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Patient Discharges with Cirrhosis* Hospital Discharges Associated with Cirrhosis are Increasing 600000 8.4% 500000 400000 403,664 411,029 436,901 444,882 459,496 498,181 300000 200000 100000 0 2004` 2005 2006 2007 2008 2009 *ICD-9-CM codes 571.2, 571.5, and 571.6, all listed diagnoses Healthcare Cost and Utilization Project, US Department of Health and Human Services. Available at http://hcupnet.ahrq.gov/hcupnet.jsp. Accessed 04/24/12.
Complications of Cirrhosis: Focus on Hepatic Encephalopathy Primary complications include: Ascites Jaundice Variceal hemorrhage Hepatic encephalopathy Other complications that can occur include: Spontaneous bacterial peritonitis Hepatic hydrothorax Hepatorenal syndrome Portopulmonary hypertension Hepatocellular carcinoma Portal vein thrombosis Lefton HB et al. Med Clin N Am 2009;93:787-799.
Patient Discharges Increased Hospital Discharges Associated with HE Parallel Those of Cirrhosis 600000 Cirrhosis* HE 500000 400000 300000 200000 498,181 436,901 444,882 459,496 403,664 411,029 345,887 323,564 239,425 215,767 182,843 196,521 100000 0 2004` 2005 2006 2007 2008 2009 *ICD-9-CM codes 571.2,571.5, and 571.6, all listed diagnoses ICD-9-CM codes 291.2, 348.30, and 472.2, all listed diagnoses Healthcare Cost and Utilization Project, US Department of Health and Human Services. Available at http://hcupnet.ahrq.gov/hcupnet.jsp. Accessed 04/24/12.
Prevalence of HE: Two Forms are Recognized Covert hepatic encephalopathy (CHE) affects approximately 20% to 60% of patients with liver disease 2 Has been called subclinical encephalopathy or minimal encephalopathy (MHE) in the past 3 International Society for Hepatic Encephalopathy and Nitrogen Metabolism has recently endorsed using the term covert encephalopathy 3 Overt hepatic encephalopathy (OHE) occurs in: 30% to 45% of cirrhotic patients 2 10% to 50% of patients with TIPS 2 TIPS = transjugular intrahepatic portosystemic shunt. 1 Mullen KD, et al. Semin Liver Dis. 2007;27(Suppl 2):32-47. 2 Poordad FF. Aliment Pharmacol Ther. 2006;25(Suppl 1):3-9. 3 Mullen KD, Prakash RK. Clin Liver Dis 2012;16:91-93,
Characterization of HE Stages Overt HE Stages Normal Covert HE I II III IV coma Categorization is often arbitrary and varies between raters Simple Clinical Diagnosis Worsening cognitive dysfunction Bajaj JS, et al. Hepatology. 2009;50:2014-2021.
Diagnosis of Covert HE Patients with covert HE have no clinical signs and symptoms of overt HE The diagnosis of covert HE is only possible through specialized psychometric and neurological measures No consensus on diagnostic criteria or diagnostic tests has been established Bajaj JS et al. Hepatology 2009;50:2014-2021. Mullen KD. Aliment Pharmacol Ther 2006;25(suppl 1):11-16.
Diagnostic Methods for Detecting Covert HE Methods Advantages Limitations Formal neuropsychological assessment Established and well-recognized clinical significance Expensive Time-consuming Short neuropsychological batteries Easy to administer in office setting Inexpensive Rapid results High sensitivity for discerning MHE from other encephalopathies Test often copyrighted Limited access Computerized tests (CFF, ICT, reaction times, etc.) Easy to apply Limited data on diagnostic significance Require standardization Neurophysiologic tests (EEG, spectral EEG, P300) Allows for objective repeat testing Equipment Limited data on diagnostic significance CFF = critical flicker frequency; ICT = inhibitory control test; P300 = auditory event-related evoked potential. Adapted from: Mullen KD, et al. Semin Liver Dis. 2007;27(Suppl 2):32-47.
Diagnosis of Overt HE Clinical recognition of the distinctive neurologic features of HE Knowledge that underlying cirrhosis is present Exclusion of all other etiologies of neurologic and/or metabolic abnormalities Identification of precipitating factors Severity can be measured using West Haven Criteria Adapted from Mullen KD. Semin Liver Dis. 2007;27(suppl 2):3-9.
West Haven Criteria for Grading Mental State in Patients With Cirrhosis Grade Features 0 No abnormalities detected I II III IV Trivial lack of awareness Euphoria or anxiety Shortened attention span Impairment of addition or subtraction Lethargy or apathy Disorientation for time Obvious personality change Inappropriate behavior Somnolence to semi-stupor Responsive to stimuli Confused Gross disorientation Bizarre behavior Coma, unable to test mental state Bajaj JS, et al. Aliment Pharmacol Ther. 2011;33:739-747.
Hepatic Encephalopathy: Pathophysiology HE pathogenesis appears to be multifactorial and involves: An increase in nitrogenous substances in the systemic circulation, derived from production in the gut Cerebral edema, due to uptake of ammonia into astrocytes where it is combined with intracellular glutamate Oxidative stress Inflammatory mediators Adapted from Mullen KD et al. Semin Liver Dis. 2007;27(suppl 2):32-47.
Consequences of Covert HE Increased progression to OHE: >50% develop overt HE within 30 months 1 Significantly diminishes quality of life 2 Significantly diminishes working and earning capacity in blue-collar workers 2 Impairs driving on structured driving tests 3,4 Increases risk of traffic accidents and violations 5 1. Hartmann IJ, et al. Am J Gastroenterol. 2000;95(8):2029-2034. 2. Groeneweg M, et al. Hepatology. 1998;28(1):45-49. 3. Wein C, et al. Hepatology. 2004;39(3):739-745. 4. Watanabe A, et al. Metab Brain Dis. 1995;10(3):239-248. 5. Bajaj JS, et al. Am J Gastroenterol. 2007;102(9):1903-1909.
Development of clinical HE Probability of OHE in Patients With and Without MHE 110 100 90 80 70 60 50 40 30 20 10 0 (25) (91) (21) (88) (20) P <.001 MHE positive (11) MHE negative (84) 0 10 20 30 40 Months Adapted from: Hartmann IJ, et al. Am J Gastroenterol. 2000;95(8):2029-2034.
Survival, % Overt HE is Associated with a Poor Prognosis <50% survival at 1 year after diagnosis of HE; <25% survival at 3 years 100 80 60 40 20 42% survival at 1 year 23% survival at 3 years 0 0 12 24 36 48 Months Bustamante et al. J Hepatol. 1999;30:890-895.
ICU and One Year Mortality of Patients with Severe HE Isolated HE* (n=45) Other HE Patients (n=26) p Glasgow Coma Scale at Admission 8.2 0.6 6.7 4.4 0.10 Child-Pugh Score 11 1.6 11 1.8 0.06 ICU Mortality 4 (8.9%) 21 (80.7%) <0.001 1-Year Mortality 12 (30%) 24 (92%) <0.001 *Patients with HE, but no acute renal failure or vasopressor use during ICU stay. HE patients with acute renal failure and/or vasopressor use during ICU stay. Fichet J et al. J Crit Care 2009;24:364-370.
Multivariate Analysis for ICU and 1-Year Mortality of Patients with Severe HE Vasopressor use and acute renal failure were the main independent predictors of ICU death and 1-year mortality Variables Odds ratio ICU Mortality 95% CI p Odds ratio 1-Year Mortality 95% CI Vasopressor Use 7.67 1.40-41 0.02 11.30 1.20-90 0.03 p Acute Renal Failure or Hepatorenal Syndrome Severity of Acute Illness (SAPSII)* 7.32 1.50-35 0.01 5.32 1.10-32 1.03 0.98-1.07 0.17 1.07 0.97-1.04 0.04 0.70 *SAPSII, Simplified Acute Physiology Score Fichet J et al. J Crit Care 2009;24:364-370.
Comparative Outcome Probabilities for Various Complications of Cirrhosis Complication Survival at 1 year Survival at 3 years Varices (non-bleeding) w/o ascites 1 97% NA Ascites ± varices 1,2 80% 50% Bleeding Varices ± Ascites 1 43% NA Hepatic Encephalopathy 3 42% 23% Projected survival rates 1 year after diagnosis of overt HE are comparable to survival rates of cirrhotic patients with bleeding varices NA=Not Available 1. Adapted from D Amico G et al. J Hepatol 2006;44:217-231. 2. Arroyo V, Colmenero J. J Hepatol. 2003;38:S69-S89. 3. Adapted from Bustamante et al. J Hepatol. 1999;30:890-895. 19
Minimal HE Affects Quality of Life in Cirrhotic Patients 30 Cirrhosis With MHE (n=48) Cirrhosis W/O MHE (n=131) Reference Population (n=594) 25 Mean SIP Score* 20 15 10 5 0 SIP Scales * Sickness Impact Profile (SIP) used to determine influence of chronic disease on patients daily functioning; scores range from 0 (best score) to 100 (worst score). Groeneweg M, et al. Hepatology. 1998;28:45-49.
Score HE Affects Health-Related Quality of Life According to Presence and Degree 100 80 Short Form-36 Questionnaire Results US Norms No HE (n=35) MHE (n=36) OHE (n=89) 60 40 20 0 Physical Functioning Physical Role Bodily Pain Arguedas M et al. Dig Dis Sci 2003;48:1622-1626. General Health Vitality Social Functioning Emotional Role Mental Health Physical Summary Mental Summar y
Burden of Cirrhosis and HE: Impact of Cirrhosis-Related Expenses on Daily Life Impact Within Past 3 Years % 80 60 40 56% 46% 104 patients (70% male, median MELD 12, 44% HCV, 49% veterans) 44% had previous HE (all were on lactulose while 23% had severe previous HE and were on both rifaximin and lactulose) 20 15% 11% 10% 7% 7% 0 Bajaj JS, et al. Am J Gastroenterol 2011;106:1646-1653.
Burden of Cirrhosis and HE: Impact of Cirrhosis- Related Medical Expenses on Adherence Impact Within Past Year 50 N=104 40 36% % 30 26% 20 10 12% 10% 5% 0 Lost insurance Missed appointments Did not take meds Took less than prescribed meds Missed procedures Bajaj JS, et al. Am J Gastroenterol 2011;106:1646-1653.
Burden of Cirrhosis and HE: Impact on Ability to Work No Previous HE (n=58) Previous HE (n=46) P value Age (years) 58.6 57.1 0.272 MELD score 10.7 15.5 0.00001 Currently working 81% 12.5% 0.001 Need to decrease hours 39% 71% 0.017 Worse off regarding job 47% 74% 0.009 Worse off financially 61% 85% 0.019 Median longest period free of work 21 days 365 days 0.035 Debt from cirrhosis 36% 54% 0.06 Bajaj JS, et al. Am J Gastroenterol 2011;106:1646-1653.
Utilization and Outcome of Critical Care in Patients With Cirrhosis Reviewed 2006 Nationwide Inpatient Sample (NIS) of the Health Care Utilization Project to identify hospitalization records with cirrhosis and/or portal hypertensive complications 65,072 discharge records met the inclusion criteria, which projected to 317,300 cirrhosis hospitalizations (95% CI, 300;100-334,400) Characteristics of patients requiring critical care Mean age: 55.5 years Male: 63% Ascites: 49% Encephalopathy: 41% Variceal bleeding: 14% Hepatorenal syndrome: 12% Kim W, et al. Hepatology. 2010;52(Suppl S1):910A-911A.
Utilization and Outcome of Critical Care in Patients With Cirrhosis Increased risk of death and hospital charges associated with complications In-Hospital Death Total Charges Factor Odds Ratio P % Increase P ICU care 13.9 <.01 280% <.01 Encephalopathy 2.0 <.01 28% <.01 Hepatorenal syndrome 6.1 <.01 45% <.01 Ascites 1.1 <.01 23% <.01 Variceal hemorrhage 0.8 <.01 36% <.01 HCC 1.5 <.01 9%.08 Kim W, et al. Hepatology. 2010;52(Suppl S1):910A-911A.
Current Treatment Options for HE Drug Name Drug Class Indication Lactulose Rifaximin Neomycin Metronidazole Vancomycin Poorly absorbed disaccharide Non-aminoglycoside semi-synthetic, nonsystemic antibiotic Aminoglycoside antibiotic Synthetic antiprotozoal and antibacterial agent Aminoglycoside antibiotic Decrease blood ammonia concentration Prevention and treatment of portal-systemic encephalopathy Reduction in risk of OHE recurrence in patients 18 years of age Adjuvant therapy in hepatic coma Not approved for HE Not approved for HE Adapted from: http://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/gastrointestinaldrugs Advisory Committee/UCM203247.pdf. Accessed 02/17/11; http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022554lbl.pdf. Accessed 02/17/11.
Accredited by: Treatment
OHE Treatment Goals Acute episode of HE Treatment of precipitating factors Improvement in mental status Evaluation for liver transplant Out-patient management after an episode of HE Prevention of recurrent episodes of HE Improvement of daily functioning Evaluation for liver transplant Bajaj JS. Aliment Pharmacol Ther. 2010;31:537-547.
Proposed Terminology for Prophylactic Treatment of HE Treating patients with covert HE to prevent development of a first episode is referred to as primary prophylaxis of HE Preventing recurrence of HE in patients who had a previous episode of HE is referred to as secondary prophylaxis of HE Sharma BC et al. Gastroenterology. 2009;137:885-891.
Secondary Prophylaxis of OHE: Lactulose vs Placebo Open-label randomized controlled trial Consecutive cirrhotic patients who recovered from HE randomized to receive lactulose (n=70) or placebo (n=70) Primary end point was development of OHE Median follow-up of 14 months (range 1-20 months) Sharma BC, et al. Gastroenterology. 2009:137:885-891.
Probability of hepatic encephalopathy Probability of Developing HE in Patients Receiving Prophylactic Lactulose vs Placebo 1.0 0.8 0.6 0.4 0.2 P=.001 0.0 Patients at risk* 0.00 2.00 4.00 6.00 8.00 10.00 12.00 14.00 16.00 18.00 20.00 Follow-up in months Lactulose 61 60(1) 59(2) 58(3) 51(8) 45(9) 38(11) 28(12) 10(12) 7(12) 1(12) Placebo 64 62(1) 59(4) 50(13) 37(24) 33(27)28(27) 19(29) 13(30) 8(30) 4(30) *Values in parentheses indicate the cumulative number of subjects who developed HE. Sharma BC, et al. Gastroenterology. 2009:137:885-891.
Side Effects in Patients Receiving Prophylactic Lactulose vs Placebo Lactulose (n=61) Placebo (n=64) Diarrhea 14 (23%) --- Abdominal bloating 6 (10%) --- Distaste to lactulose 8 (13%) --- Constipation --- 10 (16%) All patients could tolerate and remained compliant to lactulose therapy Sharma BC, et al. Gastroenterology. 2009:137:885-891.
Secondary Prophylaxis of HE: Rifaximin vs Placebo Rifaximin 550 mg BID for 6 mo (n=140) Discontinued n=52 (37%) Breakthrough HE: n=28 Adverse event: n=8 Death: n=6 Patient request: n=6 Exclusion criteria: n=1 Other: n=3 Randomization 1:1 N=299 (Randomized Controlled Trial) Placebo for 6 mo (n=159) Discontinued n=93 (58%) Breakthrough HE: n=69 Patient request: n=9 Adverse event: n=7 Death: n=3 Exclusion criteria: n=3 Other: n=2 Completed Study n=88 Completed Study n=66 Bass NM, et al. N Engl J Med. 2010;362:1071-1081.
Rifaximin Treatment in HE: Lactulose Use at Baseline and During Study Rifaximin (n=140) Placebo (n=159) Lactulose use at baseline n (%)* 128 (91.4) 145 (91.2) Lactulose use during study n (%)* 128 (91.4) 145 (91.2) *During the study, 3 patients who had been receiving lactulose discontinued the therapy and another 3 patients started lactulose (1 in the rifaximin group and 2 in the placebo group). Bass NM, et al. N Engl J Med. 2010;362:1071-1081.
Patients (%) Rifaximin Treatment in HE: Time to First Breakthrough Episode (Primary End Point) 100 80 (77.9%) Rifaximin 60 40 Placebo (54.1%) 20 0 Hazard ratio with rifaximin, 0.42(95% CI, 0.28-0.64) P<.001 0 28 56 84 112 140 168 Days since randomization Bass NM, et al. N Engl J Med. 2010; 362(12):1071-1081.
Patients (%) Rifaximin Treatment in HE: Time to First HE-Related Hospitalization (Secondary End Point) 100 80 (86.4%) Rifaximin 60 Placebo (77.4%) 40 20 0 Hazard ratio with rifaximin, 0.50(95% CI, 0.29-0.87) P=.01 0 28 56 84 112 140 168 Days since randomization Bass NM, et al. N Engl J Med. 2010; 362(12):1071-1081.
Rifaximin and HE: Side Effects Similar to Placebo The incidences of adverse events did not differ significantly between the two study groups (P>.05 for all comparisons) Adverse Events Reported in 10% of Patients in Either Study Group Event, n (%) Any event Nausea Diarrhea Fatigue Peripheral edema Ascites Dizziness Headache Rifaximin (n=140) 112 (80.0) 20 (14.3) 15 (10.7) 17 (12.1) 21 (15.0) 16 (11.4) 18 (12.9) 14 (10.0) Placebo (n=159) 127 (79.9) 21 (13.2) 21 (13.2) 18 (11.3) 13 (8.2) 15 (9.4) 13 (8.2) 17 (10.7) Bass NM, et al. N Engl J Med. 2010;362:1071-1081.
Rifaximin Long Term Efficacy and Safety: Patient Disposition Randomized Controlled Trial (6 months) Rifaximin 550 mg b.i.d. n=140 Open Label Maintenance Continuing Rifaximin 550 mg b.i.d. n=70 RCT N=299 New patients n=170 All Patients OLM N=322 Placebo n=159 Switched from placebo to Rifaximin 550 mg b.i.d. n=82 Concomitant lactulose use was permitted throughout the RCT and OLM trial Mullen KD et al. J Hepatol 2011;54(Suppl 1):S49.
Infection Rates Remain Stable During Long-Term Rifaximin Treatment RCT Placebo n=159; PEY=46 Infection Incidence, n (rate*) RCT Rifaximin n=140; PEY=50 All Rifaximin n=392; PEY=510 Any infection 49 (1.32) 46 (1.12) 214 (0.72) Cellulitis 3 (0.066) 3 (0.060) 34 (0.071) C.difficile infection 0 2 (0.040) 6 (0.012) Peritonitis 6 (0.131) 3 (0.060) 22 (0.044) Pneumonia 1 (0.022) 4 (0.080) 42 (0.084) Sepsis/Septic shock Urinary tract/ kidney 5 (0.109) 2 (0.040) 31 (0.062) 14 (0.320) 9 (0.187) 83 (0.193) *Rate = number of subjects/person exposure years (PEY) All rifaximin = rifaximin treated patients from both randomized controlled trial (RCT) and open label maintenance trial Sanyal A et al. J Hepatol 2012;56(Suppl 2):S255-S256.
Complications Seen During Long-Term Administration of Rifaximin Patients were followed for up to 5 years, death, or liver transplantation Rifaximin (n=23) Controls (n=46) P value Variceal bleeding (%) 35.0 59.5 P=.011 Hepatic encephalopathy (%) 31.5 47.0 P=.034 Spontaneous bacterial peritonitis (%) 5.5 46.0 P=.027 Hepatorenal syndrome (%) 4.5 51.0 P=.037 Death 7 / 23 (30.4%) 24 / 46 (52.2%) -- 5-year cumulative probability of survival (%) 61 13.5 P=.012 Vlachogiannakos J, et al. Hepatology. 2010:52(Suppl S1):328A-329A.
Primary Prophylactic Therapy: MHE Treatment Goals Goals of primary prophylactic therapy Delay progression to overt HE Improve quality of life Maintain employment status Preserve driving privilege Prakash R, Mullen KD. Nat Rev Gastroenterol Hepatol. 2010;7:515-525.
Lactulose for Primary Prophylaxis of Overt HE in Cirrhotic Patients: Results Median follow-up 12 months 70 60 P=0.29 53% 60% Lactulose No Lactulose % of Patients 50 40 30 20 10 0 32/ 60 36/ 60 MHE at Baseline P=0.02 11% 6/ 55 30% Developed OHE 9% 15/ 50 5/55 P=0.16 Died 20% 10/ 50 Sharma BC et al. J Hepatol 2012;56(Suppl 2):S238.
Lactulose Improves Health-related QoL in Patients With MHE 25 0 months 3 months 20 Score 15 10 5 0 Prasad S, et al. Hepatology. 2007;45:549-559.
Rifaximin vs Placebo: Reversal of MHE Placebo (n=45) Rifaximin (n=49) P<.0001 Patients Showing Reversal of MHE (%) P<.0001 Duration of Treatment Sidhu S, et al. Am J Gastroenterol. 2011;106:307-316.
Rifaximin Improves Health-related QoL in Patients With MHE 20 P=.002 Baseline (n=42) 8 Weeks (n=37) Mean SIP Score 15 10 P=.000 5 P=.007 P=.050 P=.00 0 Total Psych Total Physical Sleep/Rest Work Home Mgmt Rec/Pastimes Eating Total SIP Sidhu S, et al. Am J Gastroenterol. 2011;106:307-316.
Rifaximin Improves Driving Simulator Performance: Methods Minimal HE patients were diagnosed using a cognitive battery of 5 tests All who were current car drivers without overt HE were included in an 8-week trial Trial involved at baseline Driving and navigation simulation Quality of life and Sickness Impact Profile Ammonia MELD score Patients were randomized to rifaximin 550 mg or placebo BID All tests repeated on the 8-week visit Bajaj JS, et al. Gastroenterology 2011;140:478-487.
Rifaximin Improves Driving Simulator Performance: Results Rifaximin (n=21) Placebo (n=21) P value Improved cognitive tests 91% 61%.02 Reduced total driving errors 76% 33%.013 Reduced speeding tickets 81% 33%.005 Reduced illegal turns 62% 19%.012 Reduced collisions 43% 33%.751 Bajaj JS, et al. Gastroenterology 2011;140:478-487.
Reversibility of HE Traditional concept: Most OHE events are potentially reversible Only those patients who succumb to the precipitating event (i.e., bleeding, infection) are not reversible Patients who regain consciousness and survive a severe HE event typically seem to return to their baseline level of cognitive functioning with supportive care, or with disaccharides, or with rifaximin A subset of patients with OHE continue to suffer with symptoms and are classified as chronic persistent HE that may not be reversible with medical therapy Neuropathologic characteristics found in brains of patients with HE at autopsy suggest that the concept of complete reversibility requires more in-depth analysis Frederick RT. Clin Liver Dis 2012;16:147-158.
Psychometric Test Results Before and After Development of First Episode of OHE Patients tested before and after first episode of OHE (n=15) Pre-OHE Post-OHE p-value MELD score (median) 9 10 0.10 Number connection test-a (sec) 40 12 48 35 0.33 Number connection test-b (sec) 98 22 142 98 0.11 Digit symbol test (points) 51 14 47 15 0.21 Block design test (points) 29 13 33 20 0.39 ICT targets (% correct) 93 9 93 11 0.96 ICT lures (# responded to) 12 8 18 10 0.03 ICT lures (first half: runs I-III) 8 5 9 5 0.12 ICT lures (second half: runs IV-VI) 4 4* 8 5 0.012 *p=0.00001 in the first half compared with the second half indicating successful learning Bajaj JS et al. Gastroenterology 2010;138:2332-2340.
Persistence of Cognitive Impairment after OHE: Results Prior OHE No OHE P value NCT-A 65 44 0.02 NCT-B 146 102 0.01 DST 32 45 <0.0001 LTT time 130 100 0.02 LTT errors 49 31 0.1 SDT 86 74 0.2 BDT 13 34 <0.0001 Lures 16 15 0.6 Weighted lures 31 18 0.01 Targets 77% 92% 0.001 N=163 Bajaj JS et al. J Hepatol 2012;56(Suppl 2):S242.
Persistence of Cognitive Impairment after OHE: Results No OHE Prior OHE 1 st Half 2 nd Half 1 st Half 2 nd Half Lures 7.9 5.5 6.7 8* 8.4 5.5 7.7 5.3 Weighted lures 11 8 8 7* 18 13 15 14 Targets (%) 94.7 17.4 97.0 16.9* 75.7 29.4 75.7 29.1 Patients without prior OHE improved significantly on ICT from 1 st to 2 nd half, but those with prior OHE could not improve their performance indicating poor learning capability and persistent cognitive dysfunction *P<0.0001 on paired t-test Bajaj JS et al. J Hepatol 2012;56(Suppl 2):S242.
Impact of Preoperative OHE on Neurocognitive Function after Liver Transplantation Neurocognitive abnormalities were more severe in liver transplant recipients that had suffered from OHE prior to OLT Domains OHE-PreLT (n=25) PHES Results No OHE-PreLT (n=14) Controls (n=20) NCT-A (seconds) 34.0 8.3* 23.3 8.4 19.6 3.9 NCT-B (seconds) 98.4 30.5* 76.0 35.1 54.5 17.0 Digit symbol (points) 41.2 8.9* ǂ 50.4 9.8 54.6 8.4 Serial dotting (seconds) 61.3 25.2 59.3 20.1 54.8 18.1 Line tracing (seconds) 77.0 22.7 78.1 18.2 70.7 26.2 Line tracing (errors) 11.0 11.9 10.4 15.0 5.4 4.9 *p<0.001 vs. controls; p<0.01 vs. No HE-PreLT; ǂ p<0.05 vs. No HE-PreLT. Sotil EU et al. Liver Transpl 2009;15:184-192.
Conclusions The incidence of cirrhosis is increasing and the incidence of hepatic encephalopathy parallels the increase in cirrhosis HE has a negative impact on a cirrhotic patient s quality of life Patients diagnosed with covert HE have a high probability of experiencing an overt HE episode Primary prophylactic treatment of covert HE patients with either lactulose or rifaximin is effective in preventing overt HE
Conclusions (cont) Overt HE is associated with a poor prognosis Survival is <50% at one year, similar to survival of patients with bleeding varices Secondary prophylactic treatment following an overt HE episode with either lactulose or rifaximin is effective in preventing a recurrent episode of overt HE Recent evidence suggests that cognitive impairment associated with overt HE may not be completely reversible
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Thank you for supporting this program For additional CME offerings, please visit www.chronicliverdisease.org