Percutaneous microwave ablation for HCV-related hepatocellular carcinoma: Efficacy, safety, and survival.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) has a poor prognosis if managed late. Percutaneous microwave ablation (MWA) emerged as one of the top therapeutic decisions for non-surgical patients. The aim of the present study aim was to evaluate the efficacy, side effects, and survival after MWA of hepatitis C virus (HCV)-related HCC tumors with spectrum sizes up to 5 cm. MATERIALS AND METHODS: Fifty-nine patients with early HCC were treated in the Hepatology Department using percutaneous MWA. Patients were assessed for side effects and efficacy that includes the rate of complete ablation, primary or de novo recurrence, and survival. RESULTS: Complete ablation was achieved in 57 (96.6%) patients treated by MWA, with a minor complication rate of 3.3% (n=2) including liver abscess formation and abdominal skin burn. The ablation rates in lesions <3 versus 3-5 cm were not different. Of the patients, 3 (5%) had primary recurrence in the treated HCC tumors, de novo lesions (secondary recurrence) developed in 8 (13.5%, 5 of them >3 cm), and 2 (3.3%) had malignant portal vein thrombosis. The survival rates were 95.4% and 69% at 1 and 2 years, respectively. CONCLUSION: Percutaneous MWA had achieved a safe and effective treatment with good overall survival in patients with HCV-related HCC.

Entecavir and other nucleos(t)ide analogs prophylaxis in hepatitis B virus-related liver transplantation: long-term efficacy and safety.

BACKGROUND AND AIM: Although hepatitis B virus (HBV) recurrence after liver transplantation (LTx) has been reduced since the application of the combination of hepatitis B immunoglobulin (HBIG) and nucleos(t)ide analogs (NUCs), the optimum regimen to prevent HBV recurrence with LTx favorable outcome is still not clear. AIM: The aim was to evaluate the efficacy and safety of NUCs prophylaxis (±HBIG) against HBV recurrence after LTx. PATIENTS AND METHODS: This was a retrospective cohort-longitudinal study on 44 HBV-related post-LTx patients on anti-HBV prophylactic therapy. They included the entecavir (ETV)-based (n=34, 30 males) and the other NUC-based (n=10, 7 males) groups±HBIG. RESULTS: The median age was 63.5 (60-70) years in ETV and 62.5 (55-65) years in other NUCs groups. The mean follow-up duration was 6.09±1.83 years in ETV-based group and 6.3±1.89 years in other NUCs-based group. The mean ETV duration was 3.47±3.04 years. In ETV+HBIG patients, none of them developed HBV recurrence throughout the ±8 years. In the 14 patients on ETV+other NUC+HBIG, four developed HBsAg positive and then transformed to HbsAb positive at the end of ±8 years without hepatitis or detectable HBV-DNA. Liver graft function showed nonsignificant difference for ETV-based patients, in comparison with other NUC groups (P=0.09). With subdivision, the graft function was maintained significantly better in ETV+HBIG or other NUCs+HBIG (P=0.04) groups. None of our patients reported NUCs-related complications or adverse effects. CONCLUSION: ETV and other NUCs were effective and safe as a long-term prophylaxis of HBV recurrence after LTx, leading to a good graft function. HBsAg temporally reappeared in a minority of patients, where all showed HBsAb seroconversion without detectable HBV-DNA or clinical hepatitis.

Transforming growth factor-beta1 gene C-509T and T869C polymorphisms as possible risk factors in rheumatic heart disease in Egypt.

OBJECTIVE: The objective of this study was to investigate the possible relationship between the TGF-beta1 gene C-509T and T869C polymorphisms and rheumatic heart disease (RHD), as well as their clinical significance. METHODS: Seventy-three patients with RHD diagnosed by echocardiography (mean age 31.7 +/- 14.7 y, male: female ratio 20:53) and, fifty-five age and sex-matched unrelated healthy volunteers (normal control) were included. Patients were classified according to age into children (n=24, mean age 14.4 +/- 3.1 y, and adults (n=49, mean age 40.2 +/- 9.9 y). TGF-beta genomic DNA was extracted and amplified using primers specific for C-509T and,T869C polymorphisms. Genotyping was performed by restriction fragment length polymorphism analysis (RFLP). RESULTS: T869C TT genotype was found significantly more frequently in RHD (total population) (OR: 3.27; [95% CI: 1.13-9.46]; P = 0.02), in children (OR: 6.0; [95% CI: 1.74-20.65]; P = 0.002) and in patients with combined valvular disease (CVD) (OR: 4.06; [95% CI: 1.32-12.48]; P = 0.01) compared to control subjects. 869T allele frequency was significantly higher in adults (OR: 1.89; [95% CI: 1.07-3.33]; P = 0.02), children (OR: 2.32; [95% CI: 1.16-4.66]; P = 0.0 1) and the total population (OR: 2.02; [95% CI: 1.21-3.39]; P = 0.006). C-509T genotypes distributions were not different between RHD patients and control subjects. However, -509T allele seems to confer susceptibility to RHD (OR: 1.78; [95% CI: 1.02-3.11]; P = 0.04). Both adults and children showed no significant difference in the genotypes distribution and allelic frequencies of TGF-beta1 C-509T polymorphism. In addition, genotype distribution and allelic frequencies of C-509T or T869C did not have any relation with the severity of the valvular affection. CONCLUSION: TGF-beta1 T869C TT genotype, 869T allele and 509T allele are possible risk factor for RHD in Egypt. Future studies on larger populations are warranted.

Nucleotide mutations associated with hepatitis B e antigen negativity.

One hundred and forty four patients with chronic hepatitis B were tested to identify new mutations associated with hepatitis B e antigen (HBeAg) negativity, using a full genome sequence analysis. All the patients were Chinese and had hepatitis B virus infection of genotype C. Patients with none of the pre-core or core promoter mutations were significantly (P < 0.001) less common in the group with anti-HBe (13%) than in the group with HBeAg (56%). The complete nucleotide sequence was determined in four anti-HBe-positive patients who had neither pre-core nor core promoter mutations and in five HBeAg-positive patients who also had neither of these mutations (the groups were matched for age and sex). Six mutations were found to be significantly more common in the former group than in the latter: G529A (3/4 vs. 0/5), C934A (4/4 vs. 1/5), A1053G (4/4 vs. 1/5), G1915T/A (4/4 vs. 0/5), T2005C/A (4/4 vs. 0/5), and C3026T (3/4 vs. 0/5). Three of the six mutations were significantly more common in the four anti-HBe-positive patients who had neither pre-core nor core promoter mutations, compared to 11 HBeAg-positive patients who had pre-core and core promoter mutations, and also compared to 15 anti-HBe-positive patients who had pre-core and core promoter mutations, suggesting further the specificity of these mutations. Of the six mutations, two resulted in amino acid substitution in the polymerase protein, and one is located near the enhancer I region. The results suggest that the six newly discovered mutations are associated with HBeAg negativity.

Assessment of KL-6 as a tumor marker in patients with hepatocellular carcinoma.

AIM: To investigate the clinical significance of KL-6 as a tumor marker of HCC in two different ethnic groups with chronic liver disease consecutively encountered at outpatient clinics. METHODS: Serum KL-6 was measured by the sandwich enzyme immunoassay method using the KL-6 antibody (Ab) as both the capture and tracer Ab according to the manufacturer's instructions (Eisai, Tokyo, Japan). Assessment of alpha fetoprotein (AFP) and protein induced vitamin K deficiency or absence (PIVKA-II) was performed in both groups using commercially available kits. RESULTS: A significantly higher mean serum KL-6 (556+/-467 U/L) was found in HCC in comparison with non-HCC groups either with (391+/-176 U/L; P<0.001) or without (361+/-161 U/L; P<0.001) liver cirrhosis (LC). Serum KL-6 level did not correlate with either AFP or PIVKA-II serU/Levels. Using receiver operating curve analysis for KL-6 as a predictor for HCC showed that the area under the curve was 0.574 (95%CI = 0.50-0.64) and the KL-6 level that gave the best sensitivity (61%) was found to be 334 U/L but according to the manufacturer's instructions; a cut-off point of 500 U/L was used that showed the highest specificity (80%) in comparison with AFP and PIVKA-II (78% vs 72% respectively). Combining the values of the three markers improved specificity of AFP for HCC diagnosis from 78% for AFP alone; 93% for AFP plus PIVKA-II to 99% for both plus KL-6 value (P<0.001). Mean serum alkaline phosphatase level was significantly higher in KL-6 positive (564+/-475) in comparison with KL-6 negative (505+/-469) HCC patients (P = 0.021), but such a difference was not found among non-HCC corresponding groups. CONCLUSION: KL-6 is suggested as a tumor for HCC. Its positivity may reflect HCC-associated cholestasis and/or local tumor invasion.

Hepatocellular carcinoma: recent trends in Japan.

During the past 20 years, primary liver cancer, 95% of which is hepatocellular carcinoma (HCC), has ranked third in men and fifth in women as a cause of death from malignant neoplasm in Japan. The numbers of deaths and death rate from HCC showed a sharp increase beginning in 1975. Although both hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are important causes, HCV-related HCC has accounted for most of the recent increase and now represents 75% of all HCC in Japan. Geographically, HCC is more frequent in western than eastern Japan, and the death rate of HCC in each prefecture correlates with prevalence of anti-HCV. Among patients with HCV-related HCC, a history of blood transfusion was a relatively important source of infection in the 1990s, whereas community-acquired infections increased after 2000. There was a negative correlation between the duration from onset of infection to development of HCC and the age at onset. Interferon therapy for chronic hepatitis C has reduced the risk for HCC, indicating that early detection of HCV carriers and better treatment will contribute to improved outcomes. Nationwide screening for HCV and HBV began in 2002 in Japan, and reduction of HCC is anticipated. Further research should focus on mechanisms of carcinogenesis by HCV and HBV, development of more effective treatments, and establishment of early detection and treatment approaches. Better understanding of HCC unrelated to HCV and HBV and possibly because of steatohepatitis and diabetes should also be a major concern in future studies.

Factors predisposing to the occurrence of cryoglobulinemia in two cohorts of Egyptian and Japanese patients with chronic hepatitis C infection: ethnic and genotypic influence.

The association between cryoglobulinemia and hepatitis C virus (HCV) infection has been reported. However, the factors underlying its wide variation of occurrence have not yet been well identified. To investigate this, cryoglobulinemia was studied in four cohorts of Egyptian and Japanese patients. Fifty Egyptian patients with chronic hepatitis C, infected with genotype 4 (the predominant HCV genotype in Egypt), were compared with 50 age- and sex-matched Japanese patients, infected with HCV genotype 1b (the predominant HCV genotype in Japan). Thirty-two Egyptian and 30 age- and sex-matched Japanese patients with chronic hepatitis B were included as controls. All patients were noncirrhotic. Antinuclear antibody (ANA), immunoglobulins (Ig), and cryoglubulins were assessed. Results showed a significantly higher prevalence of cryoglobulinemia in chronic hepatitis C Japanese genotype 1b (40%) as compared with Egyptian genotype 4 (14%), P = 0.003, while no difference was found between Japanese (17%) and Egyptian chronic hepatitis B controls (13%). Symptomatic cryoglobulinemia was more prevalent in the Japanese than in the Egyptian chronic hepatitis C group (10% vs. 4%), but the difference was not statistically significant. Univariate analysis showed no association between cryoglobulinemia and either age, sex, alanine aminotransferase level, or HCV viral load in Japanese or Egyptian patients, while the mean IgM level was significantly higher in the cryoglobulin-positive than in the cryoglobulin-negative chronic hepatitis C patients in each group (P = 0.003 and 0.017, respectively). Cryoglobulinemia was found to be significantly associated with both high IgG level (P = 0.020), and positive ANA (P < 0.001) in Japanese patients with chronic hepatitis C, genotype 1b but not in Egyptians with genotype 4. Multivariate analysis showed that the only factors predisposing to cryoglobulinemia were Japanese ethnicity with HCV genotype1b (P = 0.002, OR = 2.56), high IgM level of >245 mg/dl (P = 0.018, OR = 2.05) and female gender (P = 0.040, OR = 1/0.66). In conclusion, cryoglobulinemia is prevalent in Japanese patients with chronic hepatitis C infected with genotype 1b, but cryoglobulinemia is not common in Egyptians with HCV genotype 4. Although it was not possible to evaluate ethnicity and HCV genotype separately in this study, HCV genotype 1b appears to predispose more to cryoglobulinemia than does genotype 4. Female gender and high serum IgM level were also related.

Clinical significance of T.T. virus infection in maintenance hemodialysis patients of an endemic area for hepatitis C infection.

Clinical significance of TTV infection was analyzed in Egyptian hemodialysis (HD) patients. Forty-seven Egyptian patients on maintenance HD and 50 age-matched volunteer blood donors were investigated. TT virus (TTV) DNA detection and genotyping were performed using a semi-nested polymerase chain reaction with specific primers. The prevalence of TTV DNA in patients on HD (66%) was significantly (P<0.001) higher than in blood donors (24%) with genotype 1b predominance (89%) in both. Clinical background including mean age, sex, history of blood transfusion, and positive markers for either hepatitis B virus (HBV) or hepatitis C virus (HCV) did not differ between TTV DNA positive and negative HD patients. However, the mean duration of HD was significantly (P=0.032) shorter in the TTV positive patients (28+/-19 months) than in the negative ones (45+/-34 months). Mean alanine aminotransferase level in patients with HCV infection alone (41+/-24 IU/l) did not differ from that in patients with both co-infection (33+/-28 IU/l), but was significantly higher than that in patients with TTV infection alone (26+/-10 IU/l). Occurrence of chronic hepatic changes in patients with TTV infection alone (7%) was significantly less common than those with HCV infection alone (100%, P<0.001) or those with both co-infection (100%, P<0.001). Serum level of HCV core protein was similar between patients with HCV infection alone and those with co-infection with TTV. In conclusion, the prevalence of TTV infection is high in Egyptian patients on regular HD, especially with shorter duration on HD. No clinical significance of TTV virus could be elicited in HD Egyptian patients; neither it showed any clinical impact as a co-infection with HCV.