IN P RIMARY C ARE S ETTING Thwin Maung Aye National University - - PowerPoint PPT Presentation

END STAGE LIVER DISEASE

IN

PRIMARY CARE SETTING

Thwin Maung Aye National University Hospital 18th October 2014

ROLE OF FAMILY PHYSICIAN

 Understanding natural history of cirrhosis and

shared care with the institution

 Prevention of liver cirrhosis  Understanding tumor (HCC) biology and

surveillance

 Understanding role of liver transplant and timely

referral

OBJECTIVES OF THE TALK

 To acknowledge the common scenarios, outline

management plan and appreciate role of primary physician

 To update new DAA for hepatitis C  To understand the rationale and indication of

transplantation for appropriate referral

COMMON SCENARIOS?

• 1. Known fatty liver, regular follow up with LFT and

USG which was reported as nodular surface

• 2. First time diagnosis of HBsAg+ve in view of

abnomal LFT. USG reported as nodular surface

• 3. Patient present with leg swelling. Blood tests

showed abnormal LFT and nodular liver surface

COMMON SCENARIOS?

• 4. Patient known cirrhotic but defaulted follow up and

came to see you with bleeding PR

• 5. Known cirrhotic patient, on diuretics, lactulose and

propranolol and come to see with confusion and worsening of ascites before hospital appointment

• 6. Patient came for weight loss, jaundice and palpable

mass in RHC

CASE SCENARIO FOR ESLD

 50 years old man, Mr Ng, came to see you as a routine

follow up for her hypertension, diabetes and

• hyperlipidaemia. He has been taking amlodipine, glipizide

and simvastatin. He had no compliant. His BP was 140/90 mmHg and BMI was 30. Other clinical examination were

• unremarkable. USG done was reported as early cirrhosis

and mild splenomegaly. His blood tests were as followed.

 Hb 12, TWC 5.2, Platelet 120  Na 135, K 3.5, Urea 7, creatinine 98,  AST 80, ALT 68, Albumin 32, Bilirubin 8, AFP 5, INR 1.2  HBA1c 7.8, LDL 3.2, cholesterol 5.8, Tg 1.2

WHAT ARE YOU GOING TO DO NEXT?

A) Review his... B) Refer to ho... C) Refer to ho... D) A+B E) A+C

0% 0% 0% 0% 0%

A) Review history & investigations and optimize the control his metabolic syndrome and review in 3-6 months B) Refer to hospital in view of USG finding C) Refer to hospital in view of transaminitis D) A+B E) A+C

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15

IF YOU PLAN TO REFER, WHAT WILL YOU DO

BEFORE REFERRAL?

A) Further relevant hist... B) Hepatitis marker C) Dietician review D) Compliance to medic... E) All of above

0% 0% 0% 0% 0% A) Further relevant history including social history B) Hepatitis marker C) Dietician review D) Compliance to medication E) All of above

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15

IF HBSAG+VE, WHAT IS POSSIBLE DIAGNOSIS?

A ) N A S H B ) H e p B l i v e r . . . C ) C r y p t

• g

e n i c . . . D ) A l c

• h
• l

i c c . . . D ) A + B

0% 0% 0% 0% 0%

A) NASH B) HepB liver cirrhosis C) Cryptogenic cirrhosis D) Alcoholic cirrhosis D) A+B

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15

WHAT IS/ARE YOUR PLAN(S) OF MANAGEMENT?

A) Life style ... B) Optimizatio... C) Further eva... D) Referral to... E) All of abov...

0% 0% 0% 0% 0% A) Life style modification (dietician review , exercises) B) Optimization of his metabolic syndrome control C) Further evaluation of hepatitis B / other aetiologies D) Referral to hospital for evaluation of possible cirrhosis E) All of above

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15

MR NG WAS REFERRED TO NUH DC

Here are the tests / evaluation done in NUH Confirmed Child A cirrhosis after the followings. Hepatitis B viral load: 6 log, HBeAg-ve, HBeAb+ve Hepatitis C (-)ve, HIV (-)ve, Autoimmune screening (-)ve Fibroscan: 19.8 kpa Liver biopsy: NI 4/16, Fibrosis 5/6 Tenofovir was started OGD: Small 2 column of varices, for surveillance Advice on low salt diet Advice for regular 6 monthly follow up in NUH

MR NG HAS REGULAR FOLLOW UP WITH YOU

FOR HIS METABOLIC SYNDROME. WHAT IS YOUR CONCERN REGARDING HIS CIRRHOSIS?

A) No concern ... B) Adequate co... C) make sure h... D) All above E) All above e...

0% 0% 0% 0% 0%

A) No concern as he has appointment with NUH B) Adequate control of his metabolic syndrome C) make sure he has regular follow up for varices and HCC D) All above E) All above except A

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15

BEFORE HIS NUH APPOINTMENT , YOU SAW HIM

FOR HIS REGULAR CLINIC. MR NG SAID HE NOTICED ABDOMINAL DISTENSION WITHIN 1-2 WEEKS. WHAT IS YOUR IMPRESSION?

A) ascites from cirrhosis ... B) Portal vein thrombosis.. C) Poor compliance to di.. D) To rule out Cardiac / ... E) All of above

0% 0% 0% 0% 0%

A) ascites from cirrhosis progression B) Portal vein thrombosis / HCC C) Poor compliance to diet particularly salt intake D) To rule out Cardiac / Renal failure E) All of above

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15

WHAT WILL YOU DO NEXT?

A) Start diur... B) Further ev... C) Bring forw... D) All above E) All above e...

0% 0% 0% 0% 0% A) Start diuretics straightaway and review again B) Further evaluation including blood tests and USG C) Bring forward his appointment with NUH D) All above E) All above except A

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15

MR NG HAS USG AND BLOOD TESTS DONE BY

• YOU. THE RESULTS WERE AS FOLLOWED.

 USG: moderate ascites, no focal lesion in the liver

was reported

 Albumin 28  INR 1.5  Creatinine 98, Na 130  Bilirubin 10, ALP 150  AFP 7.5,  Hb 10.5, TWC 3.8, Platelet 110  Child B

WHAT IS YOUR NEXT PLAN OF MANAGEMENT?

A) Start Diuretics and re... B) To monitor his weigh... C) Dietary advice togeth.. D) Send to NUH for fur... E) All above except D

0% 0% 0% 0% 0% A) Start Diuretics and review in 1-2 weeks B) To monitor his weight and renal function C) Dietary advice together with salt restriction D) Send to NUH for further management rather than bringing forward E) All above except D

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15

MR NG WAS SEEN BY NUH AS APPOINTMENT

WAS BROUGHT FORWARD

 NUH made minor adjustment of diuretics for ascites

Dignostic paracentesis showed neutrophil count of > 250 and ciprofloxacin was started

 Repeat OGD: Moderate varices 2 columns and beta

propranolol was started

 Appointment was given in 3 months to review (with scan

and blood tests)

WHAT IS YOUR CONCERN NOW?

A) Cirrhosis care must b... B) Joint care with you is s...

0% 0%

A) Cirrhosis care must be under NUH B) Joint care with you is still possible titrating diuretics, monitoring compliant of meds and diet and follow up

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15

JUST BEFORE APPOINTMENT WITH NUH , HIS SON

CALLED YOU TO TELL YOU THAT MR NG IS CONFUSED AND VERY SLEEPY. WHAT DO THINK THE POSSIBLE CAUSE(S)?

A) Hepatic encephalopathy B) Stroke C) Sepsis D) Dehydration and ure... E) Possible all above

0% 0% 0% 0% 0%

A) Hepatic encephalopathy B) Stroke C) Sepsis D) Dehydration and ureamic encephalopathy E) Possible all above

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15

WHAT WILL YOU DO NEXT?

A) Review the ... B) Advice to s...

0% 0%

A) Review the patient to find

• ut precipitating

causes B) Advice to send to NUH straightaway

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15

THE FOLLOWINGS ARE FINDINGS WHEN YOU

REVIEW.

 GCS 15/15, drowsy but orientated to time, place , person  BP 100/70mmHg, HR 90/min, afebrile, HC 7, neurology: NAD,

PR: stale maleana

 Bloods: Na 130, Urea 18, Creatinine 180, CRP 15, INR 1.5, Hb

10.2, platelet 120

 No new drugs were taken lately

WHAT IS YOUR IMPRESSION?

A) Electrolyte imbalance B) Grade I encephalopathy C) Variceal Bleeding D) Sepsis E) Possible all of above

0% 0% 0% 0% 0%

A) Electrolyte imbalance B) Grade I encephalopathy C) Variceal Bleeding D) Sepsis E) Possible all of above

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15

WHAT IS YOUR NEXT ACTION?

A) Give stat dose of bro.. B) Stop diuretics C) 2 large bore IV plug an... D) Advice to go to ED, ... E) All of above

0% 0% 0% 0% 0%

A) Give stat dose of broad spectrum antibiotics B) Stop diuretics C) 2 large bore IV plug and IV drip D) Advice to go to ED, NUH ASAP E) All of above

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15

MR NG WAS ADMITTED TO NUH. HE WAS TREATED FOR

VARICEAL BLEEDING BY EVL, ANTIBIOTICS, PPI. ELECTROLYTE WAS CORRECTED. HE HAD REPEAT USG SCAN DURING ADMISSION.

 USG showed suspicious lesion in segment 6 about 1.2 cm and

confirmed HCC with CT after his AKI settled

 Further blood tests: Bill 34, INR 1.8, Creatinine 132, Albumin

27, Moderate ascites, Ecolic in blood

 Multidisciplinary team discussion on risk of treatment of HCC

in view of his Child C status vs liver transplant option as of MELD 20 (MELD 20-29: mortality 76% 3 months) once infection is under control

LEARNING POINTS

 Natural history of cirrhosis  stable but can be suddenly deteriorating  Joint care will optimize patient’s condition  Adjusting threshold of both sides for optimizing care  Recognition of primary care involvement in cirrhosis  Antiviral reduced risk of HCC not prevent HCC

ROLE OF FAMILY PHYSICIAN

 Shared care of patients with institution

 Ascites, hepatic encephalopathy, GI bleeding

 HCC surveillance / understanding of tumor biology

 6-12 monthly scan and LFT, AFP

 Timely referral to liver transplant centre

 Clinical indications (CP score, bleeding, ascites, HE, HCC)  MELD ≥15

 Prevention of cirrhosis

 Alcohol abuse, screening for viral hep, control risk factors for NAFLD  Vaccination programme

NATURAL HISTORY OF END STAGE LIVER DISEASE

Fattovich et al. Hepatology 1995; Liaw et al. Liver 1989; Ikeda et al. J Hepatol 1998.

Cirrhosis 18-20% HCC 6-15% Decompensation 20-30% Death

DIAGNOSIS OF CIRRHOSIS

Modality Ultrasound CT MRI Sensitivity 65-95% 65-84% 68-87% Specificity 38-93% 68-80% 70-92% Accuracy 64-88% 67-72% 68-70%

Kudo M et al. Intervirology 2008; 51: Suppl 1, Ito K et al. Radiology 1999; 211(3): 723-36. Kristin N et al. Scan J Gastroenterol 2005;40:76-82.

TRANSIENT ELASTOGRAPHY

Shaheen, Am j Gastro 2007, Castera J Hepatol 2008

Metavir score All HBV NAFLD/NASH PSC/PBC HCV % >F2 fibrosis 50-82% 58% 49-50.4% 60% 2.5-65% Cutoff level 4-7.9 7 6.6-8.7 7.3 4.5-8.7 AUROC 0.74-0.86 0.81 0.86-0.87 0.920 0.72-0.83

PORTAL HYPERTENSION & CONSEQUENCES

 Ascites and its consequences

 Ascites responsive to diuretics  Recurrent ascites (intolerance, poor compliance, resistant)  SBP

 Hepatic encephalopathy

 Precipitating causes (infection, electrolyte, GI bleeding, stroke,

constipation, poor compliance, neuro meds)

 GI bleeding

 Variceal bleeding (oesophageal / gastric)

ASCITES

 Treatment of underlying cause  Salt (/fluid) restriction(2g/day ie 88mmol/day) when?  Diuretics (Spironolactone / +/- frusemide)

Stop beta blocker, ACEI and ARB

 Weight monitoring (weight loss ≤ 0.5kg)  Spontaneous bacterial peritonitis

 Primary prophlaxis (ascite fluid albumin <1.0g/dL, bil>2.5)  Secondary prophylaxis

 Response assessment

 Responsive, intolerant, compliance, resistant

ROLE OF MIDODRINE FOR ASCITES

 Hepato-renal syndrome  hypotension, post ascites drainage  Diuretics resistant recurrent ascites  Oral formula 7.5-12.5 mg TDS  Improve clinical outcome and survival

Comparison of midodrine and albumin in the prevention of paracentesis-induced circulatory dysfunction in cirrhotic patients: a randomized pilot study J Hepatol 2012;56:348-354

VAPTANS FOR ASCITES

 Vasopressin receptor antagonists  For euvolaemic and hypervolaemic hyponatraemia

(tolvaptan1)

 For ascites rather then HypoNa (Satavaptan2)  Side effects, doubtful survival benefit and cost

effectiveness

• 1. Cardenas A, Gines P, Marotta P, Czerwiec F, Oyuang J, Guevara M, Afdhal NH. Tolvaptan, an oral

vasopressin antagonist, in the treat- ment of hyponatremia in cirrhosis. J Hepatol 2012;56:571-578

• 2. Wong F, Watson H, Gerbes A, Vilstrup H, Badalamenti S, Bernardi M, Gines P, et al. Satavaptan for the

management of ascites in cirrho- sis: efficacy and safety across the spectrum of ascites severity. Gut 2012;61:108-116

HEPATIC ENCEPHALOPATHY

• Lactulose (reduced absorption of ammonia)
• Rifaximine
• BO at least 2-3 /day
• Precipitating factors
• Infection
• Electrolyte
• Compliance
• GI bleeding
• CVA
• Constipation
• Drugs (neuro suppressant)

RIFAXIMIN IN HEPATIC ENCEPHALOPATHY

Prevention of recurrent HE Minimal, Overt or prevention of recurrent HE

The Effects of Rifaximin in Hepatic Encephalopathy. Aliment Pharmacol Ther. 2014;40(2):123-132

VARICEAL BLEEDING

• Baseline severity of cirrhosis (Child-Pugh)
• Rate of progression of cirrhosis
• ± Medication and Compliance (Propranolol/Carveidolol)
• Last scope and findings (site of varices) & treatment
• Splanchnic vasoconstrictors and antibiotics

Carveidolol Vs Propranolol ?

Carvedilol for primary prophylaxis of variceal bleeding in cirrhotic patients with haemodynamic non-response to propranolol.Gut.2013 Nov;62(11):1634-41. doi: 10.1136/gutjnl-2012-304038. Epub 2012 Dec 18

HEPATOCELLULAR CARCINOMA (HCC)

• Tumor biology
• High risk nature of tumor
• Size and number of tumor
• Level of AFP
• Treatment history
• Last surveillance duration
• Previous treatment and modality
• Resection
• TACE
• RFA

STEREOTACTIC BODY RADIATION THERAPY (SBRT)

 Precisely deliver external radiation therapy to tumor  Few side effects  Requires high degree of precision  Un-resectable tumor, not suitable for convetional RT

RISK FOR HCC & LIVER-RELATED DEATH

IN HEPB IMMUNE CONTROL CARRIER

 1932 inactive carriers in REVEAL-HBV

 Seronegative for HBeAg  Serum HBV DNA <10,000 copies (<2000 IU)/mL  No cirrhosis, HCC, nor elevated ALT

Annual incidence rates Inactive carriers Controls (sAg-ve) Adjusted hazard ratio 95% CI HCC 0.06% 0.02% 4.6 2.5-8.3 Liver-related deaths 0.04% 0.02% 2.1 1.1-4.1

Older age and alcohol drinking habits were independent predictors of risk for carriers of inactive HBV to develop HCC

Chen JD et al. Gastroenterology 2010;138:1747-54.

GOALS OF TREATMENT

 APASL guidelines 2008

To permanently suppress HBV replication.

The ultimate long-term goal is to achieve “durable response” to prevent hepatic decompensation, reduce or prevent progression to cirrhosis and/or HCC, and prolong survival

 AASLD guidelines 2012

To achieve sustained suppression of HBV replication and remission of

liver disease. The ultimate goal is to prevent cirrhosis, hepatic failure and HCC.

 EASL guidelines 2009

To improve quality of life and survival by preventing progression of the disease to cirrhosis, decompensated cirrhosis, end-stage liver disease, HCC and death. This goal can be achieved if HBV replication can be suppressed in a sustained manner.

Liaw YF et al. Hepatol Int 2008; 2: 263–83; Lok AS et al. Hepatol 2009; AASLD Practice Guidelines; EASL, J Hepatol 2012; Vol.57 167-185.

SELECTION OF TREATMENT FOR CHB

Oral nucleosides

 One tab/d  Very few side effects  Can be used for the whole

spectrum of CHB cases

 Suppresses virus but does

not eradicate

 HBeAg seroconversion 20-

25%

 Long term therapy is the

norm

 Moderate cost

Immunomodulators

 Once weekly injections  Many side effects but usually

tolerable

 Cannot be used for advanced

liver disease

 Can clear virus in small % of

patients

 HBeAg seroconversion >30%  Treatment course is 48 wks  Expensive

INTERNATIONAL GUIDELINES ON RECOMMENDATIONS

AASLD Chronic Hepatitis B: Update 2009. Hepatology 2009;50:1-36 EASL Clinical Practice Guidelines: Management of chronic hepatitis B. J Hepatol. 2012; Vol.57 167-185 Liaw, Hpeatol Int (in press) 20112

2012 EASL

• Drugs with high potency and low resistance rate , eg. ETV,

TDF

2009 AASLD

• Drugs with high potency and high genetic barrier, eg. ETV,

TDF

• LAM, ADV and LdT are not preferred for for naïve patients

2012 APASL

• ETV or TDF is the preferred Nuc

IMPROVEMENT IN FIBROSIS (ENTECAVIR)

IMPROVEMENT IN FIBROSIS (TENOFOVIR)

REDUCE HCC OCCURENCE

HCC INCIDENCE IN ENTECAVIR TREATMENT

HCC INCIDENCE IN NON-CIRRHOTICS

Hepatitis C structure target for new Direct Antiviral Agent

Combination therapy

Future speculation

New drugs on the horizon Predictors of response Combination therapy concept Timeline? Now or wait ?

WHY PATIENT NEEDS TRANSPLANT AND WHEN?

 Patient’s ESLD survival  Life expectancy and OLT survival (1 yr 80-90%)  Organ availability and waiting time  Blood group  Child score / MELD  Quality of life from the disease

Summary flowchart for cirrhosis and complication

PREVENTIVE AND COMMUNITY ASPECT

 Ensure adequate nutrition (including calorie & protein

intake) and supplement (eg. Zinc)

 Alcohol cessation, community programme  Prophylactic antibiotics for SBP (for bleeding)  Osteoporosis risk assessment and primary prevention  Life style modification for NAFLD/NASH  Vaccination for hepatitis A, B, pneumonia, influenza  Compliance to treatment and follow up

Thank you for your attention