GI bleeding, dehydration or over-diuresis, constipation, a new sedative or opioid, electrolyte disturbance) rather than escalating lactulose further; if none is found, reassess for a large spontaneous or TIPS-related portosystemic shunt that may need specialist-directed embolization.
5. Diuretic-induced acute kidney injury, hyponatremia, or hyperkalemia — hold the diuretic(s), correct the precipitating factor, and restart cautiously at a lower dose once resolved rather than resuming the prior dose unchanged.
6. MELD ≥15, or any decompensation event, in a patient not yet referred — refer for transplant evaluation now; do not wait for a "sicker" threshold.^[1]

• Restricting dietary protein to "protect" against hepatic encephalopathy — this is outdated, does not reliably help, and worsens sarcopenia and malnutrition.^[7]
• Routinely correcting an elevated INR with fresh frozen plasma or vitamin K, or transfusing platelets, before a low-risk procedure based on lab values alone — INR and platelet count do not reliably predict bleeding risk in cirrhosis ("rebalanced hemostasis").^[8]
• Prescribing or continuing an NSAID, ACE inhibitor, or ARB in a patient with ascites — all three reduce renal perfusion in a perfusion-dependent state and are explicitly flagged to avoid.^[4]
• Uncapped or long-duration high-dose acetaminophen use, particularly in decompensated cirrhosis, malnutrition, or ongoing alcohol use (see Drug Tables for a more conservative dosing ceiling in that setting).
• Stopping an NSBB outright for a single mildly low blood pressure reading rather than first checking whether the resting heart-rate target is otherwise appropriately controlled and reducing the dose rather than discontinuing.
• Missing spontaneous bacterial peritonitis because the presentation lacked classic severe abdominal pain — a low threshold for diagnostic paracentesis is appropriate for any new fever, abdominal discomfort, or otherwise-unexplained worsening encephalopathy or renal function in a patient with ascites.^[4]
• Increasing lactulose indefinitely for encephalopathy that isn't improving instead of searching for and correcting a precipitant.
• Over-titrating lactulose past the 2-3 stools/day target, causing dehydration that can itself precipitate encephalopathy.
• Combining an NSBB with band ligation for primary variceal prophylaxis — current guidance reserves that combination for secondary prophylaxis, not first-time prevention.^[5]
• Treating a first decompensation event as "just another flare" managed and discharged without transplant-centre referral, or waiting for a higher MELD before referring.^[1]
• Missing hepatocellular carcinoma surveillance because the patient has felt clinically stable for a long stretch — surveillance is time-based, not symptom-triggered.

How to use this table: Doses are adult doses and require patient-specific confirmation (renal/hepatic function, weight, allergy history). Pediatric dosing is weight-based per the current product monograph unless stated. Drug pricing is intentionally omitted. Select any drug name to open its complete Pharmasist Drug Database page.

Diuretics for ascites — dosed together, not alone

Titrate spironolactone and furosemide together, maintaining the 100:40 ratio at every step, to a maximum of 400 mg/160 mg daily.

Large-volume paracentesis adjunct

Nonselective beta-blockers — primary/secondary variceal-bleed prophylaxis

Titrate to a resting heart rate of 55-60 beats/min or the stated maximum dose, whichever comes first; hold/reduce for symptomatic hypotension.

Hepatic encephalopathy

Spontaneous bacterial peritonitis prophylaxis

Primary and secondary prophylaxis are long-term/indefinite; a GI-bleed-related course is short and separate.

Medications to avoid or dose-adjust in cirrhosis

Reduced hepatic clearance, hypoalbuminemia, and renal-perfusion dependence (once ascites is present) all argue for caution with these agents.

Coagulopathy management around procedures

INR and platelet count do not reliably predict bleeding risk in cirrhosis; avoid routine prophylactic correction.