12-phase flow (12)

1. 1FRAME
   ICP = pruritus (palms/soles, worse nocturnally, often without primary rash) + elevated non-fasting total bile acids ≥ 10 µmol/L ± mild transaminitis, presenting in 2nd/3rd trimester (typically > 24 wk). FETAL stillbirth risk is bile-acid-concentration-dependent (Ovadia 2019 IPD meta-analysis PMID 30773280: ≥ 100 µmol/L → HR 30.5 vs lowest tier). Delivery-timing decision is the primary clinical lever (SMFM Consult #53 Lee 2021 PMID 33197417: 36+0 wk if bile acids ≥ 100; 36+0–39+0 wk if < 100). UDCA is first-line for maternal SYMPTOM relief (GRADE 1A) but PITCHES RCT (Chappell 2019 Lancet PMID 31378395) showed no fetal-outcome benefit — counsel accordingly.
   inputs: gestational_age_weeks
   advance: GA + clinical phenotype documented; ICP pretest probability set; bile-acid tier informed delivery-timing decision framework
2. 2ENTRY
   Recognise ICP via pruritus pattern (palms/soles, nocturnal, typically without primary rash) ± elevated transaminases ± elevated bile acids; or recurrence in known prior ICP; or markedly elevated bile acids on screening. Differential at entry: PUPPP / atopic eruption of pregnancy (rash-dominant), pemphigoid gestationis (urticarial plaques + bullae), scabies (interdigital + nocturnal but with characteristic burrows), HELLP/pre-eclampsia (HTN + proteinuria + low platelets + transaminitis), AFLP (hypoglycemia + coagulopathy + encephalopathy), viral/drug-induced hepatitis (marked transaminase elevation + risk-factor history).
   inputs: pruritus_distribution_severity_and_timing
   advance: ICP clinical pattern confirmed or alternative diagnosis routed; lab workup initiated
3. 3CONTEXT
   Capture GA exact, prior ICP / familial cholestasis (recurrence 60-90%), multifetal gestation, estrogen/progesterone exposure history, pre-existing liver disease (viral hepatitis, PBC, PSC, autoimmune hepatitis), regional/ethnic background (Latin American, South Asian populations have higher prevalence), current medications (drug-induced cholestasis differential). Critical for pretest probability + delivery-timing + postpartum contraception counseling.
   inputs: prior_icp_or_familial_cholestasis, multifetal_gestation_status, estrogen_or_progesterone_exposure_history, known_liver_disease_or_hepatitis
   advance: Risk-factor context + comorbidity context captured
4. 4RED_FLAGS
   Bile acids ≥ 100 µmol/L (highest-risk tier; stillbirth HR 30.5 per Ovadia 2019 PMID 30773280) → delivery at 36+0 wk (SMFM 2021 GRADE 1B). New HTN + proteinuria + transaminitis → pre-eclampsia/HELLP route (ob.pre-eclampsia.core.v1 / ob.hellp-syndrome.v1). Hypoglycemia + coagulopathy + encephalopathy → AFLP route (ob.acute-fatty-liver-of-pregnancy.v1). Fever + marked transaminase elevation → viral hepatitis / chorioamnionitis ddx. Markedly elevated bilirubin + prolonged PT → vitamin K coagulopathy + PPH preparedness.
   inputs: maternal_temperature, maternal_bp, serum_total_bile_acids_non_fasting
   advance: Highest-risk bile acid tier identified; alternative diagnoses (PE/HELLP/AFLP) routed or excluded; vitamin K coagulopathy assessed
5. 5INITIAL_WORKUP
   Non-fasting serum total bile acids (defining lab) + ALT/AST + total/direct bilirubin + GGT + PT/INR + CBC + viral hepatitis serology (HAV, HBV, HCV, HEV) + RUQ ultrasound (rule out biliary obstruction; ICP imaging typically normal). Document bile acid tier (< 40 / 40-99 / ≥ 100 µmol/L per Ovadia 2019 PMID 30773280). Establish baseline for serial weekly trending until delivery.
   inputs: serum_total_bile_acids_non_fasting, liver_function_tests_alt_ast_bilirubin_ggt, pt_inr_baseline, cbc_with_platelets, viral_hepatitis_serology_hav_hbv_hcv_hev, right_upper_quadrant_ultrasound
   actions: panel.cbc, panel.lft, panel.coag
   advance: Bile acid tier set + LFTs + PT/INR documented; viral hepatitis ruled out; RUQ US confirms no biliary obstruction
6. 6BRANCHING_WORKUP
   If AST > 1000 OR markedly tender hepatomegaly OR risk-factor history → expand viral hepatitis ddx (HAV IgM, HBV core IgM, HCV PCR, HEV IgM, EBV/CMV PCR; consider acetaminophen level if exposure). If young + atypical + ANA-positive → autoimmune hepatitis workup. If HELLP features (low platelets + schistocytes + LDH) → workup.preeclampsia + ob.hellp-syndrome.v1. If hypoglycemia + coagulopathy + encephalopathy → AFLP workup (Swansea criteria; ob.acute-fatty-liver-of-pregnancy.v1). MRCP only if biliary dilation on US.
   actions: workup.preeclampsia, workup.abnormal_lft
   advance: Differential narrowed; alternative diagnoses routed or excluded
7. 7DIFFERENTIAL
   Viral hepatitis (HAV, HBV, HCV, HEV — HEV especially in endemic regions; severe in pregnancy); pre-eclampsia / HELLP (HTN + proteinuria + low platelets + transaminitis); AFLP (Swansea criteria; hypoglycemia + coagulopathy + encephalopathy); choledocholithiasis / cholecystitis (RUQ pain + biliary dilation on US); drug-induced liver injury (medication history; especially antibiotics, antiepileptics); autoimmune hepatitis (ANA, SMA, anti-LKM); primary biliary cholangitis (AMA-positive); PUPPP / atopic eruption / pemphigoid gestationis / scabies (rash-dominant skin disorders).
   advance: ICP anchored as diagnosis OR alternative diagnosis confirmed and routed
8. 8RISK_STRATIFICATION
   Bile acid tier drives delivery timing per Ovadia 2019 PMID 30773280 + SMFM 2021 PMID 33197417: < 40 µmol/L (lowest tier — stillbirth ~ 0.13%; deliver 39+0 wk per SMFM); 40-99 µmol/L (intermediate — stillbirth ~ 0.28%; deliver 36+0-39+0 wk per SMFM); ≥ 100 µmol/L (highest tier — stillbirth ~ 3.44%, HR 30.5; deliver at 36+0 wk per SMFM GRADE 1B). Co-existing risk modifiers: multifetal gestation, MSAF, prior stillbirth, GA already past delivery threshold.
   inputs: serum_total_bile_acids_non_fasting, gestational_age_weeks, multifetal_gestation_status
   advance: Bile-acid-tiered delivery-timing decision documented
9. 9TREATMENT
   URSODEOXYCHOLIC ACID (ursodiol) 10-15 mg/kg/day PO divided BID-TID for maternal pruritus (SMFM 2021 GRADE 1A; Lee PMID 33197417). PITCHES RCT (Chappell 2019 Lancet PMID 31378395) showed UDCA does NOT reduce adverse perinatal composite — symptom-relief indication only; counsel patient. ANTIHISTAMINES (diphenhydramine 25-50 mg PO q6h PRN, hydroxyzine 25 mg PO q6h PRN) for adjunct pruritus relief. EMOLLIENTS / topical cooling / oatmeal baths (non-pharm). VITAMIN K1 (phytonadione) 10 mg PO daily if PT prolonged or markedly elevated bilirubin (counter PPH risk). ANTENATAL CORTICOSTEROIDS (betamethasone via ob.preterm-labor.v1 ALPS regimen) if delivery anticipated < 37 wk and no prior course. DELIVERY at GA threshold per bile acid tier (SMFM 2021). AVOID cholestyramine (interferes with vitamin K absorption; superseded by UDCA). Rifampicin is a second-line option in refractory ICP but only with hepatology + MFM input — not routine.
   inputs: serum_total_bile_acids_non_fasting, gestational_age_weeks, pt_inr_baseline
   advance: UDCA initiated, adjunctive antihistamine + emollients prescribed, vitamin K if coagulopathy, delivery date set per bile acid tier
10. 10DISPOSITION
    OUTPATIENT for most: weekly bile acids + LFTs + antenatal fetal surveillance + delivery scheduled per bile acid tier. ED entry for new severe presentation (markedly elevated bile acids, intolerable pruritus, jaundice, suspected AFLP/HELLP overlap). INPATIENT for delivery admission per bile acid tier or for severe ICP with coagulopathy + PPH preparedness.
    inputs: gestational_age_weeks
    advance: Level of care set; delivery scheduled with appropriate L&D coordination
11. 11MONITORING
    Weekly serum total bile acids + ALT/AST + total bilirubin + PT/INR until delivery. Antenatal fetal surveillance (NST and/or BPP) starting at GA when delivery would be triggered by abnormal results (SMFM 2021 GRADE 2C); frequency individualised by bile acid tier. Pruritus severity scoring (visual analog 0-10). PT/INR re-check after vitamin K supplementation. Cervical readiness assessment for delivery timing. Continuous EFM intrapartum.
    inputs: serum_total_bile_acids_non_fasting, liver_function_tests_alt_ast_bilirubin_ggt, pt_inr_baseline, fetal_heart_rate_baseline
    actions: panel.lft, panel.coag
    advance: Serial trending stable or improving; delivery executed per timing decision
12. 12FOLLOWUP
    Symptoms typically resolve within days to a few weeks postpartum; bile acids + LFTs normalise within 4-8 wk. Persistent biochemical abnormalities > 3 mo postpartum → outpatient hepatology referral (rule out underlying PBC, PSC, hepatitis B/C, autoimmune hepatitis). Counsel ~ 60-90% recurrence in subsequent pregnancies + early presentation in any future pregnancy with pruritus. Estrogen-containing contraception relative caution (can re-trigger cholestasis; progestin-only or non-hormonal preferred until biochem normalised). Mental-health screen (EPDS) — chronic pruritus + stillbirth fear carries psychological burden.
    advance: Postpartum biochem normalised, recurrence + contraception counseling delivered, hepatology referral if persistent abnormalities, mental-health support arranged