• Alanine aminotransferase
• Biomarker
• K359R
• Missense SNPs
• PRKCG
• Serine-threonine kinases

It is generally accepted that the incidence of hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-associated patients is higher than that in hepatitis B virus (HBV)-associated patients. The reason why this difference in the incidence of HCC occurs in patients with HBV and HCV infections remains unclear. We report the possibility that the contributing power of inflammation, which is the main risk factor for developing HCC, may be different with HBV and HCV infections.

To investigate this, we surveyed the hazard ratio of inflammation for HCC development which was identified by serum alanine aminotransferase (ALT) levels between patients with HBV and HCV infections.

The PubMed database was searched (2001-2021) for studies published in English regarding the incidence of HCC identifying 8924 HBV-and 7376 HCV- infected patients. From these studies, interferon-treated patients with both HBV and HCV infections were excluded. Furthermore, in HBV patients, those administered nucleos(t)ide analogues were excluded, and in HCV patients, those administered direct acting antivirals were also excluded. Studies citing hazard ratios of HCC regarding inflammation (serum elevated alanine aminotransferase levels) were selected. Finally, there were 14 studies of HBV- infected patients and 8 studies of HCV-infected patients. We calculated the hazard ratio in patients in an inflammatory state (serum ALT levels were above the normal range).

In the 14 studies of HBV patients, the average hazard ratio (HR) of elevated ALT for developing HCC was 2.74 [1.98-3.77] and that in the 8 studies of HCV-infected patients was 5.51 [3.08-9.83]. The HR of inflammation for HCC development in HCV-associated liver diseases is about twice that in HBV-associated liver diseases. HR in HCV-infected patients was significantly (P = 0.0391) higher than that in HBV-infected patients. In hepatitis B patients, the abnormal range adopted was 28-45 IU/L, and in hepatitis C patients, it was 20-50 IU/L. It was demonstrated that the abnormal ALT levels adopted in hepatitis B and C patients were very similar in this series.

The difference in the incidence of HCC development between HBV and HCV patients may depend on the difference in the hazard risk of ALT between HBV and HCV infections.

• Hazard ratio of alanine aminotransferase
• Hepatitis B virus
• Hepatitis C virus
• Hepatocellular carcinoma
• Elevated alanine aminotransferase

• Autoimmune liver disease
• Hepatitis B virus-related chronic hepatitis
• Hepatitis C virus-related chronic hepatitis
• Hepatocellular carcinoma
• Tumor microenvironment

• Carcinoma, Hepatocellular
• Forkhead Transcription Factors
• Humans
• Immunotherapy
• Liver Neoplasms
• T-Lymphocytes, Regulatory
• Transcription Factors
• Tumor Microenvironment

AIM: To analyze the risk factors of hepatocellular carcinoma (HCC) recurrence after radiofrequency ablation (RFA) treatment with HCV-associated hepatitis.

METHODS: Twenty-six patients with HCV-associated HCC who were followed-up for more than 12 mo were selected for this study. Risk factors for distant intrahepatic recurrences of HCC were evaluated for patients in whom complete coagulation was achieved without recurrence in the same subsegment as the primary nodule. Twelve clinical and tumoral factors were examined: Age, gender, nodule diameter, number of primary HCC nodule, Child-Pugh classification, serum platelet, serum albumin, serum AST, post RFA AST, serum ALT, post RFA ALT, post RFA treatment.

RESULTS: Distant recurrences of HCC in remnant liver after RFA were observed in 14 cases and in the number of primary HCC nodules (P = 0.047), and the serum platelets (P = 0.030), the clear difference came out by the recurrence group and the non-recurrence group. The cumulative recurrence rates after 1 and 2 years were 30.8% and 86.8%, respectively for primary multinodular HCC, and 15.4% and 29.5% respectively, for primary uninodular HCC. In addition the 1-year recurrence rates for patients with serum albumin more than 3.4 g/dL and less than 3.4 g/dL were 23.1% for both, but the 2-years recurrence rates were 89.0% and 23.1%, respectively. The number of primary HCC nodules (relative risk, 6.970; P = 0.016) were found to be a statistically significant predictor for poor distant intrahepatic recurrence by univariate analysis.

CONCLUSION: Patients who have multiple HCC nodules, low serum platelets and low serum albumin accompanied by HCV infection, should be carefully followed because of the high incidence of new HCC lesions in the remnant liver, even if coagulation RFA is complete.

• Hepatocellular carcinoma
• Radiofrequency ablation

• Aged
• Carcinoma, Hepatocellular/epidemiology
• Carcinoma, Hepatocellular/surgery
• Carcinoma, Hepatocellular/virology
• Catheter Ablation
• Female
• Hepatitis C, Chronic/epidemiology
• Humans
• Incidence
• Liver Neoplasms/epidemiology
• Liver Neoplasms/surgery
• Liver Neoplasms/virology
• Male
• Middle Aged
• Multivariate Analysis
• Neoplasm Recurrence, Local/epidemiology
• Prognosis
• Risk Factors

AIM: The survival time of patients with hepatocellular carcinoma (HCC) after resection is hard to predict. Both residual liver function and tumor extension factors should be considered. A new scoring system has recently been proposed by the Cancer of the Liver Italian Program (CLIP). CLIP score was confirmed to be one of the best ways to stage patients with HCC. To our knowledge, however, the literature concerning the correlation between CLIP score and prognosis for patients with HCC after resection was not published. The aim of this study is to evaluate the recurrence and prognostic value of CLIP score for the patients with HCC after resection.

METHODS: A retrospective survey was carried out in 174 patients undergoing resection of HCC from January 1986 to June 1998. Six patients who died in the hospital after operation and 11 patients with the recurrence of the disease were excluded at 1 mo after hepatectomy. By the end of June 2001, 4 patients were lost and 153 patients with curative resection have been followed up for at least three years. Among 153 patients, 115 developed intrahepatic recurrence and 10 developed extrahepatic recurrence, whereas the other 28 remained free of recurrence. Recurrences were classified into early (≤ 3 year) and late (> 3 year) recurrence. The CLIP score included the parameters involved in the Child-Pugh stage (0-2), plus macroscopic tumor morphology (0-2), AFP levels (0-1), and the presence or absence of portal thrombosis (0-1). By contrast, portal vein thrombosis was defined as the presence of tumor emboli within vascular channel analyzed by microscopic examination in this study. Risk factors for recurrence and prognostic factors for survival in each group were analyzed by the χ² test, the Kaplan-Meier estimation and the COX proportional hazards model respectively.

RESULTS: The 1-, 3-, 5-, 7-, and 10-year disease-free survival rates after curative resection of HCC were 57.2%、28.3%、23.5%、18.8% and 17.8%, respectively. Median survival time was 28, 16, 10, 4, and 5 mo for CLIP score 0, 1, 2, 3, and 4 to 5, respectively. Early and late recurrence developed in 109 patients and 16 patients respectively. By the χ² test, tumor size, microsatellite, venous invasion, tumor type (uninodular, multinodular, massive), tumor extension (≤ or > 50% of liver parenchyma replaced by tumor), TNM stage, CLIP score, and resection margin were the risk factors for early recurrence, whereas CLIP score and Child-Pugh stage were significant risk factors for late recurrence. In univariate survival analysis, Child-Pugh stages, resection margin, tumor size, microsatellite, venous invasion, tumor type, tumor extension, TNM stages, and CLIP score were associated with prognosis. The multivariate analysis by COX proportional hazards model showed that the independent predictive factors of survival were resection margins and TNM stages.

CONCLUSION: CLIP score has displayed a unique superiority in predicting the tumor early and late recurrence and prognosis in the patients with HCC after resection.

• Adolescent
• Adult
• Aged
• Carcinoma, Hepatocellular/pathology
• Carcinoma, Hepatocellular/surgery
• Child
• Disease-Free Survival
• Female
• Humans
• Liver Neoplasms/pathology
• Liver Neoplasms/surgery
• Male
• Middle Aged
• Neoplasm Recurrence, Local
• Neoplasm Staging
• Predictive Value of Tests
• Prognosis
• Retrospective Studies
• Risk Factors

• carcinoma, hepatocellular/etiology
• carcinoma, hepatocellular/surgery
• carcinoma, hepatocellular/drug therapy
• liver neoplasms/etiology
• liver neoplasms/surgery
• liver neoplasms/drug therapy
• human
• review

• Animals
• Carcinoma, Hepatocellular/etiology
• Carcinoma, Hepatocellular/secondary
• Carcinoma, Hepatocellular/therapy
• Humans
• Liver Neoplasms/etiology
• Liver Neoplasms/secondary
• Liver Neoplasms/therapy