Management in Cirrhosis

Management in Cirrhosis

Outline Introduction Cause of cirrhosis and management General management in cirrhosis Management complication and surveillance

Clue of Chronic Liver Disease and Cirrhosis Risk factor Evidence of chronic liver disease Physical examination Sign CLD < 50% Sign portal Hypertension Laboratory AST/ALT > 1 Reverse AG ratio PT prolong Low platelet (<160000) Definite diagnosis : Liver biopsy Noninvasive test Biological Physiological

Serum Biomarker Advantages Transient elastography ARFI (pswe) 2D-SWE MR elastography Good reproducibility High applicability (95%) No cost and wide availability (non-patented) Well validated Can be performed in the outpatient clinic Most widely used and validated technique: standard to be beaten User-friendly (performed at bedside; rapid, easy to learn) High range of values (2-75 kpa) Quality criteria well defined Good reproducibility High performance for cirrhosis (AUROC >0.9) Prognostic value in cirrhosis Can be implemented on a regular US machine ROI smaller than TE but location chosen by the operator Higher applicability than TE (ascites and obesity) Performance equivalent to that of TE for significant fibrosis and cirrhosis Can be implemented on a regular US machine ROI can be adjusted in size and location and chosen by the operator Measures liver stiffness in real-time High range of values (2-150 kpa) Good applicability High performance for cirrhosis Can be implemented on a regular MRI machine Examination of the whole liver Higher applicability than TE (ascites and obesity) High performance for cirrhosis Disadvantages Non-specific of the liver Unable to discriminate between intermediate stages of fibrosis Performance not as good as TE for cirrhosis Cost and limited availability (proprietary) Limitations (hemolysis, Gilbert syndrome, inflammation...) Requires a dedicated device ROI cannot be chosen Unable to discriminate between intermediate stages of fibrosis Applicability (80%) lower than serum biomarker: (obesity, ascites, operator experience) False positive in case of acute hepatitis, extrahepatic cholestasis, liver congestion, food intake and excessive alcohol Unable to discriminate between intermediate stages of fibrosis Units (m/sec) different from that of TE (kpa) Narrow range of values (0.5-4.4 m/sec) Quality criteria not well defined Prognostic value in cirrhosis? Further validation warranted Unable to discriminate between intermediate stages of fibrosis Quality criteria not well defined Learning curve? Influence of inflammation? Further validation warranted especially in comparison with TE Not applicable in case of iron overload Requires a MRI facility Time-consuming Costly

Complication Ascites SBP Varices(Esophageal, Gastric, Ectopic) Hepatorenal syndrome Hepatopulmonary syndrome Portopulmonary Hypertension Hepatic hydrothorax SBE Hepatic encephalopathy Hepatocellular carcinoma

Cirrhosis is a series of continuous and progressive stages, not a single stage Friedman S. Gastroenterology 2008

Clinical Course of Cirrhosis (Baveno IV) D Amico G., Garcia-Tsao G., Pagliaro L.J of Hepatol 2006;44:217-231

Cause of cirrhosis Acute Chronic Viral A-E,CMV, EBV, Herpes Viral hepatits B and C Toxic Acetaminophen, Amanta, Alc, Drug Toxic Alcohol, MTX Ischemic Vascular BCS, SOS Metabolic Wilson Fatty liver Reye syndrome Autoimmune Liver disease Metabolic Wilson,Hemochromatosis alpha1 antitrypsin deficiency Fatty liver NASH Autoimmune Liver disease

Disorder Treatment Alcohol Viral hepatits B Viral hepatits C Wilson Hemochromatosis Autoimmune hepatitis Primary biliary cirrhosis NASH Quit alcohol, Nutritional support, Baclofen Peg-IFN NUC Peg-IFN with ribavirin DAA D penicillamine Zinc Phlebotomy Iron chelate for 2 nd hemochromatosis Prednisolone and Azathioprine UDCA Liver Transplantation MELD > 17 Weight reduction, Bariatric sx TZD Vitamin E

General management Correct cause : AIH, HBV, HCV, Alcohol Immunization : Hepatitis A, Hepatitis B Exercise Compensated without EV : ok EV : avoid isometric and weight training Surveillance Varices and HCC

General nutrition guidelines for cirrhosis 35 40 kcal/kg dry body weight 50% - 60% of calories as carbohydrate 20% - 30% of calories as protein (1.2 1.5 g/kg body weight) In hepatic encephalopathy : if patients is protein intolerant, consider increasing vegetable protein, dairy protein, and branched chain amino acids. 10% - 20% of calories as fat 4 7 small meals, late evening carbohydrate rich snack Low sodium diet (<2000 mg/d) only if ascites or edema Screen for deficiencies of serum zinc, calcium and vitamins A, D, E and K deficiency and supplement as needed

Management complication and surveillance Ascities Antibiotic prophylaxis in cirrhosis patient Esophageal varices Hepatorenal syndrome Hepatic encephalopathy Surveillance Varices and HCC

NO

Ascites Sodium restriction 2000 mg per day (88 mmol per day) Fluid restriction is not necessary Na < 120-125 restrict 1-1.5 lit or less than urine output Diuretic Single dose morning Spinololactone alone when minimal fluid overload Spinololactone 100 + furosemide 40 combination Shorten time to remove ascites and normokalemia Increase dose q 3-5 day No Edema : maximum 0.5 kg/day Edema : maximum 1 kg/day

Drug in cirrhosis patient Drugs To Be Avoided or Used With Caution NSAID Aminoglycoside ACEI and ARB PPI : increase risk of infection Propranolol in some condition?? Pain control in cirrhosis Avoid NSAID and Opioid Tramadol and Acetaminophen < 2-4 gm/day recommended Insomnia : Trazodone, Hydroxyzine Statin : Safely and maybe benefit

Beta blocker in Refractory ascites Close monitoring of BP, Cr, Na Reduce dose when Systolic blood pressure <90 mmhg Hyponatremia (<130 meq/l) Acute kidney injury

Refractory Ascites About 10 % Refractory ascites (Resistance) Unresponsive to sodium-restricted diet and high dose diuretic Recurs rapidly after therapeutic paracentesis Failure of diuretic therapy (Intractible) Minimal to no weight loss together with inadequate (<78 mmol per day) urinary sodium excretion despite diuretics Development of clinically significant complications of diuretics Encephalopathy Cr > 2.0 mg/dl Na <120 mmol/l K > 6.0 mmol/l

Treatment of refractory ascites Serial therapeutic paracenteses Liver transplantation Transjugular intrahepatic portasystemic stent-shunt (TIPS) Peritoneovenous shunt

Diagnosis of SBP Ascitic culture ANC (cell/mm 3 ) Negative < 250 Normal > 250 Culture-negative neutrocytic ascites Positive Monomicrobial nonneutrocytic bacterascites SBP CNNA -> 1/3 become culture positive MNBA -> 2/3 spontaneously resolved Culture no growth : 6 hrs ATB 86% Treatment Cefotaxime 2gm IV q 8 hr 5 days Ofloxacin 400 bid 8 days Without prior exposure to quinolones, vomiting, shock, HE grade II (or higher), Cr > 3 mg/ dl

Secondary peritonitis WBC many thousand Multiple organism 48 hr after treatment rising pretreatment 2/3 of Sugar < 50 TP > 1 LDH more than UNL Free perforate Sens 100, Spec 45% Non perforate sens 50% CEA > 5 or ALP > 240 Sens 92% Spec 88%

Antibiotic prophylaxis in cirrhosis 1 prophylaxis : prevent SBP and decrease mortality TP < 1.5 in ascites with Renal impair (Cr>1 or BUN > 25 or Na < 130) Liver impair (CPS 9 and TB 3) Norfloxacin 400mg OD 2 prophylaxis (Norfloxacin 400 od) : decrease SBP Recurrent SBP about 69% Everybody until no ascites or LT More drug resistance GI bleeding Ceftriaxone 1 gm V OD or Norfloxacin 400mg bid 7 days Decrease Rebleeding Infection and Short term Mortality

Variceal bleeding Acute Variceal bleeding Keep Hb 7-8 Vasoactive drugs (terlipressin(hypo Na), somatostatin, octreotide) should be used in combination with endoscopic therapy (In 12 hr) Early TIPS within 72 h Considered EV and GOV at high risk of treatment failure (CPG B to C (<14 points) with active bleeding) after fail treatment Primary prophylaxis (Propranolol, Nadolol, Carvedilol in primary) Medium to large varice (EVL or Beta blocker) Small with red wale mark sign or child C (Beta blocker) Secondary prophylaxis EVL + Betablocker Baveno VI. Journal of Hepatology 2015

Hepatorenal Syndrome Bleeding, paracentesis without plasma expansion, alcoholic hepatitis Bacterial infection, SBP Wong F et al. Gut 2011

Creatinine in cirrhosis effect by Muscle wasting Increase tubular secretion of creatinine Increase volume distributuin dilute createnine Interfere assay Cr by elevate bilirubin AKI as diagnosed with AKIN criteria associated with increased mortality in patients with cirrhosis in an AKIN stage-dependent fashion Urine NGAL 105 325 suspected HRS Journal of Hepatology 2015 vol. 62 j 968 974

ICA-AKI criteria Journal of Hepatology 2015 vol. 62 j 968 974

2-4 day in hospital 2-4 wk outpatient

Prevention Albumin infusion in the setting of spontaneous bacterial peritonitis LVP Pentoxifylline Severe alcoholic hepatitis Cirrhosis, ascites, and creatinine clearances between 41 and 80 ml/min

Therapy for HRS Liver transplantation for both type TIP for bridging?? Vasoconstrictors and albumin reduce mortality on type 1 not type 2 (Terlipressin, norepinephrine, midodrine+ octreotide)

Hepatic encephalopathy Treatment convert hepatic encephalopathy in some condition (e.g., impairment in driving skills, work performance, quality of life, or cognitive complaints) Treatment in Overt hepatic encephalopathy Lactulose (2-3 bowel movement per day) is first line Oral BCAA,IV LOLA Neomycin, Metonidazole LT No primary prophylaxis Secondary prophylaxis for overt hepatic encephalopathy Lactulose Lactulose + Rifaximin Total calories : 35-40 kcal/kg Ideal BW Total protein 1.2-1.5 gm/kg/day (Restrict only first few day in overt HE)

Surveillance Surveillance Esophageal Varices (Liver stiffness < 20 and Plt > 150000 low risk) EGD q 2-3 yrs if no EV EGD q 1-2 yr if small EV Surveillance HCC U/S q 6-12 mth ± AFP

Surveillance HCC Cirrhosis Child A-B Child C with transplantation list CH-B Male > 40 years Female > 50 years HCC in first degree relative CH-C with fibrosis 3 U/S q 6-12 month +/- AFP

High AFP > 20 ng/ml 2 with normal U/S W/U other cause and F/U AFP 3-4 month Decrease AFP : Surveillance regular No decrease AFP : Dynamic imaging

Decrease readmisson, Mortality and Expenditure