12-phase flow (12)

1. 1FRAME
   Confirm jaundice (scleral icterus, T-bili >2.5 mg/dL); rule out carotenoderma (palms/soles only, no scleral involvement); fractionate bilirubin (direct vs indirect); compute R-factor (ALT/ULN)/(ALP/ULN) — >5 hepatocellular, <2 cholestatic, 2-5 mixed; identify pregnancy phenotype if applicable (ACG 2021; ACOG 2024)
   inputs: symptom_onset_tempo, pruritus_pain_pattern, pregnancy_status
   advance: Pattern + R-factor + bilirubin fractionation classified
2. 2ENTRY
   Yellow eyes / skin, dark urine, pale stool, elevated bilirubin, Charcot triad (jaundice + fever + RUQ pain), painless jaundice + weight loss in older adult (ACG 2021; Tokyo TG18 PMID 29032610)
   inputs: age
   advance: Entry pattern recognized
3. 3CONTEXT
   Alcohol, drugs (APAP quantity/timing, isoniazid, augmentin, statins, herbals — LiverTox), travel, IV drug use, sexual, transfusion, occupational, family history, pregnancy weeks of gestation (AASLD 2023)
   inputs: alcohol_use, current_meds, travel_or_sexual_or_iv_drug_use, sex, pregnancy_weeks_gestation
   advance: Context complete
4. 4RED_FLAGS
   Acute liver failure (INR ≥1.5 + encephalopathy + no prior cirrhosis — King's College O'Grady 1989 PMID 2490426), acute cholangitis (Charcot triad + grade I-III Tokyo TG18 PMID 29032610), APAP toxicity (Rumack-Matthew nomogram — Smilkstein 1988 PMID 3059186), Hy's Law DILI (ALT >3x + T-bili >2x without obstruction — Reuben 2010 PMID 20949552), HELLP / AFLP in pregnancy (ACOG 2024)
   inputs: inr, apap_ingestion_quantity_timing, apap_level, ammonia, lactate
   actions: workup.acute_liver_failure, workup.acute_cholangitis, workup.apap_overdose
   advance: ALF / cholangitis / APAP / DILI / pregnancy phenotype identified or excluded
5. 5INITIAL_WORKUP
   CBC, LFT (fractionated bilirubin + R-factor), INR, albumin, lipase, viral hep panel A/B/C/E, RUQ US (ACG 2021; BSG 2017; AASLD 2023)
   inputs: cbc, lft, inr, albumin, lipase, viral_hepatitis_panel, ruq_ultrasound
   actions: panel.cbc, panel.lft, panel.coag, panel.pancreas, workup.abnormal_lft
   advance: Stage-1 returned
6. 6BRANCHING_WORKUP
   By pattern. Hepatocellular (R >5): autoimmune panel + iron + ceruloplasmin (<40) + α1AT + HEV + biopsy if unclear. Cholestatic (R <2): MRCP / EUS first-line; ERCP if intervention planned (Tokyo TG18 PMID 29032610); AMA for PBC (EASL 2017 PMID 28427765); pANCA for PSC. Unconjugated: haptoglobin + retic + LDH + smear + Coombs for hemolysis. Pregnancy: bile acids + PT/PTT + fibrinogen + glucose for AFLP. Neonatal: Bhutani nomogram + Coombs + G6PD (route to peds engine if exists) (AASLD 2023; ACOG 2024)
   inputs: haptoglobin_retic_ldh_coombs, autoimmune_panel, ceruloplasmin, alpha1_antitrypsin, iron_studies, mrcp_or_eus, ct_abdomen_pancreatic_protocol, bile_acids_pregnancy, fibroscan_or_biopsy
   actions: workup.hcv_initial, workup.hemolysis, workup.acute_cholangitis
   advance: Branch workup completed
7. 7DIFFERENTIAL
   By bilirubin fractionation + R-factor. UNCONJUGATED: Gilbert, hemolysis (immune AIHA, MAHA, mechanical, G6PD), ineffective erythropoiesis, drug-induced (rifampin, probenecid), Crigler-Najjar, resorbing hematoma. CONJUGATED HEPATOCELLULAR (R>5): viral A/B/C/D/E, autoimmune, ischemic (shock liver), drug-induced (APAP, INH, augmentin), Wilson, hemochromatosis, α1AT, severe NAFLD/MASH. CONJUGATED CHOLESTATIC (R<2): choledocholithiasis, cholangitis, pancreatic Ca, cholangiocarcinoma, PSC, PBC, DILI cholestatic, sepsis-related, biliary stricture, parasitic. PREGNANCY: ICP, HELLP, AFLP, pre-eclampsia. NEONATAL: physiologic, breast-milk, Crigler, hemolysis, biliary atresia (AASLD 2023; ACOG 2024)
   advance: Differential narrowed by R-factor + fractionation
8. 8RISK_STRATIFICATION
   MELD-Na (Kim NEJM 2008 PMID 18768945), MELD 3.0, Child-Pugh, King's College for ALF (O'Grady 1989 — APAP arm: pH <7.30 OR all of [INR >6.5 + creat >3.4 + grade 3-4 HE]; non-APAP arm: INR >6.5 OR any 3 of 5 [age <10 or >40, non-A-non-B/halothane/DILI, jaundice-to-encephalopathy >7 d, INR >3.5, bilirubin >17.5]), Maddrey discriminant function ≥32 + Glasgow Alcoholic Hepatitis Score (GAHS) ≥9 + Lille d-7 score for alcoholic hepatitis (STOPAH 2015 PMID 25901427), Hy's Law (ALT >3x ULN + T-bili >2x ULN without obstruction) for DILI severity (Reuben 2010 PMID 20949552), Tokyo TG18 grade I/II/III for cholangitis (Kiriyama 2018 PMID 29032610), Bhutani nomogram for neonatal phototherapy threshold
   actions: calc.meld_na, calc.meld3
   advance: Severity scored
9. 9TREATMENT
   Diagnosis-directed: NAC IV 21-h protocol for APAP within window + non-APAP ALF per ALFSG (Smilkstein 1988 PMID 3059186), DAA for HCV (AASLD/IDSA), entecavir/tenofovir for HBV (AASLD 2018 PMID 29405329), prednisolone 40 mg PO × 28 d if Maddrey ≥32 + Lille d-7 to continue/stop (STOPAH 2015 PMID 25901427), ursodeoxycholic for PBC + obeticholic 2nd-line (EASL 2017 PMID 28427765), prednisone + azathioprine for AIH, ceftriaxone + metronidazole + ERCP within 6-12 h for grade III cholangitis or 24-48 h for grade I-II (Tokyo TG18 PMID 29032610), URSO for ICP + early delivery if severe (ACOG 2024), magnesium + early delivery for HELLP/AFLP, transplant evaluation for ALF / decompensated (AASLD 2023; Lee 2011 PMID 22213561)
   advance: Diagnosis-directed plan documented
10. 10DISPOSITION
    Home (rare, outpatient initiation), ED (acute presentation, ALF rule-out, biliary obstruction), ICU (ALF, severe cholangitis with sepsis), inpatient (ALF management, ERCP, transplant evaluation), outpatient (chronic workup) (ACG 2021)
    advance: Disposition documented
11. 11MONITORING
    Serial LFT + INR + ammonia (ALF), HCC surveillance US ± AFP q6 mo if cirrhotic (AASLD HCC 2018 PMID 29624699), EGD q1-3 yr if cirrhotic, audiometry if Wilson on chelation, repeat MELD-Na for transplant list (AASLD 2023)
    advance: Monitoring plan documented
12. 12FOLLOWUP
    Hepatology / GI / oncology / transplant evaluation; route decompensated cirrhosis → gi.cirrhosis.core.v1; route HE → gi.hepatic-encephalopathy.core.v1; route APAP → tox.acetaminophen-overdose.core.v1 (AASLD 2023)
    advance: Referrals scheduled