Development of hepatocellular carcinoma from various phases of chronic hepatitis B virus infection

Background & aims There is insufficient data on the clinical course of chronic hepatitis B (CHB) patients in the immune-tolerant (IT) and immune-clearance, inactive (IC) phases over a long follow-up period. Design We enrolled 466 CHB patients from our historical cohort, including 56 IT+MA　 (mildly active), 134 IC, 230 with chronic active hepatitis (CH) and 46 with liver cirrhosis (LC), who were categorized to each phase by at least one year of follow-up period from the first visit to our hospital. We investigated long-term risks, and their factors, of developing hepatocellular carcinoma (HCC), and the transition between the clinical phases, especially in the IT+MA and IC groups. Results Of the 56 patients in the IT+MA group, 27 remained the IT+MA phase, but 29 transitioned to the CH phase and started nucleot(s)ide analogue (NA) treatment during the follow-up period. Meanwhile, of the 134 patients in the IC group, only 5 started NA treatment after progressing to the CH phase. The development of HCC from the IT+MA, IC, CH, and LC groups was observed in 2, 2, 9, and 20 cases, respectively. The cumulative incidence rates of developing HCC in the IT+MA, IC, CH, and LC groups were 9.9, 1.8, 3.0, and 53.1% at 10 years. In the CH and LC group, patients who developed HCC were older, had higher levels of FIB-4 index, M2BPGi, HBcrAg and AFP, and had lower levels of albumin and platelet counts. In CH patients, FIB-4 index levels were elevated at the diagnosis of HCC compared to baseline, whereas these decreased during the follow-up period in non-HCC patients. Conclusions HCC occurred at a certain rate among patients in the IT+MA and IC groups. Careful follow-up is required for CH patients with higher levels of FIB-4 index and/or M2BPGi because of the high incidence of HCC development. (299 words)

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High risk of hepatocellular carcinoma and death in patients with immune-tolerant-phase chronic hepatitis B

Gut ◽

10.1136/gutjnl-2017-314904 ◽

2017 ◽

Vol 67 (5) ◽

pp. 945-952 ◽

Cited By ~ 57

Author(s):

Gi-Ae Kim ◽

Young-Suk Lim ◽

Seungbong Han ◽

Jonggi Choi ◽

Ju Hyun Shim ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Chronic Hepatitis ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

Antiviral Treatment ◽

High Serum ◽

Hbv Dna ◽

Tertiary Referral Hospital ◽

Historical Cohort ◽

Immune Tolerant

ObjectiveHigh serum HBV DNA levels are associated with high risks of hepatocellular carcinoma (HCC) and cirrhosis in patients with chronic hepatitis B (CHB). Although the immune-tolerant (IT) phase is characterised by high circulating HBV DNA levels, it remains unknown whether antiviral treatment reduces risks of HCC and mortality.DesignThis historical cohort study included HBeAg-positive patients with CHB with high HBV DNA levels (≥20 000 IU/mL) and no evidence of cirrhosis at a tertiary referral hospital in Korea from 2000 to 2013. The clinical outcomes of 413 untreated IT-phase patients with normal alanine aminotransferase (ALT) levels (females, <19 IU/mL; males, <30 IU/mL) were compared with those of 1497 immune-active (IA)-phase patients (ALT ≥80 IU/mL) treated with nucleos(t)ide analogues.ResultsThe IT group was significantly younger than the IA group (mean age, 38 vs 40 years at baseline, p=0.04). The 10-year estimated cumulative incidences of HCC (12.7% vs 6.1%; p=0.001) and death/transplantation (9.7% vs 3.4%; p<0.001) were significantly higher in the IT group than the IA group. In multivariable analyses, the IT group showed a significantly higher risk of HCC (HR 2.54; 95% CI 1.54 to 4.18) and death/transplantation (HR 3.38; 95% CI 1.85 to 6.16) than the IA group, which was consistently identified through inverse probability treatment weighting, propensity score-matched and competing risks analyses.ConclusionsUntreated IT-phase patients with CHB had higher risks of HCC and death/transplantation than treated IA-phase patients. Unnecessary deaths could be prevented through earlier antiviral intervention in select IT-phase patients.

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Authors’ response: Additional more factors should be included in predicting risk of hepatocellular carcinoma in patients with chronic hepatitis B virus infection

Journal of Viral Hepatitis ◽

10.1111/jvh.13450 ◽

2020 ◽

Author(s):

Jin Won Chang ◽

Seung Up Kim

Keyword(s):

Hepatocellular Carcinoma ◽

Chronic Hepatitis ◽

Hepatitis B Virus ◽

Virus Infection ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

Hepatitis B Virus Infection ◽

Chronic Hepatitis B Virus ◽

B Virus

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Transient elastography is useful for evaluating hepatocellular carcinoma development during entecavir treatment of chronic hepatitis B virus infection

Gastroenterology Hepatology and Endoscopy ◽

10.15761/ghe.1000138 ◽

2017 ◽

Vol 2 (1) ◽

Author(s):

Masaaki Shimada ◽

Hiroaki Iwase ◽

Noboru Hirashima ◽

Nobumitsu Ryuge ◽

Noboru Urata

Keyword(s):

Hepatocellular Carcinoma ◽

Chronic Hepatitis ◽

Hepatitis B Virus ◽

Virus Infection ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

Transient Elastography ◽

Hepatitis B Virus Infection ◽

Chronic Hepatitis B Virus ◽

B Virus

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Human TP53 gene polymorphisms among patients with hepatocellular carcinoma and chronic hepatitis B in Kenya

F1000Research ◽

10.12688/f1000research.19416.1 ◽

2019 ◽

Vol 8 ◽

pp. 1364

Author(s):

Missiani Ochwoto ◽

Colins O. Oduma ◽

Julius Oyugi ◽

Dufton Mwaengo ◽

Bartholomew N. Ondigo ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Chronic Hepatitis ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

Tp53 Gene ◽

Biological Behavior ◽

Regulatory Function ◽

Female Ratio ◽

Mutational Pattern ◽

Chronic Hepatitis B Virus

Background: Human TP53 is the gatekeeper for generation of human cells and is highly conserved. Any alteration/mutation to TP53 adversely affects the regulatory function of the protein, potentially resulting in cancer. This study investigated mutations in codons 7 and 249 of TP53, among patients with hepatocellular carcinoma (HCC) and chronic hepatitis B virus (HBV) infection at the Moi Teaching and Referral Hospital (MTRH), Eldoret, Kenya. Methods: In total, 33 HBV-positive patients attending MTRH hospital between September 2013 and July 2017 were purposely selected from medical records for the study; those with HCC were confirmed from the cancer registry. The patients were aged between 25-67 years, with a male-to-female ratio of 1.1:1. Blood samples were collected from the patients. DNA was extracted, amplified and sequenced using TP53 forward and reverse primers. Gene mutation detection and analysis was done on exons 4 and 7 Results: Of the 33 patients, 75.8% were chronically infected with HBV and had HCC; the rest were HBsAg positive without HCC. Homozygous proline was prevalent (54.5%) at exon 4 codon 72, followed by heterozygous Arg/Pro (33.3%) and lastly homozygous Arg/Arg (12.1%,). Pro/Pro allele was frequent in HCC group while Arg/Arg allele was common in patients without HCC. There was no significant association between the HCC and codon polymorphisms (p=0.12). In exon 7, codon 249, 24.2% of patients had an Arg-Ser mutation of which, 75.0% had HCC and 25.0% did not. There was no significant association between HCC patients and codon 249 mutation (p=0.15). Conclusion: TP53 is a gene gate keeper, the mutations under study may dependently play a role in HCC development. This study did not find any association or clear mutational pattern between P53 mutations and HCC development. Therefore, TP53 mutation is a poor indicator for prognosis and a tumor’s biological behavior among HBV-positive subjects in Kenya.

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