Ncpf

NON CIRRHOTIC PORTAL FIBROSIS

1. Non cirrhotic portal fibrosis Shankar Zanwar

2. Intrahepatic causes of portal hypertension

3. Definition Banti (1898) – synd. of splenomegaly and hypersplenism  PHT and anaemia in the absence of haematological disease. Non cirrhotic portal fibrosis/ idiopathic portal hypertension is Disease of unknown etiology Involves of small and medium branches of portal vein presence of portal hypertension Liver structure and function primarily remains normal NCPF recommendations APASL, Hep Intl, 2007

4. Epidemiology NCPF recommendations APASL, Hep Intl, 2007

5. Etio -pathogenesis factors Unknown, ultimately cause portal venous injury Environmental – Poverty Arsenic exposure – in 10% of cases Low levels of ADAMTS13 levels A Goel , C Eapen , IJG, 2016 Agents - Infections – endotoxins Host Prothrombotic diorders Autoimmunity – ↓ T1 lymphocytes, CD8 lymphocytes Sarin S K, J Hep 2014

6. Possible etiological factors Infections – bacterial, protozoal , schistosomiasis Drugs – Azathioprine, Vinyl chloride, copper sulphate( nila thotha ), didanosine , vitamin A Prothrombotic states – MPD(JAK 2), MTHFR etc Immune diseases – SLE, scleroderma, celiac disease

7. Pathogenesis animal model R Khanna , SK Sarin , J of Hep, 2014

8. Hemodynamics R Khanna , SK Sarin , J of Hep, 2014

9. Age and gender NCPF recommendations APASL, Hep Intl, 2007

10. Clinical manifestations Mass in LUQ – 12-69% Splenomegaly – 26-97% Anemia – 90% Variceal bleed – 32-84% - commonest Palpable liver – 33-54% Decompensation – 8- 20% Ascites – 9- 34% Edema feet – 4-18% R Khanna , SK Sarin , J of Hep, 2014

11. Lab findings Hypersplenism – 27-87% Abnormal LFT – 18-73% High bilirubin – 9- 31% Deranged INR – 4-81% Hypoalbuminemia – 16% Autonomic dysfunction – 25 – 67% ↓ α adrenergic response R Khanna , SK Sarin , J of Hep, 2014

12. Radiological features No e/o cirrhosis Subcapsular parenchymal atrophy Hyperechoic bands surrounding portal vein branches Peripheral pruning of PV br , sudden cut-off of 2 nd and 3 rd degree branches – withered tree appearance Splenomegaly, gamma gandy bodies Gurkaynak , j clin USG, 1998

13. Histopathology Phleboscleosis in 2/3 of PV – 40-100% Dilated portal venules – 40-70% Porto-portal fibrosis – 30-60% Portoseptal fibrosis – 17-60% NRH/FNH – 20-70% Dilated sinusoids - 90% Histological hallmark – Obliterative portal venopathy R Khanna , SK Sarin , J of Hep, 2014

14. Diagnostic criteria APASL criteria Presence of mod – sev splenomegaly E/o of PHT – varices of collaterals Doppler – patent – spleno -portal axis and HV LFTs – normal Biopsy - no e/o cirrhosis/ parenchymal injury Other features Absence of signs of CLD Absence of viral markers

15. HIV and NCPF Prevalence NCPF/IPH in HIV around 0.45 – 1% May be due to HAART especially didanosine Recurrent opportunistic infections hypercoagulability HIV per se due to infection of stellate cells Predominantly in males (50-100%), MSMs or prolonged infection (mean >11.5y) and IRIS HIV-NCPF patients are older, ↓ plts and CD4, ↑ LFTs Median kPa – 9.5, median HVPG 8mmHg LTx need reported Cachay , Br J Med, 2011

16. Natural history Long term survival after bleed management – 80-100% In 25-33%, slow parenchymal atrophy  decompensation Decompensations/complications – over 7 yrs after diagnosis PVT 46% Ascites 50% Liver failure 21% Hillaire , Gut 2002 Portal biliopathy – 9-40% of cases

17. Management Acute episodes Volume resuscitation Vasoactive drugs – somatostatin, octreotide and terlipressin EVL and EST effective 80-90% Glue for GOV-2 and IGV1 Secondary prophylaxis – NSBB and EVL equal efficacy NSBB – 47% ↓ in grade of varices, 18 % minor S/e Sarin SK, Gastroenterology, 2010

18. Prevention of bleed Primary prophylaxis All patients with moderate to massive splenomegaly, with suspected NCPF should have screeing OGD Primary EVL recommended for large varices but no consensus on NSBB BRTO is an option for large gastric varices Decompressive surgery is not recommended for primary prophylaxis

19. Secondary prophylaxis TIPS – uncontrollable bleed, recurrent variceal hemorrhages despite endotherapy and severe PHG bleed Surgical shunt – When accompanied by EHPVO – shunt surgeries effective mode of treatment Prevents recurrent bleeds, improves hypersplenism , with minimal risks of HE

20. Differences between NCPF and IPH NCPF IPH Gender Equal F>M 3:1 Age (Mean) 30y 40-45 Autoimmune factors Rare Common Parenchymal nodules Common Rarer Bile duct proliferation Common Rarer WHVP Normal Higher Hematemesis 94% 40% NCPF recommendations APASL, Hep Intl, 2007

21. NCPF mimickers Hepatic schistosomiasis Causatives – S. Mansoni , S. Japonicum Larval form reside in superior rectal tributaries, later in SMV Liver disease occurs due to entrapment of eggs in portal venules (<50mm)  granulomatous inflammation  fibrosis – Symmers pipe stem fibrosis 4-8% of these develop PHT Altered Th1/Th2 response

22. C/f of schistosomiasis are simliar to NCPF or EHPVO Diagnosis – eggs in stools or rectal Bx Stool micorscopy – Kato Katx method Serological tests using ELISA of egg antigens USG – thickened PV, septae along PV giving fish scale network appearnace CT shows capsular and septal calcification , irregular hepatic countour Natural history correlates with no. of eggs that parallels with eggs in stool

23. Treatment Praziquantel – complete resolution in 28.5% over 3-5 years - ↓ spleen size, SMV and SV diameter Recent metanalysis – artemesinin superior to praziquantel PHT – treatment as i NCPF Devascularisation surgeries better hemodynamic improvement than DSRS in schistosomiasis .

24. Congenital hepatic fibrosis Rare developmental disorder Abnormal ductal plate formation, irregular bile ducts  periportal fibrosis Majority (64%) a/w ARPKD, 25.6% a/w Caroli’s synd. remaining are isolated Median age at ∆ - 0-20 years Those a/w Caroli’s present with cholangitis (86%) and PHT(34%) Esopahgeal varices and hyperseplnism is common Ascites, HE and HPS is rare

25. Increased risjk of cholangioca . No relation between ARPKD severity and liver involvement LFTs usually normal except for cholangitis Imaging – dilated IHBR, enlarged left lobe, splenomagly +/- cysts in liver and kidney PHT treatment as in NCPF Definitive treatment is SLKT

26. Nodular regenerative hyperplasia Cause of NCPH in Europe(27%) and Japan(14%) Higher (7X) in people > 80 years Cause Chemotherpay Immunosuppresants Inflammator disorders Neoplastic disorders Pathogenesis – adaptive hyperplastic reaction of hepatocytes to functional/mechanical alteration in portal flow

27. HPE – complete/partial transformation of parenchyma into regenerative nodules with characteristic absence of septae PHT – result of presinusoidal compression Majority asymptomatic, symptomatics – c/f of PHT with preserved liver function Imaging nonspecific – nodules, variable enhancement , MRI – hyper in T1, hypo/ iso on T2 Rx – treatment of cause, PHT – endotherapy / TIPS.

28. Thank you