Jaw-Ching Wu

Publications of Jaw-Ching Wu

• The Effect of Age on the Long-term Prognosis of Patients With Hepatocellular Carcinoma After Resection Surgery: A Propensity Score Matching Analysis.

  Authors: Chien-Wei Su, Hao-Jan Lei, Gar-Yang Chau, Hung-Hsu Hung, Jaw-Ching Wu, Cheng-Yuan Hsia, Wing-Yiu Lui, Yu-Hui Su, Chew-Wun Wu, Shou-Dong Lee

  Archives of surgery (Chicago, Ill. : 1960). 02/2012; 147(2):137-44.

  The effect of age on the clinicopathologic manifestations of hepatocellular carcinoma (HCC) and on the survival rate in patients with HCC after resection surgery remains controversial. We aim toThe effect of age on the clinicopathologic manifestations of hepatocellular carcinoma (HCC) and on the survival rate in patients with HCC after resection surgery remains controversial. We aim to compare the clinicopathological features and prognoses between younger and older patients with HCC undergoing resection. Retrospective review. A tertiary medical center. We enrolled 1074 consecutive patients with HCC who were undergoing a partial hepatectomy. Patients who were 55 years of age or younger were defined as the younger group (n = 374), and patients who were older than 55 years of age were defined as the older group (n = 700). The postoperative prognoses of the younger and older groups using multivariate analysis and propensity score matching analysis. The younger patients had better liver functional reserve but more aggressive tumor factors than did the older patients. After a median follow-up of 41.0 months, 543 patients died. The cumulative 10-year survival rates were 41.3% in younger patients and 28.8% in the older patients (P = .02). However, using both multivariate analysis and propensity score matching analysis, we failed to demonstrate that age was an independent risk factor associated with overall survival. Besides, there were 643 patients with tumor recurrence after surgery. Using both multivariate analysis and propensity score matching analysis, we found that the incidence of tumor recurrence in younger patients was comparable to that in the older patients. Age is not a risk factor to determine the prognosis of patients with HCC who underwent resection. Older patients with HCC who have good liver functional reserve are encouraged to receive resection surgery.

• Younger hepatocellular carcinoma patients have better prognosis after percutaneous radiofrequency ablation therapy.

  Authors: Wei-Yu Kao, Yi-You Chiou, Hung-Hsu Hung, Chien-Wei Su, Yi-Hong Chou, Teh-Ia Huo, Yi-Hsiang Huang, Wen-Chieh Wu, Han-Chieh Lin, Shou-Dong Lee, Jaw-Ching Wu

  Journal of clinical gastroenterology. 09/2011; 46(1):62-70.

  To evaluate the impact of age on the prognosis of patients with hepatocellular carcinoma (HCC) undergoing percutaneous radiofrequency ablation (RFA). Whether age plays an important role in theTo evaluate the impact of age on the prognosis of patients with hepatocellular carcinoma (HCC) undergoing percutaneous radiofrequency ablation (RFA). Whether age plays an important role in the outcomes of HCC after RFA remains controversial. Two hundred fifty-eight consecutive treatment naive HCC patients who underwent RFA were enrolled. Patients aged ≤ 65 years (n = 100) were defined as the younger group and those aged > 65 years (n = 158) were the elderly group. Their clinicopathologic features and prognosis were compared. Younger patients had a higher male-to-female ratio, higher prevalence of hepatitis B virus, and smaller tumor size than elder patients. After median follow-up of 28.5 ± 18.7 months, 45 patients died. The cumulative 5-year survival rates were 81.3% and 65.4% in younger and elder HCC patients, respectively (P = 0.008). Multivariate analysis disclosed that age > 65 years, serum albumin level ≤ 3.7 g/dL, prothrombin time international normalized ratio > 1.1, α-fetoprotein (AFP) > 20 ng/mL, and no antiviral therapy after RFA were independent risk factors associated with poor overall survival. Besides, there were 163 patients with tumor recurrence after RFA. Multivariate analysis showed that age > 65 years, platelet count ≤ 10/mm, AFP > 20 ng/mL, multinodularity, and tumor size > 2 cm were the independent risk factors predicting recurrence. Both liver functional reserve (serum albumin level, prothrombin time international normalized ratio, platelet count, and antiviral therapy) and tumor factors (tumor size, number, and AFP level) were crucial in determining post-RFA prognosis in HCC patients. Moreover, younger HCC patients have better overall survival and lower recurrence rate after RFA compared with elder patients.

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• Risk factors for long-term prognosis in hepatocellular carcinoma after radiofrequency ablation therapy: the clinical implication of aspartate aminotransferase-platelet ratio index.

  Authors: Wei-Yu Kao, Yi-You Chiou, Hung-Hsu Hung, Yi-Hong Chou, Chien-Wei Su, Jaw-Ching Wu, Teh-Ia Huo, Yi-Hsiang Huang, Han-Chieh Lin, Shou-Dong Lee

  European journal of gastroenterology & hepatology. 06/2011; 23(6):528-36.

  Percutaneous radiofrequency ablation (RFA) is one of the first-line curative therapies for hepatocellular carcinoma (HCC), but factors affecting the prognosis remain unclear. This study aimed toPercutaneous radiofrequency ablation (RFA) is one of the first-line curative therapies for hepatocellular carcinoma (HCC), but factors affecting the prognosis remain unclear. This study aimed to evaluate the prognostic factors associated with the prognosis in patients with HCC undergoing RFA. The study enrolled 190 treatment-naïve patients with HCC (<5 cm). Factors were analyzed in terms of overall survival and recurrence. After a median follow-up of 30.7±17.5 months, 41 patients died and 149 patients were alive. Of the 112 patients who developed tumor recurrence, 61 had local recurrence and 51 had distant intrahepatic recurrence. The 5-year overall survival rate and recurrence rate were 65.5 and 73.6%, respectively. Factors associated with overall mortality were, age older than 65 years (P=0.019), aspartate aminotransferase-to-platelet ratio index (APRI) of more than 1 (P=0.015), prothrombin time international normalized ratio of more than 1.1 (P=0.013), multinodularity (P=0.024), and Child-Pugh grade B (P=0.036). Besides, multivariate analysis disclosed that APRI of more than 1 (P=0.002), multinodularity (P<0.001), and tumor size of more than 2 cm (P=0.002) predicted higher incidence of developing recurrence after RFA. Factors determining local recurrence were, age older than 65 years (P=0.030), APRI of more than 1 (P=0.003), multinodularity (P=0.019), and tumor size of more than 2 cm (P=0.015), whereas only APRI of more than 1 (P=0.013) and multinodularity (P<0.001) were independent risk factors predictive of intrahepatic distant metastasis. Both multinodularity and APRI are associated with overall survival and recurrence for patients with HCC after RFA therapy. Consequently, APRI seems to serve as a feasible marker for predicting the prognosis of patients with small HCC undergoing RFA.

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• Impact of body mass index and viral load on liver histology in hepatitis B e antigen-negative chronic hepatitis B.

  Authors: I-Cheng Lee, Yi-Hsiang Huang, Che-Chang Chan, Teh-Ia Huo, Chi-Jen Chu, Chiung-Ru Lai, Pui-Ching Lee, Chien-Wei Su, Jaw-Ching Wu, Han-Chieh Lin, Shou-Dong Lee

  Clinical nutrition (Edinburgh, Scotland). 05/2011; 30(5):647-52.

  The impact of overweight and obesity on chronic hepatitis B (CHB) is unclear. This study was to examine the relationship among body mass index, viral load and liver histology in HBeAg-negativeThe impact of overweight and obesity on chronic hepatitis B (CHB) is unclear. This study was to examine the relationship among body mass index, viral load and liver histology in HBeAg-negative CHB. The study retrospectively investigated 136 HBeAg-negative chronic hepatitis B patients who had undergone liver biopsies in Taiwan. Factors associated with significant liver histology were analyzed. Definitions of overweight and obesity for the Asian population were body mass index≥23 kg/m(2) and ≥25 kg/m(2), respectively. The prevalence of overweight, obesity, and type 2 diabetes mellitus in the 136 patients were 22.8%, 52.2%, and 12.5%, respectively. Multivariate analysis identified obesity, AST>40 U/L, HBV DNA>20,000IU/mL and platelet count<150 × 10(9)/L as independent factors associated with significant liver fibrosis. Similarly, overweight/obesity, ALT>80 U/L, HBV DNA>1,000,000IU/mL, and platelet count<150 × 10(9)/L were independent predictors of significant hepatic necro-inflammation. By stratification, high BMI and high viral load patients had more advanced stage and grade of liver histology. Body mass index and HBV viral loads may have synergistic effect on disease progression in HBeAg-negative CHB. Both controlling body weight and anti-viral therapy are important in the management of CHB.

• Comparative analysis of noninvasive models to predict early liver fibrosis in hepatitis B e Antigen-negative Chronic Hepatitis B.

  Authors: I-Cheng Lee, Che-Chang Chan, Yi-Hsiang Huang, Teh-Ia Huo, Chi-Jen Chu, Chiung-Ru Lai, Pui-Ching Lee, Chien-Wei Su, Hung-Hsu Hung, Jaw-Ching Wu, Han-Chieh Lin, Shou-Dong Lee

  Journal of clinical gastroenterology. 03/2011; 45(3):278-85.

  Portal or bridging fibrosis is an indication for antiviral treatment in patients with chronic hepatitis B (CHB). An early marker predictive of liver fibrosis in hepatitis B e antigen (HBeAg)-negativePortal or bridging fibrosis is an indication for antiviral treatment in patients with chronic hepatitis B (CHB). An early marker predictive of liver fibrosis in hepatitis B e antigen (HBeAg)-negative CHB patients can alert clinicians to plan for treatment before disease progression. To predict early and significant liver fibrosis (Ishak score ≥2) in HBeAg-negative CHB by validating several noninvasive markers derived from CHC. One hundred seventy-seven consecutive treatment-naive HBeAg-negative CHB patients who underwent liver biopsy were divided into a training group (n=121) and a validation group (n=56). Factors associated with liver fibrosis were analyzed. Multivariate analysis identified Lok's model ≥0.87, cirrhosis discriminant score greater than 4, and positive alanine aminotransferase ratio platelet score as independent factors associated with liver fibrosis in the training group. The area under the receiver operating characteristic curve revealed that Lok's model was better than cirrhosis discriminant score in predicting liver fibrosis in both the training and the validation groups. In patients with hepatitis B virus DNA greater than 2000 IU/mL or greater than 20,000 IU/mL, Lok's model showed equal prediction value (area under the receiver operating characteristic curve 0.709 and 0.704, respectively). Lok's model could also discriminate high and low hepatitis B virus DNA loads. In general, liver biopsy can be avoided in one-third (58 of 177) of patients by Lok's model. Lok's model ≥0.87 can be an early marker of liver fibrosis in HBeAg-negative CHB patients. Lok's model has clinical applications not only for CHC, but also for HBeAg-negative CHB.

• Queckenstedt's test headache response is associated with increased jugular venous flow volume during migraine attack.

  Authors: Chi-Hsiang Chou, Jong-Ling Fuh, Shuu-Jiun Wang, Han-Hwa Hu, Jaw-Ching Wu, Yu-Ting Cheng

  Ultrasound in medicine & biology. 01/2011; 37(1):23-8.

  Cephalic venous congestion induced by Queckenstedt's (Q)-test, i.e., transient compression of bilateral internal jugular veins (IJV), can aggravate headache intensity during migraine attacks,Cephalic venous congestion induced by Queckenstedt's (Q)-test, i.e., transient compression of bilateral internal jugular veins (IJV), can aggravate headache intensity during migraine attacks, especially in patients with throbbing pain. We hypothesized that the IJV flow volume was related to the Q-test response. Ultrasonography was used to measure the flow volume of bilateral IJV in migraine patients during acute attacks and interictal periods and in normal controls. All acute migraine patients underwent Q-test in a supine position. "Q-test headache response" was designated by the changes in headache intensity (0-10 scale) before and 30 s after the Q-test. Thirty-nine acute migraine patients, 20 interictal migraine patients and 23 noxrmal controls completed the study. Acute migraine patients had higher bilateral IJV flow volume than both interictal patients and normal controls (973.4 ± 348.2 vs. 733.8 ± 210.1 vs. 720.3 ± 244.9 mL/min, p = 0.001). In acute migraine patients, bilateral IJV flow volume was the only independent variable related to the Q-test headache response (adjusted R(2)= 0.422). Thus, the IJV flow volume was increased during migraine attacks and was directly related to the Q-test response. It may be used as a research tool for peripheral sensitization during acute migraine attacks.

• A comparison of prognosis between patients with hepatitis B and C virus-related hepatocellular carcinoma undergoing resection surgery.

  Authors: Wei-Yu Kao, Chien-Wei Su, Gar-Yang Chau, Wing-Yiu Lui, Chew-Wun Wu, Jaw-Ching Wu

  World journal of surgery. 01/2011; 35(4):858-67.

  The impact of viral factors on the prognosis of hepatocellular carcinoma (HCC) remains controversial because of heterogeneous populations included in previous reports. This study aims to compareThe impact of viral factors on the prognosis of hepatocellular carcinoma (HCC) remains controversial because of heterogeneous populations included in previous reports. This study aims to compare clinicopathologic features and prognoses between patients with hepatitis B- and hepatitis C-related HCC who underwent resection surgery. We enrolled 609 patients with positive serum hepatitis B virus (HBV) surface antigen (HBsAg) and negative serum antibody against hepatitis C virus (anti-HCV) as the B-HCC group and 206 patients with negative serum HBsAg and positive anti-HCV as the C-HCC group. The overall survival rates and cumulative recurrence rates were compared between these two groups. B-HCC patients were significantly younger, predominantly male, had better liver functional reserve, but more advanced tumor stage than C-HCC patients. After a median follow-up period of 40.6 months, 427 patients had died. Furthermore, 501 patients had tumor recurrence after surgery. The postoperative overall survival rates (p = 0.640) and recurrence rates (p = 0.387) of the two groups were comparable. However, the overall survival rate was higher in the B-HCC group than in the C-HCC group in the cases of transplantable HCC (p = 0.021) and Barcelona-Clinic Liver Cancer stage A HCC (p = 0.040). Viral etiologies were not apparent in determining outcomes of HCC patients who underwent resection due to heterogeneous studied populations. In early-stage HCC, B-HCC patients had better outcomes than C-HCC patients did because of better liver reserve and less hepatic inflammation.

• Survival rates are comparable after radiofrequency ablation or surgery in patients with small hepatocellular carcinomas.

  Authors: Hung-Hsu Hung, Yi-You Chiou, Cheng-Yuan Hsia, Chien-Wei Su, Yi-Hong Chou, Jen-Huey Chiang, Wei-Yu Kao, Teh-Ia Huo, Yi-Hsiang Huang, Yu-Hui Su, Han-Chieh Lin, Shou-Dong Lee, Jaw-Ching Wu

  Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 01/2011; 9(1):79-86.

  Differences in efficacy of radiofrequency ablation (RFA) and surgical resection (SR) are not clear for patients with hepatocellular carcinoma (HCC). From 2002 to 2007, 419 patients with HCCs ≤5 cmDifferences in efficacy of radiofrequency ablation (RFA) and surgical resection (SR) are not clear for patients with hepatocellular carcinoma (HCC). From 2002 to 2007, 419 patients with HCCs ≤5 cm were enrolled consecutively in the study. Among these patients, 190 and 229 patients received RFA and SR, respectively, as their first treatment. Factors were analyzed in terms of overall survival and recurrence by multivariate analysis and propensity score matching analysis. The SR group had younger age, a higher male-to-female ratio, higher prevalence of hepatitis B virus, lower prevalence of hepatitis C virus, better liver function reserve, and larger tumor size than the RFA group. The cumulative 5-year overall survival rates were 79.3% in the SR group and 67.4% in the RFA group. During the follow-up period, tumors recurred in 244 patients in a median time of 14.5 ± 15.7 months. Before propensity-score matching, the RFA group had shorter overall survival time (P = .009) and higher tumor recurrence rate (P < .001) than the SR group. After matching, RFA was comparable to SR in overall survival time (P = .519), but the RFA group still had a greater incidence of tumor recurrence (P < .001). In patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 HCC, RFA was as effective as SR for overall survival time and recurrence. Patients with small HCCs have a higher rate of tumor recurrence following RFA than surgery, but overall survival rates are comparable between therapies. RFA is as effective as surgery in patients with BCLC stage 0 HCC.

• Correlation between clinical indication for treatment and liver histology in HBeAg-negative chronic hepatitis B: a novel role of alpha-fetoprotein.

  Authors: I-Cheng Lee, Yi-Hsiang Huang, Che-Chang Chan, Teh-Ia Huo, Chi-Jen Chu, Chiung-Ru Lai, Pui-Ching Lee, Chien-Wei Su, Hung-Hsu Hung, Jaw-Ching Wu, Han-Chieh Lin, Shou-Dong Lee

  Liver international : official journal of the International Association for the Study of the Liver. 09/2010; 30(8):1161-8.

  It is unclear whether clinical indication for antiviral treatment is in agreement with histological indication in HBeAg-negative chronic hepatitis B (CHB). This study aimed to clarify thisIt is unclear whether clinical indication for antiviral treatment is in agreement with histological indication in HBeAg-negative chronic hepatitis B (CHB). This study aimed to clarify this relationship and identify factors associated with liver histology. We investigated 152 consecutive, treatment-naïve, HBeAg-negative CHB patients who had undergone liver biopsies at a tertiary medical centre in Taiwan. Clinical indications for treatment included a serum alanine aminotransferase level more than twice the upper limit of normal and an hepatitis B virus DNA level > 2000 IU/ml. Factors associated with the histological indication (Ishak's grade > or = 7 and/or stage > or = 2) were analysed. The association between the clinical and the histological indications was significant (P=0.011). However, the agreement was poor (kappa value=0.197). In patients satisfying the clinical indication, age > 52 years [odds ratio (OR)=2.669, P=0.042], serum alpha-fetoprotein (AFP) level > 7 ng/ml (OR=7.070, P<0.001) and platelet count < 130 x 10(9)/L (OR=11.720, P=0.025) were identified to be independent factors associated with histological indication. In patients who did not satisfy the clinical indication, multivariate analysis revealed that only an AFP level > 7 ng/ml (OR=10.345, P=0.021) was independently associated with histological indication. Combining the clinical indication and/or AFP level > 7 ng/ml to predict liver histology, the sensitivity and the negative predictive value could improve from 86 to 94.4% and 66.7 to 81% respectively. AFP level is associated with liver histology in HBeAg-negative CHB. Serum AFP level can serve as a surrogate indicator to identify patients who need antiviral treatment.

• Comparison of self-reported cutaneous allodynia and brushing allodynia during migraine attacks.

  Authors: Chi-Hsiang Chou, Jong-Ling Fuh, Jaw-Ching Wu, Shuu-Jiun Wang

  Cephalalgia : an international journal of headache. 06/2010; 30(6):682-5.

  This study compares the results of brushing allodynia (BA) during migraine attacks to those of self-reported cutaneous allodynia. We recruited 100 patients (20 with chronic migraine, 80 with episodicThis study compares the results of brushing allodynia (BA) during migraine attacks to those of self-reported cutaneous allodynia. We recruited 100 patients (20 with chronic migraine, 80 with episodic migraine) and performed a gauze-brushing test to detect BA. A previous experience of cutaneous allodynia was queried. Seventeen patients reported having allodynia before, whereas 22 patients exhibited BA. The frequency of self-reported allodynia (12.5% vs. 35.0%, p = .040) but not BA (21.3% vs. 25.0%, p = .765) differed between patients with episodic migraine and those chronic migraine. Patients with aura (N = 8) had a higher frequency of both self-reported allodynia (62.5% vs. 12.2%, p = .003) and BA (87.5% vs. 17.6%, p < .001) than those without aura (N = 92). Some allodynia symptoms, including avoidance of washing hair, touching the head, combing hair and lying on the site of head pain, were associated with BA (all p < .05). Our study showed that BA during migraine attacks correlated well with prior allodynia symptoms. The frequencies of BA and self-reported allodynia depend on the composition of different migraine subtypes and the timing of the gauze-brushing test.

• Magnetic resonance angiography in reversible cerebral vasoconstriction syndromes.

  Authors: Shih-Pin Chen, Jong-Ling Fuh, Shuu-Jiun Wang, Feng-Chi Chang, Jiing-Feng Lirng, Ying-Chen Fang, Ben-Chang Shia, Jaw-Ching Wu

  Annals of neurology. 05/2010; 67(5):648-56.

  To investigate the evolution and clinical significance of vasoconstriction on magnetic resonance angiography (MRA) in patients with reversible cerebral vasoconstriction syndromes (RCVS). PatientsTo investigate the evolution and clinical significance of vasoconstriction on magnetic resonance angiography (MRA) in patients with reversible cerebral vasoconstriction syndromes (RCVS). Patients with RCVS were recruited and followed up with MRA examinations until normalization of vasoconstriction or for 6 months. The vasoconstriction severity of the major cerebral arterial segments (M1, M2, A1, A2, P1, P2, and basilar artery) was scored on a 5-point scale: 0 (0-<10%), 1 (10-<25%), 2 (25-<50%), 3 (50-<75%), and 4 (> or =75%). Subjects with at least 1 segment with a vasoconstriction score > or =2 were eligible for the study. Initial mean scores of single or combined arterial segments were used to predict ischemic complications. Seventy-seven patients with RCVS (8 men/69 women; average age 47.7 +/- 11.6 years) finished the study with a total of 225 MRAs performed. The mean number of arterial segments involved was 5.3 +/- 3.0 in the initial MRA. Vasoconstriction scores reached their maximum 16.3 +/- 10.2 days after headache onset, close to the average timing of headache resolution (16.7 +/- 8.6 days). Vasoconstriction evolved in a parallel trend among different arterial segments. Seven (9.1%) patients developed posterior reversible encephalopathy syndromes (PRES). Six (7.8%) patients had ischemic stroke. A logistic regression model demonstrated that the M1-P2 combined score was associated with highest risk of PRES (odds ratio [OR], 11.6, p = 0.005) and ischemic stroke (OR, 3.4; p = 0.026). MRA evaluation in patients with RCVS is valid. Vasoconstriction was pervasive and outlasted headache resolution. Vasoconstrictions in M1 and P2 are important determinants for PRES and ischemic stroke.

• Reactivation of hepatitis B virus after transarterial chemo-embolization for hepatocellular carcinoma in one patient with negative hepatitis B surface antigen.

  Authors: Hung-Hsu Hung, Chien-Wei Su, Jaw-Ching Wu, Shou-Dong Lee

  Journal of hepatology. 03/2010; 52(3):463-5.

• Systemic amyloidosis manifesting as a rare cause of hepatic failure.

  Authors: Hung-Hsu Hung, De-Feng Huang, Cheng-Hwai Tzeng, Cheng-Hsi Su, Tung-Ping Su, Hung-Chieh Chen, Shyh-Haw Tsay, Han-Chieh Lin, Jaw-Ching Wu, Shou-Dong Lee, Chien-Wei Su

  Journal of the Chinese Medical Association : JCMA. 03/2010; 73(3):161-5.

  In 1854, the term "amyloid" was first used in the description of a liver specimen at autopsy by Virchow. The kidneys and heart are the most commonly involved organs in amyloidosis; liver andIn 1854, the term "amyloid" was first used in the description of a liver specimen at autopsy by Virchow. The kidneys and heart are the most commonly involved organs in amyloidosis; liver and gastrointestinal tract involvement is less common, and the symptoms are usually mild. Here, we report the case of a 57-year-old male patient who presented with oral hemorrhagic bullae, thrombocytopenia and jaundice. Disseminated intravascular coagulation profile was positive. Abdominal sonography showed ascites, and abdominal computed tomography disclosed heterogeneous enhancement of the liver, with focal low attenuation regions and splenomegaly with poor contrast enhancement. Liver decompensation was highly suspected. Diagnostic laparoscopy with liver biopsy and colonoscopic biopsy from the rectum were subsequently performed. Typical apple-green birefringence was demonstrated on polarized light microscopy by Congo red staining. Systemic amyloidosis was diagnosed and colchicine prescribed. However, liver function deteriorated and intermittent gastrointestinal bleeding was found during the patient's hospitalization. The patient died due to uncorrectable coagulopathy and massive gastrointestinal bleeding. The final diagnosis was idiopathic amyloidosis with hepatic failure. Although amyloidosis rarely presents with hepatic failure, it should be considered in patients with signs of liver decompensation. Clinicians should be aware of this rare but potentially lethal presentation and arrange appropriate treatment promptly.

• Hepatocellular carcinoma with presentation of budd-Chiari syndrome.

  Authors: Wei-Yu Kao, Hung-Hsu Hung, Hsueh-Chieh Lu, Han-Chieh Lin, Jaw-Ching Wu, Shou-Dong Lee, Chien-Wei Su

  Journal of the Chinese Medical Association : JCMA. 02/2010; 73(2):93-6.

  Budd-Chiari syndrome is defined as hepatic venous outflow obstruction at any level from the small hepatic veins to the junction of the inferior vena cava and the right atrium independent of theBudd-Chiari syndrome is defined as hepatic venous outflow obstruction at any level from the small hepatic veins to the junction of the inferior vena cava and the right atrium independent of the underlying disease. We report here a 40-year-old male patient who complained of abdominal fullness and bilateral lower leg edema for 1 month. A physical examination disclosed bilateral lower leg edema. Abdominal sonography revealed a small amount of ascites with thrombosis of the inferior vena cava and right hepatic vein. Viral hepatitis marker tests showed positive hepatitis B surface antigen. Tumor markers showed elevated serum a-fetoprotein levels. Computed tomography and magnetic resonance imaging confirmed hepatocellular carcinoma with inferior vena cava and right hepatic vein thrombosis. Therefore, hepatocellular carcinoma with Budd-Chiari syndrome was diagnosed. The patient was treated with intravenous heparin, which was then changed to oral warfarin. Although it is relatively rare, clinicians should be aware of hepatocellular carcinoma with Budd-Chiari syndrome when leg edema occurs without hypoalbuminemia in patients with chronic hepatitis B, because these patients are in the high-risk group for developing hepatocellular carcinoma. Regular follow-up of chronic hepatitis B, including biochemical and sonography surveillance, should be performed.

• Fibrosis and AST to platelet ratio index predict post-operative prognosis for solitary small hepatitis B-related hepatocellular carcinoma.

  Authors: Hung-Hsu Hung, Chien-Wei Su, Chiung-Ru Lai, Gar-Yang Chau, Che-Chang Chan, Yi-Hsiang Huang, Teh-Ia Huo, Pui-Ching Lee, Wei-Yu Kao, Shou-Dong Lee, Jaw-Ching Wu

  Hepatology international. 01/2010; 4(4):691-9.

  Although advanced liver fibrosis is crucial in the development of hepatocellular carcinoma (HCC) for patients with chronic hepatitis B, whether it is associated with the recurrence of HCC afterAlthough advanced liver fibrosis is crucial in the development of hepatocellular carcinoma (HCC) for patients with chronic hepatitis B, whether it is associated with the recurrence of HCC after resection remains obscure. This study was aimed to compare the outcomes for patients with minimal or advanced fibrosis in solitary small hepatitis B virus (HBV)-related HCC. This study enrolled 76 patients with small (<5 cm) solitary HBV-related HCC who underwent resection. The outcomes of patients with minimal and advanced fibrosis in non-tumor areas were compared. Serum markers were tested to assess the stage of hepatic fibrosis and to predict prognosis. Fourteen patients with an Ishak fibrosis score of 0 or 1 were defined as having minimal fibrosis; the remaining 62 patients were defined as having advanced fibrosis. During a follow-up period of 77.0 ± 50.7 months, 41 patients died. The overall survival rate was significantly higher (P = 0.018) and recurrence rate was lower (P = 0.018) for patients in the minimal fibrosis group. Aspartate aminotransferase-platelet ratio index (APRI) exhibited the most reliable discriminative ability for predicting advanced fibrosis. The overall survival rate was significantly higher (P = 0.003) and recurrence rate was lower (P = 0.005) for patients with an APRI of 0.47 or less. For patients with solitary small HBV-related HCC who underwent resection, minimal fibrosis is associated with a lower incidence of recurrence and with better survival. APRI could serve as a reliable marker for assessing hepatic fibrosis and predicting survival.

• Pro-205 of Large Hepatitis Delta antigen and Pro-62 of Major Hepatitis B Surface Antigen influence the Assembly of Different Genotypes of Hepatitis D Virus.

  Authors: Hsuan Hui Shih, Chiaho Shih, Hsei-Wei Wang, Chien-Wei Su, I-Jane Sheen, Jaw-Ching Wu

  The Journal of general virology. 11/2009;

  Hepatitis B surface antigen (HBsAg) is essential for the assembly and infection of hepatitis D virus (HDV). The assembly efficiency of genotype 1 HDV is higher than that of genotype 2, while the P62LHepatitis B surface antigen (HBsAg) is essential for the assembly and infection of hepatitis D virus (HDV). The assembly efficiency of genotype 1 HDV is higher than that of genotype 2, while the P62L of major HBsAg further compromises the assembly of genotypes 2 and 4 HDV. This study investigated the influences of proline residues in the carboxyl end of large hepatitis delta antigen (HDAg-L) on the assembly of HDV of different genotypes. Expression vectors containing the HDAg-L gene or full length HDV genome of genotypes 1, 2, or 4 were co-transfected with plasmids expressing the HBsAg proteins that bear either praline or leucine residues at position 62 (P62 or L62, respectively). Of the eight HDV genotypes, only genotype 1 has Pro-205 in HDAg-L, while genotypes 2 and 4 have Arg-205. The Arg-205 to Pro-205 substitution in HDV-2 and -4 markedly increased the assembly efficiencies of HDAg-L and whole HDV gnomes, even in the presence of HBsAg with Leu-62. In contrast, secreted genotype 1 HDV or HDAg-L was significantly reduced when arginine or alanine replaced Pro-205. When HBsAg contained Pro-62, the influence of Pro-205 on assembly decreased. In conclusion, both Pro-205 of the HDAg-L and Pro-62 of the major HBsAg play critical roles in the assembly of HDV of different genotypes. The presence of Pro-205 in genotype 1 HDV may account for its higher assembly efficiencies and wider distribution.

• Geographic variations of predominantly hepatitis C virus associated male hepatocellular carcinoma townships in Taiwan: identification of potential high HCV endemic areas.

  Authors: Wei-Wen Su, Chien-Hung Chen, Hans Lin, Sheng-Shun Yang, Ting-Tsung Chang, Ken-Sheng Cheng, Jaw-Ching Wu, Shun-Sheng Wu, Chuan-Mo Lee, Chi-Sin Changchien, Chien-Jen Chen, Jin-Chuan Sheu, Ding-Shinn Chen, Sheng-Nan Lu

  Hepatology international. 09/2009;

  PURPOSE: The proportion of B-HCC cases in Taiwan has progressively decreased over the last 20 years. It was not really due to an overall decrease in B-HCC but due to an increase in HCV-related HCC.PURPOSE: The proportion of B-HCC cases in Taiwan has progressively decreased over the last 20 years. It was not really due to an overall decrease in B-HCC but due to an increase in HCV-related HCC. The identification of potential HCV endemic areas in Taiwan has consequently become important. METHODS: Data were collected retrospectively from eight Taiwan medical centers from 1981 to 2001, the geographical variations of male C-HCC townships in Taiwan were illustrated on maps. Goodness of fit was used to compare the anti-HCV prevalence in townships and cities, with the mean anti-HCV prevalence for Taiwan as a whole. Township-, city-, and county-specific prevalence of anti-HCV was presented as the median, ranges, and SMRs. RESULTS: Geographic variation can be analyzed in only 263 townships and cities. The maps were designed on the basis of different SMRs. The mean anti-HCV prevalence for male HCC patients in Taiwan was 31.9% (95% confidence interval: 30.7-33.0). Twenty-five townships distributed throughout central-western and south-western Taiwan have significantly higher prevalence (P < 0.05) (12 townships SMR >/= 2; 13 townships 1.5 </= SMR < 2). Twenty-two townships have significantly lower prevalence (P < 0.05) (6 townships 0.5 </= SMR<1; 16 townships SMR < 0.5). Four different patterns of geographic variation in different counties were also noted and demonstrated. CONCLUSION: We successfully highlighted some potential high HCV endemic townships in Taiwan.

• Comprehensive analysis of the independent effect of twist and snail in promoting metastasis of hepatocellular carcinoma.

  Authors: Muh-Hwa Yang, Chih-Li Chen, Gar-Yang Chau, Shih-Hwa Chiou, Chien-Wei Su, Teh-Ying Chou, Wei-Li Peng, Jaw-Ching Wu

  Hepatology (Baltimore, Md.). 08/2009;

  The epithelial-mesenchymal transition (EMT) is critical for induction of invasiveness and metastasis of human cancers. In this study we investigated the expression profiles of the EMT markers, theThe epithelial-mesenchymal transition (EMT) is critical for induction of invasiveness and metastasis of human cancers. In this study we investigated the expression profiles of the EMT markers, the relationship between EMT markers and patient/tumor/viral factors, and the interplay between major EMT regulators in human hepatocellular carcinoma (HCC). Reduced E-cadherin and nonmembranous beta-catenin expression, the hallmarks of EMT, were shown in 60.2% and 51.5% of primary HCC samples, respectively. Overexpression of Snail, Twist, or Slug, the major regulators of EMT, was identified in 56.9%, 43.1%, and 51.4% of primary HCCs, respectively. Statistical analysis determined that Snail and Twist, but not Slug, are major EMT inducers in HCC: overexpression of Snail and/or Twist correlated with down-regulation of E-cadherin, nonmembranous expression of beta-catenin, and a worse prognosis. In contrast, there were no such significant differences in samples that overexpressed Slug. Coexpression of Snail and Twist correlated with the worst prognosis of HCC. Hepatitis C-associated HCC was significantly correlated with Twist overexpression. HCC cell lines with increased Snail and Twist expression (e.g., Mahlavu) exhibited a greater capacity for invasiveness/metastasis than cells with low endogenous Twist/Snail expression (e.g., Huh-7). Overexpression of Snail or/and Twist in Huh-7 induced EMT and invasiveness/metastasis, whereas knockdown of Twist or Snail in Mahlavu reversed EMT and inhibited invasiveness/metastasis. Twist and Snail were independently regulated, but exerted an additive inhibitory effect to suppress E-cadherin transcription. Conclusion: Our study provides a comprehensive profile of EMT markers in HCC, and the independent and collaborative effects of Snail and Twist on HCC metastasis were confirmed through different assays. (HEPATOLOGY 2009.).

• Risk factors for early and late recurrence in hepatitis B-related hepatocellular carcinoma.

  Authors: Jaw-Ching Wu, Yi-Hsiang Huang, Gar-Yang Chau, Chien-Wei Su, Chung-Ru Lai, Pui-Ching Lee, Teh-Ia Huo, I-Jane Sheen, Shou-Dong Lee, Wing-Yiu Lui

  Journal of hepatology. 07/2009;

  BACKGROUND/AIMS: Hepatitis B virus (HBV) levels correlate with the development of hepatocellular carcinoma (HCC), but the role of viral load in HCC recurrence after tumor resection remains unclear.BACKGROUND/AIMS: Hepatitis B virus (HBV) levels correlate with the development of hepatocellular carcinoma (HCC), but the role of viral load in HCC recurrence after tumor resection remains unclear. Herein we aimed to investigate the role of viral load in HCC recurrence following tumor resection. METHODS: From 1990 to 2002, 193 HBV-related HCC patients who underwent tumor resection in Taipei Veterans General Hospital were enrolled. Serum HBV DNA level and mutations were analyzed for association with early and late recurrence, together with other clinical variables. RESULTS: During a follow-up of 58.2+/-44 months, 134 patients had HCC recurrence. Multivariate analysis showed that multinodularity (Hazard ratio [HR], 95% confidence interval [CI]; 2.232, 1.021-4.878), macroscopic venous invasion (4.693, 1.645-13.391), AFP >20ng/ml (3.891, 1.795-8.475), and cut margin 1cm (3.333, 1.487-7.470) were correlated with early recurrence (within two years of operation) of HCC. In addition, multivariate analysis determined that Ishak hepatic inflammatory activity >6 (4.658, 1.970-11.017), multinodularity (3.266, 1.417-7.526), ICG-15 >10% (2.487, 1.095-5.650) and HBV DNA level >10(6) copies /ml (2.548, 1.040-6.240) were significantly associated with late recurrence (>two years after resection). Patients with high viral loads tended to have higher Ishak inflammatory (7.00+/-3.07 vs. 5.33+/-2.96, p=0.001) and fibrosis scores (4.17+/-2.01 vs. 3.20+/-2.41, p=0.007) than those with lower loads. CONCLUSIONS: Tumor factors were associated with early HCC recurrence while high viral loads and hepatic inflammatory activity were associated with late recurrence. Pre- and post-operative antiviral and anti-inflammatory therapies may be crucial in reducing late recurrence.

• Generation of cytotoxicity against hepatitis delta virus genotypes and quasispecies by epitope modification.

  Authors: Yi-Hsiang Huang, Jaw-Ching Wu, Wei-Li Peng, Teh-Ia Huo, Hsuan Hui Shih, Keng-Hsin Lan, Chien-Wei Su, Shou-Dong Lee

  Journal of hepatology. 03/2009;

  BACKGROUND/AIMS: Quasispecies are likely responsible for virus escape from host immune surveillance. The aim of this study was to enhance the immune response against varied sequences within the HDVBACKGROUND/AIMS: Quasispecies are likely responsible for virus escape from host immune surveillance. The aim of this study was to enhance the immune response against varied sequences within the HDV quasispecies in an attempt to control chronic delta hepatitis. METHODS: The HLA-A2 restricted peptides spanning aa 43-51 of HDAg and three variant peptides bearing single amino acid substitutions were synthesized. Their immunogenicity and capacity to induce effective CTL responses were studied in HHD-2 mice. RESULTS: Native HDV epitope produced limited cytotoxic immune response. Two modified HDV peptides (HDV 43-51 1Y; tyrosine substitution in positive 1, and 43-51 3A; alanine substitution in position 3) could enhance not only the binding affinity with HLA-A2.1 molecules but also the immunogenicity. Ex vivo interferon-gamma ELISPOT and CTL assays revealed that the two modified epitopes-induced CTLs had a higher functional avidity and produced stronger cytotoxicity to lyse constitutively HDAg-expressing Hep-G2 cells. Interestingly, the spectrums of the T cell receptor (TCR) cross-reactivity are broadened and response to multiple HDV variants by the enhanced epitopes immunization. CONCLUSIONS: The modified HDV peptides can enhance the immunogenicity and the induced CTLs can cross-react with multiple HDV variants. Combination with the two enhanced epitopes might be a potential immunotherapeutic agent to control HDV quasispecies in HLA-A2 chronic hepatitis D patients.