목차 - 삼성서울병원 · 2016-01-26 · Metabolism and detoxification of drug and hormone 4. Storage function 5. ... Cytosol Galactose Galactokinase 14C-galactose breath test

목차

간기능 해석과 협진 보기 ……………………………………………… 7

바이러스 간염 따라잡기 2016 …………………………………… 29

간경변 환자의 응급 합병증 진료 ………………………………… 47

간암 환자의 진료 …………………………………………………… 83

2016 gastroenterology Winter School

Session 1. 간

간기능 해석과 협진 보기

강 원 석


Contents

Understanding of liver function test

Perioperative hepatic dysfunction

Prediction of surgical risk in patients with liver diseases

Wonseok Kang, M.D., Ph.D.

Department of Medicine Samsung Medical Center

SungKyunKwan University School of Medicine

Evaluation of “Liver Function Test” and Assessment of Perioperative Risk

2016 gastroenterology Winter School 7

Liver function test (LFT)

“Liver function test” is a misleading term as this includes several biochemical tests that reflect liver injury and not liver function.

Liver function test - liver biochemical tests : AST, ALT, Alkaline phosphatase, g-GT (liver enzyme levels), bilirubin (excretory function), albumin, prothrombin time (synthetic function)

- quantitative liver function tests : Indocyanine green (ICG) clearnace test

Functions of liver

1. Metabolism of carbohydrate, amino acid, and fat

2. Synthesis and degradation of protein

3. Metabolism and detoxification of drug and hormone

4. Storage function

5. Excretory function

8 2016 gastroenterology Winter School

AST/ALT Ratio and Liver Disease

< 1 1 - 2 > 2 >3 (AST < 300) (AST > 500)

Majorities of advanced fibrosis Alcoholic Ischemic liver disease /cirrhosis liver disease hepatitis

Alcoholic Malignant disease liver disease involving liver

AST/ALT ratio

Aminotransferase

• Markers of hepatocellular necrosis

- released from cytosol into blood AST ALT

Source liver, heart, skeletal muscle liver kidney, brain, pancreas, lung, WBC, RBC Location cytoplasm and mitochondria cytoplasm T1/2 12-22 h 37-47 h • No correlation between aminotransferase level with either the

degree of hepatocyte necrosis or prognosis.


Gamma-Glutamyl Transpeptidase (GGT)

• Synthesis: hepatocyte & biliary epithelium • Role in diagnosis of liver disease

1. Differential diagnosis of increased ALP 2. Marker of chronic alcohol ingestion

• Elevation of g-GT in alcohol abuser - due to microsomal enzyme induction and impaired clearance (half life of 7-10 days increases to 28 days) • Sensitive, but not specific for liver disease - COPD, DM, hyperthyroidism, rheumatoid arthritis, medications (barbiturates, carbamazepine, cimetidine, furosemide, heparin, isotretinoin, methotrexate, oral contraceptive, phenytoin, valproate)

Alkaline phosphatase (ALP)

• More than 80% of seum ALP is from the liver or bone. • Hepatic ALP may be distinguished from bone ALP by

isoenzyme fractionation • Concomitant rise in g-GT confirms a hepatobiliary source. • Raised ALP levels are sometimes observed with primary

or secondary hepatic tumors or infiltrative disease (lymphoma, granuloma, amyloid, abscess), and non-hepatic disease (heart failure, hyperthyroidism, and renal cell carcinoma)


Albumin

• Albumin is quantitatively the most important plasma protein synthesized by the liver.

• 12~15g albumin is synthesized daily by the normal liver.

• Cirrhotic patients (Child C) can only produce ~4g albumin.

• In liver disease, the fall in serum albumin concentration is slow as the half life of albumin is about 22 days.

Plasma proteins synthesized by the liver

Protein Normal concentration Albumin 40-50 g/L Prothrombin (factor II) Fibrinogen* 2-6 g/L a1-antitrypsin* 2-4 g/L a-fetoprotein < 10 U/L a2-macroglobulin 2.2-3.8 g/L Ceruloplasmin* 0.2-0.4 g/L Complements (C1, C3, C6) Hemopexin 0.8-1 g/L Transferrin*, ferritin*

* Acute phase reactors


Quantitative liver function tests

Site Substrate(test) Function Clearance/retention tests

Cytosol Galactose Galactokinase 14C-galactose breath test

Indocyanine green (ICG)

ICG clearance test

Microsome (Cytochrome

P450)

Aminopyrine N-demethylation Aminopyrine breath test

Caffeine N-demethylation Caffeine breath test

Lidocaine N-deethylation Lidocaine/MEGX test

Antipyrine Hydroxylation/ demethylation

Sinusoidal receptor

membrane

Galactose-terminated

glycoprotein

Asialoglycoprotein receptor

Prothrombin Time (PT)

• Prothrombin thrombin Ca, thromboplastin

• Deficiency in one of the clotting factors synthesized by the liver (I, II, V, VII, IX, X) prolonged PT – Vitamin K dependent clotting factors : II, XII, IX, X

• PT can be prolonged in liver disease as well as in vitamin K deficiency - DDx : vit K 10mg IV or IM PT correction > 30% after 24 hr

• The most sensitive prognostic factor in acute and chronic liver disease


Perioperative risk in patients with liver disease

• Patients with liver disease - Derangement in biochemical function - Changes in pharmacodynamic variables of anesthetic agents,

muscle relaxants, and pain killers - Bleeding tendency - RES dysfunction infection

• Underlying liver disease predispose - Deterioration of postoperative liver function and liver failure

- Postoperative morbidity and mortality

Indocyanine green (ICG) clearance test

• ICG is a dye removed from the circulation by the liver after intravenous injection.

• ICG is taken up exclusively by hepatocytes, the clearance of low dose of ICG is used to measure liver blood flow.

• With administration of higher dose of ICG, the uptake process becomes saturated, the maximal removal of ICG can be calculated and this reflects functional hepatic mass rather than blood flow in the liver.

Imamura H, et al. J Hepatobiliary Pancreat Surg 2005


Other Parameters Which Cause Hepatic Blood Flow Reduction during Surgery

• Hypoxia • Hypotension • Vasoactive agents • Hypercarbia

– Effect on splanchnic sympathetic nerve – Adequate pCO2 : 35 – 40 mmHg

Perioperative hepatic dysfunction

• Decrease hepatic portal blood flow during surgery 1. Decreased sensitivity to catecholamines - Blunted response to intra-operative hypovolemia or hemorrhage 2. Anesthetic agents further suppress sympathetic nervous system 3. Systemic vasodilatation and negative inotropic effect of anesthetic agents

• Effect of anesthesia on liver 1. Decrease hepatic blood flow - Most inhalation agents 2. Direct hepatotoxic effect

• Effects of other drugs on liver 1. Increased half-life of benzodiazepines (midazolam, penthotal), narcotics (morphine, fentanyl), Lidocaine


Type of Surgery

• Exploratory laparatomy – Reduced blood flow to intestine and liver – Stress-induced release of cathecolamine,

vasopressin and activation of renin-angiotensin system

– Greatest blood flow reduction in upper abdominal surgery, especially biliary surgery

• Amount of hepatic blood flow reduction – Herniorrhaphy or mastectomy : 24% – Subtotal gastrectomy or cholecystectomy : 58%

Prediction of Surgical Risk

1. Type of surgery 2. Degree of liver dysfunction 3. Preoperative clinical status


• Chronic hepatitis – Asymptomatic, good synthetic function

• Minimal or no increase in hepatic risk – Symptomatic, poor synthetic function

• High risk • Surgery should be postponed

• Alcoholic hepatitis

- Similar to viral hepatitis

- High risk in jaundiced, decompensated liver disease

- Elective surgery should be postponed

Surgical Risk in Patients with Liver Disease (2)

Surgical Risk in Patients with Liver Disease (1)

• Asymptomatic elevation of ALT – Fatty liver, chronic hepatitis, Drug induced liver injury – No or minimal increase in hepatic morbidity and mortality

if ALT rise < 5 X UNL • Isolated elevation of bilirubin

– Gilbert – No risk factor

• Acute hepatitis – Morbidity : 12 – 33 % – Mortality : 10 – 42 % – Elective surgery should be postponed


Mortality after surgery in patients with liver cirrhosis in SMC

Study population January 2003 ~ December 2008 Retrospective review of the charts of 491 patients with cirrhosis undergoing surgical procedures except liver under general anesthesia

Statistical analysis Kaplan Meier analysis Cox regression analysis Receiver-operation characteristic(ROC) plots

Risk factors for surgery in patients with cirrhosis

Factor Mortality(%) Ascites 37 – 83 Albumin < 3 gm/dl 58 Bilirubin > 3 gm/dl 44 – 62 PT > 1.5 sec control 63 Emergency surgery 45 – 86 Abdominal surgery 35 Preoperative infection 64 Child class A 5 – 10 B 31 C 76


CTP class

No. of patients

Mortality, No. of patients at risk (%)

30-days 90-days

A 385 4 (1.0%) 8 (2.1%)

B 95 10 (9.5%) 21 (22.1%)

C 11 4 (36.4%) 6 (54.5%)

Relationship between CTP Score and Postoperative Mortality

Cho HC, et al. Eur J Gastroenterol Hepatol 2011;23

Median age, yr (range) 60 (51 – 66)

Gender, n (%)

Female 172 (35%)

Male 319 (65%)

Etiology, n (%)

Hepatitis B 322 (65.6%)

Hepatitis C 67 (13.6%)

Cryptogenic 62 (12.6%)

Alcoholic 29 (6.0%)

Others 11 (2.2%)

Emergency surgery, n (%) 69 (14%)

Patient Characteristics


CTP score vs. MELD score

Child-Turcotte-Pugh (CTP) score

Includes subjective parameters (ascites,encephalopathy) Arbitrary cutoff values (+) Patients within class are not homogenous Reflects portal hypertension

MELD score

Objective variables only (bilirubin, PT INR, Cr) Weights variables according to risk of mortality Each 1-point increase makes an incremental contribution

to risk Does not reflect portal hypertension

Kaplan-Meier Curves Estimating Mortality after Surgery : CTP Score

7-9

10-15

5-6

P=0.000


CTP score


LC-MELD score

MELD Mortality < 7 5.7% 8 – 11 10.3% 12 – 15 25.4% > 20 > 50% Teh SM et al. Gastroenterology 2007;132:1261-1269

• MELD 5 – 20 MELD 1점당 사망률 1% 증가 • MELD > 20 MELD 1점당 사망률 2% 증가 Northup PG et al. Ann Surg 2005;242:244–251

MELD Score

• MELD score = 3.78 × loge bilirubin (mg/dL) + 11.20 × loge INR + 9.57 × loge creatinine (mg/dL) + 6.43

• http://www.mayoclinic.org/meld/mayomodel9.html

• Developed to predict the prognosis of patients undergoing TIPS

• Introduced by UNOS for liver transplantation priority


15-19

≥25

0-4 5-9 10-14 20-24

Kaplan-Meier Curves Estimating Mortality after Surgery : MELD Score


MELD score

MELD scores

No. of

patients

Mortality, No. of patients at risk (%)

30-days 90-days

0-4 164 1 (0.6%) 3 (1.8%)

5-9 205 7 (2.9%) 12 (5.9%)

10-14 71 2 (2.8%) 5 (7%)

15-19 24 1 (4.2%) 5 (20.8%)

20-24 10 3 (30%) 3 (30%)

≥25 17 4 (23.5%) 7 (41.2%)

Relationship between MELD Score and Postoperative Mortality



LC – Mayo Clinic Model

• Factors predicting postoperative mortality in LC patients

– MELD, ASA score, age

• American Society of Anesthesiology class (ASA class)

Class I Normal healthy

Class II Patient with mild systemic disease

Class III Pt. w/severe systemic disease

Class IV Pt. w/ severe systemic disease that is a

threat to life.

Class V Morbid pt. who is not expected to survive

without the operation

Class VI A declared brain dead pt. whose organs

are being removed for donor

ROC Curve for 30-Day Mortality

Area Under the Curve CTP scores MELDNa scores MELD scores

Pairwise test with a critical ratio z CTP, MELD MELD, MELDNa CTP, MELDNa

: Adjusted p=0.053 : Adjusted p=0.151 : Adjusted p=0.661

0.866 0.814 0.732



Preoprative clinical status

• High mortality is associated with – Infection – Emergency surgery – Hypoxia – Heart failure – Acute renal failure

LC – Mayo Clinic Model


Liver cirrhosis – general anesthesia contraindication

- Absolute • Child C, MELD score > 25

– Relative • Child B, MELD score > 15 • Surgery is permissible with after thorough

preoperative preparation (except cardiac surgery and hepatic resection).

Contraindications to elective surgery in patients with liver disease

1. Acute alcoholic hepatitis 2. Acute viral hepatitis 3. Child class C cirrhosis 4. Fulminant hepatic failure 5. Severe chronic hepatitis 6. Severe coagulopathy

PT prolongation > 3 sec Platelet count < 50,000 /mm3

7. Severe extrahepatic complications ARF, cardiomyopathy, heart failure, hypoxemia

Friedman LS et al, Hepatology 1999


Conclusions

CTP, MELD and MELD-Na scoring systems predicts postoperative mortality in cirrhotic patients undergoing surgery

ICG clearance test is the most widely used quantitative liver function test in the preoperative evaluation of liver function.

Careful preoperative risk assessment, patient selection, and

management of advanced liver disease might decrease morbidity and mortality from surgery in patients with liver disease.

Optimizing Medical Therapy

1. Restore PT prolongation < 3 sec – Vitamin K, FFP

2. Maintain PLT > 100,000/l 3. Bleeding time correction

– DDAVP 4. Aggressive control of ascites

– Prevent wound dehiscence and abdominal wall herniation 5. Electrolyte correction 6. Maintain renal function 7. Prophylactic treatment of varices 8. Nutritional support


바이러스 간염 따라잡기 2016

최 문 석


초기 평가 중 잊지 말아야 할 것

1. 병력 청취(약제 복용력!)와 신체 검사

2. CBC, AST/ALT, ALP, GGT, bilirubin, albumin, creatinine, prothrombin

time

3. HBeAg/anti-HBe, 혈청 HBV DNA 정량검사 (real-time PCR법)

4. anti-HCV 검사 (comment: 간기능 이상)

5. IgG anti-HAV

6. 복부 초음파검사, 혈청 알파태아단백검사

B형 간염과 C형 간염 따라잡기 2016

성균관의대 삼성서울병원 소화기내과최 문 석


B형간염 치료: 어떤 약물로 시작하나?

• PEG-IFN– patient with predictors of favorable response

– esp. young female considering pregnancy

• First-line NUC monotherapy– the most potent drugs with the optimal resistance profile

– tenofovir or entecavir should be used (A1)• *tenofovir preferred: previous exposure to low genetic barrier

drug, poor drug compliance, concern of pregnancy

• *entecavir preferred: current or high risk of renal impairment

2012 EASL guideline* Personal preference

B형 간염: 누구를 치료할 것인가

• 국내 보험 적응증

– e항원 양성간염: HBV DNA > 20,000 IU/mL, AST/ALT > 2ⅹULN

– e항원 음성간염: HBV DNA > 2,000 IU/mL, AST/ALT > 2ⅹULN

– 대상성 간경변증: HBV DNA > 2,000 IU/mL

– 비대상성 간경변증, 간암: HBV DNA (+)

* 항암치료, 면역억제, 이식 등 (100/100)

2014.05 현재


약이 잘 안 듣는 경우

• Primary non-response– < 2 log10 IU/ml decrease in HBV DNA level from baseline at 6

months of therapy

• Partial virological response (PVR)– a decrease in HBV DNA of > 2 log10 IU/ml but detectable HBV

DNA after at least 6 months of therapy in compliant patients

• Virological breakthrough

2015 KASL guideline

환자를 어떻게 모니터링할 것인가?

• Finite treatment with NUC in HBeAg (+) patients– HBeAg and anti-HBe every 6 months– HBV DNA by a sensitive PCR assay every 3–6 months – HBsAg at 12-month intervals after anti-HBe seroconversion

• Long-term therapy with NUC– HBV DNA levels at month 3 and then every 3–6 months

• the frequency of follow-up measurement might be decreased during therapy with entecavir or tenofovir

• Renal monitoring– Serum creatinine (estimated creatinine clearance) and serum

phosphate levels during adefovir or tenofovir therapy in all CHB patients

– Serum creatinine levels (estimated creatinine clearance) during nucleoside analogue therapy in CHB patients at high renal risk(C1)

2012 EASL guideline


2015 KASL guideline

• 테노포비어 단독 또는 테노포비어와 뉴클레오시드 유사체의 병합 (A1)

• 테노포비어를 사용할 수 없는 경우 아데포비어와 뉴클레오시드 유사체의 병합 (B1)

• 대상성 간기능을 가진 환자에서는 라미부딘을 중단하고페그인터페론 알파 투여 (B2)

약물을 어떻게 바꿀 것인가?

* Check compliance and resistance profile!

• Primary non-response

– a rapid switch to tenofovir or entecavir (B1)

• Partial virologic response during treatment with

– lamivudine, telbivudine; change to a more potent drug (entecavir

or tenofovir), preferentially without cross-resistance (A1)

– entecavir, tenofovir; stick to the current treatment (debatable)

• Virological breakthrough

2012 EASL guideline


2015 KASL guideline

• 테노포비어 단독 또는 테노포비어와 엔테카비어의 병합(B1)

• 테노포비어를 사용할 수 없는 경우에는 아데포비어와 엔테카비어의 병합 (B2)

2015 KASL guideline

• 테노포비어 단독 치료 또는 테노포비어와 엔테카비어의병합 (B1)

• 테노포비어와 뉴클레오시드 유사체(엔테카비어 이외)의병합 (B2)

• 테노포비어를 사용할 수 없는 경우에는 아데포비어와 엔테카비어의 병합 (B2)


교체투여- 보험적용확대 (부작용, 순응도, 비용)

2013.06.01 개정 가이드라인

-기존 약제에 내성이 확인되지 않은 상태에서 다른 약제로 교체투여는?

① 치료반응 불충분 및 무반응

② 임신

③ 타당한 사유가 있는 약물 순응도 감소

④ 객관적으로 증명된 심한 부작용 등에 사례별로 인정 가능

2015.05.01 보험적용확대

내성, 치료반응 불충분 및 무반응, 임신, 객관적으로 증명된 심한 부작용

에는 급여인정하며, 복약 순응도 개선 필요, 비용 효과성 개선 등은 의학적

타당성을 감안하여 사례별로 급여 인정함

보건복지부 고시 제 2015-68호

2015 KASL guideline

• 테노포비어 단독• 테노포비어 기반 병합 요법 고려

– High viral load– 아데포비어내성/다약제 내성 (N236T, A181T/V)– 간경변/decompensation/ALF


14

C형간염치료의진화: 유전자형 1형환자의완치율향상

*In genotype 1b patients.DAA, direct-acting antiviral; PegIFN, pegylated interferon; PI, protease inhibitor RBV, ribavirin

1. McHutchison JG et al. N Engl J Med 1998;339:1485–1492. 2. Poynard T et al. Lancet 1998;352:1426–1432. 3. Fried MW et al. N Engl J Med 2002;347:975–982. 4. Poordad F et al. N Engl J Med 2011;364:1195–1206.

5. Jacobson IM et al. N Engl J Med 2011;364:2405–2416. 6. Lawitz E et al. Lancet Infect Dis 2013;13:401–408. 7. Afdhal N et al. N Engl J Med. 2014;370:1889–1898. 8. Manns M et al. Lancet 2014;384:1597–1605

IFN1 IFN+RBV1,2 PegIFN+ RBV3

PIs+ PegIFN+ RBV4–5

New DAAs + PegIFN + RBV6

IFN-free regimens7,8

200119981991 2011 2013–2014

7

28–31

56

68–75

90 90*–99

0

20

40

60

80

100

SVR

(%)

단독 약제에서 다른 단독 약제로 변경인정

임신 혹은 임신을 원할 때객관적으로 증명된 심한 부작용저비용 약물로의 전환?

사례별 인정/불인정고비용 약물로의 전환주관적 부작용/드문 부작용/보고되지 않은 부작용

병용 요법에서 단독 약제로 변경인정

임신 혹은 임신을 원할 때객관적으로 증명된 심한 부작용저비용 약물로의 전환

사례별 인정/불인정고비용 약물로의 전환주관적 부작용/드문 부작용/보고되지 않은 부작용

Generic drug으로의 변경

안정적인 바이러스 반응을 보이는 경우의 교체 투여


15

C형간염치료의진화: 유전자형 2형환자의완치율향상

1. McHutchison JG et al. N Engl J Med 1998;339:1485–1492. 2. Poynard T et al. Lancet 1998;352:1426–1432. 3. Jacobson IM et al. N Engl J Med 2013;368:1867–1877. 4. Lawitz E et al. Lancet Infect Dis 2013;13:401–408.

5. Zeuzem S et al. N Engl J Med 2014;370:1993–2001. 6. Lawitz E et al. AASLD 2013;abstract LB-4 . 7. Nelson DR et al. AASLD 2014: abstract LB-3

IFN1,2 IFN+RBV3–5 PegIFN+ RBV3–5

PIs+ PegIFN+ RBV

New DAAs + PegIFN + RBV5,6

IFN-free regimens3–5,7

200119981991 2011 2013–2014

29–33

61–8074–83

N/A

96–100 98–100

0

20

40

60

80

100

SVR

(%)


Daclatasvir + Asunaprevir치료성적: RAV = 낮은 SVR

18

GT 1b patients with baseline sequence data and excluding non-virologic failures (N = 979)

McPhee F, et al. APASL 2015; poster 1549.

NS3/4A Protease Inhibitors (PI) -previrTelaprevir, BoceprevirAsunaprevirSimeprevirParitaprevirGrazoprevir

NS5A Inhibitors -asvirLedipasvirDaclatasvirOmbitasvirVelpatsvirElbasvir

NS5B Nucleos(t)ide Inhibitors (NI) –buvir

Sofosbuvir

C E1 E2 p7 NS2 NS3 NS4A NS4B NS5A NS5B

새로운경구약물 DAA

NS5B Nonnucleoside Inhibitors (NNI)

Dasabuvir

Beclabuvir

–buvir

♥

♥♥ ♥♥♥

♥♥♥


VALENCE 연구결과: Sofosbuvir + 리바비린 -대상군별성적분석

유전자형 2형 유전자형 3형SOVALDI + RBV

12 weeks N=73

SOVALDI + RBV 24 weeks

N=250초치료 97% (31/32) 93% (98/105) 간경변 (-) 97% (29/30) 93% (86/92)간경변 (+) 100% (2/2) 92% (12/13)치료경험 (+) 90% (37/41) 77% (112/145)간경변 (-) 91% (30/33) 85% (85/100)간경변 (+) 88% (7/8) 60% (27/45)

SOVALDI full Prescribing Information. Gilead Sciences, Inc. December 2013.20

‡

19

67%

95%

56%47% 50%

82%

30% 31%

93%97%

90%90% 92%82%

96% 100% 100%

80% 67% 78%63%

38%

78%93%

61% 61%71%

89%

62% 66%84%

93%

77%

0

20

40

60

80

100

Sofosbuvir등록임상시험결과

Regimen

NEUTRINO1,2

SOF + IFN + RBV(N=327)

FISSION1,2

SOF + RBV vs IFN + RBV(N=499)

POSITRON2,3

SOF + RBV vs PBO(N=278)

FUSION2,3

SOF + RBV(N=201)

VALENCE2

SOF + RBV(N=323)

Patient Characteristics

Treatment-naïve17% had cirrhosis at screening

Treatment-naïve 20% had cirrhosis at screening

Interferon-intolerant 16% had cirrhosis at screening

Non-responders 34% had cirrhosis at screening

Treatment-naïve, -experienced

Genotype 1, 4, 5, 6 2, 3 2, 3 2, 3 2, 3

Treatment Duration

12 weeks 12 weeks: SOF + RBV24 weeks: P/R

12 weeks 12 weeks16 weeks

12 weeks (GT-2)24 weeks (GT-3)

Safety

• >20%: fatigue, headache, nausea, insomnia, anemia

• 5 discontinuations due to AEs

• >10%: fatigue, headache, nausea, insomnia

• 3 discontinuations due to AEs in SOF group and 26 in IFN + RBV group

• >10%: fatigue, nausea, headache, insomnia, pruritus, anemia

• 1 patient in 12-week group discontinued due to AEs

• ≥15%: fatigue, nausea, headache, insomnia

• N/A

Patie

nts,

%

Percentage of Patients Achieving SVR12 in Phase 3 Trials With Sofosbuvir-Based Regimens

AE=adverse event; GT=genotype; IFN=pegylated interferon; PBO=placebo; RBV=ribavirin; SOF=sofosbuvir; SVR=sustained virologic response. 1. Lawitz E et al. N Engl J Med. 2013;368(20):1878-1887. 2. Sovaldi [prescribing information]. Gilead Sciences, Inc. Foster City, CA. 3. Jacobson IM et al. N Engl J Med. 2013;368(20):1867-1877.

GT-2GT-3

12 weeks16 weeks

SOF + RBVIFN + RBV


Clin Liver Dis 2014;3:137-140

21

99 97 98 99 94 93 96 94 96 99 99

0

20

40

60

80

100

ION-1GT 1 treatment-naïve

including cirrhotics

ION-3GT 1 treatment-naïve

non-cirrhotic

ION-2 GT 1 treatment-experienced

including cirrhotics and PI failures

LDV/SOF LDV/SOF+RBV

12 Weeks 24 Weeks 12 Weeks 24 Weeks12 Weeks

SV

R12

(%)

HARVONI ® [PI]. Gilead Sciences, Inc. Foster City, CA March 2015; Afdhal N, et al. N Engl J Med 2014; 370: 1889-98; Afdhal N, et al. N Engl J Med 2014; 370: 1483-93; Kowdley K, et al. N Engl J Med 2014; 370: 1879-88Data on File, Gilead Sciences, Inc.

8 Weeks

107/111

102/109

108/109

110/111

211/217

210/213*

213/217

215/217

202/215

201/216

208/216

*excluding one subject with genotype 4 infectionError bars represent 95% confidence intervals.

효과요약 (ITT 분석): 유전자형 1형

97% (1887/1951) overall SVR rate– Similar efficacy was observed between the RBV-free and RBV-containing treatment arms

3% (64/1951) did not achieve SVR– 1.8% (36) relapsed– 1.3% (26) were either lost to follow up or withdrew consent– 0.1% (2) virologic breakthrough (both due to non-adherence)

ION Phase 3 Program (ION-1, ION-2, ION-3) ‡


24

HCV Genotypes 2-3 (Abbreviated)

미국간학회 Guidance

Population Recommended Alternative

GT 2

TNNo cirrhosis • SOF+RBV 12 weeks

• SOF+DCV 12 weeks (RBV-intolerant)

Cirrhosis • SOF+RBV 16 weeks • SOF+DCV 16 weeks

TE (PegIFN+RBVor SOF+RBV failure)

±Cirrhosis• SOF+RBV 16 or 24 weeks (PegIFN+RBV)• SOF+DCV±RBV 24 weeks IFN-ineligible (SOF+RBV)• SOF+PegIFN+RBV 12 weeks (SOF+RBV)

• SOF+PegIFN+RBV12 weeks (PegIFN+RBV)

GT 3

TNNo cirrhosis • SOF+PegIFN+RBV 12 weeks

• SOF+DCV 12 weeks • SOF+RBV 24 weeks for IFN-ineligible

Cirrhosis • SOF+PegIFN+RBV 12 weeks• SOF+DCV±RBV 24 weeks

TE (PegIFN+RBVor SOF+RBV failure)

No cirrhosis

• SOF+PegIFN+RBV 12 weeks (PegIFN+RBV)• SOF+DCV 12 weeks (PegIFN+RBV)• SOF+DCV+RBV 24 weeks (SOF+RBV, IFN-ineligible)• SOF+PegIFN+RBV 12 weeks (SOF+RBV)

Cirrhosis

• SOF+DCV+RBV 24 weeks (PegIFN+RBV, IFN-ineligible)• SOF+PegIFN+RBV 12 weeks (PegIFN+RBV)• SOF+DCV±RBV 24 weeks (SOF+RBV)• SOF+PegIFN+RBV 12 weeks (SOF+RBV)

‡

AASLD/IDSA/IAS–USA. Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org. Accessed August 7, 2015

23

유전자형 1b 치료

미국간학회 Guidance

Population Recommended

GT 1b

TN

No cirrhosis

• LDV/SOF 12 weeks • OBV/PTV/RTV+DSV 12 weeks• SOF+SMV±RBV 12 weeks • SOF+DCV 12 weeks

Cirrhosis

• LDV/SOF 12 weeks • OBV/PTV/RTV+DSV+RBV 12 weeks• SOF+SMV±RBV 24 weeks • SOF+DCV±RBV 24 weeks

TE (PegIFN +RBV failure)

No cirrhosis

• LDV/SOF 12 weeks • OBV/PTV/RTV+DSV 12 weeks • SOF+SMV 12 weeks• SOF+DCV 12 weeks

Cirrhosis

• LDV/SOF 24 weeks or LDV/SOF+RBV 12 weeks • OBV/PTV/RTV+DSV 12 weeks • SOF+SMV±RBV 24 weeks• SOF+DCV±RBV 24 weeks

TE (SOF + RBV ±PegIFN failure)

No cirrhosis • LDV/SOF+RBV 12 weeks

Cirrhosis • LDV/SOF+RBV 24 weeks

TE (PI + PegIFN + RBV or PI + SOF failure)

No cirrhosis• LDV/SOF 12 weeks (PI+PegIFN+RBV)• LDV/SOF+RBV 12 weeks (SOF+SMV)• SOF+DCV 12 weeks (PI + PegIFN + RBV)

Cirrhosis• LDV/SOF 24 weeks or LDV/SOF+RBV 12 weeks (PI+PegIFN+RBV)• LDV/SOF+RBV 24 weeks (SOF+SMV)• SOF+DCV±RBV 24 weeks (PI + PegIFN + RBV)

‡

AASLD/IDSA/IAS–USA. Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org. Accessed August 7, 2015


2015 EASL guideline

2015 EASL guideline


약물상호작용: 심혈관계약물

*Coadministration of amiodarone and sofosbuvir combined with another direct acting antiviral such as daclatasvir or simeprevir may result in serious symptomatic bradycardia and is not recommended. The mechanism of the effect is unknown.Green: No clinically significant interaction expected.

Amber: Potential interaction which may require a dosage adjustment, altered timing of administration or additional monitoring.

Red: These drugs should not be co-administered.

SIM, simeprevir; DCV, daclatasvir; SOF, sofosbuvir; SOF/LDV, sofosbuvir plus ledipasvir; 3D, ritonavir-boosted paritaprevir, plus ombitasvir and dasabuvir.

EASL Guidelines 2015; http://www.hep-druginteractions.org/ (Accessed May 2015); SOVALDI▼ (sofosbuvir), Gilead Sciences Europe Ltd. SmPC, March 2015; OLYSIO▼(simeprevir), Janssen Products LP. SmPC, March 2015; Limited. DAKLINZA▼ (daclatasvir), Bristol-Myers Squibb Pharmaceutical. SmPC October 2014) HARVONI▼(ledipasvir/sofosbuvir), Gilead Sciences Europe Ltd. SmPC, November 2014 VIEKIRAX▼ (ombitasvir/paritaprevir/ritonavir), AbbVie Ltd. SmPC, January 2015 EXVIERA▼(dasabuvir), AbbVie Ltd. SmPC, January 2015); HARVONII▼ (ledipasvir/sofosbuvir), Gilead Sciences Europe Ltd. SmPC, November 2015;

*

‡

약물상호작용: 고지혈증약물

Green: No clinically significant interaction expected.


Red: These drugs should not be co-administered.SIM, simeprevir; DCV, daclatasvir; SOF, sofosbuvir; SOF/LDV, sofosbuvir plus

ledipasvir; 3D, ritonavir-boosted paritaprevir, plus ombitasvir and dasabuvir.EASL Guidelines 2015; http://www.hep-druginteractions.org/ (Accessed May 2015); SOVALDI▼ (sofosbuvir), Gilead Sciences Europe Ltd. SmPC, March 2015; OLYSIO▼(simeprevir), Janssen Products LP. SmPC, March 2015; Limited. DAKLINZA▼ (daclatasvir), Bristol-Myers Squibb Pharmaceutical. SmPC October 2014) HARVONI▼(ledipasvir/sofosbuvir), Gilead Sciences Europe Ltd. SmPC, November 2014 VIEKIRAX▼ (ombitasvir/paritaprevir/ritonavir), AbbVie Ltd. SmPC, January 2015 EXVIERA▼(dasabuvir), AbbVie Ltd. SmPC, January 2015); HARVONII▼ (ledipasvir/sofosbuvir), Gilead Sciences Europe Ltd. SmPC, November 2015;

‡


약물상호작용: 면역억제제






‡

약물상호작용: 중추신경계약물






‡


DAA 기반 C형간염치료시고려사항

HCV 유전자형과바이러스혈증의정도

섬유화혹은간경변의진행정도

기존치료및이에대한반응

동반질환및기존복용약물

약물: 작용부위, 약물상호작용, 약제내성

투여가능여부및비용-효과– 유전자 1형: DAA vs. DAA ± P/R (LDV/SOF)– 유전자 2형: DAA vs. DAA± P/R vs. PR (SOF/R)– 유전자 3형: PR vs. DAA vs. DAA ± P/R (PR vs. SOF/DCV)

완치 > 90%

독성 (-)

높은순응도

필수

짧은치료기간

범유전자형

높은내성장벽 도움

C형간염치료: 요구조건

약물상호반응 (-)

약제복용간편성

Nicebonus


간경변 환자의 응급 합병증 진료

신 동 현


What is cirrhosis?

간경변응급합병증진료

Dong Hyun Sinn M.D., Ph.D.

Department of Medicine, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, Korea

2016 GI winter school


정맥류출혈

Journal of hepatology; 2015: 63:743

Today’s topic: 응급합병증?

Variceal bleeding

Hepatic encephalopathy

Ascites/Hepatorenal syndrome/AKI

Infection


Pathophysiology of Varix Bleeding


Management of acute variceal bleeding

General management NPO

IV volume (avoid volume overload)

Airway

Target BP: SBP 90 – 100

Target HR: < 100/min

Transfusion: FFP, transfusion

Why sudden increase in portal pressure?


Why should be conservative?

Normal

Portal HTN

Key tips in general management

Blood resuscitation should be done cautiously and conservatively

plasma expanders

to maintain hemodynamic stability

(SBP 100, HR < 110/min, CVP 2~6 cmH2O)

pRBC

to maintain the haemoglobin at approx. 8 g/dL depending on other factors such as patients co-morbidities, age,

haemodynamic status, and presence of ongoing bleeding clinically (1b;A)


Role of transfusion in patients undergoing EVL

Platelet use ?

FFP use ?

Elective EVL vs. Emergency EVL?

Why should be conservative?


Management of acute variceal bleeding

Vasoconstrictor

Antibiotics

IV proton pump inhibitors

Endoscopic therapy within 12 hour

Lactulose use to prevent hepatic encephalopathy

Salvage: S-B tube, TIPS

FFP or platelet transfusion?

PT prolonged, but decreased protein C and other changes lead to a rebalanced or even hypercoagulable state in cirrhosis.

INR is not adequate measure of hemostasis

Platelet >50,000 may be needed in hemostasis.


Mechanism

Mechanical strangulation with rubber bands

Thrombosis

Necrosis of the mucosa

Band fall off in a few days

Superficial esophageal ulceration

Heals with scars

Usually limited over the superficial esophageal mucosa

Cardenas. Clin Liver Dis 2010;14:251

Endoscopic band ligation (EBL)

Bleeding control rate: 90%

Rebleeding rate: 30%

Compared to sclerotherapy Less rebleeding

Lower mortality

Fewer treatment sessions

Fewer complications



Technique

Continuous suction on the varix

Varix fill the cap

“red out” sign appear

Band fire

DO NOT advance further banding should commence in the most distal portion of the esophagus, near the GE junction


Time course

7 days later


Arakawa M, Semin Liver Dis 2002

Begin with most distal part

활동성출혈인경우출혈부위

나출혈바로아래를처음에결

찰하고지혈을확인하나.

위식도접합부위상부 5-10mm 부터 5cm 부위까지차례로시행한다.

2011 KASL guideline

Red out sign



Paraesophageal varix

No Yes

Importance of banding from most distal portion of the esophagus

scar varix


Role of PPI after EVL

Pantoprazole reduces the size of postbanding ulcers after variceal band ligation: a randomized, controlled trial. (Hepatology 2005;41:588)

Long-term administration of PPI reduces treatment failures after esophageal variceal band ligation: a randomized, controlled trial. (J Gastroenterol2012;47:118)

Course after EVL


Is topical pharyngeal anesthesia beneficial ?

Is routine sedation or topical pharyngeal anesthesia beneficial during upper endoscopy?

Ristikankare et al, Gastrointest Endosc 2004;60:686

Are you comfortable during upper endoscopy ?

Predicting which patients can undergo upper endoscopy comfortably without conscious sedation

Abraham et al, Gastrointest Endosc 2002;56:180


Through-the-scope local anesthesia

Single-blinded RCT

Duration: 2013.7.19 ~ 11.15

Total 197 persons was screened

90 examinees enrolled

Study: 45 vs. Control group: 45

Excluded 107 persons

Refuse : 19

Age ≥ 70 : 39

Failed exam : 2

Post status gastrectomy : 1

Sedated exam : 46

Main hypothesis


Secondary variables: patients

VAS scale Through the scope(n = 45)

Conventional(n = 45) P value

Satisfaction 6.0 (4.0 – 8.0) 7.0 (4.0 – 8.0) 0.20

Nausea/vomiting 4.0 (1.0 – 6.5) 4.0 (1.0 – 6.0) 0.62

Abdominal pain 0 (0 – 1.0) 1.0 (0 – 1.5) 0.27

Cough 0 (0 – 1.0) 0 (0 – 1.0) 0.47

Dyspnea 0 (0 – 2.5) 1.0 (0 – 3.0) 0.24

Values are expressed as median (quartile)

Overall satisfaction rate

p = 0.65


Role of sedation in EVL

Midazolam during EVL????

What’s your opinion???


수면내시경관련

사고는계속되고

있고, 계속될

것이다. 왜?


Level of sedation and analgesia

Conscious sedation Purposeful response to verbal or tactile stimulation

Ventilatory and cardiovascular function are maintained

Deep sedation Purposeful response to painful stimulation

Airway support may be required

General anasthesia Unarousable, even to painful stimulation

Airway support is required, and cardiovascular function may be impaired

Effect of benzodiazepine

Hypnosis Muscle relaxation Ptosis Intense sedation Amnesia* Reduced attention* Slight sedation* Anxiolysis*

* Modern endpoint for sedation during endoscopy

Lazzaroni. Endoscopy 2001;33:103-108


Key to successful acute varicel bleeding manage

General management Conservative blood resuscitation

Key is portal pressure!!!

Endoscopic management Appropriate topical anesthesia

Sedation ? (Deep sedation must be avoided!)

Banding from far distal part

Midazolam

Water-soluble, short acting imidazo benzodiazepine Dose: 0.035 – 0.070 mg/kg (2.1 – 4.2 mg/60 kg) Initial dose: 1-2mg than additional 1mg at 2 minute interval Half life: 3hr (1.8 – 6 hours) Peak: 0.5 – 1 hour Oversedation can inhibit cooperation Paradoxic excitation

Antagoninst: flumazenil (Anexate®)- Half life: 50 minutes- Can be used in cases with oversedation- (Am J Gastroenterol 2000;95:809-811)


Hepatic encephalopathy

Neuropsychiatric syndrome!!

Diagnosis of exclusion

No test with high sensitivity/specificity!!!

Start by asking a question!! Another cause???

2011 KASL guideline

Today’s topic: 간성혼수


Classification

Underlying disease A: ALF, B: Portosystemic shunt, C: Cirrhosis

Severity Minimal, grade 1, 2, 3 and 4 (coma)

Time course Episodic, recurrent, persistent (always present + interspersed with

relapse of overt HE)

Precipitating factors None vs. precipitated

Differential diagnosis


4 항목을기억할것을권고하고있음.

Key question

정말 HE가맞나?

Type, grade, course, precipitation은무엇인가?

유발원인


Definition

Today’s topic: 복수및 HRS

Gut 2015;64:531


HRS

Management


Today’s topic: 감염

HRS

Identify patients late, with relatively advanced renal failure.

Serum creatinine (not all same!!!, cirrhosis???)

Terlipressin + albumin, may be too late!!!

Terlipression responses better when Cr is lower.

Moore Hepatology 2013;57:435


Pathogenesis of sepsis in cirrhosis

Altered defense against bacteria Reduced bacterial clearance

facilitated bacterial translocations Increased intestinal permeability

bacterial overgrowth

Genetic immune defect

Excessive pro-inflammatory cytokines responses (TNF-a, IL-6 etc)

Fernandez et al, J. Hepatol 2012;56:S1-S12

General consideration

Cirrhosis patients have increased risk to develop bacterial infection, sepsis, sepsis-induced organ failure and death.

Common causes Spontaneous bacterial peritonitis (SBP) Urinary tract infections Pneumonia Cellulitis

Risk factors Child-Pugh score Variceal bleeding Low ascitic protien levels Prior episode of SBP



Work-up


Diagnosis of bacterial infection

Early diagnosis and treatment is pivotal!

Some patients are asymptomatic at initial stage.

Complete work-up should be considered for all patients at admission, and whenever a hospitalized patients clinically deteriorates Diagnostic paracentesis, ascites culture

Urinary sediment and culture

Chest X-ray



Other markers in cirrhosis

C-reactive protein (CRP)/Procalcitonin (PCT) Acute phase serum proteins

CRP produced by liver

Concern for its use, but AUC range 0.64 to 0.91

Lower CRP needs careful interpretation in child C cirrhosis

PCT produced by thyroidal tissues

Superiority over CRP, but controversial


Limitation of common markers in cirrhosis

SIRS criteria Temperature ≥38 or ≤36 Heart rate ≥ 90/min Tachypnea ≥ 20/min or PaC02 ≤ 32 WBC ≥ 12,000 or ≤ 4000 or >10% immature NP

Cirrhosis patients Tachycardia due to hyperdynamic circulation Reduced heart rate due to beta blocker Decreased WBC due to hypersplenism




SBP

Sx pain, fever, vomiting, ileus, diarrhea, encephalopathy, GI bleeding, renal

impairment

Dx PMN ≥ 250 cells/mm3

DDx Secondary peritonitis

Runyon’s criteria (≥ 2, sen:67%, Spe 90%)– Glucose < 50 mg/dl– Protein > 10 g/L– LDH (ascites) > normal serum levels

High level of amylase and bilirubin in ascitic fluid. Polymicrobic infection Abdominal CT



Inappropriate antibiotics use (%)

26.7

66.7

55.1

80

0

20

40

60

80

100

Community-acquired (n = 30)

Health-care related(n = 3)

Hospital acquired(n = 69)

Resistant pathogen(n = 45)

30-days mortality rate according to Child Class

Appropriate use (100%)

Inappropriate use (83.5%)

P = 0.42

Appropriate use (63.8%)

Inappropriate use (18.4%)

P = 0.01

Child A or B (n = 48) Child C (n = 66)


Albumin administration

IV albumin in SBP Reduces incidence of renal failure (33% to 10%) Improves hospital survival (71% to 90%) 1.5 g/kg at diagnosis, followed by 1g/kg on D3

Risk factors for hepatorenal syndrome Bilirubin > 4 mg/dl or Cr > 1.0 mg/dl (33-57%) Bilirubin < 4 mg/dl or Cr < 1.0 mg/dl (<8%)

Routine albumin use in low-risk patients should not be done. Albumin cannot be subsitutued by artificial plasma expander Albumin in unselected cirrhotic patients with non-SBP infection is not associated

with clinically relevant effect.


Risk for ESBL in SBP



Take home message

정맥류출혈

중요한것은 “문맥압” – overhydration에유의하자

항생제, Lactulose잊지말자

내시경을잘하자

간성혼수

정말간성혼수인가항상의심하자

간성혼수가맞다면분류를하자 (Type C, grade 3, episodic, precipitated etc…)

Severe sepsis and septic shock

Goal (must be achieved within 6 hours) Mean arterial pressure ≥ 65 mmHg Central venous pressure: 8 – 12 mmHg Central venous oxygen saturation ≥ 70% Urine output ≥ 0.5 ml/kg/h

Fluid Albumin, artificial colloids, crystalloids Crystalloids (requires more fluid, results in more edema)

Vasoactive drugs 1st line: Norepinephrine, dopamine (not usually effective, since already present high cardiac

outputs) 2nd line: vasopression (less responsive d/t hyporeactivity) Terlipression: under investigation

Stress dose steroid Only for vasopressor-unresponsive septic shock. On clinical trial



Any questions?

[email protected]

Take home message

급성신기능장애

빠른원인교정이중요하다

감염

항상의심하자적절한항생제를잘쓰자


간암 환자의 진료

곽 금 연


2016-01-22 1

Geum-Youn GwakDepartment of Medicine, Samsung Medical Center,

Sungkyunkwan University School of Medicine, Seoul, Korea


Neoplasm146.6

Cerebrovasculardisease

53.2

Cardiovascular disease

46.9Suicide

31.2Diabetes

20.7Pneumonia

14.9

Lower respiratory tract infection

14.2

Liver disease13.8

Traffic acidents13.7

Hypertensive disease9.6

Others147.2

Major causes of death in year 2010

National statistics Korea, http://www.index.go.kr

Lung cancer:31.3 Liver cancer: 22.5 (2nd) Stomach cancer: 20.1


1987: recombinant DNA vaccines launched

1988: HBV vaccination for school age children

1991: Listed on vaccination guideline for children

1995: universal HBV vaccination for newborn infants

2002: Start of HBV vertical transmission prevention program

(A) Suh et al, Intervirology 2006;49:70, (B) Park. Korean J Gastroenterol 2005;45:217

(A) (B)


남녀비는 4-6 대 1

환경적인요인과

체질적인요인이

함께관여 남자

여자

삼성서울병원, 남녀비 = 6:1

0

2

4

6

8

10

10-19 20-29 30-39 40-49 50-59 60-

1234

(%)

Age

1: Literature review of 74 studies between 1980 – 19892: 1998 Korea National Health and Nutrition Examination Survey3: 2001 Korea National Health and Nutrition Examination Survey4: 2005 Korea National Health and Nutrition Examination Survey

Choi, Korean J Pediatr 2008;51:696


담배를피우면간세포암의위

험이최고 3 - 4배정도

술도마시고담배도피우면간

세포암의발생확률은기하급

수적으로상승

술을마시면간세포암이최고 6배까지잘생김

간 염

간경변증

간세포암

간염바이러스에의한 경우도술을 마시면간세포암이 더 잘생김


비만과 간세포암

Regimbeau JM. Liver Transpl 2004

지방간염과 간세포암


Yu MW. Cancer Res 1995

식이와 간세포암

당뇨와 간세포암


Gelatti U. J Hepatol 2005

커피와 간세포암






Stage I(9.5%)

Stage II(38.3%)

Stage III(28.2%)

Stage IV-A(17.3%)

Stage IV-B(6.7%)

Registered HCC patients during 1990 - 2008 at Korean Liver Cancer Study Group On-line registration site by 42 Hospitals across Korea (n = 10,042)

www.klcsg.or.kr




Laparoscopy Robot

• Minimally invasive surgery has gained much popularity recently.

• Lesser pain, faster recovery, better cosmesis

Ann Surg 2009;250: 831–841

1 year 2 year 3 year 4 yearLaparoscopic 79.5 55.4 51.1 51.1Open 82.3 67.2 57.2 54

1 year 2 year 3 year 4 yearLaparoscopic 95.9 87.2 84.5 84.5Open 95.9 92.2 88.6 88.6

Disease free survival

Overall survival

Laparotomy



Post-TACE Immediate RFATACECT

화학요법과 선택적 허혈에의한 종양괴사효과

제한점 반복적 치료에도 암이 완전히소실되는 빈도가 낮음

크기가 큰 종양에서 치료효과가 낮음

시술관련 부작용 발생

문맥혈전증 환자에서 제한적효과를 보임


1 min 10 min 20 min


Radiotherapy• 간암 방사선치료 기법의 획기적 발전이차원 삼차원 체부정위방사선 양성자치료


Surgical therapy(17.8%)

Local ablation therapy(13.7%)

Others(5.2%)

Transcatheterarterial

chemoembolization(63.3%)


www.klcsg.or.kr

0

1000

2000 1,387 (27%)

55(1%)

1,157(23%)

2,411 (47%)

72(1.4%)

22(0.4%)

29(0.6%)

14(0.3%)

788(15%)



Number 1 yr 2 yrs 3 yrs 4 yrs 5 yrs

Stage I 460 88.5% 80.0% 68.5% 58.9% 54.7%

Stage II 1,836 78.4% 65.6% 55.0% 48.6% 42.5%

Stage III 1,374 59.0% 44.6% 35.1% 29.7% 25.2%

Stage IV-A 893 34.5% 22.2% 17.8% 14.8% 11.3%

Stage IV-B 319 31.0% 18.5% 13.4% 10.8% 8.9%

www.klcsg.or.kr

SMC 연도별 치료 트렌드



Reproduced from World Health Organization1

• Treatment begins with titration of ATC analgesics until optimal balance between pain control and side effects is achieved2

– WHO recommends long-acting opioids, e.g. morphine, hydromorphone and oxycodone, for moderate to severe pain1

– However, WHO recommendations do not provide direct guidance for the treatment of BTcP3

1. World Health Organization. Cancer pain relief – 2nd ed. 1996.2. Mercadante S and Arcuri E. Pain: Clinical Updates 2006;XIV:1–4. 3. Patt RB and Ellison NM. Oncology 1998;12:1035–1046.

1. Bennett D et al. P&T 2005;30:296–301.2. Coluzzi PH. Am J Hosp Palliat Care 1998;15:13–22.

Wong-Baker Faces pain rating scale1

Reproduced from Bennett et al1

Numerical intensity scale2

Reproduced from Coluzzi2

Descriptive intensity scale2

Reproduced from Coluzzi2





Documents

목차 - 삼성서울병원 · 2016-01-26 · Metabolism and detoxification of drug and hormone 4. Storage function 5. ... Cytosol Galactose Galactokinase 14C-galactose breath test