1. Medical Grand Round - Disease review
Variceal Hemorrhage
고위험 환자(소화성궤양의 과거력, 65세 이상의 고령, 고용량 비스테로이드소염제, 스테로이드 사용, 항응고제 사용, 아스피린을 포함한 비스테로이드소염제의 중복 사용
R4 윤 경 한 / Prof. 김병호/김정욱

2. INDEX Natural history Epidemiology Pathophysiology Predictive factors
Prevention & Treatment

3. Natural history & Epidemiology
Gastroesophageal varices are present in almost half of patients with cirrhosis at the time of diagnosis
Development and growth of gastroesophageal varices each occur at a rate of 7% per year
The 1-year rate of a first variceal hemorrhage is approximately 12% (5% for small varices and 15% for large varices)
Epidemic 지역은 hepatitis가 유행하나 Endemic 지역은 pig 등을 소비하면서 sporadic하게 발생함.
Endemic 지역(미국)의 pig 들을 조사해 보니 HEV RNA 양성 비율이 높았다.

4. Natural history & Epidemiology
Variceal size, red wale marks on varices and advanced liver disease (Child class B or C) identify patients at a high risk for variceal hemorrhage
The 1-year rate of recurrent variceal hemorrhage is approximately 60%
The 6-week mortality with each episode of variceal hemorrhage is approximately 15 to 20%
Epidemic 지역은 hepatitis가 유행하나 Endemic 지역은 pig 등을 소비하면서 sporadic하게 발생함.
Endemic 지역(미국)의 pig 들을 조사해 보니 HEV RNA 양성 비율이 높았다.

5. Pathophysiology Structural
: distortion of liver vascular architecture by fibrosis and regenerative nodules
Functional
: increased hepatic vascular tone due to endothelial dysfunction and decreased nitric oxide bioavailability

6. Predictive factors Location of varices Size of varices
Appearance of varices
Clinical features of the patient
Variceal pressure
Varix 있는 군이 없는 군에 비해 사망률이나 decompensation 될 확률 높음.
Capsule은 덜 invasive 하지만 정확도 떨어짐.

7. Predictive factors Location of varices Size of varices
The mean transfusion requirement in patients with bleeding gastric varices was higher than in those with esophageal varices (4.8 vs 2.9 units per patient)
Size of varices 
Laplace's law; vessel radius ↑→ wall tension ↑
F1: Small, straight varices
F2: Enlarged, tortuous varices that occupy less than one-third of the lumen
F3: Large, coil-shaped varices that occupy more than one-third of the lumen
Varix 있는 군이 없는 군에 비해 사망률이나 decompensation 될 확률 높음.
Capsule은 덜 invasive 하지만 정확도 떨어짐.

8. Small varices (<5mm) Large varices (>5mm)F1 F2 F3
직선 또는 사행성(serpiginous)
폭도 작다(small width)
염주상(bead form),
구불구불한(tortuous)
내강의 1/3 미만
결절형(nodular),
종괴형(massive)
내강의 1/3 이상

9. Predictive factors Appearance of varices Clinical features
Red wale marks
Cherry red spots
Clinical features 
Child-Pugh score
History of a previous variceal bleed
Variceal pressure 
The variceal pressure may be an important predictor for variceal hemorrhage
Portal hypertension : > 5mmHg
>20mmHg -> Poor outcome
Bleeding 있으면 6주이내 1/3 그다음 6주이내 1/3

10. (Hepatic venous pressure gradient)
HVPG
(Hepatic venous pressure gradient)
HVPG = WHVP - FHVP
Free hepatic vein pressure
Wedged hepatic vein pressure
5mmHg 이상이면 PH
Nature Reviews Gastroenterology and Hepatology 6,   (October 2009)

11. Grey’s Anatomy Season 9 Episode 22 “Do You Believe in Magic?”

12. Prevention & Treatment
1st variceal hemorrhage
Acute variceal hemorrhage
Recurrent variceal hemorrhage

13. Prevention & Treatment
Splanchnic vasoconstrictors
: vasopressin and somatostatin
Portal hypertension
Nitric oxide ↑
: nitrates,simvastatin
Nonselective beta-adrenergic blockers
:β1-blockade - cardiac output↓
β2-blockade - splanchnic vasoconstriction
to the intrahepatic circulation-NO
Sclerotherapy – sclerosing agent
Transjugular intrahepatic portosystemic shunt (TIPS) / surgically
Endoscopic procedures
: Variceal ligation, Variceal sclerotherapy

14. 식도정맥류 환자에서 초출혈 예방을 위한 접근 방법 대한간학회, 2011 간경변증 가이드라인
1st variceal hemorrhage
Heart rate
: 25%↓- resting or 55/min
: Propranolol 160mg/day(maximum)
Follow up
: Endoscopic procedure → after 1-3 months → every months
병합은 예방과 생존율에 차이 없었고, 부작용만 증가.
EVL은 정맥류 소실까지 하지만 주기 및 추적검사 시기는 확립된 것없음.
식도정맥류 환자에서 초출혈 예방을 위한 접근 방법 대한간학회, 2011 간경변증 가이드라인

15. Prevention & Treatment
Acute variceal hemorrhage
Prevention & Treatment
General management
NPO, Transfusion, IV line, airway
BP : mmHg
HR : ≤100/min
CVP : 1-5mmHg
Hb : ≥8g/dL, Platelet : ≥50,000/mm3
Massive transfusion
Epidemic 지역은 hepatitis가 유행하나 Endemic 지역은 pig 등을 소비하면서 sporadic하게 발생함.
Endemic 지역(미국)의 pig 들을 조사해 보니 HEV RNA 양성 비율이 높았다.

16. Prevention & Treatment
Acute variceal hemorrhage
Prevention & Treatment
Medication
Terlipressin
- Survival ↑
- Effect on hepatorenal syndrome
- Ischemic heart disease
- 1st day : 2mg q 6hrs
- 2nd & 3rd day : 1mg q 4hrs
Somatostatin
Octreotide
Splanchnic vasoconstriction
Nausea, vomiting
- Somatostatin
: Bolus 250 μg -> 250 μg/hr (6 mg/day) infusion for 2-3 days
- Octreotide
: Bolus 50 μg -> 50 μg/hr infusion for 3-5days
Antibiotics
- Bacterial infection ↓
- Survival ↑
- Ceftriaxone iv 1 g qd for 5-7days
- Norfloxacin p.o 400mg bid for 5-7days
Epidemic 지역은 hepatitis가 유행하나 Endemic 지역은 pig 등을 소비하면서 sporadic하게 발생함.
Endemic 지역(미국)의 pig 들을 조사해 보니 HEV RNA 양성 비율이 높았다.

17. Prevention & Treatment
Acute variceal hemorrhage
Prevention & Treatment
Endoscopic procedure
1st treatment : medical treatment & endoscopic procedure
Endoscopic variceal ligation (EVL)
If failure -> Endoscopic injection sclerotherapy (EIS)
Salvage therapies
Standard medical therapy fails -> 10%-20% of patients
Balloon tamponate -S-B Tube(Sengstaken Blakemore Tube)
Transjugular intrahepatic portosystemic shunt (TIPS)
Shunt surgery
급성 정맥류 출혈 환자는 1차 치료로 약물 치료와 내시경 치료를 권장한다
S-B Tube(Sengstaken Blakemore Tube)

18. Significant improvement in survival among high-risk patients
(patients with an HVPG >20 mm Hg)

19. Prevention & Treatment
Recurrent variceal hemorrhage
Prevention & Treatment
Medication(Nonselective β blocker) + Endoscopic procedure
HVPG
12mmHg↓ or reduced by more than 20% from the baseline
Rate of recurrent variceal hemorrhage is lowest (approximately 10%)
No more endoscopic procedure
Salvage therapy
TIPS : Child-Pugh A or B (standard therapy failure patients)
Rebleeding ↓ but Encephalopathy ↑
Mortality – No significant difference
Liver transplantation
단독보다 병합치료가 더 성적이 좋음.
TIPS는 내시경이나 약물 치료가 실패한 경우
LT는 indication이 된다면 구조 치료법으로 고려

20. Case O 다음 중 가장 적절한 조치를 취한 전공의는 누구인가요? 1. 응급 내시경 당직 선생님께 전화한 오신주 선생님
2. 대량 수혈을 시행한 김동연 선생님
3. IV line을 확보하고 Terlipressin, PPI 등의 약물 투여를 한 이지훈 선생님
4. S-B tube insertion 하고 중환자실 입원을 설명한 문정락 선생님
5. 1시간 째 연락되지 않는 정수웅 선생님
Chief complaint
Hematemesis onset : 1 hour ago
Present illness
M/53, 매일 소주 5병이상 마시던 자로, 2014년 1월 외부병원에서 AVN, Lt로 THR 시행 받은 환자. 당시 간경화 진단을 듣고 금주하며 지내던 중 내원 저녁 10시경 밥공기 한 그릇 가량의 토혈 4차례 발생하여 응급실 내원

21. PPI(IESOZ 80mg bolus & 8mg/hr infusion)
IV line 18G 2군데이상 or C-line
Notify
Terlipressin
(ITLPS) 2mg q 6hrs
PPI(IESOZ 80mg bolus & 8mg/hr infusion)
Antibiotics
: Ceftriaxone
(AAXON1) 1g qd
Somatostatin - Bolus 250 μg -> 250 μg/hr (6 mg/day) (ISOMA 6mg + FNS5B -> 20cc/hr)

22. Terlipressin (ITLPS) 1mg q 4hrs for 2days
Endoscopic procedure success
Terlipressin (ITLPS) 1mg q 4hrs for 2days
Ceftriaxone(AAXON1) 1g qd for 6days
Endoscopic procedure failure
S-B tube insertion
Notify to department of radiology for TIPS
Beta blocker (BIDLA or BCVD6)
Follow up endoscopy (after 1~3moths -> every 6~12months)

23. References
Guadalupe Garcia-Tsao, Jaime Bosch. Management of Varices and Variceal Hemorrhage in Cirrhosis. N Engl J Med 2010;362:
The Korean Association for the Study of the Liver Clinical Practice Guideline for Liver Cirrhosis, Update.
AASLD PRACTICE GUIDELINES. Prevention and Management of Gastroesophageal Varices and Variceal Hemorrhage in Cirrhosis. HEPATOLOGY, Vol. 46, No. 3, 2007.
Prediction of the first variceal hemorrhage in patients with cirrhosis of the liver and esophageal varices. A prospective multicenter study. N Engl J Med.;319(15):983.
Harrison’s internal medicine 18th edition.
Epidemic 지역은 hepatitis가 유행하나 Endemic 지역은 pig 등을 소비하면서 sporadic하게 발생함.
Endemic 지역(미국)의 pig 들을 조사해 보니 HEV RNA 양성 비율이 높았다.