Presence of steatosis does not increase the risk of Hepatocellular Carcinoma in patients with Chronic Hepatitis B over long follow-up

Background: The prevalence of metabolic and cardiovascular diseases is rising worldwide. However, little is known about the impact of such disorders on hepatic disease progression in chronic hepatitis B (CHB) during the era of potent nucleo(s)tide analogues (NAs). Methods: We retrospectively analyzed a single-center cohort of 602 CHB patients, comparing the frequency of liver cirrhosis at baseline and incidences of liver-related events during follow-up (hepatocellular carcinoma, liver transplantation and liver-related death) between CHB patients with a history of diabetes, obesity, hypertension or coronary heart disease (CHD). Results: Rates of cirrhosis at baseline and liver-related events during follow-up (median follow-up time: 2.51 years; NA-treated: 37%) were substantially higher in CHB patients with diabetes (11/23; 3/23), obesity (6/13; 2/13), CHD (7/11; 2/11) or hypertension (15/43; 4/43) compared to CHB patients without the indicated comorbidities (26/509; 6/509). Multivariate analysis identified diabetes as the most significant predictor for cirrhosis (p = 0.0105), while comorbidities did not correlate with liver-related events in pre-existing cirrhosis. Conclusion: The combination of metabolic diseases and CHB is associated with substantially increased rates of liver cirrhosis and secondary liver-related events compared to CHB alone, indicating that hepatitis B patients with metabolic comorbidities warrant particular attention in disease surveillance and evaluation of treatment indication.

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Early Normalization of Alanine Aminotransferase during Antiviral Therapy Reduces Risk of Hepatocellular Carcinoma in HBV Patients

Journal of Clinical Medicine ◽

10.3390/jcm10091840 ◽

2021 ◽

Vol 10 (9) ◽

pp. 1840

Author(s):

Sehwa Kim ◽

Yoonseok Lee ◽

Soo Min Bang ◽

Haein Bak ◽

Sun Young Yim ◽

...

Keyword(s):

Risk Factors ◽

Hepatocellular Carcinoma ◽

Chronic Hepatitis ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

Alanine Aminotransferase ◽

Antiviral Treatment ◽

Antiviral Agents ◽

Independent Risk Factors

Potent antiviral agents effectively reduce liver-related events in patients with chronic hepatitis B. This study aimed to determine whether alanine aminotransferase normalization using potent antiviral agents was related to hepatocellular carcinoma development. From 2007 to 2017, we included 610 patients with chronic hepatitis B who received entecavir or tenofovir disoproxil fumarate. The patients were divided into the alanine aminotransferase normalization group (Gr.1) and non-normalization group (Gr.2) within a year of potent antiviral treatment. Liver-related events included hepatic encephalopathy, variceal bleeding, and ascites. The mortality rate and hepatocellular carcinoma incidence were investigated for each group. The patients who showed ALT normalization at 1 year of treatment were 397 (65.1%) of 610. During a median follow-up period of 86 months, 65 (10.7%) patients developed hepatocellular carcinoma. The cumulative incidence of hepatocellular carcinoma was significantly lower in Gr.1 than in Gr.2 (p < 0.001). Risk factors for alanine aminotransferase non-normalization were body mass index, cholesterol, and liver cirrhosis at baseline. Male sex, age, platelet level, alcohol use, presence of cirrhosis at baseline, and non-normalization after 1 year of treatment were independent risk factors for hepatocellular carcinoma. Alanine aminotransferase normalization within 1 year of initiating antiviral agents reduces the risk of hepatocellular carcinoma development.

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Presence of Hepatic Steatosis Does Not Increase the Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B Over Long Follow-Up

Microbiology Insights ◽

10.1177/1178636120918878 ◽

2020 ◽

Vol 13 ◽

pp. 117863612091887

Author(s):

Chong Teik Lim ◽

George Boon Bee Goh ◽

Huihua Li ◽

Tony Kiat-Hon Lim ◽

Wei Qiang Leow ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Chronic Hepatitis ◽

Hepatitis B ◽

Hepatic Steatosis ◽

Chronic Hepatitis B ◽

Significant Risk ◽

Conclusive Evidence ◽

Nonalcoholic Fatty Liver ◽

Cox Analysis

Background: Chronic hepatitis B (CHB) infection and nonalcoholic fatty liver disease (NAFLD) are liver diseases which may lead to hepatocellular carcinoma (HCC) formation. Both disease entities have been attributed independently to increase risk of HCC development. While concomitant hepatic steatosis in patients with CHB are becoming more frequent in view of increasing NAFLD prevalence, there is no conclusive evidence linking presence of hepatic steatosis and increased HCC risk in patients with CHB infection. This study explores the association of hepatic steatosis among CHB-infected individuals in HCC development. Methods: This is a retrospective study on a cohort of patients with CHB who underwent liver biopsy between January 2000 and December 2014. They were stratified according to presence and severity of histologically proven hepatic steatosis and subsequently followed up to evaluate the association between hepatic steatosis and HCC development. Results: Among 289 patients with a median follow-up of 111.1 months, hepatic steatosis was present in 185 patients (64.0%). In all, 27 patients developed HCC on follow-up and 21 of them had hepatic steatosis. Univariate Cox analysis showed that age (hazard ratio [HR] = 1.08, 95% CI = 1.042-1.12), type 2 diabetes mellitus (T2DM) (HR = 4.00, 95% CI = 1.622-9.863), and Ishak score (HR = 1.221, 95% CI = 1.014-1.472) were associated with HCC development, whereas multivariate Cox analysis demonstrated that age and T2DM (HR = 2.69, 95% CI = 1.072-6.759) were significant risk factors for development of HCC. Conclusions: Concurrent hepatic steatosis in patients with CHB infection is not a risk factor for hepatocellular carcinoma formation.

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389 LOW RISK OF HEPATOCELLULAR CARCINOMA RECURRENCE AFTER LIVER TRANSPLANTATION: A 3-YEAR FOLLOW-UP STUDY IN 78 PATIENTS WITH CHRONIC HEPATITIS B

Journal of Hepatology ◽

10.1016/s0168-8278(08)60391-8 ◽

2008 ◽

Vol 48 ◽

pp. S151 ◽

Cited By ~ 1

Author(s):

P. Lampertico ◽

M. Vigano ◽

S. Bhoori ◽

F. Agnelli ◽

M.F. Donato ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Transplantation ◽

Chronic Hepatitis ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

Low Risk ◽

Follow Up Study ◽

Hepatocellular Carcinoma Recurrence

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Impact of Tenofovir Alafenamide Vs. Entecavir on Hepatocellular Carcinoma Risk in Patients With Chronic Hepatitis B

10.21203/rs.3.rs-466650/v1 ◽

2021 ◽

Author(s):

Hye Won Lee ◽

Young Youn Cho ◽

Beom Kyung Kim ◽

Hyein Lee ◽

Jae Seung Lee ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Chronic Hepatitis ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

Teaching Hospitals ◽

Decompensated Cirrhosis ◽

Kaplan Meier ◽

Treatment Naïve ◽

Tenofovir Alafenamide

Abstract Background & aims: Whether entecavir (ETV) or tenofovir alafenamide (TAF) is better at preventing hepatocellular carcinoma (HCC) development among patients with chronic hepatitis B (CHB) remains unclear. The present study was conducted to explore the ability of these two antivirals to prevent HCC.Methods: From 2012 to 2019, treatment-naïve CHB patients undergoing ETV or TAF therapy were recruited at three academic teaching hospitals. The TAF group comprised patients starting TAF as first-line antiviral and those switching antivirals from tenofovir disoproxil fumarate to TAF. Patients with decompensated cirrhosis or HCC at enrollment were excluded from the analysis. Cumulative probabilities of HCC were assessed using the Kaplan-Meier method.Results: In total, 1,810 patients (1,525 and 286 in ETV and TAF groups, respectively) were recruited. The annual HCC incidence was statistically not different between the ETV and TAF groups (1.67 vs. 1.19 per 100 person-years, respectively) with an adjusted hazard ratio (HR) of 0.681 (p=0.255), as determined by multivariate analysis. Male, hypertension, liver cirrhosis, FIB-4 index, and albumin were independent prognostic factors for HCC development. Propensity score-matched and inverse probability of treatment weighting analyses yielded similar results, with non-statistically different HCC incidence between the ETV and TAF groups (1.07 vs. 1.19 per 100 person-years (HR=0.973; p=0.953) and 1.67 vs. 1.89 per 100 person-years, respectively (HR=0.949; p=0.743).Conclusions: These findings suggest that ETV- and TAF-treated CHB patients have similar risk of developing HCC. Further studies with the larger sample size and longer follow-up are needed to validate these results.

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A patient with chronic hepatitis B who developed hepatocellular carcinoma with hypervascularity in 9 years of close follow-up

Kanzo ◽

10.2957/kanzo.63.24 ◽

2022 ◽

Vol 63 (1) ◽

pp. 24-34

Author(s):

Masanari Kosaka ◽

Tomokazu Kawaoka ◽

Yusuke Johira ◽

Yuki Shirane ◽

Ryoichi Miura ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Chronic Hepatitis ◽

Hepatitis B ◽

Chronic Hepatitis B

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Older Age and High Α-fetoprotein Predict Higher Risk of Hepatocellular Carcinoma in Chronic Hepatitis B-Related Cirrhotic Patients Receiving Nucleos(T)ide Analogue Therapy: A Retrospective Cohort Study

10.21203/rs.3.rs-668622/v1 ◽

2021 ◽

Author(s):

Ching-Chih Hu ◽

Cheng-Hao Weng ◽

Chih-Lang Lin ◽

Pei-Hung Chang ◽

Man-Chin Hua ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Chronic Hepatitis ◽

Hepatitis B ◽

Incidence Rate ◽

Chronic Hepatitis B ◽

Cox Regression ◽

Annual Incidence ◽

Cox Regression Analysis ◽

Cirrhotic Patients

Abstract Background: Nucleos(t)ide analogues (NUCs) were proved to reduce hepatocellular carcinoma (HCC) development in patients with chronic hepatitis B (CHB) infection, but data was limited on the efficacy in the CHB patients with cirrhosis. Methods: We retrospectively analyzed data from 447 patients with CHB-related cirrhosis, who initiated tenofovir/entecavir therapy during April 2007 and August 2013. They were divided into HCC (n=48) and non-HCC (n=399) groups. The mean follow-up period was 63.2 ± 34.2 months.Results: Forty-eight patients (10.7%) developed HCC during surveillance. The annual incidence rate of HCC was 2.04 (95% CI: 1.52–2.68) per 100 person-year. The cumulative incidence of HCC was 0.9%, 9.8% and 22.1% at the 1, 5 and 10 years, respectively. Significant predictors for HCC identified using multiple Cox regression analysis were age ≥50 years (hazard ratio [HR]: 2.34, 95% confidence interval [CI] = 1.08–5.1) and α-fetoprotein (AFP) ≥8 ng/ml (HR: 2.05, 95% CI = 1.1–3.84). The incidence rate of HCC was further analyzed in subgroups according to the risk factors identified by multivariate cox regression. The incidence rate of HCC was 8.67-fold higher in patients with age ≥50 years and AFP ≥8 ng/ml (3.14 per 100 person-year, 95% CI = 1.99–4.72) than those with age <50 years and AFP <8 ng/ml (0.36 per 100 person-year, 95% CI = 0.06–1.19).Conclusion: The cirrhotic CHB patients with age <50 years and AFP <8 ng/ml have the lowest annual incidence of HCC. However, the cirrhotic patients with age ≥50 years or/and AFP ≥8 ng/ml have significantly higher risk for HCC and warrant careful surveillance schedule for HCC development.

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

PLoS ONE ◽

10.1371/journal.pone.0261878 ◽

2021 ◽

Vol 16 (12) ◽

pp. e0261878

Author(s):

Takanori Suzuki ◽

Kentaro Matsuura ◽

Yoshihito Nagura ◽

Etsuko Iio ◽

Shintaro Ogawa ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Chronic Hepatitis ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

Incidence Rates ◽

Historical Cohort ◽

Chronic Hepatitis B Virus ◽

Immune Tolerant ◽

One Year

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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