1 1 COMPLICATIONS OF CIRRHOSIS OBSERVATIONS OF AN AGING HEPATOLOGIST COMPLICATIONS OF CIRRHOSIS Philip C. Delich, M.D. Faculty Disclosure Dr. Delich has indicated that he does not have any relevant financial relationships or affiliations that may have a direct bearing on the subject matter of this CME activity. THE EPIDEMIC OF CIRRHOSIS NAFLD/NASH HCV HBV
2 2 DEFINITION OF CIRRHOSIS Cirrhosis End stage of any chronic liver disease Characterized histologically by regenerative nodules surrounded by fibrous tissue Clinically there are two types of cirrhosis: Compensated Decompensated GROSS IMAGE OF A NORMAL AND A CIRRHOTIC LIVER Normal Cirrhosis Irregular surface Nodules HISTOLOGICAL IMAGE OF A NORMAL AND A CIRRHOTIC LIVER Normal Cirrhosis Nodules surrounded by fibrous tissue
3 3 Diagnosis of Cirrhosis Gold standard=liver biopsy Usually not necessary Physical exam findings (spiders, palmer erythema, gynecomastia, hepatosplenomegally) Labs- thrombocytopenia, AST>ALT Radiologic Evidence Diagnostic Algorithm DIAGNOSTIC ALGORITHM Patient with chronic liver disease and any of the following: Yes No Physical findings: Laboratory findings: Enlarged left hepatic lobe Thrombocytopenia Splenomegaly Impaired hepatic synthetic function Stigmata of chronic liver disease Yes No Yes Liver biopsy not necessary for the diagnosis of cirrhosis Radiological findings: Small nodular liver Intra-abdominal collaterals Ascites Splenomegaly Colloid shift to spleen and/or bone marrow No Liver biopsy MANAGEMENT OF WELL COMPENSATED CIRRHOSIS Rx. Cause (HCV,HBV, wt. loss in NASH, phlebotomy in hemochromatosis etc) Screen for esophageal varices Screen for hepatocellular carcinoma Optimize transplant candidacy Observe for signs of decompensation.
4 4 Decompensated cirrhosis- cirrhosis with signs of liver failure (ascites, edema, hepatic encephalopathy etc) SURVIVAL TIMES IN CIRRHOSIS Decompensation Shortens Survival 100 Probability of survival All patients with cirrhosis Median survival ~ 9 years Gines et. al., Hepatology 1987;7:122 Decompensated cirrhosis Months Median survival ~ 1.6 years 180 Complications of cirrhosis Ascites refractory ascites SBP hepatorenal syndrome Variceal Bleeding Hepatic Encephalopathy HCC
5 5 Uncomplicated Ascites Low Na diet Combination diuretics (spironolactone 100mg- 400mg/day, furosamide 40mg-160mg/day) Therapeutic Paracentesis Refractory Ascites Serial paracentesis with IV albumin infusion (8 grams/liter removed) TIPSS (Transjugular Intrahepatic Porto-systemic Shunt) - contraindicated in patients with history of hepatic encephalopathy, advanced disease (bili >3 etc), elderly Spontaneous Bacterial Peritonitis Frequent complication Approx. 30% in hospitalized patients Diagnosed with paracentesis->250 PMNs per HPF Rx-3 rd gen. cephalosporine x 5 days 70% recurrence in one year prophylactic antibiotics
6 6 Hepatorenal Syndrome Rapidly progressive renal failure in setting of liver failure Absence of other causal factors No improvement with fluid challenge oliguria low urine Na Rx. Of Hepatorenal syndrome Vasoconstrictors (oral midodrine-5 mg TID) Octreotide 100ug SQ TID Volume expansion (IV albumin) Variceal Bleeding Frequent complication (33-50% lifetime risk in cirrhotics) High mortality (20%) Increased risk with progression of liver disease. Preventable and treatable
7 7 PREVALENCE OF ESOPHAGEAL VARICES IN CIRRHOSIS Prevalence of Esophageal Varices in Cirrhosis % Overall Child A Child B Child C Pagliaro et al., In: Portal Hypertension: Pathophysiology and Management, 1994: 72 VARICES INCREASE IN DIAMETER PROGRESSIVELY Varices Increase in Diameter Progressively No varices Small varices Large varices 7-8%/year 7-8%/year Merli et al. J Hepatol 2003;38:266 MANAGEMENT ALGORITHM FOR THE PROPHYLAXIS OF VARICEAL HEMORRHAGE - SUMMARY Prophylaxis of Variceal Hemorrhage Diagnosis of Cirrhosis Endoscopy No Varices Small Varices Medium/Large Varices Follow-up EGD in 2-3 years* Follow-up EGD in 1-2 years* *EGD every year in decompensated cirrhosis Beta-blocker therapy Stepwise increase until maximally tolerated dose Continue beta-blocker (life-long) No Contraindications Contraindications or Beta-blocker intolerance Endoscopic Variceal Band Ligation
8 8 Management of Acute bleeding Octreotide (50 ug bolus 50 ug/hr infusion Prompt diagnosis with endoscopy Band ligation if esophageal varices TIPPS for gastric varices or salvage if not endoscopically managable HIGH RISK OF SBP-NEED ANTIBIOTIC PROPHYLAXIS! (3 RD GEN. CEPHALOSPORINE) ENDOSCOPIC VARICEAL BAND LIGATION Endoscopic Variceal Band Ligation Bleeding controlled in 90% Rebleeding rate 30% Compared with sclerotherapy: Less rebleeding Lower mortality Fewer complications Fewer treatment sessions THE TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNT Transjugular Intrahepatic Portosystemic Shunt Hepatic vein TIPS Portal vein Splenic vein Superior mesenteric vein
9 9 Secondary prophylaxis against variceal bleeding Non-selective beta blockers (nadolol or propranololtritrate to pulse 60 and tolerance) Serial endoscopic banding Q2-4 weeks until varices obliterated then yearly for surveillance. Hepatic Encephalopathy Neuro-psychological disorder resulting from inability of failing liver to remove nitrogenous waste products of protein metabolism from circulation. CLINICAL DIAGNOSIS-ammonia levels do not correlate well with diagnosis or stage of encephalopathy. HEPATIC ENCEPHALOPATHY IS A CLINICAL DIAGNOSIS Hepatic Encephalopathy Is A Clinical Diagnosis Clinical findings and history important Ammonia levels are unreliable Ammonia has poor correlation with diagnosis Measurement of ammonia not necessary Number connection test Slow dominant rhythm on EEG
10 10 ASTERIXIS IS THE HALLMARK IN THE DIAGNOSIS OF HEPATIC ENCEPHALOPATHY Asterixis STAGES OF HEPATIC ENCEPHALOPATHY Stages of Hepatic Encephalopathy Confusion Drowsiness Somnolence Coma Stage TREATMENT OF HEPATIC ENCEPHALOPATHY Treatment of Hepatic Encephalopathy Identify and treat precipitating factor Infection GI hemorrhage Prerenal azotemia Sedatives Constipation Lactulose (adjust to 2-3 bowel movements/day) Protein restriction, short-term (if at all)
11 11 Antibiotics for hepatic encephalopathy Generally secondary agents in lactulose failures Work through alteration of gut flora decreased absorption of nitrogenous wastes. Neomycin (500 mg TID)- cheap-theoretical risk of renal toxicity and deafness Xifaxan (400 mg TID)-very expensive perhaps safer and more effective. Natural benzodiazepines and Hepatic Encephalopathy Activated GABA-ergic tone in H.E. Poorly delineated GABA receptor agonists with action similar to benzodiazepines activate GABA receptors. Therefore, benzodiazepines ppt H.E. and are contraindicated in cirrhosis. EXTREME CARE NECESSARY WHEN TREATING ALCOHOL WITHDRAWAL IN CIRRHOSIS! Epidemic of Hepatocellular Carcinoma Directly related to increased incidence of cirrhosis. Cirrhosis fertile ground for HCC HCV related cirrhosis carries 1-4%/year risk of HCC Hepatitis B even higher and virus alone without cirrhosis carries risk (oncogenic)
12 12 HCC-Rationale for Screening Early tumors potentially resectable (occasionally) and frequently curable with transplantation (Milan criteria). Evolving treatments increasingly helpful even if cure not feasible (chemoembolization, radiofrequency ablation, cryotherapy) HCC Screening Imaging modalities (US vs. CT vs. MRI) AFP-probably not useful but still done. Frequency needs to be Q 6 mo to be effective. Screen stage 3 and 4 fibrosis patients. In hepatitis B, all infected patients at risk and need to be screened. Pearls in management of cirrhosis Cirrhosis is clinical diagnosis that rarely requires liver biopsy. Low platelet count cirrhosis until proven otherwise. AST>ALT =cirrhosis (or alcoholic liver disease) Always consider SBP and when in doubt, rule it out Avoid benzodiazepines and use extreme care in treatment of alcohol withdrawl in cirrhotics.
13 13 Pearls continued Screen cirrhotics for varices and HCC regularly Hepatic Encephalopathy is a clinical diagnosisammonia levels not useful. Band esophageal varices to obliteration. Remember low Na diets in management of ascites. Cirrhosis is a catabolic state-low protein diets rarely useful. Think about transplantation early in decompensation. SURGERY AND CIRRHOSIS INCREASED RISK OF ANESTHESIA INCREASED RISK OF HEPATIC ENCEPHALOPATHY WITH POST- OP PAIN MANAGEMENT VERY HIGH RISK IN MAJOR CAVITIES (CHEST AND ABDOMEN) CONTRAINDICATED IN DECOMPENSATED CIRRHOSIS UNLESS TRUE EMERGENCY! HOSPICE AND END STAGE LIVER DISEASE APPROX. 50% MORTALITY OVER 2 YEARS BENZODIAZEPINES AND OPIATES RELATIVELY CONTRAINDICATED IN CIRRHOSIS HEPATIC COMA! PAIN USUALLY NOT AN ISSUE EXCEPT ASCITES RELATED DISTENSION MANAGED BY TAP AND NOT OPIATES!
14 14 PREVENTION BEST MEASURE MOST CIRRHOSIS IN WESTERN COUNTRIES IS LIFESTYLE RELATED DISEASE (OBESITY/IVDA/ALCOHOL) VACCINATION AGAINST HEPATITIS A AND B EDUCATION AND LIFESTYLE MODIFICATION ESSENTIAL
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