심 재 준심 재 준 Am J Gastroenterol 2007;102:

Introduction  Hepatocellular carcinoma  Detected at an advanced tumor state  Precluding effective treatment  HCC surveillance in patients at risk  US and or AFP every 6-12mo  Cirrhosis and HCC  HCC underlying cirrhosis ; >80%  European and American guidelines for HCC management  “to those cirrhotics who would be treated if diagnosed with HCC”

Introduction  The Child-Pugh(CP) classification  Severity of cirrhosis and its prognosis  Cost-effective surveillance to which patients?  Child A : effective  Child B : ?  Child C : futile  Yuen MF et al, Hepatology 2000;31:330-5  Class B : prognostic benefit  Trevisani F et al, Am J Gastroenterol 2002;97:734  Class B : borderline significancy  Class B: Surveillance? Gray zone

Introduction  Advances in HCC, LC management  Major advances in HCC management in recent years  More sensitive diagnostic imaging, TACE, optimized the therapeutic strategy  Reduction of cirrhosis-related mortality due to an improved management of its complications  The time has come to re-evaluate surveillance for HCC in intermediate/advanced cirrhosis  Surveillance of class B / class C ?

Aim  Whether surveillance improves the prognosis of patients belonging to classes B and C at the time of HCC diagnosis.

Methods – 1. Patients  Cohort study  The ITA.LI.CA database  1,834 HCC (January 1987 to December 2004 at 10 medical institutions)  Eligible criteria  the interval of surveillance  the C-P class at the time of HCC diagnosis  608 patients: 468 class B and 140 class C cases  Exclusion criteria  class A (1084 patients),  class unreported (59 patients)  surveillance interval unspecified (83 patients)  Patients group  Group 1 : 252 (41.4%), HCC was detected during regular surveillance  every 6 (172 cases [68.3%]) or 12 (80 [31.7%]) months  Group 2 : 356 (58.6%), in whom HCC was detected "incidentally,"  during examination for other diseases (181 patients [50.8%]), or because of symptom appearance (175 patients [49.2%]).

Methods  Etiology and Diagnosis of Cirrhosis  HBV, HCV, Alcoholic, multietiology  Others : cryptogenic, hereditary hemochromatosis, PBC  Diagnosis and Staging of HCC  Histology or cytology ; 42 patients  AFP>200ng/mL, typical imaging features  Unifocal, paucifocal( 3nodules), infiltrating, massive  United Network of Organ Sharing(UNOS) system, CLIP system  Statistical Analysis  to minimize the lead time bias (Schwartz’s formula, Cancer 1961;14: )  The calculated lead time(t) : 238 days(6mo), 121 days(1yr) t = DT x 3 x log(d1/d0)/log(2)

Lead time bias ScreeningSymptoms Death Survival time Survival time with screening Adams PC et al. Hepatology 2004;39:

Length bias Screening test Tumor doubling time Fast growing tumor 1 case detected Slow growing tumor 3 cases detected Adams PC et al. Hepatology 2004;39:

Results : Child-Pugh B patients

Figure 1. Survival of Child-Pugh class B patients according to the modality of cancer diagnosis Group 1 ; 17.1, 95% CI 13.5~20.6 months Group 2 ; 12.0, 95% CI 9.4~14.6 months Group 1: 16.0, 95% CI 12.9~19.0 months, p=0.253, if OLT(-)

Results : Table 3. Variables associated with survival in Child-Pugh B patients

Results :Child-Pugh C patients

Figure 2. Survival of Child-Pugh class C patients according to the modality of cancer diagnosis Group 1 ; 7.1, 95% CI 2.1 ~ 12.1 months Group 2 ; 6.0, 95% CI 4.1~7.9 months

Results : Table 6. Variables associated with survival in Child-Pugh C patients

Discussion  Relation between liver function and outcome of surveillance  Only two, in Hong Kong and Italy  Hong Kong :  Low class B cases  Only compared with symptomatic patients  Length bias, lead time bias ; not adjusted  Italy  Improved HCC, cirrhosis management  Doubled sample size

Discussion  OLT ; liver transplantation  Class B;  crucial to achieve a better survival rate by surveillance  Age, extrahepatic comorbidity, ability of transplantation  Class C;  Patients for OLT : screening is strongly recommended  OLT 불가능한 class C 환자는 ?  HCC vs. cirrhosis-related mortality

Discussion  Limitation  Not randomized trial  Incidental detection by US…  Effect of some biases  Selection bias  Surveyed Class B : younger, HCV, non-alcoholics  Intercenter heterogeneity of HCC Mx  Disease-specific mortality ; not assessed

Conclusions  Class B  간암 조기 발견을 위한 surveillance 는 생존률을 증 가  특히, 간암 발견 당시 간이식이 가능한 환자들을 더 중점으로 해야 하겠다.  Class C  간암 발생 전에 간이식을 고려해야 하겠고 이런 환자 들이 surveillance 의 대상이 되겠다.  그 외 환자들에게는 간암 surveillance 가 의미 없다.