Shravan Nadkarni: Post-hepatectomy Liver failure (PHLF) – Lets dive right in!

Shravan Nadkarni, Consultant Surgical Oncologist at  Karnataka Cancer Therapy and Research Institute Hubli-Dharwad, made the following post on Twitter:

“Post-hepatectomy Liver failure (PHLF) – Dreaded complication of a difficult surgery

Is there a unifying definition of PHLF?

What are the preventive strategies?

How best can it be managed?

Lets dive right in!

Leading cause of post-hepatectomy mortality

Rx Challenges?

Heterogeneity- Lack of uniform diagnostic Cx despite ISGLS Defn(2001)- variations prevalent
Predictability- Accurate preop predictions difficult
Therapy- No effective Rx once PHLF occurs

Prevention:

Applies to patients with Ⓝ and abⓃ preop liver func (provided other causes ruled out Eg. biliary Obs)

In preop INR/Bili- PHLF def INCREASING Sr Bil/INR on/after POD5 / need of FFP, clotting factors to maintain INR

Y POD5? (Reissfelder 2011)- median levels return to Ⓝ by

Severity –

Grade A – Non-clinically relevant postop deterioration of LFT – no deviation from expected course, no need of additional evaluation, managed in ward
Grade B – deviation frm usual postop course; managed without invasive Rx (FFP, albumin, NIV) transfer to intermediate care/ICU; Might need imaging & goal directed Rx
Grade C – Critical condition; Need Invasive Rx (drainage, hemodialysis, intubation, pressors)

Periop Mortality (Reissfelder 2011) – PHLF Gr A, B, C : 0%, 12%, 54%

“50-50” Criteria (Balzan et al, 2005) – combination of prothrombin time index <50% & Sr bilirubin >50 mmol/L (2.9 mg/dL) on POD 5

Sensitivity & Specificity in predicting PHLF – 50% & 97%

Peak Sr Bilirubin > 7 mg/dL – Sen/Spe : 93% & 94%)

ISGLS PHLF def does not provide general cut-off levels nor uses strict preop values to define INR & Bil

Levels are in reference to Ⓝ range acc to local labs & helps eliminate confounding fac & holds true regardless of d extent of resection/underlying disease status

Other scores – CTP- preop use to predict postop Px established. But, postop use confounded by bil obst, use of FFP/alb, bile leak MELD- designed for risk assessment for cirrhotics scheduled for TIPSS & to prioritize for LTx- but as a postop measure of func is controversial

Pitfalls of ISGLS Defn-

Clinical relevance of Gr A?
No distinction b/w 1° & 2° liver failure
Time point of applicability – POD 5 limited possibilities left to substantially influence & potentially Rx postop liver dysfunc since regeneration starts almost immediately

Therefore there seems to be an urgent need to develop predictive models for the 1st 48 postop hrs – guiding better Rx decisions to prevent PHLF than Rx it since Rx options are limited & most measures are at best ‘supportive’

Preop models to predict/stratify risk for PHLF ?

Combination of aspartate aminotransferase/platelet ratio index (APRI) & albumin–bilirubin grade (ALBI) score – Good preop risk assessment of postop outcomes
French Risk calculator for PHLF in cirrhotics

Need validation

Risk factors for PHLF – click here to view details.

FLR & PHLF – Functional liver remnant estimated by preop CT 3D recon correlates well with postop liver weight

Expressed as a % of liver minus d tumour –

Cut-off –

Healthy Liver – 20-30% FLR (0-6% PHLF)
Pre-existing liver disease (cirrhotics/cholestasis)- 40%

FLR is quantitative; presumes remnant liver to b optimally functional

ChemoRx effects/Liver dis – not accounted for

∴ Func assessment (quality) + FLR (quantity)

Post-PVE augmentation of FLR function is heterogenous

∴ total liver function & its distribution in FLR

Augmentation of FLR –

Portal V Embolization (PVE) -> compensatory growth of the FLR
ALPPS – accelerated 2-stage Sx combining PV occlusion + parenchymal transection induces rapid growth of FLR
PVE + HVE – of the specimen to be resected FLR hypertrophy

Management –

Goal – support organ function for spontaneous recovery

Symptom Mx – all aspects of modern intensive organ & patient support

Medical – Supportive measures
Surgical – Liver Tx
ECLS – details here.

Medical –

Antibiotics – prophylactic Abx – No benefit; if PHLF develops, aggressive Abx Rx infectious complications
Source control – imaging drainage of septic foci, ERAS, early drain removal, culture-directed Abx Rx
Lactulose – for hep enceph

Surgical – LTx The only definitive Rx in PHLF

Issues – Optimal time point of Tx? Justified in light of donor organ shortages?

∴ Rescue Rx, tertiary centres, for benign pathology

ECLS – bridging impaired function

Molecular adsorbent circulating system (MARS) – improved detoxification in acute/acute-on-chr liver failure – No survival benefit in RCT
Modified fractionated plasma separation & adsorption (Prometheus)
Single-pass albumin dialysis

Prevention strategies for PHLF:”

Source: Shravan Nadkarni/Twitter