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 BiomarkerTransient

elastographyARFI (pSWE) 2D-SWE MR elastography

Advantages

•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, extra-

hepatic cholestasis, liver

congestion, food intake

and excessive alcohol

intake

•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, HerpesViral hepatits B and C

Toxic

• Acetaminophen, Amanta, Alc, DrugToxic• Alcohol, MTX

Ischemic

Vascular

• BCS, SOS

Metabolic

• Wilson

Metabolic• Wilson ,Hemochromatosis

• alpha1 antitrypsin deficiency

Fatty liver

• Reye syndromeFatty liver• NASH

Autoimmune Liver disease Autoimmune Liver disease

Disorder Treatment

Alcohol Quit alcohol, Nutritional support, Baclofen

Viral hepatits B Peg-IFNNUC

Viral hepatits C Peg-IFN with ribavirinDAA

Wilson D penicillamineZinc

Hemochromatosis PhlebotomyIron chelate for 2nd hemochromatosis

Autoimmune hepatitis Prednisolone and Azathioprine

Primary biliary cirrhosis UDCA

NASH Weight reduction, Bariatric sxTZDVitamin E

Liver Transplantation

MELD > 17

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

• 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

General nutrition guidelines for cirrhosis

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 portasystemicstent-shunt (TIPS)

• Peritoneovenous shunt

Diagnosis of SBPAscitic culture

Negative Positive

ANC (cell/mm3)

< 250 NormalMonomicrobialnonneutrocytic

bacterascites

> 250Culture-negative

neutrocytic ascites 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

Free perforate Sens 100, Spec 45%Non perforate sens 50%

• 2/3 of • Sugar < 50

• TP > 1

• LDH more than UNL

• 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

Wong F et al. Gut 2011

Bacterial infection, SBP

Bleeding, paracentesis

without plasma expansion, alcoholic hepatitis

Journal of Hepatology 2015 vol. 62 j 968–974

• 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

ICA-AKI criteria

Journal of Hepatology 2015 vol. 62 j 968–974

2-4 day in hospital2-4 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/ml2 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