UPDATE ON THE MANAGEMENT OF COMPLICATIONS OF PORTAL HYPERTENSION

Transcription

1 UPDATE ON THE MANAGEMENT OF COMPLICATIONS OF Mitchell L. Shiffman, MD, FACG Director Liver Institute of Virginia Bon Secours Health System Richmond and Newport News, VA Liver Institute of Virginia Education, Research and Treatment for Patients with Liver Disease POTENTIAL CONFLICTS OF INTEREST Bayer: Advisor Speaker

2 ETIOLOGIES Cirrhosis Non-cirrhotic portal hypertension Vascular insults Cardiac or pulmonary disease Liver diseases in the absence of cirrhosis NON-CIRRHOTIC Imaging suggests a normal appearing liver Hepatic synthetic and metabolic function is intact Platelet count is normal AST/ALT ratio < 1.0

3 CATEGORIES AND ETIOLOGIES Pre-hepatic Hepatic Post-hepatic Pre Sinusoidal Post Portal vein thrombosis Splenic vein thrombosis Sarcoidois Primary Biliary cirrhosis Primary sclerosing cholangitis Cirrhosis Hepatic vein sclerosis/occlusion Pulmonary hypertension with TR Right sided CHF with TR IVC webs Hepatic vein thrombosis HEPATIC VENOUS PRESSURE IVC RA Free HV Wedge HV RA IVC Free HV Wedge HV HVPG Normal <5 Pre- Hepatic Pre- Sinusoidal Post- Post- Hepatic E E E E + E E E E

4 PORTAL VEIN THROMBOSIS ROLE OF ANTICOAGULATION Anti-coagulation for PVT No Possible Definate Cirrhosis Long standing Cavernous transformation No cirrhosis Chronic PVT Hypercoaguable state No cirrhosis Acute symptomatic PVT Abdominal pain Bowel ischemia Bacteremic or intrahepatic abcess Short term anticoagulation Long term if hypercoguable state S Parikh et al Am J Med 2010; 123: ETIOLOGY IN CIRRHOSIS Hepatocytes Space of Disse Stellate cells Kupffer and endothelial cells

5 ETIOLOGY IN CIRRHOSIS Stellate cells secrete collagen matrix Kupffer and endothelial cells ETIOLOGY IN CIRRHOSIS Stellate cells secrete collagen matrix Endothelial cells fatten Fenestrations close

6 SEQUENCE OF EVENTS Sinusoidal fibrosis and loss of endothelial fenestrations Loss of sinusoidal compliance Sinusoidal pressure increases Salt and water retention Portal hypertension develops when HVPG exceeds 12 mm Hg Collateral circulation Shunting portal blood ASCITES VARICES HEPATIC ENCEPHALOPATHY COMPLICATIONS Gastrointestinal bleeding Ascites and edema Hepato-renal syndrome Hyponatremia Hepatic encephalopathy Malnutrition Infections Hepatocellular carcinoma

7 PORTAL HYPERTESNION VARICES AND PLATELET COUNT Platelet Count (x1000) None Small Medium Large VARICEAL SIZE AJ Sanyal et al. Gastrointest Endosc 2006; 64: ESOPHAGEAL VARICIES APPEARANCE AND GROWTH 80 % of Patients Varices at Baseline: None Small M Merli et al. J Hepatol 2003; 38: YEARS

8 PREVENTING VARICIES FROM FORMING BETA-BLOCKERS Free of Varicies (%) N= MONTHS Placebo Timolol R Groszman et al. N Engl J Med 2005; 353: PREVENTING FIRST VARICEAL BLEED BAND LIGATION vs BETA-BLOCKERS Banding Delta Chen /26 (4%) 2/30 (7%) 3% Sarin /45 (9%) 12/44 (27%) 18% De /15 (13%) 1/15 (7%) -6% Jutabha /18 (0%) 1/17 (6%) 6% De la Mora /12 (8%) 2/12 (17%) 9% Lui /44 (7%) 9/66 (14%) 7% Lo /50 (20%) 16/50 (32%) 12% Schepke /75 (25%) 22/77 (29%) 4% TOTAL 40/285 (14%) 65/311 (21%) 7% MS Khuroo et al. Aliment Pharmacol Ther 2005; 21:

9 ESOPHAGEAL VARICES APPROACH Cirrhosis Endoscopy if platelets < 150,000 No Varicies Small Varicies Medium-Large Varicies Follow-up EGD Q 2-3 years Longacre AV, G Garcia-Tsao. Clin Liver Dis 2006; 10: Follow-up EGD Q 1-2 years Beta-Blockers or Band Ligation NON-ESOPHAGEAL VARICES Gastric varices Spontaneous-spleno-renal shunt Portal hypertensive gastropathy Gastric antral vascular ectasia (GAVE) Portal hypertensive enteropathy Portal hypertensive colonopathy

10 GASTRIC VARICES Short Gastric Gastric Varices (GOV 1 or 2) 25% of all GOV SMV SPONTANEOUS SPLENO-RENAL SHUNT GASTRIC VARICES Gastric Varices (GOV 1 or 2) 25% of all GOV SMV SPONTANEOUS SPLENO-RENAL SHUNT

11 GASTRIC FUNDAL VARICES Cardia (GOV1 and 2) Associated with Spontaneous Spleno-renal shunt Preferential flow through the low resistance shunt pathway Tend to rebleed following the initial bleed Difficult to manage Sclerotherapy Cyanoacrylate glue TIPS Embolize or balloon occlude the short gastric blood supply to gastic varices and/or the SSRS GASTRIC FUNDAL VARICES SCLEROTHERAPY GV (n=60) GOV1 (n=18) GOV2 (n=27) Number of sessions 2.6 ± ± ± 1.4 Amount of sclerosant (ml) 20.7 ± ± ± 14.6 Successful obliteration (%) Time until obliteration (wks) 6.9 ± ± ± 5.9 Rebleeding (%) Follow-up (months) 24.2 ± ± ± 26.4 SK Sarin Gastrointest Endosc 1997; 46:8-14.

12 GASTRIC FUNDAL VARICES CYANOACRYLATE GLUE 3 Randomized controlled trials versus sclerotherapy or banding Hemostasis achieved >90% Costly Not FDA approved for use in portal hypertensive bleeding Can glue the scope closed if inexperienced or not careful GASTRIC FUNDAL VARICES TIPS TIPS Embolize Short Gastric Gastric Varices (GOV 1 or 2) 25% of all GOV SMV SPONTANEOUS SPLENO-RENAL SHUNT

13 SPONTANEOUS SPLENO-RENAL SHUNT BRTO TIPS Gastric Varices (GOV 1 or 2) 25% of all GOV SMV BALLON OCCLUDED RETROGRADE TRANSVENOUS OBLITERATION GASTRIC FUNDAL VARICES BRTO Balloon occluded retrograde transvenous obliteration Effective over 90% of the time 5 year rebleeding rate 1.5% Shunts blood flow back to the liver Can be utilized to treat refractory hepatic encephalopathy when associated with SSRS T Ninoi et al. Am J Roentgenol 2005; 184: Y Takuma et al. Clin Gastro Hepato 2005; 3: H Arai et al. World J Gastroenterol 2006; 28:

14 DEVELOPMENT OF ASCITES % of Patients YEARS G D Amico et al. J Hepatol 2006; 44: The most common complication of cirrhosis and portal hypertension Leads to other complications: Hepatorenal syndrome Hyponatremia COMPLICATIONS OF ASCITES MORTALITY 100 SURVIVAL (%) None SBP Refractory Hypo-Na HRS MONTHS R Planas et al. Clin Gastroenerol Hepatol 2006;

15 ASCITES IMPACT OF BETA-BLOCKERS SURVIVAL (%) Beta-blockers No Yes MONTHS T Serste et al. Hepatology 2010; 52: ASCITES MANAGEMENT Sodium restriction Avoid IV saline when hospitalized Diuretics Aldactone Lasix Paracentesis - Remove as much as possible TIPS when refractory to diuretics Limiting factors: Acute Kidney Injury Hyponatremia mg mg Intravenous 25% albumin Tolvaptan

16 HYPONATREMIA INTRAVENOUS ALBUMIN SODIUM (meq/l) DAYS Sodium Creatinine CREATININE (mg/dl) PA McCormick et al. Gut 1990; 31: RISK OF HCC PLATELET COUNT Cumulative Rate (%) Chronic HCV HALT-C trial N= 1,005 P< Platelet Count: < > YEARS AS Lok, et al. Gastroenterology. 2008;136:

17 SUMMARY Consider and evaluate for non-cirrhotic etiologies when cirrhosis is not obvious Portal vein thrombosis requires anti-coagulation only when acute, symptomatic, hypercoagulable state and in the absence of cirrhosis Look for varices in patients with cirrhosis and thrombocytopenia Only treat medium-large varices that are at risk for bleeding Gastric varies are frequently associated with a spontaneous spleno-renal shunt SUMMARY Beta blockers lead to hypotension and may reduce survival in patients with ascites IV albumin is highly effective therapy when ascites is associated with anasarca, acute kidney injury and hyponatremia Thrombocytopenia is associated with an increased risk for hepatocellular carcinoma