We aimed to determine the surveillance performance of alpha‐fetoprotein (AFP), lectin‐reactive AFP (AFP‐L3), des‐gamma‐carboxy prothrombin (DCP), and their combinations for the early detection of ...hepatocellular carcinoma (HCC) by using prospectively collected longitudinal samples in patients at risk. Among 689 patients with cirrhosis and/or chronic hepatitis B who participated in four prospective studies, 42 HCC cases were diagnosed, selected, and matched with 168 controls for age, sex, etiology, cirrhosis, and duration of follow‐up in a 1:4 ratio. Levels of AFP, AFP‐L3, and DCP at the time of HCC diagnosis, month −6, and month −12 were compared between cases and controls. Of 42 HCC cases, 39 (93%) had cirrhosis, 36 (85.7%) had normal alanine aminotransferase levels, and 31 (73.8%) had very early‐stage HCC (single <2 cm). AFP and AFP‐L3 began to increase from 6 months before diagnosis of HCC in cases (P < 0.05), while they remained unchanged in controls. At HCC diagnosis, the area under the receiver operator characteristic curves (AUROCs) for AFP, AFP‐L3, and DCP were 0.77, 0.73, and 0.71, respectively. Combining AFP and AFP‐L3 showed a higher AUROC (0.83), while adding DCP did not further improve the AUROC (0.86). With the optimal cutoff values (AFP, 5 ng/mL; AFP‐L3, 4%), the sensitivity and specificity of AFP and AFP‐L3 combination were 79% and 87%, respectively. The sensitivity of ultrasonography was 48.6%, which was increased to 88.6% and 94.3% by adding AFP and AFP + AFP‐L3, respectively. Conclusion: Among three biomarkers, AFP showed the best performance in discriminating HCC cases from controls; the AFP and AFP‐L3 combination, adopting cutoff values (5 ng/mL and 4%, respectively), significantly improved the sensitivity for detecting HCC at a very early stage.
BACKGROUNDIt is unclear whether the level of serum hepatitis B virus (HBV) DNA at baseline affects the on-treatment risk of hepatocellular carcinoma (HCC) in hepatitis B e antigen-positive ...(HBeAg-positive), noncirrhotic patients with chronic hepatitis B (CHB).METHODSWe conducted a multicenter cohort study including 2073 entecavir- or tenofovir-treated, HBeAg-positive, noncirrhotic adult CHB patients with baseline HBV DNA levels of 5.00 log10 IU/mL or higher at 3 centers in South Korea between January 2007 and December 2016. We evaluated the on-treatment incidence rate of HCC according to baseline HBV DNA levels.RESULTSDuring a median 5.7 years of continuous antiviral treatment, 47 patients developed HCC (0.39 per 100 person-years). By Kaplan-Meier analysis, the risk of HCC was lowest in patients with baseline HBV DNA levels of 8.00 log10 IU/mL or higher, increased incrementally with decreasing viral load, and was highest in those with HBV DNA levels of 5.00-5.99 log10 IU/mL (P < 0.001). By multivariable analysis, the baseline HBV DNA level was an independent factor that was inversely associated with HCC risk. Compared with HBV DNA levels of 8.00 log10 IU/mL or higher, the adjusted HRs for HCC risk with HBV DNA levels of 7.00-7.99 log10 IU/mL, 6.00-6.99 log10 IU/mL, or 5.00-5.99 log10 IU/mL were 2.48 (P = 0.03), 3.69 (P = 0.002), and 6.10 (P < 0.001), respectively.CONCLUSIONOn-treatment HCC risk increased incrementally with decreasing baseline HBV DNA levels in the range of 5.00 log10 IU/mL or higher in HBeAg-positive, noncirrhotic adult patients with CHB. Early initiation of antiviral treatment when the viral load is high (≥8.00 log10 IU/mL) may maintain the lowest risk of HCC for those patients.FUNDINGPatient-Centered Clinical Research Coordinating Center (PACEN) (grant no. HC20C0062) of the National Evidence-based Healthcare Collaborating Agency; National R&D Program for Cancer Control through the National Cancer Center (grant no. HA21C0110), Ministry of Health and Welfare, South Korea.
Hepatitis B virus (HBV) reactivation becomes a challenging issue with increasing use of immunosuppressive agents and cytotoxic chemotherapy for varied medical conditions, including cancer. The ...spectrum of HBV reactivation in the setting of immunosuppression may vary from asymptomatic reactivation to liver failure leading to death. HBV reactivation can hamper the course of planned therapies and diminish the effects of therapies; thus, it adversely affects the prognosis of the original disease and the survival of the patients. There is mounting evidence that HBV reactivation can be prevented and managed if patients are screened to determine their risk for HBV reactivation and are treated prophylactically before therapy with immunosuppressive agents or cytotoxic chemotherapy is initiated. In this article, we review the diagnostic criteria and clinical outcomes of HBV reactivation, discuss how immunosuppressive therapy may influence the risk of HBV reactivation, and outline strategies to prevent HBV reactivation.
It was suggested that normalization of serum alanine aminotransferase (ALT) levels at 1 year of antiviral treatment is associated with a lower risk of hepatic events in patients with chronic ...hepatitis B (CHB). However, it remains unclear whether earlier ALT normalization is associated with lower hepatocellular carcinoma (HCC) risk, independent of fatty liver or cirrhosis and on-treatment virological response (VR), in patients with CHB.
We analyzed 4,639 patients with CHB who initiated treatment with entecavir or tenofovir using landmark analysis and time-dependent Cox analysis. We defined normal ALT as ≤35 U/L (men) and ≤25 U/L (women) and VR as serum hepatitis B virus DNA <15 IU/mL.
During a median 5.6 years of treatment, 509 (11.0%) patients developed HCC. ALT normalization occurred in 65.6% at 1 year and 81.9% at 2 years and was associated with a significantly lower HCC risk in landmark (P < 0.001) and time-dependent Cox analyses (adjusted hazard ratio AHR 0.57; P < 0.001). Compared with ALT normalization within 6 months, delayed ALT normalization at 6-12, 12-24, and >24 months was associated with incrementally increasing HCC risk (AHR 1.40, 1.74, and 2.45, respectively; P < 0.001), regardless of fatty liver or cirrhosis at baseline and VR during treatment. By contrast, neither earlier VR (AHR 0.93; P = 0.53) nor earlier hepatitis B e antigen seroclearance (AHR 0.91; P = 0.31) was associated with a significantly lower HCC risk.
In patients with CHB treated with entecavir or tenofovir, earlier ALT normalization was independently associated with proportionally lower HCC risk, regardless of fatty liver or cirrhosis at baseline and on-treatment VR.
Few large-scale studies have been published regarding the association between autoimmune hepatitis (AIH) and risk of osteoporotic fracture. This study aimed to determine the risk of developing an ...osteoporotic fracture in patients with AIH.
We used claims data from the Korean National Health Insurance Service between 2007 and 2020. Patients with AIH (n = 7,062) were matched with controls (n = 28,122) based on age, sex, and duration of follow-up using a ratio of 1:4. Osteoporotic fractures included fractures of the vertebrae, hip, distal radius, and proximal humerus. The incidence rate (IR) and IR ratio of osteoporotic fracture were compared between the 2 groups, and their associated factors were evaluated.
During a median follow-up period of 5.4 years, 712 osteoporotic fractures occurred in patients with AIH with an IR of 17.5 per 1,000 person-years. Patients with AIH had a significantly higher risk of osteoporotic fractures than matched controls, with an IR ratio of 1.24 (95% confidence intervals, 1.10-1.39, P < 0.01) in the multivariable analysis. Female sex, older age, history of stroke, presence of cirrhosis, and use of glucocorticoids were associated with an increased risk of osteoporotic fractures. In the 2-year landmark analysis, longer duration of glucocorticoid exposure was associated with an incremental increased risk of osteoporotic fracture.
Patients with AIH had an increased risk of osteoporotic fracture compared with controls. The presence of cirrhosis and long-term use of glucocorticoids further adversely affected osteoporotic fracture in patients with AIH.
The initiation of antiviral treatment in patients with chronic hepatitis B with compensated cirrhosis and low-level viremia (LLV; HBV DNA 15-2,000 IU/mL) remains controversial. We sought to compare ...the long-term outcomes of these untreated patients according to their viremic status.
Six hundred twenty-seven untreated patients with chronic hepatitis B with compensated cirrhosis were analyzed retrospectively. The risk of hepatocellular carcinoma (HCC) and liver-related clinical events, including hepatic decompensation, were compared between patients with LLV and undetectable HBV DNA. Patients who received antiviral treatment were censored during treatment initiation.
The mean age of the patients was 54.7 years, 64.4% of whom were male. During the study period, 59 patients developed HCC (20 and 39 in the undetectable and LLV groups, respectively) with an annual incidence of 2.44/100 person-years. Multivariable analysis revealed that the LLV group was associated with a significantly higher risk of HCC (adjusted hazard ratio: 2.36, P = 0.002) than the undetectable group. In the 204 propensity score-matched cohort, the LLV group had a 2.16-fold greater risk of HCC than the undetectable group ( P = 0.014). Liver-related clinical events occurred in 121 patients with an annual incidence of 5.25/100 person-years. Despite not reaching statistical significance, the LLV group tended to have a higher risk of liver-related events in the propensity score-matched cohort (hazard ratio: 1.14, P = 0.50).
Compared with patients with undetectable HBV DNA, those with compensated cirrhosis and LLV had a significantly higher risk of HCC. Antiviral treatment should be advised for these patients.
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