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Holistic Approach of Hepatitis B virus Treatment

ตับอักเสบบี แนวทางการรักษาแบบองค์รวม

Narong Khuntikeo (ณรงค์ ขันตีแก้ว) 1




ตับอักเสบบี แนวทางการรักษาแบบองค์รวม

Holistic Approach of Hepatitis B virus Treatment

ผศ.นพ.ณรงค์  ขันตีแก้ว

ภาควิชาศัลยศาสตร์  คณะแพทยศาสตร์  มหาวิทยาลัยขอนแก่น

Narong  Khuntikeo,MD.

Department of Surgery, KhonKaen University

 

 The major risk factors for HCC include cirrhosis from chronic hepatitis B or C virus infection1, alcohol use, hereditary hemochromatosis, other cause of liver injury such as α-1 antirypsin deficiency, autoimmune hepatitis, primary biliary cirrhosis, and tyrosinemia, Approximately 80% to 90 % of HCCs arise in cirrhosis. The remaining 10%  to 20% are in 2 groups of patients: (1) those with chronic hepatitis B infection  who develop HCC in the absence of cirrhosis,presumably secondary to the effects of hepatitis B virus integration, and in the other causes, and (2) older individuals in countries with a low incidence of hepatitis B virus who present with sporadic- onset HCC in the absence of discernable risk factors 

Treatment Options  (see the APPENDIX)

          The best outcomes of therapy are achieved with liver transplantation, surgical resection, or local ablative therapies that are must effective when applied to early stage HCC.

          Liver Transplantation

          Hepatic resection and transplantation offer the greatest chance for cure in patients with HCC3-4  using the selection criteria of 1 tumor smaller than 5 cm or up to 3 tumors smaller than 3 cm and no vascular invasion, 5-year survival rates of up to 70% and recurrence rates less than 15% have been reported.

Liver resection

          Liver resection is the preferred treatment of HCC in all noncirrhotic patients and in cirrhotic patients with well preserved liver function who are not candidates for liver transplantation.  Liver resection achieves 5-year survival rates of 30% to 50%, although in ideal candidates 5-year survival rates of 50% to 70% have been reported.

Local Modalities of Therapy

          Local modalities of therapy for HCC include local ablative methods, such as percutaneous ethanol injection (PVE) and radiofrequency ablation (RFA), and locoregional therapies, including transarterial chemoemblization (TACE), transarterial radioembolization, and conformal beam radiation. 5-8

Systemic Approaches  Therapy

          For patients with disease that has spread beyond the liver, few eftective options are available. Chemotherapy, either as a single agent or in combination, has provided only limited benefit for patients with unresectable or metastatic HCC. Responses to doxorubicin have been approximately 10% with short median survival9 . Combination of cisplatin (Platinol), interferon, doxorubicin(Adriamicin), and fluorouracil(PIAF) has been evaluated in several trials. One clinical trial reported a 26% partial response rate and a median overall survival rate of 8.9 months.

          Due to limited benefit of chemotherapy, hormonal therapy have been evaluated. Several trials showed potential benefit with tamoxifen compared with a placebo, but recent multicenter trials of tamoxifen compared with best supportive care, showed no benefit of tamoxifen10 .  

          Current trials are focusing on targeted or novel therapies such as antiangiogenic agents11 .

Conclusions     Liver resection and transplantation for HCC have provided a potentially curative option for selected patients with localized disease. Many treatment optians are available for patients with localized HCC. Metastatic spread of HCC continues to  be a therapertic challenge. Although the potential  treatment options are increasing, the response rate and duration  of response continue to be low. Clinical trials is still critical to making advances in this area of HCC treatment.

 

APPENDIX

Table 1  Okuda Staging

 

Negative

Positive

Tumor size

<50 % of  liver

> 50% of liver

Ascites

Absent

Present

Serum albumin

>3 g/dl

< 3 g/dl

Bilirubin

<3 mg/dl

> 3 mg/dl

Okuda I: No positive factor : Okuda II: 1 or 2 positive factors, Okuda III: 3 or 4 positive factors.

Table 2   The BCLC Staging Classification

Staging

PST

Tumor Status

Liver Functional status

Tumor

Okuda

Stage

Stage A: early HCC

A 1

 

A 2

 

A 3

 

A 4

StageB: intermediate HCC

StageC: advanced HCC

 

StageD: end-stage HCC

 

0

 

0

 

0

 

0

0

1-2*

 

3-4t

 

Single

 

Single

 

Single

 

3tumor  <3 cm

Large multinodular

Vascular invasion or

Extrahepatic spread*

Any

 

I

 

I

 

I

 

I-II

I-II

I-II

 

III

 

No portal hypertension and normal bilirubin

Portal hypertension and normal bilirubin

Portal hypertension and abnormal bilirubin

Child-Pugh A-B

Child-Pugh A-B

Child-Pugh A-B

 

Child-pugh C*

 

Stage A and B : All criteria should be fulfilled.

Stage C : At least one criteria*   : PST 1-2 or vascular invasion/extrahepatic spread.

Stage D: At least one criteria : PST 3-4 or Okuda stage III/Child-Pugh C.

PST= performance Scale (0:normal activity, 1: symptoms but nearly fully ambulatory, 2: some bed time,

but needs to be in bed  in less than 50% of normal day time, 3: needs to be in bed greater than 50% of normal

day time, 4: unable to get out of bed)

Table 3  French Classification

Weight

0

1

2

3

Karnofsky index1  (%)

> 80

 

 

<80

Serum bilirubin(µmol/l)

<50

 

 

> 50

Serum alkaline-phosphatase(ULN2 )

<2

 

> 2

 

Serum alpha-fetoprotein(µg/l)

<35

 

> 35

 

Portal obstruction(ultrasonography)

No

yes

 

 

1  Karnofsky score > 80% : complete autonomy of the patient.

2  ULN: upper limit of normal range.

Table 4  TNM classification of hepatocellular carcinomas

Classification

Definition

T1

Solitary tumor without vascular invasion

T2

Solitary tumor with vascular invasion or multiple tumors none more than 5 cm

T3

Mulitple tumors more than 5 cm or tumor involving a major branch of the portal or hepatic vein(s)

T4

Tumor(s) with direct invasion of adjacent organs other than the gallbladder or with perforation of the visceral peritoneum

Stage of TNM classification

I

T1/NO/MO

II

T2/NO/MO

III

III A T3/NO/MO

III B T1/N1/MO

         T2/N1/MO

         T3/N1/MO

IV

IV A  T4/any N/MO

IV B any T/any N/M1

T = tumor; N = nodes; M = metastasis; NO = without  regional lymph nodes; N1 = with regional lymph nodes; MO = without distant metastasis; M1= with distant metastasis.

 

Table 5 Weight of the Six Prognostic Factors in the Chinese University Prognostic Index

Variable

Weight (CUPI score)a

TNM

I and II

IIIa and IIIb

IVa and IVb (reference)

Asymptomatic disease on presentation

Ascites

AFP > 500ng/ml

TB (µmol/L)

     < 34 (reference)

     34-51

    > 52

ALP > 200 IU/L

 

-3

-1

0

-4

3

2

 

0

3

4

3

 

CUPI: Chinese University Prognostic Index; AFP: œ-fetoprotein: TB: Total bilirubin;ALP: alkaline phosphatase.

CUPI score: summation of the weights of TNM staging+asymptomatic disease on presentation+ascites+AFP+TB+ALP(low-risk group, CUPI score< 1; intermediate risk group, CUPI score = 2-7; high-risk group, CUPI score ≥8). For instance, the estimated survival for a patient diagnosed with TNM stage lllb hepatocellular carcinoma with ascites, AFP 10,000 ng/mL, TB 20 µmol/L and ALP 100 IU/L is calculated as follows.

(-1)+(0)+(3)+(2)+(0)+(0)=4. The patient belongs to the intermediate risk group, with a median survival of 3.7 months (95% confidence interval, 3.1-4.3 months)

 

 

 

 

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