common problems in gi opd how to advise patients in gi opd

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How to Advise Patients in GI OPD

รศ.นพ. เฉลมิรฐั บญัชรเทวกลุDivision of Gastroenterology and Hepatology

Rajavithi Hospital, Ministry of Public Health, Bangkok

College of Medicine, Rangsit University, Thailand

Common Problems in GI OPD

• GERD

• Dyspepsia, PUD, HP and NSAIDs

• Asymptomatic gallstone

• Chronic constipation

• IBS

• Chronic hepatitis B and C

• Cirrhosis and portal HT

• NAFLD

Patient Education: Contents

Key investigations• Indications and risks

• Red flag signs

Medications• How they work

• Efficacy and duration

• Possible side effects

Non-pharmacologic therapy and lifestyle

modifications

Questions and answers

About the disease• Cause and mechanism

• Natural history

GERD

GERD: Disease Overview

• Cause: dysfunction of LES → reflux of stomach content causes troublesome symptoms and/or complications

• Risk factors: hiatal hernia, obesity, pregnancy, etc.

• Not life threatening, but symptoms can affect QOL

• Prognosis: NERD/mild EE (>85% of Thai pt.) –good, occasionally relapse; Severe EE – often relapse without PPI, complications may occur

• Risk for CA: very low (Barrett’s <1% in Asia)

Symptoms Suggestive of GERD

NCCP

Stop/step down

On-demand/continuous PPI

EGDYes

NR Response

Recurrent symptoms

Alarm symptoms*

LSM + double-dosePPI 8 wk

Double dose or switch PPI (standard-dose)

8-12 wk

Thailand GERD Guideline 2020

No

▪ Dysphagia

▪ Odynophagia

▪ Recurrent

vomiting

▪ GI bleed

▪ Anemia

▪ Wt. lossExclude other

conditions

LSM + double-dosePPI 8-12 wk

Refractory GERD

If presence of

typical symptoms

NR

NR

Typical

Response

Response

NR

LSM + standard-dosePPI 4-8 wk

Response

Extra-esophageal

NR

EGD

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GERD: Lifestyle Modification

• Weight reduction – for pt. with overweight or recent weight gain

• Stop smoking

• Avoid NSAIDs

• Try not wearing tight clothing and body shapers

• Eat smaller portions of food; don’t eat too much

• Avoidance of meals 2-3 hour before bedtime recommended if nocturnal GERD

• Head of bed elevation (4-6”) if nocturnal GERD

• Routine global elimination of food that can trigger GERD not recommended – selective elimination could be considered

Adapted from American Gastroenterological Association GI-patient-center

GERD Common Trigger Foods

ชา/กาแฟ Alcohol อาหารมนั น า้อดัลม

Chocolate กระเทยีม หวัหอม มะเขอืเทศ

ผลไมร้สเปรีย้ว Peppermint อาหารรสเผ็ด เนย/ชสี

Sleep Positions and GERD

Definition: gastric acid recovery to a pH level <4 for at least 60 consecutive minutes in the night period

GERD: Medications and Sx

• PPI – mainstay treatment for GERD

– Should be taken 15-45 min before meal

– Duration: 4-8 wk – then PRN (maintenance >6-12 mo for severe EE/LPR)

– Side effects – rare (long-term effect?)

• Other meds: antacids, alginates, prokinetics, H2RA

• Laparoscopic fundoplication

– Indications: PPI-responsive GERD who don’t want to take long-term PPI (efficacy ~ PPI) and refractory GERD with large hiatal hernia

– Complications: <1% mortality, 25% dysphagia, bloating, 30-60% need rescue PPI after 2-5 yr

Potential Risks of Long-term PPI

Trophic effects due

to hypergastrinemia

Chronic acid

suppressive state

Other/unclear

mechanisms

• ⇩ Absorption of calcium, Mg, iron

and vitamin B12

• ⇧ Risk of infections: C. difficile,

viral AGE, enteric infections, SBP

and pneumonia

• Formation of fundic gland polyps

• ⇧ Progression of atrophic gastritis

• Carcinoid tumors have been

reported in animals (not in human)

• Interstitial nephritis

• ⇧ CKD

• ⇧ Dementia

• ⇧ Myocardial infarction

• ⇧ Ischemic stroke

Drug-drug

interactions

• Altered metabolism by CYP450

(3A4, 2C19) e.g. clopidogrel

• Altered absorption due to

⇧ gastric pH e.g. digoxin, ARV

• Other/unclear mechanisms?

Dyspepsia and H. pylori

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H. Pylori : Disease Overview

• One of the most common cause of peptic ulcer, gastritis, dyspepsia and CA stomach

• If not eradicated: dyspepsia or ulcer recurrence 60-90% within 1 yr

• Transmission: fecal-oral, human-to-human

• Prevalence: in Thai adults

– Asymptomatic ~30%

– NUD/uninvestigated dyspepsia 30-50%

– PUD 70-80%

Thai Guideline for Dyspepsia 2018

*Alarm symptoms: dysphagia,

evidence of GI blood loss,

unexplained weight loss,

persistent vomiting

Uninvestigated dyspepsia(exclude medications and other organic diseases)

Yes

Age onset of dyspepsia ≥50 yr or

alarm symptoms* at any age

EGD with HP test

Trial of PPI +/-

prokinetics 4-8 wk

Refer to specialist for further

investigation and treatment

Test and

treat HP

No

Abnormal

findingNormal

finding

Not

resolved

Specific

treatmentFunctional dyspepsia

(trial of PPI +/- prokinetics

TCAs and/or

cytoprotective agents)

Not resolved

Urea Breath Test (UBT)

• High sensitivity (90%) and specificity (95-100%)

• Preparation: NPO 4 hr; stop PPI (≥2 wk), antibiotics and bismuth (≥4 wk) before testing

• Non-invasive diagnosis and post-Rx follow-up

• A very small risk of allergic reactions

H. pylori Eradication Regimens

1st line

therapy

10-14 days standard triple therapy

Thailand Consensus on H. pylori Treatment 2015. Asian Pac J Cancer Prev 2016;17:2351-60

2nd line

therapy

10 days sequential or concomitant therapy

14-day quadruple

therapy14-day levofloxacin-

based triple therapy

Susceptibility testing (E-test or molecular test):

not to use resistant antibiotics

Eradication rate ~80%

Thailand HP resistance data: Clarithro ~14%, Metro ~36%, Levoflox ~7%

H. pylori Eradication Regimens

Standard triple therapy

• PPI BID + Amoxy 1 g BID + Clarithro 500 mg BID x 10-14 d

Concomitant therapy

• PPI BID + Amoxy 1 g BID + Clarithro 500 mg BID +

Metro 400 mg TID x 10 d

Sequential therapy

• PPI BID + Amoxy 1 g BID x 5 d, then PPI BID + Metro 400 mg BID + Clarithro 500 mg BID x 5 d

Quadruple therapy

• PPI BID + Bismuth 525 mg BID + Metro 400 mg BID/TID

+ Clarithro 500 mg BID or Tetra 500 mg QID x 14 d

Levofloxacin-based triple therapy

• PPI BID + Amoxy 1 g BID + Levoflox 500 mg OD x 14 d

*Metronidazole-based triple therapy is less effective

H. Pylori : General Advice

About the treatment

• Emphasize the importance of regimen compliance (e.g. adequate duration 10-14 d, PPI timing)

• Emphasize consequences of non-adherence

• Ask about the history of drug allergy (e.g. antibiotics, ASA, salicylates) and previous use of antibiotics (e.g. clarithromycin, levofloxacin)

• Anticipate treatment-related side effects e.g. N-V, metallic taste, diarrhea, GI upset and black stool

• Successful treatment → reduces symptoms, reduces ulcer recurrence, reduces gastritis progression and the reduces CA

• Post-Rx FU: by UBT (or stool Ag or EGD for GU)

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H. Pylori : General Advice

Prevention

• Quite difficult to prevent

– Average re-infection rate in Thailand ~3% per yr(may be more if family members are HP+)

• Eat clean/cooked food; drink clean water

• Use middle spoon

• Wash your hands after you use the toilet and before you prepare or eat food

Dyspepsia: Lifestyle Modification

• Stop smoking (or don’t smoke)

• If possible, avoid taking ASA or NSAIDs

• Avoid alcohol, caffeine and carbonated drinks

• Avoid eating too spicy or any food that aggravate your symptoms

• Eat small, low-fat meals during the day

• Eat at slow pace; chew food with care and fully

• Allow enough time for meals

• Don’t eat right before you go to bed or exercise

• Sleep with your head raised slightly

• Get enough rest


Adapted from Asian Consensus Report. Miwa H, et al. J Gastroenterol Hepatol 2011

Functional Dyspepsia: Medications

Postprandial distress

syndrome (PDS)Epigastric pain syndrome

(EPS)

Predominant symptom(s) ?

Bothersome postprandial

fullness

Bothersome

early satiation

Bothersome

epigastric burning

Bothersome

epigastric pain

ปวด/เจ็บ แสบรอ้น อ ิม่เร็ว อดึแนน่

Adapted from Asian Consensus Report. Miwa H, et al. J Gastroenterol Hepatol 2011

Response after 4-8 wk

Functional Dyspepsia: Medications

PPI with or without

prokinetics

Response after 4-8 wk

Prokinetics with

or without PPI

• TCA, anxiolytics• Rebamipide

• Mucoprotective agents• Psychotherapy

Discontinue or on-demand

Predominant symptom(s) ?

Discontinue or on-demand

Postprandial distress

syndrome (PDS)Epigastric pain syndrome

(EPS)

Dyspepsia: Common Drugs

Domperidone

• Helps your stomach move more properly

• Anti-emetic effects (PRN for N-V)

• Possible side effects:

– QT prolongation (esp. patients with age >60 yrand taking QT-prolonging drugs or CYP3A4 inh.)

– Increased prolactin: galactorrhea, gynecomastia

Tricyclic antidepressants (low doses)

• Helps reducing visceral hypersensivity

• Possible beneficial effects on mood

• Possible side effects: dry mouth, somnolence, constipation, QT prolongation

Peptic Ulcers and NSAIDs

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PUD/NSAIDs: General Advice

• NSAIDs and ASA reduce GI mucosal defense (reduces PG: systemic effects >> local irritation)

– 25% → dyspepsia

– 15-30% → gastritis or PUD

– 1-2% → ulcer complications yearly

• Taking NSAIDs only if necessary

– At the lowest doses

– Taken with foods (not guarantee protection)

• Avoid alcohol and smoking

• Check for H. pylori , if long-term NSAIDs is planned

• Pt. with GI risk factors should take PPI to prevent NSAID-induced ulcer complications (+ dyspepsia)

Risk Factors for NSAID-induced Ulcer Complications

High risk1. History of a previously complicated ulcer 13.5x2. Multiple (>2) risk factors

*H. pylori is an independent and additive risk factor and needs to be treated

Moderate risk (1-2 risk factors)1. Age >65 years 5x2. High dose NSAID therapy 7x3. A previous history of uncomplicated ulcer 6x4. Concurrent use of aspirin (inc. low-dose), 9x

anticoagulants, 6xor corticosteroids 2.2x

Low risk1. No risk factors

Lanza FL, et al. ACG Practice Guideline 2009

Risk Factors for NSAID-induced Ulcer Complications

High risk1. History of a previously complicated ulcer 13.5x2. Multiple (>2) risk factors

Lanza FL, et al. ACG Practice Guideline 2009

Recurrent PU bleeding

15-40% in 1 yr

Recommendations for the Prevention of NSAID-Induced Ulcer Complications

Low GI risk Mod. GI risk High GI risk

Low CV

risk

• NSAID alone (the least

ulcerogenic NSAID

at the lowest

effective dose)

• NSAID + PPI

• [COX-2 inh.]

• Alternative Rx

if possible

• COX-2 inh. + PPI

High CV*

risk(ASA

required)

• Naproxen +

PPI

• Naproxen +

PPI

• Avoid NSAIDs

and COX-2 inh.

• Use alternative

Rx

*High CV risk: 10-yr risk of CV events ≥10% (low-dose ASA is recommended)

Adapted from Lanza FL, et al. ACG Practice Guideline 2009

Asymptomatic Gallstone

Gallstone: Disease Overview

• Prevalence: 5-20% of Thai adults

• Risk factors: female, obesity, older age

Asymptomatic

GS

Biliary colic

20%

Symptomatic GS

Cholecystitis <10%

CBD stone <5%

GS pancreatitis <5%

GS ileus <0.1%

Mirrizi synd <0.1%

GB cancer <0.1%

Recurrence

30-40%

x10 of

asymp GS

1-3%/yr

12-30%

5-40%

(1-2%/yr)

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Indications for LC in Asymptomatic GS

Controversial indications: DM, thalassemia, non-functioning GB,

concomitant cholecystectomy during another abdominal surgery,

certain occupations e.g. pilot, frequent traveler

Indications Reasons

Living in or traveling to

remote areasHigh morbidity if GS compl. develop

Undergoing bariatric

surgery for severe obesity

High risk for developing GS and difficult

to access by endoscopy after surgery

SOT candidates High morbidity if GS compl. develop

GS size >3 cm Higher risk for GB cancer

Porcelain GB Higher risk for GB cancer

American Indians Higher risk for GB cancer

Young age High risk for developing GS compl.

GS: Medications and Sx

• LSM: wt. reduction, avoid fatty meals

• Medications – often not recommended

– UDCA: thins the bile, may slowly dissolve small cholesterol stones (GS can recur after stop)

• Laparoscopic cholecystectomy (LC)

– Minimally invasive Sx: often admit for 1-2 d, go back to normal activities within 1-2 wk

– Complications (in good hands): bile duct injury 0.4-0.5% (5/1,000), mortality 0.15%

– Long-term effects: no significant effects on bile pool and fat absorption (<10% of patients may complain of mild diarrhea and dyspepsia)

Chronic Constipation

Management of Chronic Constipation

Lifestyle modification PLUS

On-demand conventional laxatives in mild or intermittent symptoms

Continuous conventional laxatives in moderate-severe symptoms

Exclude secondary causes*

Colonoscope if positive alarm features

Refractory constipation

No response

Ensure compliance and

optimize laxatives

No response

Optimize the lowest

effective dose

Thailand Constipation

Guideline 2020

*Secondary causes of constipation e.g. medications, metabolic disturbance (esp. hypercalcemia, hypokalemia, hypothyroid), structural and neurological diseases

Constipation and IBS: Red Flag Features

• Recent onset of

constipation in older

age (>50 yr)

• Persistent pain

• Rectal bleeding

• Obstructive symptoms

Ford AC, Talley NJ. BMJ 2012

• Weight loss

• Fever

• Family history of CRC

• Anemia

• Stool occult blood +

• Elevated CEA level

Colonoscopy: General Advice

• OPD procedure (~30 min), under IV sedation

• Requires bowel preparation

• Indications:

– Suspicious for colonic disease

– CRC surveillance (e.g. age ≥50 yr, FHx of CRC)

• Complications:

– Pain, bleeding, perforation

– Overall risk: 3-4/1,000

– 2-3% for polypectomy

• Alternatives:

– Stool occult blood test (FIT)

– DCBE or CT colonography

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Constipation: General Advice

• Educate your patient that normal bowel function varies widely, from 3 BM/day to 3 BM/week

• Eat well-balanced diet with fresh fruits, veggies and a lot of water

• Set aside time to go to the toilet (preferably in the morning; may be after breakfast)

• Go to the toilet when you feel like you have to

• Don’t ignore the urge to have a bowel movement

• Don’t spend more time on the toilet than it takes to pass a stool (maximum 10 min)

• Exercise regularly

• Be patient; feeling better takes time and effort


High Fiber Diet

ขา้วบารเ์ลย์

บล็อคโครี่Berries

แครอท

แอปเป้ิล

อะโวคาโด

ขา้วกลอ้ง

Artichoke

อลัมอนด์

ลกูแพร์

ขา้วโอต๊

ขา้วโพด

ถ ัว่ลนัเตา

ซเีรยีล

ผกัใบเขยีว

Medications for Chronic Constipation

Stimulant laxatives

Bulk (fiber) laxatives

Newer agents

• Ex: psyllium, methylcellulose, bran

• Mech: retaining water in stool (need

to drink adequate water) →

increasing stool bulk

• SE: flatulence, bloating, gut

obstruction (rare)

• Ex: senna, bisacodyl, caster oil

• Mech: stimulate myenteric plexus →

increasing intestinal peristalsis

• SE: abdominal pain, electrolyte

imbalance (rare); long-term use →

melanosis coli, cathartic colon (rare)

• Lubiprostone (ClC-2 activator)

• Prucalopride (5-HT4 agonist)

• Elobixibat (bile acid

transporter inhibitor)

• SE: N-V, headache, diarrhea

Osmotic laxatives

• Ex: MOM, lactulose, PEG

• Mech: Increasing the flow of

water into intestine

• SE: flatulence, bloating,

abdominal cramping, electrolyte

imbalance (rare)

Constipation: Step-up Approach

• High fiber diet

• Bulk/fiber laxatives

• Lubricant/stool softeners

Mild

efficacy

• Osmotic laxatives (dose-dependent)

• Stimulants (dose-dependent)

Second-line

or purgative • Newer agents:

e.g. lubiprostone, prucalopride

• NaP, caster oil (not for long-term use)

• Enema

Moderate/high

efficacy





Exclude secondary causes



No response


optimize laxatives

No response

Optimize the lowest

effective dose


Guideline 2020





Exclude secondary causes



Refer for anorectal physiologic studies

Clinical suggestive of

dyssynergistic defecation*

No response


optimize laxatives

No response

Consider new agents

for 1-2 wk if available

No response Yes

Optimize the lowest

effective dose

No


Guideline 2020

*

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Further Tests for Refractory Chronic Constipation in Thailand

Colonic transit time DefecographyAnorectal manometry

Irritable Bowel Syndrome (IBS)

IBS: Disease Overview

• Diagnosis: based on clinical (ROME IV criteria: abdominal pain associated with defecation, change in frequency or form of stool for ≥3 mo in the past ≥6 mo) + R/O organic disorders

• Types: IBS-Constipation, IBS-Diarrhea, IBS-Mixed

• Common aggravating factors: stress, mens, certain foods, and medications (e.g. iron, calcium, Mg, NSAIDs, opioids, anticholinergic, CCBs, etc.)

• Prognosis:

– Chronic; often off and on

– Risks of developing cancer or other organic disorders do not differ from general population

Adapted from Mearin F, et al. Rev Esp Enferm Dig 2016

IBS: Symptom-based Medications

• Psyllium up to 30 g/d

• PEG 17-34 g/d

• Osmotic laxatives

• Lubiprostone 8 mg BID

• Linaclotide 290 mg OD

• Probiotics

• Rifaximin 550 mg TID x14 d

• Loperamide 2-4 mg/d

• Cholestyramine

• Ramosetron 5 mg OD

• Alosetron 0.5-1 mg BID

• Eluxadoline 100 mg BID

• Antispasmodics: mebeverine, peppermint oil, dicyclomine

• TCAs: nortriptyline, amitriptyline, desipramine

• SSRIs: fluoxetine, setraline, citalopram

• Probiotics

Constipation Diarrhea

Pain

IBS: General Advice

• Reassurance; IBS is a “POSITIVE” diagnosis

• Emotional stress and certain foods e.g. caffeine, fatty foods or alcohol can cause abd. symptoms and loose stools in many people but are more likely to impact those with IBS

• Low FODMAP diet: if bloating, abd. pain, diarrhea

– Fermentable

– Oligosaccharides

– Dissacharides (e.g. lactose)

– Monosaccharides (excess fructose)

– And

– Polyols (e.g. mannitol , sorbitol, and xylitol)


IBS: About FODMAPs

• Low FODMAPs diet may reduce bloating, abd. pain, diarrhea

• 2-4 week trial to gauge clinical response

• For responders: stepwise reintroduction of individual FODMAPs to identify triggers

FODMAPs

FODMAPs draw water

from the SB causing

DIARRHEA

Gut bacteria in the

colon ferments

FODMAPs giving off

GAS – bloating, pain,

wind, distension,

constipation, and

explosive stools

Small

bowel

Colon

Gas

Gas

Gas

Gas

FODMAPs are a collection of

short-chain CBHs that aren’t

absorbed properly in the gut,

which found naturally in

many foods and food

additives and can trigger

symptoms in people with IBS

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แอปเป้ิล

แตงโม

นมววั

ไอศครมี

ถ ัว่เหลอืง

สารให ้

ความหวาน

บรอคคอลี่

หวัหอม

Chronic Hepatitis B

CHB: Treatment Indications

High HBV-DNA • >2,000 IU/ml

Significant liver inflammation

and/or fibrosis• ALT > 2 xULN* for ≥3 mo

• Biopsy: HAI ≥4 or Metavir ≥F2

• Fibroscan >7.0 kPa

+

NO (inactive or

borderline CHB)

YES

(active CHB)

• Continue monitor• Discuss treatment

HCC surveillance by US + AFP q 6-12 mo: if male >40 yr,

female >50 yr, FHx of HCC and advanced fibrosis

HBeAg + or –

*Upper limit of normal for ALT = 35 U/L for males and 25 U/L for females

Assessment of Liver Histology

Liver Biopsy Transient Elastography

❑ Gold standard

❑ Assess all histological aspects

❑ Evaluate cause(s) of liver disease

❑ Pain, bleeding and organ injury

3:100 need blood Tx

3-10:1,000 need Sx or IR

3:10,000 death

❑ Sampling errors

❑ Need of experienced pathologist

❑ Non-invasive

❑ Allow serial reassessment

❑ Assess fibrosis ± fat (accuracy OK)

TE >7 kPa ~ significant fibrosis

TE >14 kPa ~ cirrhosis

❑ Limitations: obesity, ascites,

narrow rib spaces

❑ Altered by: operator experience,

ALT flares, CHF, non-fasting

CHB: Prophylactic Indications

Prevent reactivation

– HBsAg+ pt. undergoing immunosuppressive or chemotherapy

– HBsAg+ pt. undergoing DAA therapy for HCV

– HBsAg–/anti HBc+ pt. undergoing anti-CD20 therapy and HSCT

Prevent mother-to-child transmission

– Pregnant women with DNA >200,000 or HBeAg+ (at GA 24-32 wk until 0-3 mo after delivery)

Prevent transmission?

– HCWs or certain occupations with DNA >2,000

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CHB: General Advice

For patients without treatment indication

• Requires life-long follow-up – schedule regular visits and HCC surveillance

• Up to 40% may become active (and may require treatment) in the future

• Eating clean, cooked and healthy diet

• Avoid aflatoxin-contaminated foods

• Avoid drinking alcohol and smoking

• Avoid or talk with your doctor before using herbal products or OTC medications

• Get the HAV vaccine (test anti HAV first)

• Prevent transmission and testing family members

Aflatoxin-contaminated Foods

ปลาสลดิ

พรกิป่น

ขา้วโพด

ขา้ว

น า้มนัจากเมล็ดพชื

ถ ัว่ลสิง และถ ัว่อ ืน่ๆ

• Aflatoxins are carcinogens that are produced by certain molds (Aspergillus spp.) which grow in soil, decaying vegetation, hay, and grains

• Heat-resistant (need heat >260oc to degrade)

พรกิไทย

มนัฝร ัง่

CHB: General Advice

For patients with treatment indication

• Controllable in all cases (cure in only 1-3%)

• Requires long-term therapy: life-long for HBeAg–amd many yr for HBeAg+ (may be life-long)

• Reduce the risk of HCC (not completely prevent)

• Emphasize the importance of medication adherence and follow-up visits

• Nucleos(t)ide analogs

– Lamivudine, tenofovir, entecavir are ED drugs

– Minimal side effects, long-term safety: good

– TDF nephrotoxicity: incidence 3-15%, risk factors?, require monitoring (manageable)

Chronic Hepatitis C

If HIV+: CD4 ≥500 (no ARV)

If on ARV**: HIV-RNA <40 + CD4 ≥200

HCV Treatment by Thailand NLED 2021

❑ Age 18-70 yr

❑ HCV-RNA >5,000 IU/ml

❑ Stopped drinking/drugs ≥6 mo

❑ Not terminally-ill, ECOG 0-1

❑ GFR ≥30

❑ If cancer: received curative Rx

+ ≥6 mo disease-free

❑ If cirrhosis*: MELD ≤18

Sofosbuvir-Velpatasvir

12 wk

*If cirrhosis Child A/B: add ribavirin 600-1,000 mg/d

**Avoid drug interactions e.g. velpatasvir and efavirenz

❑ Significant fibrosis by ≥1 of …

❑ LSM e.g. Fibroscan ≥7.0 kPa

❑ Labs e.g. FIB-4 >1.45, APRI >0.5

❑ Fibrotest >0.48

❑ Liver biopsy: score ≥F2

Check HCV-RNA at ≥12 wk post-Rx

Sofosbuvir-Ledipasvir 12 wk for genotype 1 or 6

Sofosbuvir can be used in GFR <30 (US/EU-FDA OK)

Add ribavirin if genotype 3b

May also consider (not NLED)

AST/ALT, APRI, FIB-4 Interpretation

AST/ALT ratio

AST

ALT

AGE AST

ALTPLT

AST

ALT

PLT

• AST/ALT >1 indicates cirrhosis with

high specificity (94-100%) but with

low sensitivity (44-75%)

APRI

FIB-4

• APRI >0.5 has sens 82% and spec

65% for significant fibrosis

• APRI >1.0 has 70-80% sens/spec for

cirrhosis

• APRI >2.0 has high specific (91%)

but less sensitive (46%) for cirrhosis

• FIB-4 <1.45 has 90% NPV for

advanced fibrosis

• FIB-4 >3.25 has 97% spec and 60%

PPV for cirrhosis

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CHC: About DAA Therapy

• Curable in >95% of patients

• Cure = SVR = undetectable HCV-RNA at 12 wk after stop therapy → prevent (or reverse) disease progression, reduce HCC and improve survival

• DAAs are increasingly accessible

• Duration: often 12 wk

• Minimal side effects

• Emphasize medication adherence

• Check for drug interaction, avoid PPI if possible

• HCC surveillance, if advanced fibrosis (continue surveillance life-long after SVR)

Transmission: HBV and HCV

HBV HCV

Mode of

transmission

Blood/serum exposure

Sexual transmission

Mother-to-child (perinatal)

Blood/serum exposure

Heterosexual (1-2%/yr)

MSM (high risk)

Mother-to-child (<5%)

Not

transmitted

Eating, drinking, kissing,

using toilet, breast feeding

Eating, drinking, kissing,

using toilet, breast feeding

Vaccination>95% efficacy, but ↓ in elderly

& immunocompromised hostNot available

Testing family

members

Recommended → vaccinate if

antiHBs–

Recommended → avoidance

while treating the index case

Risk from

needle stick

2-50%; depends on HBV-DNA

(risk x100 vs HIV)

1.8%

(risk x10 vs HIV)

Post-exposure

management

Baseline anti-HBs, HBsAg

HBIG + vaccinate if antiHBs–

FU HBsAg (if still + at 6 mo →

evaluation as CHB)

Baseline anti-HCV

Check HCV-RNA at ≥3 wk after

exposure and FU (if still + at

3-4 mo → Rx by DAA)

Cirrhosis and Portal Hypertension

Cirrhosis: Specific Treatment and Prognosis

Overall prognosis

• Child A: median survival 10-20 yr

• Child B: median survival 3-5 yr

• Child C: median survival 1-2 yr

Etiology-specific treatment

• HBV, HCV – antiviral therapy

• Alcohol – stop drinking, reassess over time

Liver transplantation

• Indications: MELD ≥15, major decomp. events

• Outcome: >80% survival at 5 yr

• Limited access in Thailand (70-100 cases/yr)

Liver Transplant in Thailand

รายงานประจ าปีศูนยร์บับรจิาคอวยัวะสภากาชาดไทยData from 9 LT centers in Thailand

• 2554: LT in children coverage by สปสช. (UC)

• 2557: LT in adults coverage by ปกส.

• 2564: LT in adults coverage by สปสช. (UC)

•216 d 281 d 328 d 214 d 256 d

Average waiting time

257 d

Ascites: OPD Management

• Diuretics:

– Spironolactone ± furosemide (ratio 100:40 mg) with gradual titration

– Possible side effects: gynecomastia, muscle cramps, hyper/hypo-K, hypo-Na, AKI

• Moderate Na restriction (<3 g/d or เกลอื 1.5 ชช.)

– No added salt diet with avoidance of pre-prepared meals and soup

• Avoid NSAIDs

• Water restriction, if refractory ascites + hypo-Na

• LVP as needed (give IV albumin, if tap >4 lit)

• Educate: signs of SBP → come to the hospital

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EV: OPD Management

• Screen for EV by EGD (all cirrhotics?; EGD may be avoided if platelet >150,000 + TE <20 kPa)

• If no or small EV: follow-up EGD q 1-3 yr

• If large EV (size >5 mm):

– Start propranolol; titrate to keep HR 55-60/min, avoid SBP <90 mmHg

– Possible side effects: fatigue, weakness

– No need to follow-up EGD

• Avoid activities that increase abdominal pressure

• Educate: signs of UGIB →come to the hospital

Small EV Large EV

Cirrhosis: Diet and Nutrition

• Eating an adequate amount of calories (35-40 kcal/kg/d) and protein (1.2-1.5 g/kg/d)

• Split your food into 5-6 meals/snacks per day including the late evening snack (most important)

• Patients with hepatic encephalopathy may tolerate animal protein less well than vegetable and dairy proteins (but do not restrict protein)

• Branched-chain amino acid supplementation at nighttime ± morning (10-20 g/d) in patients with advanced cirrhosis or encephalopathy

• Avoid aflatoxin-contaminated foods

• Multivitamin, calcium (1-1.5 g/d) and vitamin D

• Avoid too much iron, vitamin A and manganese

Cirrhosis: Prevention of Infection

Avoidance

• Raw/uncooked foods, especially seafood

• Wound exposure to flood or seawater

• Close contact to at-risk animals or sick people

ATB prophylaxis e.g. ceftriaxone, norfloxacin

• GI bleeding (7 d)

• Previous episode of SBP

• Advanced cirrhosis + low ascitic protein (<1.5)

Vaccination

• HAV, HBV (increased severity)

• Pneumococcal (increased susceptibility + severity)

• Influenza (increased susceptibility + severity)

• COVID-19 (increased severity)

Cirrhosis: Medications and Pain Management

• Discuss the safety use of paracetamol

– In general, use <2 g/d

– Use <1 g/d if decompensated cirrhosis

– Avoid if active drinking

• Avoid NSAIDs (may precipitate AKI/fluid retention)

• Avoid herbal products and unnecessary medications (altered PK, may precipitate ACLF)

• Inform doctors that you have cirrhosis and discuss safety before taking any prescription medications

Comprehensive Care in CirrhosisIssues Do Don’t

Alcohol use Screening for alcohol use disorder Forget to reassess over time

Ascites

management

Instruct self-care, salt restriction,

weight recording, and red flags

Wait until ascites becomes

unbearable necessitating ER visit

LT referralRefer early when a patient develops

decompensated cirrhosis

Wait until the patient is

hospitalized in critical condition

Pain and med.

management

Discuss the safety use of APAP and

other medications, including HDSPrescribe NSAIDs

NutritionRecognize malnutrition, advice and

refer to dieticians earlyRestrict protein

Quality of lifeDiscuss common disabling issues

e.g. cramping, pruritus, sleep, ED

Wait for patients to bring these

issues up

Health

maintenance

Vaccination status, prevention of

infection and general health issues

(e.g. CV risks, smoking, bone dis.)

Leave all health maintenance up

to patients’ primary care

providers

HCC Screen with US + AFP every 6 mo Leave patients out of screening

Palliative careAddress goals of care and reduce

unnecessary interventions

Wait until patient is in a critical

state

Non-alcoholic Fatty Liver Disease (NAFLD)

New name = Metabolic-associated Fatty Liver Disease (MAFLD)

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Alcohol and Calories Content

Serving

size

Gram

alcohol

Calories

(kcal)

Beer

4-6% alc.

360 ml

12 oz.~10 100-150

Wine

10-15% alc.

120 ml

4 oz.~10 90-120

Whiskey, Martini

Vodka, เหลา้ขาว

36-40% alc.

45 ml

1.5 oz.~15 100-165

1 standard drink ~ 10 gram of alcohol

Alcohol and Calories Content

Serving

size

Gram

alcohol

Calories

(kcal)

Beer

4-6% alc.

360 ml

12 oz.~10 100-150

Wine

10-15% alc.

120 ml

4 oz.~10 90-120

Whiskey, Martini

Vodka, เหลา้ขาว

36-40% alc.

45 ml

1.5 oz.~15 100-165

1 standard drink ~ 10 gram of alcohol

Harmful drinking: regular drinking ≥30 g alcohol/d (>14 drinks/wk in women or >21 drinks/wk in men)

1 เป๊ก (50 ml) – 1.5 drinks

1 ก ัก๊ (150 ml) – 5 drinks

1 แบน (375 ml) – 12 drinks

1 กลม (750 ml) – 24 drinks

NAFLD

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NAFLD: Disease Overview• None to minimal progression to cirrhosis

• Similar or slightly increased overall mortality

(esp. CV disease) compared with general

population

• Increased incidence of MetS (DM, HT, DLP)

NASH

Simple

steatosis

• Increased overall mortality (CV disease,

malignancy, liver-related death) compared

with general population

• Increased incidence of MetS (DM, HT, DLP)

NASH

cirrhosis

HCC

Liver

failure

20-30% cirrhosis

in 10-20 yr

2-13% in 5-10 yr

~30% in 5-10 yr

>30% fibrosis

progression in 5 yr

Adapted from Torres DM, Williams CD, Harrison SA. Clin Gastroenterol Hepatol 2012;10:837-58

and White DL, Kanwal F, El-seraq HB. Clin Gastroenterol Hepatol 2012;10:1342-59

0-3% in 20 yr

1/3

Risk Stratification in NAFLD Patients

Adapted from Rinella ME, Sanyal AJ. Nat Rev Gastroenterol Hepatol 2016;13:196-205

Low-risk profile

▪ BMI < 30

▪ Age < 40-50 yr▪ No T2DM or MetS

features▪ Noninvasive fibrosis

estimation:• FIB-4 < 1.30

• APRI < 0.5• NFS < -1.455

▪ Fibroscan < 5 kPa

Intermediate-risk

▪ BMI > 30

▪ Age > 40-50 yr▪ Multiple features of

MetS esp. T2DM▪ Noninvasive fibrosis

estimation:• FIB-4 1.30-2.67

• APRI 0.5-1.5• NFS -1.455-0.675

▪ Fibroscan 6-11 kPa

High-risk profile

▪ AST > AST level

▪ Platelets < 150,000▪ Noninvasive fibrosis

estimation:• FIB-4 > 2.67

• APRI > 1.5• NFS > 0.675

▪ Fibroscan > 11 kPa

Likely “simple

steatosis”

Normal ALT does not exclude NASH/fibrosis

Consider liver biopsy in selected cases

Likely “significant

fibrosis and/or NASH”

Likely “advanced

fibrosis”

NAFLD: Lifestyle Modification

• Weight reduction

– Hypocaloric diet (~500 kcal energy defect/d) to induce gradual wt. loss

– Target: wt. loss ≥3-5% BW to improve steatosis and ≥7-10% BW for NASH/fibrosis

• Exclusion of NAFLD-promoting components e.g. fructose and processed food

• Alcohol: strictly keep alcohol below the threshold

• Coffee drinking (black regular coffee) is OK

• Both aerobic exercise and resistance training are effective (150-200 min/wk of moderate intensity aerobic physical activities in 3-5 sessions)

Adapted from EASL-EASD-EASO Guideline 2016

NAFLD: Medications

• Optimize treatment of metabolic comorbidities

– Statins are safe and well-tolerated in NAFLD

• Pharmacotherapy should be reserved for patients with NASH, particularly with significant fibrosis (by liver biopsy or non-invasive predictors)

• Duration: unknown; ALT often rebound after stop

• Vitamin E 400-800 IU/d

– steatosis, NASH

– Avoid higher dose (? hemorrhagic stroke, CA prostate)

• For those with DM (and IFG)

– Pioglitazone: steatosis, NASH, fibrosis

– If obese, GLP-1RA (and SGLT-2 inh) may be effective

Adapted from EASL-EASD-EASO Guideline 2016 and AASLD Guideline 2018

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Thank You for Your Attention

Email: [email protected]

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