Management of Hospitalized Patients with Cirrhosis Bilal Hameed, - PDF document

10/26/2015 Management of Hospitalized Patients with Cirrhosis Bilal Hameed, MD Division of Transplant Hepatology University of California, San Francisco I have no financial relationships to disclose within the past 12 months relevant to my presentation My presentation does not include discussion of off-label or investigational use 1

10/26/2015 Outline  Complications of cirrhosis Portal hypertension related variceal bleed 1. Ascites, hyponatremia and hydrothorax 2. Hepatic encephalopathy 3. Renal failure and HRS 4.  Infections in cirrhosis  Liver transplantation Natural History of Cirrhosis Compensated Decompensated Death cirrhosis cirrhosis Development of complications:  Variceal hemorrhage  Ascites  Encephalopathy  Jaundice 2

10/26/2015 Question  Most common decompensation in patient with cirrhosis? Variceal bleed. 1. Hepatic encephalopathy. 2. Ascites. 3. HCC. 4. Jaundice. 5. Complications in Compensated Cirrhosis 100 80 Ascites (58%) 60 Probability of Jaundice developing Encephalopathy event 40 GI hemorrhage 20 0 0 20 40 60 80 100 120 140 160 Months Gines et. al., Hepatology 1987. 3

10/26/2015 Decompensation Shortens Survival 100 Median survival 80 ~ 9 years All patients 60 with cirrhosis Probability of survival 40 Median 20 survival Decompensated ~ 1.6 years cirrhosis 0 0 20 40 60 80 100 120 140 160 180 Months Gines et. al., Hepatology 1987. Esophageal Varices  Seen in 50% patients with cirrhosis  10-15% of all GI bleeds (~ 40,000 patients)  $1.2 billion in health care expenditure 4

10/26/2015 Varices Increase in Diameter Progressively No varices No varices Small varices Small varices Large varices Large varices 7-8%/year 7-8%/year 7-8%/year 7-8%/year Merli et al. J Hepatol 2003;38:266 Merli et al. J Hepatol 2003;38:266 Large Varices Are More Likely To Rupture No Varices 100 100 p<0.01 * p<0.01 * Small Varices 75 75 % % Large Varices * * Patients Patients 50 50 2-year probability of first bleed: 2-year probability of first bleed: without without  Small varices: 7%  Small varices: 7% bleeding bleeding 25 25  Large varices: 30%  Large varices: 30% 0 36 36 0 12 12 24 24 12 12 36 36 24 24 Time (months) Time (months) * Merli et al., Hepatol 2003, * * Conn et al., Hepatology 1991 * Merli et al., Hepatol 2003, * * Conn et al., Hepatology 1991 5

10/26/2015 What is the Risk of Mortality with Variceal Bleed? • Pharmacotherapy • Endoscopic innovations 6 weeks 2 months • IR Procedures mortality 20% mortality 40% • Better ICU care 1980 2013 Better Bleeding Control Resulted in Decrease Mortality 6

10/26/2015 Case Presentation  60-year-old female with NASH cirrhosis is brought to the ER because of melena. No prior endoscopy. Hgb is 8 (baseline 11).  What is the best pharmacologic treatment option? 1. IV PPI 2. IV PPI and IV octreotide 3. PO PPI, octreotide and antibiotics 4. IV PPI, octreotide and antibiotics Case Presentation  60-year-old female with NASH cirrhosis is brought to the ER because of melena. No prior endoscopy. Hgb is 8 (baseline 11).  What is the best pharmacologic treatment option? 1. IV PPI 2. IV PPI and IV octreotide 3. PO PPI, octreotide and antibiotics 4. IV PPI, octreotide and antibiotics 7

10/26/2015 Role of Endoscopy  40-50% have non variceal source of bleeding like PUD, esophagitis, MW tear etc. Dig Dis. 2005;23:11-7 . Case Presentation  50-year-old male with HCV related cirrhosis is brought to the ER because of melena and hypotension (SBP 80 mmHg). What is the first priority in the management of this patient?  Emergent upper endoscopy.  Start antibiotics for SBP prophylaxis.  Transfuse blood.  Venous access and hemodynamic stability. 8

10/26/2015 Case Presentation  50-year-old male with HCV related cirrhosis is brought to the ER because of melena and hypotension (SBP 80 mmHg). What is the first priority in the management of this patient?  Emergent upper endoscopy.  Start antibiotics for SBP prophylaxis.  Transfuse blood.  Venous access and hemodynamic stability. Treatment of Acute Variceal Hemorrhage  General Management:  IV access and fluid resuscitation  Airway protection  Antibiotic prophylaxis  Correct coagulopathy  Specific therapy:  Pharmacological therapy  Early endoscopic therapy: band ligation  Shunt therapy: TIPS, surgical shunt 9

10/26/2015 Transfusion Strategy: Too Much is Bad!  921 pts (277 with cirrhosis)  Restrictive (Hgb <7) vs liberal transfusion (Hgb <9)  Liberal strategy had increase portal pressure and rebleeding (11% vs 22%)  Survival was improved with restrictive transfusions Villanueva et al, NEJM 2013 Prophylactic Antibiotics Improve Outcomes Control Control Antibiotic Antibiotic Absolute rate Absolute rate (n=270) (n=270) (n=264) (n=264) difference difference (95% CI) (95% CI) Infection Infection 45% 45% 14% 14% -32% -32% (-42 to –23) (-42 to –23) SBP / Bacteremia SBP / Bacteremia 27% 27% 8% 8% -18% -18% (-26 to –11) (-26 to –11) Death Death 24% 24% 15% 15% -9% -9% (-15 to –3) (-15 to –3) Meta-analysis of 5 randomized trials Bernard et al., Hepatology 1999; 29:1655 Bernard et al., Hepatology 1999; 29:1655 10

10/26/2015 Prophylactic Antibioics Reduce Probability of Recurrent Variceal Hemorrhage 1.0 1.0 Prophylactic antibiotics (n=59) Prophylactic antibiotics (n=59) 0. 0. 8 8 0. 0. No antibiotics (n=61) No antibiotics (n=61) % % 6 6 free of free of 0. 0. variceal variceal 4 4 hemorrhage hemorrhage Greatest benefit in first 0. 0. 2 2 7 days 0 24 24 0 0 3 12 12 18 18 30 30 1 2 Follow-up (months) Follow-up (months) Ofloxacin 200 mg iv q12 hr for 2 days, Ofloxacin 200 mg iv q12 hr for 2 days, then oral 200 bid for 5 days then oral 200 bid for 5 days Hou M-C et al., Hepatology 2004 Hou M-C et al., Hepatology 2004 Pharmacological Treatment for Acute Variceal Bleed  Somatostatin  Variable results in meta-analysis  Octreotide  Vasopressin  Terlipressin (Not available in US)  Vasopressin analogue  Improve survival in some studies 11

10/26/2015 Pharmacologic therapy Parameter Vasopressin Octreotide 50  bolus; 50 Dose 20 U bolus; 0.4-  /hr IV 0.6 U/min IV Hemostasis ~ 50% > 80% Rebleed ~ 50% 14-30% Complications 32-64% 0-15% Mortality 5% 0 Gastroenterology 1995;109:1289-94 Aliment Pharmacol Ther. 2004;20:S18-22 Dig Liver Dis. 2004;36:S93-100 Endoscopic Band Ligation 12

10/26/2015 Refractory Variceal Bleeding  Balloon tamponade  TIPS  Surgical shunt Transjugular Intrahepatic Portosystemic Shunt 1. Second rebleed for Hepatic Hepatic esophageal varices vein vein 2. First rebleed for gastric varices 3. Rebleed on combination TIPS TIPS endoscopic plus pharmacologic therapy (10-20%) Splenic Splenic vein vein Portal vein Portal vein Superior mesenteric Superior mesenteric vein vein 13

10/26/2015 Portal Hypertensive Bleed Gastric Varices Portal HTN Gastropathy Typical GAVE “ watermelon stomach Case  56 yr with acute variceal bleed (1 st episode)  Bleeding controlled with band ligation  No bleeding for 5 days  Child score 10. MELD 15 MAP 90 mmHg Which is the best discharge regimen? 1) Beta blockers and nitrates 2) Serial ligation alone 3) Ligation and beta blockers 4) TIPS 5) Portacaval shunt 14

10/26/2015 Case  56 yr with acute variceal bleed (1 st episode)  Bleeding controlled with band ligation  No bleeding for 5 days  Child score 10. MELD 15 MAP 90 mmHg Which is the best discharge regimen? 1) Beta blockers and nitrates 2) Serial ligation alone 3) Ligation and beta blockers 4) TIPS 5) Portacaval shunt Lowest Rebleeding Rates are Obtained in HVPG Responders and With Ligation +  -Blockers 80 80 60 60 % 40 40 Rebleeding Rebleeding 20 20 0 Untreated Untreated  -  - Sclero- Sclero-  -blockers  -blockers Ligation Ligation HVPG- HVPG- Ligation Ligation blockers blockers therapy therapy + ISMN + ISMN Responder Responder + +  -blockers  -blockers s* s* (19 trials) (19 trials)(26 trials) (26 trials) (54 trials) (54 trials) (6 trials) (6 trials) (18 trials) (18 trials) (6 trials) (6 trials) (2 trials) (2 trials) *  HVPG <12 mmHg *  HVPG <12 mmHg or >20% from or >20% from Bosch and García-Pagán, Lancet 2003; 361:952 Bosch and García-Pagán, Lancet 2003; 361:952 baseline baseline 15

10/26/2015 Acute Variceal Bleed Key Points Ascites 16

10/26/2015 Causes of Ascites Cause Proportion Cirrhosis 80% Malignancy 10% Heart Failure 4% Nephrotic Syndrome 2% Tuberculosis 2% Pancreatitis 1% Others (Budd Chiari) 1% Case  47 yr old male with hepatitis C cirrhosis now presented with new onset abdominal distention and leg swelling.  Ultrasound showed large ascites. No evidence of portal vein thrombosis. INR 2.2 7.0 66 50 140 5 62 30 17