Wei-Yu Kao

Hepatic resection can provide long-term survival of patients with non-early-stage hepatocellular carcinoma: extending the indication for resection?

BACKGROUND Indications for resection of non-early-stage hepatocellular carcinoma (HCC) remain controversial. This study aimed to identify factors that affect outcome of patients with Barcelona Clinical Liver Cancer Classification (BCLC) stage B or stage C HCC after hepatic resection. METHODS From 1991 to 2006, 478 patients with HCC (BCLC stage B, n = 318 and BCLC stage C, n = 160) who underwent resection were enrolled. Factors in terms of overall survival and recurrence were analyzed. RESULTS After a median follow-up of 29.5 months, 304 patients had died. The cumulative overall survival rate at 5 years was 46.5% in BCLC stage B patients and 29.1% in stage C patients (P < .001). Multivariate analysis disclosed that serum albumin levels ≤4 g/dL, indocyanine green retention rate at 15 minutes >10%, serum creatinine >1.2 mg/dL, multinodularity, Edmondson stage III or IV in tumor cell differentiation, and the presence of macroscopic vascular invasion were independent risk factors of poor overall survival. There were 331 patients with tumor recurrence after resection. Recurrence rate was less in BCLC stage B than that in BCLC stage C (P = .001). Multivariate analysis showed that serum albumin level ≤4 g/dL, multinodularity, cut margin ≤1 cm, and Edmondson stage III or IV were associated with the recurrence of HCC. CONCLUSION Hepatic resection can provide long-term survival benefit in selected BCLC stage B or C patients with compensated liver function, especially in those presenting with a single neoplasm without vascular invasion.

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

Goals: To evaluate the impact of age on the prognosis of patients with hepatocellular carcinoma (HCC) undergoing percutaneous radiofrequency ablation (RFA). Background: Whether age plays an important role in the outcomes of HCC after RFA remains controversial. Study: 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. Results: 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, &agr;-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 ⩽105/mm3, AFP >20 ng/mL, multinodularity, and tumor size >2 cm were the independent risk factors predicting recurrence. Conclusions: 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.

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

Objective 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 to evaluate the prognostic factors associated with the prognosis in patients with HCC undergoing RFA. Methods The study enrolled 190 treatment-naïve patients with HCC (<5 cm). Factors were analyzed in terms of overall survival and recurrence. Results 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. Conclusion 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.

Inverse association between hepatitis B virus infection and fatty liver disease: a large-scale study in populations seeking for check-up.

Background Although many studies have attempted to clarify the association between hepatitis B virus (HBV) infection and fatty liver disease, no prior studies have emphasized the relationship of HBV and fatty liver regarding different demographics of age and body mass index (BMI). Aim To investigate the correlation of HBV and fatty liver in the different demographics of age and BMI. Methods We enrolled consecutive subjects who had received health check-up services at the Taipei Veterans General Hospital from 2002 to 2009 and ultrasonography was used to diagnose fatty liver according to the practice guidelines of the American Gastroenterological Association. Results Among the 33,439 subjects enrolled in this study, fatty liver was diagnosed in 43.9% of the population and 38.9% of patients with chronic HBV infection. Multivariate analysis showed that BMI, age, waist circumference, systolic blood pressure, fasting glucose, cholesterol, alanine aminotransferase (ALT) levels, and platelet counts were positively associated, while hepatitis B surface antigen (HBsAg) positivity was inversely associated with fatty liver, especially for subjects with BMI>22.4 kg/m2 and age>50 years. On the contrary, HBV infection was positively correlated with the presence of elevated serum ALT levels in subjects with fatty liver disease regardless of their age and BMI. Conclusions Metabolic factors are important determinants for the prevalence of fatty liver. Patients with HBV infection were inversely associated with fatty liver disease than the general population, especially in older and obese patients. Furthermore, metabolic factors and HBV infection were associated with elevated serum ALT levels in fatty liver disease.

Updated thresholds for serum alanine aminotransferase level in a large-scale population study composed of 34 346 subjects

The sensitivity of current upper limit of normal (ULN) of serum alanine aminotransferase (ALT) levels for detecting chronic liver disease has been challenged recently.

Cancer risk in patients with pyogenic liver abscess: a nationwide cohort study

There has been no large‐scale population‐based study on the relationship between pyogenic liver abscesses (PLA) and subsequent cancer risk.

Prognostic significance of computed tomography scan-derived splenic volume in hepatocellular carcinoma treated with radiofrequency ablation.

Goals: To evaluate the clinical implication of splenic volume measured by computed tomography (CT) scan in hepatocellular carcinoma (HCC) patients undergoing percutaneous radiofrequency ablation (RFA). Background: Splenomegaly is an important sign of portal hypertension and poor liver function in patients with advanced liver disease. But whether it could predict the prognosis of patients with HCC is still obscure. Study: We enrolled 161 treatment-naive HCC patients. Splenomegaly was defined as splenic volume >300 mL by CT scan and its impact on prognosis was analyzed. Moreover, noninvasive serum markers were validated to predict splenomegaly. Results: A total of 78 patients were with splenomegaly, while the remaining 83 patients had normal splenic volume at the time of receiving RFA. After a median follow-up of 38.1±20.8 months, 41 patients died. The cumulative 5-year survival rates were 54.8% and 77.8% in patients with splenomegaly and in those with normal splenic volume, respectively (P=0.003). By multivariate analysis, age 65 years and older, serum albumin levels ⩽3.5 g/dL, and splenic volume >300 mL were independent risk factors associated with poor overall survival after RFA. For predicting splenomegaly by noninvasive serum markers, platelet count yielded the highest area under the curve from corresponding receiver operating curves with a level of 0.868 at a cut-off value of 11,7000/mm3. Conclusions: HCC patients with splenomegaly measured by CT scan have relatively poorer liver functional reserve than those with normal splenic volume. Splenomegaly is an independent risk factor predicting overall survival for patients with small HCC undergoing RFA.

Second primary cancers in patients with hepatocellular carcinoma: a nationwide cohort study in Taiwan

There has been no large‐scale population‐based study on the incidence and clinical manifestations of second primary cancer (SPC) after diagnosis of hepatocellular carcinoma (HCC).

Hepatocellular Carcinoma With Presentation of Budd-Chiari Syndrome

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 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.

Letter: the role of direct-acting anti-virals in determining the risk of hepatocellular carcinoma development in patients with hepatitis C virus-induced cirrhosis

EDITORS, We read the excellent paper by Mettke et al about the impact of direct-acting anti-virals (DAA) therapy for chronic hepatitis C virus (HCV) infection on the risk of hepatocellular carcinoma (HCC) development in cirrhotic patients, with great interest. Whether DAAs would alter the risk of HCC development and recurrence is still under active debate. The authors demonstrated that patients treated with DAAs had a comparable short-term incidence rate of HCC as compared to those in the historical control cohort. Of note, DAA-treated patients seemed to have a lower risk of HCC development than the untreated patients after 15 months following the initiation of DAA therapy. The findings are interesting and novel, and could provide an important message for clinical practice. Nevertheless, we have several comments. First, this study only assessed the baseline characteristics for the prediction of the risk for HCC development. Yu and colleagues proposed a non-invasive fibrosis index; the aspartate aminotransferase-to-platelet ratio index assessed 6 months after end of treatment (APRI-M6) which could predict the risk of HCC development in interferon-treated patients. The dynamic change of hepatic fibrosis, liver functional reserve, serum alpha-fetoprotein levels, as well as metabolic factors may also play important roles in determining the long-term prognosis of patients with HCV-related liver cirrhosis after anti-viral therapy. Second, the majority of patients in this study had well-preserved liver function (around 80% were in the Child-Pugh grade A and less than 5% had a MELD score > 10). However, not all of the patients with HCV-related liver cirrhosis who achieve sustained virological response (SVR) after anti-viral therapy are the same. Several recent studies have further disclosed that although most of patients who achieved SVR after DAA had a reduction of hepatic venous pressure gradient (HVPG) value, these effects were more significant in patients with a lower baseline HVPG levels. Moreover, clinical significant portal hypertension (CSPH) persisted in most of the patients; and 17% of patients even had an increase in HVPG values despite achieving SVR, especially for those with a baseline HVPG level > 15 mm Hg. As CSPH was crucial for HCC development in patients with SVR, the effects of DAAs in reducing HCC risk in patients with liver decompensation need more prospective studies to be validated. Third, although the long-term incidence of HCC seemed to be higher in the control group as compared to the DAA-treated group, the survival rates were comparable between the 2 groups of patients. It might reflect the facts that most of the patients (70%) in this study were diagnosed with HCC at an early stage (BCLC stage A) by surveillance. Consequently, 13 (65%) patients underwent curative therapies (such as liver transplantation, resection surgery and local ablation therapy), which could provide a long-term survival benefit for HCC patients. The findings indicate that strict surveillance for HCC is crucial even after the virus has been eradicated.