Recurrence of Hepatocellular Carcinoma With Epithelial–Mesenchymal Transition After Spontaneous Regression: A Case Report

Hepatocellular carcinoma (HCC) is one of the most malignant cancers and ranks as the third leading cause of cancer-related death in the world. However, some patients with untreated HCC can experience spontaneous regression, a rare phenomenon that has been observed in various malignancies.Here, we report a unique case with untreated HCC, who first underwent a spontaneous cancer regression after the spontaneous clearing of chronic hepatitis B virus (HBV) infection from the liver as evidenced by hepatitis B virus surface antigen (HBsAg) seroconversion; then developed the recurrent HCC with epithelial-mesenchymal transition (EMT) after 14 years.We hypothesized that a strengthened immune system in response to HBV infection may have led to immune-mediated spontaneous cancer regression. The later recurrence of HCC may suggest the host''s immune system was no longer able to contain HCC since aging and other chronic diseases may have significantly weakened the immune surveillance.     

Hepatocellular Carcinoma in Hepatitis D: Does it Differ from Hepatitis B Monoinfection?

Background/Aim:

Hepatitis D virus (HDV) superinfection in patients with chronic hepatitis B leads to accelerated liver injury, early cirrhosis, and decompensation. It may be speculated that hepatocellular carcinoma (HCC) may differ in these patients from hepatitis B virus (HBV) monoinfection. The aim of this study was to compare clinical aspects of hepatocellular carcinoma in patients of hepatitis D with HBV monoinfection.

Patients and Methods:

A total of 92 consecutive HCC cases seropositive for antibody against HDV antigen (HDV group) were compared with 92 HBsAg-positive and anti-HDV-negative cases (HBV group).

Results:

The features including sex, body mass index, presence of ascites, serum biochemistry, gross tumor appearance, child class, barcelona cancer liver clinic and okuda stages were not significantly different between the 2 groups. Decreased liver size was noticed more in cases of HDV compared with HBV group where the liver size was normal or increased (P=0.000). HDV patients had lower platelets (P=0.053) and larger varices on endoscopy (P=0.004). Multifocal tumors and elevated alpha-fetoprotein level >1000 IU/mL were more common in HBV group (P=0.040 and P= 0.061). TNM classification showed more stage III-IV disease in HBV group (P=0.000).

Conclusion:

Decreased liver size and indirect evidence of more severe portal hypertension and earlier TNM stage compared with HBV monoinfection indicate that HDV infection causes HCC in a different way, possibly indirectly by inducing inflammation and cirrhosis.     

Anorectal Carcinoma After Infliximab Therapy in Crohn’s Disease: Report of a Case

Infliximab, monoclonal antibody against tumor necrosis factor α, is an effective agent in the therapy of Crohn’s disease. Although therapy with infliximab is generally well tolerated, there is an obvious concern about the effect of this treatment on the incidence of cancer. We report a case of mucinous anorectal adenocarcinoma observed in a 39-year-old patient with long-standing Crohn’s disease after therapy with two courses of infliximab. The carcinoma was discovered fortuitously after abdominoperineal resection. Despite clear margins, the tumor recurred in a few months and progressed during combination chemotherapy. Although there is currently no definitive proof of a causal link between infliximab therapy and cancer, the present observation and other reports in the literature should lead to a careful evaluation of the possibility of increased cancer risk in patients treated with this new agent. Supported by a grant of Ministry of Education of the Czech Republic CEZ-MŠMT 115000021 and Research Project MZO 00179906.     

Association Between Catalase Gene Polymorphisms and Risk of Chronic Hepatitis B,Hepatitis B Virus-Related Liver Cirrhosis and Hepatocellular Carcinoma in Guangxi Population: A Case–Control Study

Reactive oxygen species (ROS) play critical roles in hepatocarcinogenesis. The catalase (CAT) enzyme is involved in the repair of ROS. Therefore, we investigate the association between CAT gene polymorphisms and the risk of hepatocellular carcinoma (HCC).A total of 715 subjects were divided into 4 groups: 111 chronic hepatitis B (CHB) patients, 90 hepatitis B virus (HBV)-related liver cirrhosis (LC) patients, 266 HBV-HCC patients, and 248 healthy controls. The polymerase chain reaction-restriction fragment length polymorphism strategy was used to detect CAT gene rs1001179, rs769217, and rs7943316 polymorphisms.Binary logistic regression analyses adjusting for sex, age, ethnicity, smoking and alcohol consumption, and body mass index suggested that subjects carrying the rs769217 T allele were at marginally increased risk of CHB, LC, and HCC, with adjusted odds ratios (ORs) of 1.51 (95% confidence interval [CI] = 1.04–2.20, P = 0.029), 1.48 (95% CI = 1.03–2.14, P = 0.035), and 1.51 (95% CI = 1.14–1.98, P = 0.004), respectively. Similarly, those individuals carrying the rs769217 TT genotype had a moderately increased risk of CHB, LC, and HCC, with adjusted ORs of 2.11 (95% CI = 1.05–4.22, P = 0.035), 2.00 (95% CI, 1.01–3.95, P = 0.047), and 1.93 (95% CI = 1.14–3.28, P = 0.015), respectively. Moreover, subjects carrying the rs769217 CT genotype and at least 1 copy of the T allele (dominant model) were 1.78 times and 1.83 times more likely to develop HCC, respectively (OR = 1.78, 95% CI = 1.16–2.73, P = 0.009 and OR = 1.83, 95% CI = 1.23–2.71, P = 0.003). This association between CAT rs769217 T alleles and HCC risk is significantly strengthened among men, nonsmokers, nondrinkers, and among individuals <50 years of age. Furthermore, we found 1 high-risk haplotype GTA for CHB (OR = 1.45, 95% CI = 1.05–2.01) and 1 protective haplotype GCA for HCC risk (OR = 0.67, 95% CI = 0.52–0.87). We did not found any significant difference in CAT rs1001179 and rs7943316 polymorphisms between controls and cases.Our findings suggest that the CAT rs769217 T allele is associated with increased risk of CHB, HBV-LC, and HBV-HCC in Guangxi population.     

Pegylated Interferon α Therapy in Chronic Delta Hepatitis: A One-Center Experience

Background:

The only established therapy for chronic viral delta hepatitis, the most severe form of viral hepatitis is treatment with pegylated-interferon α (Peg IFN α).

Objectives:

In this study, we aimed to determine the efficacy of pegylated-interferon α 2a (Peg-IFN α 2a) and 2b (Peg IFN α 2b) in the treatment of patients infected with chronic delta hepatitis virus.

Patients and Methods:

The sample size was based on available patients potentially to be recruited. Data of 63 patients receiving either Peg IFN alpha 2a or Peg IFN alpha 2b were retrospectively assessed in the present cohort study performed in Turkey. Of 56 patients completed the study, 41 received Peg IFN α 2a and 15 received Peg IFN α 2b for 12 months. Patients were evaluated for biochemical and virological responses at the end of given treatment and six months after the treatment.

Results:

Stage of fibrosis was found high in both groups (85.4% vs. 86.7%), while cirrhosis was higher in the group of Peg IFN α 2b (53.3% vs. 34.1%). At the end of treatment, either hepatitis delta virus RNA (HDV RNA) alone or both HDV RNA and hepatitis b virus DNA (HBV DNA) had negative results in 32% of patients. Although HDV RNA negativity was sustained in 30.3% of patients, negativity of both HDV RNA and HBV DNA was decreased to 19.6% six months after completion of the treatment. HBV DNA became positive in one third of patients with response at six months after completion of the treatment (10.7% of all patients). HDV RNA negativity at month six was found as a predictor of positive response. No significant difference was found between Peg IFN α 2a and Peg IFN α 2b for virological response rate.

Conclusions:

Treatment with Peg IFN α achieved a sustained negativity of HDV RNA in about one third of patients. Duration of Peg IFN α therapy might be prolonged to at least 24 months or more to prevent the occurrence of Hepatitis B virus (HBV) relapse encountered six months after completion of the treatment.     

NAFLD and Hepatocellular Carcinoma: How Big a Problem is This Really?

A definite link between non alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC) has emerged. Diabetes, older age and the presence of cirrhosis are the key risk factors for HCC in patients with NAFLD. Although the rates of development of HCC are generally lower compared with viral (HCV) aetiology, the absolute burden of NASH-related HCC is higher. Diagnostic delay, older age and the concurrent presence of severe metabolic or vascular disease limits potentially curative treatment, such as liver transplantation. Most worrisome, is the recent evidence that HCC may develop also in non-cirrhotic livers with NAFLD, particularly in the presence of multiple metabolic risk factors. In the coming decades, we expect a change in the burden of the attributable proportion of HCC shifting from viral hepatitis to NASH, as the major risk factor for HCC worldwide.     

The Epidemiological Investigation on the Risk Factors of Hepatocellular Carcinoma: A Case–Control Study in Southeast China

Incidence of hepatocellular carcinoma (HCC) ranked the fifth in male and ninth in the female counterparts, and 50% of incidence HCC cases were occurred in China with high hepatitis B virus (HBV) prevalence. HCC has seriously compromised the health status of general population in China. A case–control study of 314 HCC cases and 346 controls was conducted in Xiamen, which is an epidemic area in China for both hepatitis B infection and HCC. Face-to-face interview was conducted to gather information on demographic characteristics as well as exposure of environmental factors. Commercial enzyme-linked immunosorbent assay kits were used to determine the status of serological markers of HBV infection. Odds ratios and 95% confidence intervals were estimated by using unconditional logistic regression. Multivariate unconditional logistic regression analysis was applied to evaluate the potential interactions of variables or confounders.As expected, HBV and alcohol intake still are the major risk factors of HCC. Liver disease history and passive smoking are also associated with elevated HCC risk. Indoor air pollution and pesticide exposure have newly identified as risk factors of HCC. Fruit and tea intake can significantly lower the HCC risk.The application of HBV vaccine and reduction on alcohol intake should be further promoted in high-risk population. Fruit and tea can be served as chemoprevention in daily life due to their high accessibility.