Increasing incidence of non-HBV- and non-HCV-related hepatocellular carcinoma: single-institution 20-year study

Background We previously reported on the trends in the etiologies of hepatocellular carcinoma (HCC) diagnosed in patients between 1995 and 2009. The aims of our updated study were to evaluate the incidence, nonhepatitis B and nonhepatitis C viral (NBNC) etiologies, and clinical characteristics of HCCs occurring in patients between 1992 and 2018. Methods The study enrolled 2171 consecutive patients with HCC between 1992 and 2018. Their medical records were reviewed. The patients were divided into two groups, patients with early diagnoses from 1992 to 2009 and those with late diagnoses from 2010 to 2018. Results NBNC-HCC occurred in 514 patients (23.6%). The percentage of patients with HCC who had NBNC-HCC increased from 26.5% in 2009 to 46.3% in 2018. Patients with NBNC-HCC were older (median ages from 67 to 73 years). Type 2 diabetes mellitus (48.5–60.3%: P = 0.008), hypertension (48.5–57.4%: P = 0.047), and hyperlipidemia (39.2–53.8%: P = 0.001) increased significantly in recent years. The median FIB-4 index decreased (4.37–3.61: P = 0.026) and the median platelet count increased (15.1–17.9 × 104/μL: P = 0.013). Among the 514 patients with NBNC-HCC, 194 underwent hepatic resection for nonalcoholic steatohepatitis (NASH) (15%), alcoholic liver disease (ALD) (29%), and cryptogenic hepatitis (56%). Cirrhosis was detected in 72%, 39%, and 16% of patients with NASH, ALD, and cryptogenic hepatitis, respectively. The prevalence of cirrhosis in patients with NASH was significantly higher than the prevalence of cirrhosis in the other groups (P < 0.001). Overall, 70% of the non-malignant liver tissue of patients with NBNC-HCC was not involved with cirrhosis. On the other hand, the median FIB-4 index in patients with cryptogenic HCC was 2.56, which was a significantly lower value than those values in the other groups of patients. The FIB-4 index considered as one of useful screening of HCC. Conclusions The prevalence of NBNC-HCC has increased rapidly even in a regional university hospital. Metabolic syndrome may be an important risk factor for HCC. HCC was also found in patients with non-cirrhotic livers. The FIB-4 index may be a useful screening method for HCC in patients with NBNC.

Hepatitis viruses (excluding hepatitis C virus)

Viral hepatitis is an ancient disease which remains a major health problem worldwide. The group of hepatitis viruses includes five unrelated human viruses (A to E), which differ in their genome organization, biology, and epidemiology, while being united by their hepatotropism. About 10–15% of cases of viral hepatitis are considered as non-A to E hepatitis, whose aetiology is still unknown, but the search for which has led to the identification of several new viruses (e.g. hepatitis G virus or GB virus-C, TT, and SEN viruses) of uncertain pathogenic significance. Thus, the search for new hepatitis agents responsible for the small proportion of cases with cryptogenic hepatitis continues.

THE QUANTITATIVE DETERMINATION METHOD OF COVALENTLY CLOSED CIRCULAR DNA HBV IN PUNCTURE BIOPSY SPECIMENS OF THE LIVER

To analyze the method HBV covalent-closed circular DNA quantitative determination in liver puncture biopsies and evaluate its significance in identifying HBsAg-negative viral hepatitis B. In this work, samples of liver tissue biopsy material were used from 128 patients living in St. Petersburg, in various regions of the Russian Federation, as well as in the Republic of Uzbekistan. For quantitative analysis of HBV covalently closed circular DNA in a biopsy material a method was developed based on real-time PCR using TaqMan probes for the target fragment and for the endogenous reference gene, based on the detecting ccc HBV DNA method of Pollicino T. et al. When quantifying ccc DNA HBV in liver tissue of 18 moderately HBV activity with HBV DNA PCR positive results patients and 16 inactive HBsAg carriers, the ccc DNA HBV content was significantly different between groups (p<0.034) and in terms 1 copy of the β-globin gene among moderate activity HBV patients amounted to 1.71±1.32 copies/cell, and for inactive HBsAg carriers 0.15±0.14 copies/cell. In the group of patients with severe liver fibrosis and cirrhosis, the amount of ccc DNA HBV in liver tissue in patients with HBV averaged 2.5±0.4 copies/cell, in patients with HBV + D on average 0.7±0.25 copies/cell, in patients with HCV + HBV co-infection 0.45±0.07 copies/cell, in patients with a preliminary diagnosis of chronic hepatitis C hepatitis, on average 0.12±0.04 copies/cell, in patients with cryptogenic hepatitis 0.2± 0.05 copies/cell. A significant difference was shown between the group of patients with chronic hepatitis B with marked fibrosis and cirrhosis of the liver with other patients groups, except for the group of 18 moderate activity chronic hepatitis B patients. The values of Student’s t-test when compared with other groups were respectively: for patients with a HCV preliminary diagnosis t=5,92 p<0,05 f = 19, patients with cryptogenic hepatitis t=5,71 p<0,05 f = 18, with «inactive HBsAg carriage» t=5,55 p<0,05 f = 29, with HCV + HBV co-infection t=5,05 p<0,05 f = 15 and HBV + D co-infection t=3,82 p<0,05 f = 17. The covalently closed circular DNA HBV quantitative assessment method in liver puncture biopsies allows identifying HBsAg-negative chronic viral hepatitis B forms and also reflects the virus replication activity, which, in turn, makes it possible to assume further disease progression and evaluate the antiviral therapy effectiveness.