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Hepatocellular Carcinoma Mechanisms Associated with Chronic HCV Infection and the Impact of Direct-Acting Antiviral Treatment
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Carnitine and vitamin complex (Godex®) is widely used in patients with chronic liver disease who show elevated liver enzyme in South Korea. The purpose of this study is to identify the efficacy and safety of carnitine from entecavir combination therapy in Alanine aminotransferase (ALT) elevated Chronic Hepatitis B (CHB) patients.
130 treatment-naïve patients with CHB were enrolled from 13 sites. The patients were randomly selected to the entecavir and the complex of entecavir and carnitine. The primary endpoint of the study is ALT normalization level after 12 months.
Among the 130 patients, 119 patients completed the study treatment. The ALT normalization at 3 months was 58.9% for the monotherapy and 95.2% for the combination therapy (
ALT normalization rate was higher in carnitine complex combination group than entecavir group in CHB. Combination group was faster than entecavir mono-treatment group on ALT normalization rate. HBV DNA normalization rate and the serum HBV-DNA level were not changed by carnitine complex treatment.
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The aims of this study were (1) to identify the useful clinical parameters of noninvasive approach for distinguishing nonalcoholic steatohepatitis (NASH) from nonalcoholic fatty liver disease (NAFLD), and (2) to determine whether the levels of the identified parameters are correlated with the severity of liver injury in patients with NASH.
One hundred and eight consecutive patients with biopsy-proven NAFLD (age, 39.8±13.5 years, mean±SD; males, 67.6%) were prospectively enrolled from 10 participating centers across Korea.
According to the original criteria for NAFLD subtypes, 67 patients (62.0%) had NASH (defined as steatosis with hepatocellular ballooning and/or Mallory-Denk bodies or fibrosis ≥2). Among those with NAFLD subtype 3 or 4, none had an NAFLD histologic activity score (NAS) below 3 points, 40.3% had a score of 3 or 4 points, and 59.7% had a score >4 points. Fragmented cytokeratin-18 (CK-18) levels were positively correlated with NAS (
Serum fragmented CK-18 levels can be used to distinguish between NASH and NAFL. Further evaluation is required to determine whether the combined measurement of serum CK-18 and ferritin levels improves the diagnostic performance of this distinction.
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The distribution of hepatitis C virus (HCV) genotypes varies geographically. In Korea, genotypes 1 and 2 comprise more than 90% of HCV infections, while genotype 6 is very rare. This study compared the clinical and epidemiological characteristics of patients with genotype 6 HCV infection with those infected with HCV genotypes 1 and 2.
This was a prospective, multicenter HCV cohort study that enrolled 1,173 adult patients, of which 930 underwent HCV genotype analysis, and only 9 (1.0%) were found to be infected with genotype 6 HCV. The clinical and epidemiological parameters of the genotypes were compared.
The patients with genotype 6 HCV had a mean age of 41.5 years, 77.8% were male, and they had no distinct laboratory features. A sustained virologic response (SVR) was observed in four (67%) of six patients who received antiviral therapy. Risk factors such as the presence of a tattoo (n=6, 66.7%), more than three sexual partners (n=3, 33.3%), and injection drug use (n=3, 33.3%) were more common among genotype 6 patients than among genotypes 1 or 2.
The epidemiology and treatment response of patients infected with genotype 6 HCV differed significantly from those with genotypes 1 or 2, warranting continuous monitoring.
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Hepatocellular carcinoma (HCC) is the third most common cause of cancer deaths in the world. There have been many advances in the diagnosis of HCC during the last ten years, especially in the imaging techniques. The Korean Liver cancer study group (KLCSG), European Association for the Study of the Liver (EASL), American Association for the Study of Liver disease (AASLD), and Asian-Pacific Association for the Study of Liver (APASL) have made and changed the HCC guidelines with the advances in the imaging techniques and according to the results of the researches on HCC. We reviewed the changes of the imaging guidelines in HCC diagnosis according to the advances in the imaging techniques. Further studies will be necessary to resolve the controversies in the diagnosis of HCC smaller than 1 cm in size.
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Low-dose metronomic chemotherapy involves the frequent administration of comparatively low doses of cytotoxic agents with no extended breaks, and it may be as efficient as and less toxic than the conventional maximum tolerated dose therapy. This study evaluated the feasibility and therapeutic efficacy of metronomic chemotherapy in patients with advanced hepatocellular carcinoma (HCC) with major portal vein thrombosis (PVT).
Thirty consecutive HCC patients with major PVT with or without extrahepatic metastasis were prospectively allocated to metronomic chemotherapy consisting of epirubicin being infused through the correct hepatic artery at a dose of 30 mg/body surface area (BSA) every 4 weeks, and cisplatin (15 mg/BSA) and 5-fluorouracil (50 mg/BSA) every week for 3 weeks, with intervening 1 week breaks. The treatment response was assessed using response evaluation criteria in solid tumors (RECIST).
In total, 116 cycles of metronomic chemotherapy were administered to the 30 patients, with a median of 3 cycles given to individual patients (range, 1-15 cycles). Six patients (20.0%) achieved a partial response and six patients (20.0%) had stable disease. The median time to disease progression and overall survival were 63 days (range, 26-631 days) and 162 days (95% confidence interval; range, 62-262 days), respectively. Overall survival was significantly associated with baseline alpha-fetoprotein level (
Metronomic chemotherapy may be a safe and useful palliative treatment in HCC patients with major PVT.
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Pegylated interferon and ribavirin combination therapy is accepted as the standard antiviral treatment for chronic hepatitis C regardless of HCV genotype. This combination therapy achieves higher response rates than previous therapy, but, nevertheless, a large proportion of patients suffer from treatment failure or adverse events. Recent clinical studies of viral kinetics during antiviral treatment have led to the introduction of response-guided therapy, the concept of 'customized therapy depending on viral response', which focuses on modulation of the treatment period depending on the viral response to create a sustained viral response without unnecessary medication and costs. New upcoming direct-acting antivirals (DAAs) maximize response rate, and triple therapy including DAAs along with pegylated interferon and ribavirin combination therapy could soon be the standard therapy. In this article, we reviewed the factors affecting treatment, response guided treatment, retreatment after failure of standard treatment, management of adverse events during treatment, and new treatment options.
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Enhanced replication of hepatitis C virus (HCV) is well described in the setting of moderate to severe immunosuppression. The aims of this retrospective study were to determine the incidence of enhanced HCV replication in hepatocellular carcinoma (HCC) patients undergoing transarterial chemolipiodolization (TACL) and to identify the factors associated with enhanced replication of HCV. The clinical pattern of enhanced HCV replication was compared with hepatitis B virus (HBV) reactivation during TACL.
This study enrolled 49 anti-HCV-seropositive patients who were diagnosed with HCC between January 2005 and December 2010 and who underwent TACL using epirubicin and/or cisplatin with consecutive HCV RNA copies checked. For comparison, 46 hepatitis B surface antigen1-positive patients with HCC who were treated with TACL were also enrolled. The frequency, associated factors, and clinical outcomes of enhanced HCV replication were analyzed and compared with those of HBV reactivation during TACL.
Enhanced replication of HCV occurred in 13 (26.5%) of the 49 anti-HCV-seropositive patients during TACL. Of these 13 patients, 4 developed hepatitis, but none of the subjects developed decompensation due to the hepatitis. No significant clinical factors for enhanced HCV replication during TACL were found. Compared with HBV reactivation, the frequency of hepatitis attributed to enhanced HCV replication was significantly lower than that for HBV reactivation (8.2% vs. 23.9%,
TACL can enhance HCV replication; however, the likelihood of hepatitis and decompensation stemming from enhanced HCV replication was lower than that for HBV reactivation in patients undergoing TACL.
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E-cadherin is involved in intercellular binding and cellular polarity formation. Snail is a key regulator of the epithelial-mesenchymal transition and is closely associated with tumor invasiveness due to its ability to suppress E-cadherin expression. We investigated the expressions of E-cadherin and Snail in hepatocellular carcinoma (HCC) tissue to determine the clinical significance of these proteins in HCC.
Immunohistochemistry was used to examine the expressions of E-cadherin and Snail in resected tissues from 59 patients diagnosed with HCC. We also evaluated the relationship between the expressions of these two molecules in HCC tissue and clinicopathologic factors in the patients.
Immunohistochemistry showed that Snail was stained in 20.3% of the HCC tissues and 3.4% of noncancerous tissues. Snail was not stained in the area of E-cadherin expression. The expression of Snail in the HCC tissue was associated with poorly differentiated HCC (
The expression of Snail in HCC tissue was associated with decreased expression of E-cadherin and poorly differentiated HCC. The expression of Snail without E-cadherin staining in HCC was associated with postoperative recurrence.
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Transarterial chemoembolization (TACE) has long been used as a palliative therapy for unresectable hepatocellular carcinoma (HCC). High-dose hepatic arterial infusion chemotherapy (HAIC) has showed favorable outcomes in patients with intractable, advanced HCC. The aim of this study was to compare the effectiveness and safety of high-dose HAIC and conventional TACE using doxorubicin for advanced HCC.
The high-dose HAIC group comprised 36 patients who were enrolled prospectively from six institutions. The enrollment criteria were good liver function, main portal vein invasion (including vascular shunt), infiltrative type, bilobar involvement, and/or refractory to prior conventional treatment (TACE, radiofrequency ablation, or percutaneous ethanol injection), and documented progressive disease. Patients received 5-fluorouracil (500 mg/m2 on days 1~3) and cisplatin (60 mg/m2 on day 2 every 4 weeks) via an implantable port system. In the TACE group, 31 patients with characteristics similar to those in the high-dose HAIC group were recruited retrospectively from a single center. Patients underwent a transarterial infusion of doxorubicin every 4~8 weeks.
Overall, 6 patients (8.9%) achieved a partial response and 20 patients (29.8%) had stable disease. The
objective
response rate (complete response+partial response) was significantly better in the high-dose HAIC group than in the TACE group (16.7% vs. 0%,
High-dose HAIC appears to improve the tumor response and survival outcome compared to conventional TACE using doxorubicin in patients with intractable, advanced HCC.
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