Eduovisual
Gastrointestinal
Hepatorenal syndrome: recognition and management
— HRS-AKI (formerly type 1): Rapid rise in creatinine meeting AKI criteria (↑ ≥0.3 mg/dL in 48 h or ≥50% from baseline within 7 days). Median untreated survival ~2 weeks.
— HRS-NAKI: Includes HRS-AKD (subacute, <3 months, eGFR <60 or rising Cr <50%) and HRS-CKD (≥3 months). Slower decline; lower mortality but still poor.
— Spontaneous bacterial peritonitis (SBP) — single biggest trigger
— Large-volume paracentesis without albumin replacement
— GI bleeding, sepsis, overdiuresis
— NSAIDs, aminoglycosides, IV contrast in decompensated cirrhosis
— Portal hypertension → NO/prostaglandin-mediated splanchnic vasodilation
— ↓ Effective arterial volume → RAAS, SNS, ADH activation
— Renal cortical vasoconstriction with structurally intact kidneys (kidneys transplanted from HRS donors recover function)
Board pearl: Any cirrhotic patient admitted with ascites whose creatinine bumps — order a diagnostic paracentesis on admission to rule out SBP, the most common HRS trigger. Missing SBP is the highest-yield wrong-answer trap on Step 3 stems involving cirrhosis + AKI.
— Oliguria (<400 mL/day) often dominates
— Worsening ascites despite diuretics
— New or deepening hepatic encephalopathy
— Hypotension at baseline (SBP 85–95) — these patients live on the edge
— Jaundice progression, fatigue, anorexia
— Recent paracentesis volume and whether albumin 6–8 g/L of ascites removed was given (omission → post-paracentesis circulatory dysfunction → HRS)
— Fevers, abdominal pain, altered mental status → SBP
— Hematemesis, melena, recent variceal banding → GI bleed
— New meds: NSAIDs, ACEi/ARB, aminoglycosides, contrast study
— Diuretic escalation at home (furosemide + spironolactone)
— Recent infection (UTI, cellulitis, pneumonia, C. difficile)
— Alcohol use in last 30 days — acute alcoholic hepatitis is a major HRS substrate
— Prior SBP (recurrence rate ~70% without ppx)
— MELD trajectory — rising MELD-Na predicts HRS
— Variceal bleeds, TIPS history
— Transplant listing status (changes management urgency)
Step 3 management: On a CCS case, the first three orders for a cirrhotic with AKI are: (1) hold diuretics, NSAIDs, ACEi/ARB, nephrotoxins, (2) diagnostic paracentesis with cell count + culture, (3) IV albumin 1 g/kg/day × 2 days as the diagnostic-therapeutic volume challenge. If creatinine fails to fall after 48 hours of albumin + withdrawal of diuretics → HRS-AKI is the working diagnosis.
— Cachectic, sarcopenic, jaundiced
— Asterixis, fetor hepaticus → concurrent encephalopathy
— Somnolence in advanced disease
— Spider angiomata, palmar erythema, gynecomastia, testicular atrophy
— Dupuytren contractures, parotid enlargement (alcohol)
— Caput medusae, splenomegaly (portal hypertension)
— Terry's nails, clubbing (hepatopulmonary syndrome overlap)
— Tense ascites with fluid wave, shifting dullness
— Diffuse tenderness or rebound → SBP until proven otherwise (though SBP is often clinically silent — paracentesis regardless)
— Hepatomegaly may be absent in shrunken cirrhotic liver
— Low-normal to frankly low BP (MAP often 65–75)
— Wide pulse pressure, bounding pulses
— Resting tachycardia (often blunted if on nonselective beta-blocker)
— Warm, well-perfused extremities despite renal failure (vasodilation)
— JVP typically flat or low despite ascites — intravascular volume is depleted even when total body water is up
— Patient looks "wet" (ascites, edema) but is intravascularly dry
— POCUS: collapsible IVC, hyperdynamic LV
— This is why albumin (not crystalloid) is the volume of choice — colloid stays in the vascular space longer
Key distinction: In prerenal azotemia from GI bleed or overdiuresis, BUN/Cr >20:1, FeNa <1%, responds to volume. In HRS, same urine indices, but fails to respond after 48 h of albumin 1 g/kg/day. In ATN, muddy brown casts, FeNa >2% (less reliable in cirrhosis), urine sodium >40.
Board pearl: A cirrhotic on a nonselective beta-blocker (propranolol, nadolol) who develops HRS-AKI or refractory ascites — hold the beta-blocker. It worsens hemodynamics and is associated with increased mortality in this setting. Resume only after recovery.
— Cirrhosis with ascites
— AKI by KDIGO (↑Cr ≥0.3 mg/dL in 48 h or ≥50% from baseline within 7 days)
— No response after 2 days of diuretic withdrawal + albumin 1 g/kg/day (max 100 g/day)
— Absence of shock
— No current/recent nephrotoxins (NSAIDs, contrast, aminoglycosides)
— No macroscopic signs of structural kidney injury: proteinuria <500 mg/day, microhematuria <50 RBC/hpf, normal renal ultrasound
— CBC, CMP, Mg, Phos, LFTs, INR, lipase
— Urinalysis with microscopy — should be bland; casts or significant protein push toward ATN/GN
— Urine sodium and FeNa — typically Na <10 mEq/L, FeNa <0.2% (very low, mimicking prerenal)
— Urine creatinine for FeUrea if on diuretics (<35% suggests prerenal/HRS)
— Spot urine protein/creatinine ratio
— Lactate, blood cultures × 2
— Ascitic fluid analysis — cell count, differential, culture in blood culture bottles at bedside, albumin (SAAG), total protein, glucose, LDH
— Renal ultrasound with Doppler — exclude obstruction, assess kidney size/echotexture (should be normal in HRS), document renal artery flow
— Abdominal US/CT to assess liver morphology, portal vein patency, HCC
— CXR for hepatic hydrothorax, infection
— Urine NGAL — elevated in ATN, low in HRS; helps differentiate
— Urine IL-18, KIM-1 — research-tier
CCS pearl: On a CCS case, order paracentesis, blood cultures, urinalysis, renal US, and IV albumin on the same screen as initial labs. Delaying paracentesis by even 12 hours in suspected SBP increases mortality measurably.
— Hold all diuretics, beta-blockers, nephrotoxins
— Albumin 25% IV: 1 g/kg/day (max 100 g/day) × 2 days
— Reassess creatinine at 48 h
— No response (Cr fails to fall to within 0.3 mg/dL of baseline) → diagnose HRS-AKI and initiate vasoconstrictor therapy
— Response → diagnosis was volume-responsive prerenal AKI
— Proteinuria >500 mg/day or active sediment → workup for glomerulonephritis (HCV cryoglobulinemia, IgA, MPGN, HBV-associated MN)
— Order: complement (C3, C4), ANA, ANCA, cryoglobulins, hepatitis serologies, SPEP/UPEP, anti-PLA2R if nephrotic
— Renal biopsy rarely performed (coagulopathy, ascites) — transjugular approach if essential
— Recent hypotension, sepsis, contrast, aminoglycoside
— Muddy brown granular casts on micro
— FeNa often >2% (but unreliable on diuretics or in cirrhosis where it can be low)
— Urine NGAL elevated
— Tense ascites with bladder pressure >20 mmHg can mimic HRS — therapeutic paracentesis is both diagnostic and treatment
— Cirrhotic cardiomyopathy can produce a cardiorenal pattern
— Echo if suspected: blunted systolic response to stress, diastolic dysfunction, prolonged QT
— NT-proBNP elevated but interpret cautiously in cirrhosis
— Calculate MELD 3.0 / MELD-Na — drives transplant prioritization
— Child-Pugh class for surgical risk
— CLIF-SOFA if ACLF criteria met
Board pearl: A cirrhotic with AKI, proteinuria 3 g/day, hematuria, and low C4 — that's HCV-associated mixed cryoglobulinemia with MPGN, not HRS. Treat the underlying HCV + immunosuppression. Don't reach for terlipressin.
Key distinction: HRS = bland urine, normal kidneys structurally, no response to albumin. Anything else → look harder.
— Stage 1A: Cr <1.5 mg/dL with ≥0.3 rise — usually prerenal, manage conservatively
— Stage 1B: Cr ≥1.5 mg/dL — higher mortality, aggressive workup
— Stage 2: Cr 2–3× baseline
— Stage 3: Cr >3× baseline, ≥4 mg/dL, or RRT initiation
— Step 1 — Remove the insult: Hold diuretics, nonselective beta-blockers, NSAIDs, ACEi/ARB, nephrotoxic antibiotics. Avoid IV contrast.
— Step 2 — Identify precipitant: Paracentesis (SBP), blood/urine cultures, GI bleed eval, medication review. Treat infection empirically with ceftriaxone (community SBP) or piperacillin-tazobactam/carbapenem (healthcare-associated).
— Step 3 — Volume challenge: Albumin 1 g/kg/day × 2 days (max 100 g/day). This is both resuscitation and the diagnostic gateway to HRS.
— Step 4 — If no response at 48 h and HRS criteria met: Initiate vasoconstrictor + ongoing albumin (next chunk).
— Baseline MELD-Na — predicts response and transplant priority
— Bilirubin >10 mg/dL — lower response rates
— Cr >2.25 mg/dL at initiation — worse outcomes
— Mean arterial pressure rise ≥10 mmHg on therapy → strong response predictor
— Bridge to liver transplantation — the only definitive cure
— Reverse HRS in 40–50% with terlipressin
— Improve MAP by ≥10 mmHg or to >82 mmHg
— Refer early — every HRS-AKI patient who isn't already listed should be evaluated
— Combined liver-kidney transplant if dialysis >4–8 weeks or eGFR <30 sustained
Step 3 management: The pivot point on the exam: 48 hours of albumin without response = HRS confirmed = start vasoconstrictor. Don't keep flogging with more crystalloid — it worsens ascites and pulmonary status without correcting splanchnic underfilling.
CCS pearl: Place hepatology and transplant consults early — clock starts the moment HRS is suspected.
— Terlipressin 0.85 mg IV q6h, escalate to 1.7 mg q6h if Cr not down ≥30% by day 4
— Continue until Cr returns to within 0.3 mg/dL of baseline (complete response) or max 14 days
— Co-administer albumin 20–40 g/day throughout
— Response rate ~30–40% for full HRS reversal
— Mechanism: V1 receptor agonist → splanchnic vasoconstriction → restores effective arterial volume
— Exclude patients with SpO₂ <90% — terlipressin increases respiratory failure risk
— Avoid in ACLF grade 3 with severe respiratory or circulatory failure
— Caution in ischemic cardiovascular disease, PAD, severe asthma
— Monitor for digital/mesenteric ischemia, volume overload, hyponatremia
— Daily CXR, SpO₂, BP, fluid balance
— Norepinephrine + albumin (ICU only):
— Midodrine + octreotide + albumin (non-ICU, weakest evidence):
— Day 1: 1 g/kg (max 100 g)
— Subsequent: 20–40 g/day
— Monitor for pulmonary edema, especially with terlipressin
— Complete response: Cr to within 0.3 mg/dL of baseline → stop
— Partial response: Cr drops ≥50% but not to baseline → continue up to 14 days
— No response by day 4 at max dose: discontinue, escalate to RRT/transplant
Board pearl: A cirrhotic with HRS-AKI and SpO₂ 88% on room air — do not start terlipressin. Use norepinephrine in ICU instead. This SpO₂ cutoff is straight from the FDA label and a favorite stem.
Step 3 management: Always pair the vasoconstrictor with albumin — vasoconstrictor alone is inferior. Document MAP response at 48–72 h as your efficacy marker.
— Indications (same as any AKI): refractory hyperkalemia, acidosis, volume overload, uremic symptoms, severe azotemia
— Modality choice: CRRT preferred for hemodynamically unstable patients with cirrhosis (intermittent HD often poorly tolerated due to low MAP and intracranial pressure shifts with encephalopathy)
— Bridge intent: RRT in HRS is justified primarily as a bridge to transplant, not as destination therapy — outcomes without transplant are dismal
— Avoid initiating dialysis in patients not transplant candidates without a goals-of-care conversation
— Physiologically attractive: reduces portal pressure → reverses splanchnic vasodilation
— Selected use in HRS-AKI/NAKI: Child-Pugh ≤11, bilirubin <5, MELD <18, no severe encephalopathy
— Contraindications: Severe encephalopathy, heart failure, MELD >18, advanced age, pulmonary hypertension, active infection
— Risks: precipitates or worsens hepatic encephalopathy (up to 30%), heart failure
— Improves renal function in select patients but not first-line
— For tense ascites contributing to intra-abdominal hypertension/HRS physiology
— Always replace 6–8 g albumin per liter of ascites removed when >5 L drained
— Omitting albumin → post-paracentesis circulatory dysfunction → precipitates or worsens HRS
— All HRS patients should be evaluated urgently
— MELD exception points for HRS in some regions
— Simultaneous liver-kidney transplant (SLK) criteria:
— Safety net: kidney-after-liver allocation if renal function fails to recover post-LT
— Routine TIPS in HRS-AKI as first-line (small evidence base)
— Albumin dialysis (MARS) — no mortality benefit
— Aggressive crystalloid resuscitation
CCS pearl: On the CCS, transferring a HRS patient with rising Cr and worsening ascites to a transplant center is a graded action. Don't sit on the patient at a community hospital "trialing" more albumin past 48 hours.
Key distinction: TIPS treats the physiology; transplant treats the disease.
— Higher baseline sarcopenia and frailty — poorer transplant candidacy
— Liver Frailty Index and 6-minute walk should be incorporated in transplant evaluation
— Beware polypharmacy: NSAIDs for OA, ACEi for HTN, SGLT2 inhibitors — all can tip into HRS
— Reduced response rates to terlipressin in patients >70
— Higher cardiovascular event rate on terlipressin → screen with EKG, troponin baseline, consider stress imaging if listed for transplant
— Many cirrhotics have MASH + diabetic nephropathy or hypertensive nephrosclerosis
— Distinguishing acute HRS-NAKI vs CKD progression requires baseline Cr (look back ≥3 months)
— HRS-CKD is defined by eGFR <60 for ≥3 months without other structural cause
— Renal US: small echogenic kidneys argue for structural CKD, not pure HRS
— These patients may need SLK transplant rather than liver alone
— HRS-AKI in setting of ACLF has substantially worse prognosis
— Grade ACLF using CLIF-C ACLF score or EASL-CLIF criteria
— Grade 3 ACLF (≥3 organ failures) — 28-day mortality >70%
— Terlipressin still reasonable in ACLF grades 1–2; less effective in grade 3
— Early palliative care consultation appropriate alongside aggressive therapy
— Severe AH (Maddrey ≥32 or MELD ≥21) frequently complicated by HRS
— Prednisolone 40 mg/day × 28 days if no contraindication; assess response with Lille score at day 7
— Lille ≥0.45 → non-responder, stop steroids
— Selected severe AH non-responders may qualify for early liver transplantation at specialized centers
— Maintain albumin support; vasoconstrictor as needed
— Goals-of-care discussion is mandatory before initiating chronic RRT
— Median survival on RRT without transplant: weeks to a few months
— Time-limited trial often appropriate
Board pearl: Elderly cirrhotic on chronic NSAIDs for osteoarthritis presents with AKI — the answer is almost always stop the NSAID, give albumin, and reassess, not start terlipressin reflexively. Drug-induced prerenal AKI mimics HRS.
Step 3 management: Get a baseline Cr from the chart before labeling HRS — many "HRS" cases are CKD plus an acute insult.
— Pregnancy is uncommon in decompensated cirrhosis (subfertility) but occurs
— Acute fatty liver of pregnancy (AFLP) and HELLP can present with AKI mimicking HRS — distinguish carefully
— AFLP: hypoglycemia, ↑ammonia, coagulopathy, encephalopathy in 3rd trimester → urgent delivery is treatment
— Terlipressin is contraindicated in pregnancy (uterine contractions, fetal ischemia)
— Norepinephrine + albumin preferred if vasoconstrictor needed
— Multidisciplinary care: MFM, hepatology, transplant
— Avoid TIPS during pregnancy if possible (radiation, sedation)
— Rare; mostly biliary atresia, autoimmune hepatitis, Wilson disease, cystic fibrosis liver disease
— Same physiology, weight-based dosing
— Albumin 0.5–1 g/kg/day
— Terlipressin pediatric data limited; norepinephrine in PICU is workhorse
— Living-donor liver transplant often the bridge
— Calcineurin inhibitor (tacrolimus, cyclosporine) nephrotoxicity is the great mimic
— Check trough levels, hold or reduce dose, hydrate
— HRS can recur post-LT if graft fails
— HCV/HBV coinfection common (though HCV now curable)
— Tenofovir disoproxil — nephrotoxic; switch to TAF
— Watch protease inhibitor interactions with statins, midodrine
— Baseline hypoxemia from HPS complicates terlipressin candidacy (SpO₂ <90% cutoff)
— May force ICU norepinephrine route
— Increasingly prevalent in MASH cirrhosis
— SGLT2i → volume depletion, ketoacidosis risk → hold during acute illness
— GLP-1 RAs — hold if NPO or AKI
Key distinction: AFLP/HELLP in late pregnancy with AKI is not HRS — it's an obstetric emergency requiring delivery, not terlipressin. Misdiagnosis costs the fetus and the mother.
Board pearl: The Step 3 stem with a 32-year-old at 35 weeks gestation with jaundice, hypoglycemia, AKI, and coagulopathy is AFLP — answer is deliver the baby, not vasoconstrictor therapy.
— Progressive renal failure requiring RRT
— Refractory ascites — compounds intra-abdominal hypertension
— Hepatic encephalopathy — worsened by uremia, infection, and TIPS if performed
— Hyperkalemia, metabolic acidosis — drives RRT initiation
— Volume overload, pulmonary edema — exacerbated by aggressive albumin without monitoring
— Hyponatremia — often <125 mEq/L; correct slowly (<8 mEq/L/24 h) to avoid osmotic demyelination
— Coagulopathy bleeding — but cirrhotics are not protected from clotting; rebalanced hemostasis
— Terlipressin:
— Norepinephrine:
— Midodrine/octreotide:
— Albumin:
— TIPS: encephalopathy (30%), heart failure, hemolysis, shunt dysfunction
— Paracentesis: post-paracentesis circulatory dysfunction (if albumin omitted), hemorrhage, bowel perforation
— CRRT: citrate accumulation with hepatic dysfunction → check ionized:total Ca ratio >2.5 = toxicity
— Untreated HRS-AKI: median survival ~2 weeks
— Treated with terlipressin/albumin without LT: ~30–50% 90-day survival
— Post-liver transplant 5-year survival ~65% — transplant is transformative
Board pearl: A patient on terlipressin develops new dyspnea and bilateral infiltrates on day 3 — stop terlipressin, diurese carefully, switch to norepinephrine if ongoing vasoconstrictor needed. Don't keep pushing through.
Step 3 management: Monitor daily weights, I/Os, electrolytes, lactate, and ABG/SpO₂ in any patient on vasoconstrictor + albumin.
— Norepinephrine therapy (requires central line, arterial monitoring)
— Hemodynamic instability — MAP <65 despite albumin
— Grade 3–4 hepatic encephalopathy requiring airway protection
— Active GI bleeding with hemodynamic compromise
— Respiratory failure (hepatic hydrothorax, ARDS, terlipressin-induced)
— Severe acidosis or hyperkalemia awaiting RRT
— ACLF with ≥2 organ failures
— Hemodynamically stable on terlipressin (FDA label supports non-ICU)
— Adequate monitoring of SpO₂, MAP, fluid balance, mental status
— No active GI bleed, no respiratory compromise
— Hepatology — confirms diagnosis, manages cirrhosis complications
— Nephrology — co-manages AKI, RRT decisions
— Transplant surgery/hepatology team — even if patient is at a community hospital, call the nearest transplant center day one
— Interventional radiology — TIPS evaluation, vascular access
— Palliative care — for patients not transplant candidates, or alongside aggressive care for ACLF grade 3
— Infectious disease — if multidrug-resistant SBP or complicated infection
— Social work / case management — transplant logistics, insurance authorization, transport
— Patient is or could be a transplant candidate
— HRS-AKI not responding to 48–72 h of vasoconstrictor + albumin
— ACLF grade 2 or higher
— Need for TIPS at a high-volume center
— Severe alcohol-associated hepatitis being considered for early LT
— Not a transplant candidate (age, active substance use without sobriety pathway, comorbidities, social barriers)
— Multi-organ failure with low likelihood of recovery
— Patient/family preference for comfort
CCS pearl: On CCS, "transfer patient to transplant center" is often the correct late-game action when the local hospital has done all it can. Don't let the simulated clock burn — request transfer once HRS is confirmed and patient is a candidate.
Step 3 management: Document a code status conversation within the first 24 hours of any HRS admission — these patients deteriorate fast.
— Triggers: overdiuresis, vomiting/diarrhea, lactulose-induced, GI bleed, post-LVP without albumin
— BUN/Cr >20, FeNa <1%, bland sediment
— Responds to volume (albumin) within 48 h — this is the discriminator from HRS
— Treatment: hold diuretics, replete volume
— Triggers: prolonged hypotension, sepsis, IV contrast, aminoglycosides, vancomycin, NSAIDs
— Muddy brown granular casts, FeNa often >2% (less reliable in cirrhosis), elevated urine NGAL
— Does not respond to albumin
— Treatment: supportive, address underlying cause, RRT if needed
— Severe hyperbilirubinemia (>20 mg/dL) → bile casts in tubules
— Bilirubin-stained granular casts on urinalysis
— Treat with cholestyramine, plasmapheresis in select cases, address underlying cholestasis
— HCV → mixed cryoglobulinemic MPGN (low C4, cryoglobulins, palpable purpura, neuropathy)
— HBV → membranous nephropathy or polyarteritis nodosa
— IgA nephropathy — increased prevalence in cirrhosis ("cirrhotic glomerulonephritis")
— Active urine sediment, proteinuria >500 mg/day, hematuria
— NSAIDs — afferent vasoconstriction; common stem trigger
— ACEi/ARBs — efferent vasodilation
— Aminoglycosides, vancomycin, amphotericin — direct nephrotoxins
— Tenofovir DF — proximal tubulopathy
— Iodinated contrast (rare but possible)
— Tense ascites with intra-abdominal pressure >20 mmHg (measure via bladder pressure)
— AKI from renal vein/parenchymal compression
— Therapeutic paracentesis rapidly reverses
Key distinction: All of the above produce AKI in a cirrhotic. Only HRS requires vasoconstrictor therapy. The wrong diagnosis sends the patient toward harm — terlipressin in undiagnosed ATN won't help and may cause ischemia.
Board pearl: A cirrhotic post-contrast CT with AKI 24 h later and muddy brown casts → that's contrast-induced ATN, not HRS. Hold contrast, supportive care.
— Up to one-third of cirrhotic AKI cases
— Can coexist with HRS or precede it (SBP triggers HRS)
— Hypotension, lactate elevation, leukocytosis
— Treatment: early broad-spectrum antibiotics, albumin, source control — fluid resuscitation but albumin preferred to crystalloid in cirrhotics
— Avoid hydroxyethyl starch — increases AKI/mortality
— Diastolic dysfunction, blunted systolic reserve, prolonged QT
— Elevated BNP/NT-proBNP, but cirrhosis raises baseline
— Echo: E/e' >15, LA enlargement
— Right heart catheterization in select cases
— Treatment differs: cautious diuresis, address volume overload, not vasoconstrictor
— Common in advanced cirrhosis with sepsis
— Hypotension refractory to vasopressors
— Random cortisol <15 mcg/dL or delta <9 on cosyntropin → consider hydrocortisone 200 mg/day
— Frequent overlap with HRS
— Hydronephrosis on US
— Causes: BPH, stones, retroperitoneal malignancy
— Treatment: catheterization, urology consult
— Schistocytes, thrombocytopenia, elevated LDH, low haptoglobin
— TTP, HUS, DIC (DIC common in decompensated cirrhosis)
— ADAMTS13 if TTP suspected
— Malignancy (HCC paraneoplastic), milk-alkali, vitamin D
— Volume depletion + nephrogenic DI pattern
— Statin use, fall in alcohol intoxication, seizure
— CK markedly elevated, urine myoglobin
— Hydration, alkalinization
— Cirrhotics with sarcopenia have falsely low baseline creatinine — a "rise from 0.6 to 1.0" may represent more than it appears. Cystatin C is a better marker but not always available.
Key distinction: Cirrhotic AKI is a Venn diagram, not a single diagnosis. Many patients have two or three simultaneous mechanisms (SBP + HRS + drug-induced ATN). Treat all of them.
Board pearl: Refractory hypotension in a septic cirrhotic on max vasopressors — check random cortisol and consider stress-dose hydrocortisone. Hepatoadrenal syndrome is a real entity.
— Norfloxacin 400 mg PO daily (or ciprofloxacin 500 mg daily, or TMP-SMX DS daily in US where norfloxacin is unavailable)
— Indications:
— Sodium restriction <2 g/day
— Spironolactone + furosemide (100:40 ratio) — only resume after renal recovery and careful monitoring
— Serial therapeutic paracentesis with albumin 6–8 g per L removed for tense or refractory ascites
— Consider TIPS or transplant evaluation for refractory ascites
— Hold during HRS-AKI episode
— Resume cautiously after recovery if compensated and BP tolerates
— Avoid if SBP +1 or refractory ascites with SBP <90 — associated with mortality
— Use carvedilol 6.25–12.5 mg/day in selected compensated patients per Baveno VII
— NSAIDs (including OTC ibuprofen, naproxen, ketorolac)
— Aminoglycosides unless no alternative
— ACEi/ARB in decompensated cirrhosis with ascites
— IV contrast unless essential and pre-hydrated
— Alcohol cessation — counsel, refer to addiction medicine, naltrexone/acamprosate (avoid disulfiram), AUDIT-C screening
— HCV — DAA therapy (sofosbuvir/velpatasvir 12 weeks) — cures >95%, slows progression
— HBV — entecavir or tenofovir alafenamide (TAF preferred in renal disease)
— MASH — weight loss, GLP-1 RA, resmetirom (if available), control DM/HTN/dyslipidemia
— Autoimmune hepatitis — prednisone + azathioprine
— Hep A, Hep B, pneumococcal (PCV20 or PCV15→PPSV23), annual influenza, COVID, RSV, shingles if eligible
Step 3 management: At discharge after HRS reversal, the prescription pad should include: albumin plan for future paracentesis, SBP prophylaxis if indicated, lactulose/rifaximin if encephalopathy history, etiology-specific therapy, and a transplant clinic appointment.
— Hepatology clinic within 1–2 weeks post-discharge
— Labs: CMP, INR, CBC, MELD-Na every 1–2 weeks initially, then monthly when stable
— Transplant clinic visit within 2 weeks if listed or being evaluated
— Primary care follow-up at 1 month for medication reconciliation and comorbidity care
— Weight, orthostatic vitals, abdominal exam
— Mental status assessment (number connection test, animal naming for covert encephalopathy)
— Cr, BUN, electrolytes — especially Na (target ≥130), K
— Bilirubin, INR — drives MELD
— Platelets, albumin
— Urine sodium if guiding diuretic adjustment (spot UNa <30 = under-restricted diet or insufficient diuretic)
— Ultrasound ± AFP every 6 months in all cirrhotics
— Especially important post-HRS recovery — patients are alive, must not miss HCC
— EGD per Baveno VII — if no varices and compensated, q2–3 years; if small varices, annual; if large or post-bleed, banding program
— Nonselective beta-blocker decision individualized
— Strict alcohol abstinence — if alcohol-related; document sobriety for transplant listing (typically 6 months minimum, though early LT pathways exist)
— Dietary: 2 g sodium, adequate protein (1.2–1.5 g/kg/day — do not restrict in encephalopathy per current guidelines), late evening snack to reduce muscle catabolism
— Fluid restriction only if Na <125
— Medication list review — patient must know to avoid NSAIDs, ask pharmacy
— Sick-day plan: when to call (decreased urine, confusion, fever, abdominal pain, weight gain >2 lb/day, melena)
— Vaccinations updated at follow-up
— Prehabilitation for transplant: resistance training, nutrition, BCAA supplementation in selected patients
— Physical therapy if deconditioned
— Hepatic encephalopathy → driving counsel (impaired reaction time)
Board pearl: A cirrhotic post-HRS with covert encephalopathy who drives a school bus — the physician's duty to counsel against driving until cognitive testing improves is a high-yield ethics/safety crossover item.
CCS pearl: Schedule next appointment within 7–14 days on the CCS discharge screen — generic "1 month" is usually wrong for this fragile population.
— HRS-AKI in a non-transplant candidate carries a median survival of weeks
— Early, structured goals-of-care discussion is mandatory — not optional
— Document code status, healthcare proxy, advance directive within 24 hours of admission
— Offer time-limited trial of vasoconstrictor + dialysis with predefined endpoints
— Palliative care consult in parallel with aggressive care is standard, not "giving up"
— Listing decisions involve medical, psychosocial, and substance use criteria
— Alcohol abstinence requirements historically 6 months but increasingly individualized — early LT for severe AH at select centers
— Avoid discriminatory denial based on socioeconomic status alone — UNOS/OPTN principles require equitable evaluation
— Insurance navigation often becomes a determinant; case management critical
— Patient with grade 2–3 hepatic encephalopathy lacks decisional capacity — engage surrogate
— Consent for terlipressin must include respiratory failure risk, ischemic complications
— Consent for TIPS must include encephalopathy risk (~30%)
— Living donor liver transplant raises additional donor consent obligations
— Hepatic encephalopathy with cognitive impairment → counsel against driving; some states require physician reporting (e.g., CA, PA)
— Document the conversation
— Firearm safety conversation if depression/suicidality present (common with chronic illness, alcohol disorder)
— Medication reconciliation at discharge — NSAIDs, ACEi, herbal supplements (kava, comfrey hepatotoxic) often missed
— Avoid "automatic" home diuretic resumption — written instructions on when to restart and how to titrate
— Pharmacy callback within 72 h to verify adherence
— Closed-loop communication of pending labs/cultures to outpatient team
— Alcohol use disorder records protected under 42 CFR Part 2 — special consent for release
— HIV status in coinfected patients protected
— In ACLF grade 3 non-candidates, continued escalation may be non-beneficial; ethics consult appropriate when family and team disagree
Board pearl: A cirrhotic with HRS and grade 3 encephalopathy whose family insists on "everything" but who is not a transplant candidate — engage palliative care and ethics, frame a time-limited trial, and document.
Step 3 management: Always confirm decisional capacity before consenting a cirrhotic with encephalopathy — capacity, not competence, is the operative concept.
Board pearl: If the stem mentions a cirrhotic with bland urine, FeNa <0.2%, and no improvement after 2 days of albumin — terlipressin + albumin is the answer (or norepinephrine if SpO₂ <90% or ICU). Liver transplant evaluation is the long answer.
Step 3 management: When in doubt, albumin first, paracentesis early, transplant referral always.
— 58-year-old man with alcoholic cirrhosis, ascites, admitted with abdominal pain and fever. Paracentesis: PMN 450/mm³. Started ceftriaxone. On day 3, Cr rises from 1.0 → 2.4 despite IV fluids.
— Answer: Albumin 1 g/kg/day × 2 days; if no response, terlipressin + albumin. The trap: "increase IV crystalloid" (wrong — colloid preferred and patient needs vasoconstrictor logic).
— Cirrhotic underwent 8 L paracentesis without albumin replacement. Next day, BP 88/52, Cr 2.0 from baseline 0.8.
— Answer: Post-paracentesis circulatory dysfunction; give albumin — and the test wants you to recognize this could evolve into HRS.
— Cirrhotic with HRS-AKI, SpO₂ 87% on room air, scheduled for terlipressin.
— Answer: Hold terlipressin (boxed warning for respiratory failure). Use norepinephrine + albumin in ICU.
— Cirrhotic on naproxen for knee pain develops AKI. Urine bland, FeNa 0.3%.
— Answer: Stop NSAID, give albumin, reassess. Likely prerenal AKI, not HRS — albumin challenge clarifies.
— Cirrhotic with HRS on nadolol for varices.
— Answer: Hold the beta-blocker during HRS episode.
— HRS-AKI on terlipressin + albumin × 14 days, partial response, Cr still 2.8.
— Answer: Refer for liver transplant evaluation (or SLK if criteria met); consider RRT as bridge.
— Cirrhotic with HCV, AKI, proteinuria 2.5 g/day, hematuria, low C4, palpable purpura.
— Answer: Cryoglobulinemic GN, not HRS. Treat HCV (DAAs) ± immunosuppression.
— 30-year-old at 34 weeks with jaundice, AKI, hypoglycemia, coagulopathy.
— Answer: Delivery, not vasoconstrictor.
— Patient discharged after first SBP episode. What ppx?
— Answer: Norfloxacin 400 mg PO daily (or ciprofloxacin/TMP-SMX in US) — lifelong.
— Patient with recurrent encephalopathy drives a truck.
— Answer: Counsel against driving; in some states, physician reporting required.
Board pearl: The most common wrong answer across these stems is "give more crystalloid" or "start dopamine." Neither helps. Albumin + vasoconstrictor + transplant pathway is the winning trio.
Hepatorenal syndrome is functional AKI in advanced cirrhosis driven by splanchnic vasodilation and renal vasoconstriction, diagnosed by exclusion after a 48-hour albumin challenge in a patient with bland urine and no structural kidney disease, treated with terlipressin (or norepinephrine) plus albumin as a bridge to definitive liver transplantation.
Board pearl: Three things win exam points reliably — paracentesis on admission, albumin before crystalloid, and transplant referral before day 3. Memorize the SpO₂ <90% terlipressin contraindication and the post-LVP albumin dose (6–8 g/L). These are the highest-frequency, lowest-effort discriminators on Step 3 stems involving cirrhotic AKI.
Step 3 management: Diagnose by exclusion, treat by vasoconstriction, bridge by transplantation — and never forget the precipitant that started it all.