Additional role of liver stiffness measurement in stratifying residual hepatocellular carcinoma risk predicted by serum biomarkers in chronic hepatitis B patients under antiviral therapy.

BACKGROUND: The risk of hepatocellular carcinoma (HCC) remains among patients who are treated with antiviral therapy (AVT). The degree of liver fibrosis has been suggested as an important biomarker to stratify the risk of developing HCC. We tested whether liver stiffness (LS) measured using transient elastography is useful over two noninvasive serum biomarkers of fibrosis [the aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 (FIB-4)]. PATIENTS AND METHODS: A retrospective cohort of 1014 CHB patients who were under AVT with nucleos(t)ide analogs for at least a year was analyzed. The risk of HCC development according to serum biomarkers (APRI and FIB-4) and LS was compared. RESULTS: The HCC risk was higher for those with a higher degree of liver fibrosis, as estimated by the LS, APRI, and FIB-4. When the two serum biomarkers were used to group the patients, the 3-year HCC incidence rates were 7.3, 3.0, and 1.3% for both high APRI (≥0.5) and FIB-4 (≥1.45) scores, either a high APRI or FIB-4 score, and both low APRI and FIB-4 scores, respectively (P<0.001). Among the 758 patients with discordant or both low APRI and FIB-4 scores, the LS value was high (>6) for a significant proportion of the patients (39.9%). The HCC risk was significantly different according to the LS value (3-year HCC incidence rate of 1.1, 2.0, and 6.8% for LS <6, 6-9, and >9, respectively, P<0.001). CONCLUSION: Among CHB patients under AVT, LS could stratify risk for HCC, including patients with discordant or both low APRI and FIB-4 score. This finding indicates that LS measurement plays an additional role over the serum biomarkers in stratifying the residual risk of HCC.

Non-invasive tests for liver disease severity and the hepatocellular carcinoma risk in chronic hepatitis B patients with low-level viremia.

BACKGROUND & AIMS: We tested whether non-invasive tests for liver disease severity can stratify hepatocellular carcinoma (HCC) risk in chronic hepatitis B virus (HBV)-infected patients showing low-level viremia (LLV, HBV DNA <2000 IU/mL). METHODS: A retrospective cohort of 1006 chronic hepatitis B patients showing persistently LLV, defined by at least two consecutive assessments in the year before enrolment, was assessed for HCC development. Two non-invasive serum biomarkers, the aspartate aminotransferase to platelet ratio index (APRI) and the Fibrosis-4 (FIB-4), were tested. Cirrhosis was defined with ultrasonography. RESULTS: During a median 5.1 years of follow-up, HCC developed in 36 patients. HCC incidence rate at 5 years was significantly higher for cirrhotic patients (19/139, 13.7%), but was not null for non-cirrhotic patients (17/867, 2.0%, P<.001). APRI at a cut-off of 0.5 was more specific but less sensitive for HCC development, and FIB-4 at a cut-off of 1.45 was more sensitive but less specific. When both APRI and FIB-4 were used to group patients, the 5-year cumulative HCC incidence rate was 13.9%, 1.4% and 1.2% for both high, any high, and both low APRI and FIB-4 score among all patients (n=1006, P<.001), respectively, and was 11.4%, 1.5% and 0.4% in the same respective order among non-cirrhotic patients (n=867, P<.001). CONCLUSIONS: The combined use of two non-invasive serum biomarkers (APRI and FIB-4) could stratify HCC risk for chronic HBV-infected patients with LLV.

Patient-reported Outcomes in Asian Patients With Chronic Hepatitis C Treated With Ledipasvir and Sofosbuvir.

Prevalence of chronic hepatitis C (CH-C) infection in patients of Asian ancestry ranges between 1% and 20%. Interferon (IFN)- and ribavirin (RBV)-containing regimens for CH-C have a negative impact on patient-reported outcomes (PROs) during treatment. The aim of this study was to assess the impact of IFN-free RBV-free sofosbuvir (SOF)-based regimens on PROs in CH-C patients of Asian ancestry. In this observational retrospective study, the PRO data from 12 multicenter multinational phase 3 clinical trials (2012-2015, conducted in Europe, North America, Australia, and New Zealand) of SOF-based regimens with and without IFN, ledipasvir (LDV), and/or RBV were used. At baseline, during treatment, and post-treatment, patients completed 4 validated PRO questionnaires (SF-36, CLDQ-HCV, FACIT-F, and WPAI:SHP). The resulting PROs in Asian patients were compared across the treatment regimens. Of 4485 of the trials' participants, 106 patients were of Asian ancestry (55.7% male, 69.8% treatment-naïve, 17.0% cirrhotic). In comparison with other patients, the Asian CH-C cohort was younger, had lower BMI, and lower rates of pre-treatment psychiatric comorbidities (anxiety, depression, sleep disorders) (all P < .05). At baseline, Asian patients also had lower SF-36 physical functioning scores (on average, by -5.6% on a normalized 0-100% PRO scale, P = .001). During treatment, Asian CH-C patients experienced a decline in their PRO scores while receiving IFN and/or RBV-containing regimens (up to -19.6%, P < .001). In contrast, patients receiving LDV/SOF experienced no PRO decrement and improvement of some PRO scores during treatment (+9.0% in general health of SF-36, P = .03). After achieving SVR-12, some of the PRO scores in Asian patients improved regardless of the regimen (up to +9.3%, P < .001). In multivariate analysis of Asian patients, the use of LDV/SOF was independently associated with higher PRO scores during and soon after the end of treatment (betas +15.0% to +29.3%, all P < .05). Other predictors of PRO impairment included depression, type 2 diabetes mellitus, and cirrhosis. The use of IFN- and RBV-free LDV/SOF regimens leads to PRO improvement in Asian patients with CH-C during treatment. Achieving SVR-12 results in improvement of PRO scores.

The change of the quantitative HBsAg level during the natural course of chronic hepatitis B.

BACKGROUND: There is insufficient information about HBsAg levels and their correlation with serum hepatitis B virus (HBV) DNA in chronic hepatitis B (CHB). AIMS: We aimed to describe HBsAg levels during various phases of CHB and to investigate the correlation with serum HBV DNA levels. METHODS: A total of 645 treatment-naïve Korean CHB patients were included in this retrospective cross-sectional study. They were categorized into immune tolerance (IT, n=56), HBeAg-positive hepatitis (EPH, n=150), inactive carrier (IC, n=274) and HBeAg-negative hepatitis (ENH, n=165). The baseline HBsAg and HBV DNA levels were measured. RESULTS: The mean HBsAg titres (log IU/ml) differed (P<0.001): IT 4.29, EPH 3.64, IC 2.05 and ENH 3.23. In 645 patients, HBsAg and HBV DNA showed a significant correlation (r=0.693, P<0.001), and this was also observed in the IT, EPH and IC groups (r=0.664, r=0.541, r=0.505, respectively, all P<0.001), but not in the ENH group (r=0.093, P=0.321). Age had a negative correlation with HBsAg (r=-0.451, P<0.001). The cirrhotic patients had a significantly lower HBsAg level than the non-cirrhotic patients (2.41 ± 1.36 vs. 3.02 ± 1.21 log IU/ml, P<0.001). CONCLUSIONS: The HBsAg level varied significantly in different phases of CHB and was correlated with HBV DNA during the IT, EPH and IC phases. These findings can provide additional information to understand the natural course and pathogenesis of CHB.

Association of a single nucleotide polymorphism near the interleukin-28B gene with response to hepatitis C therapy in Asian patients.

BACKGROUND AND AIMS: A single nucleotide polymorphism near the interleukin-28B (IL28B) gene has been shown to predict hepatitis C virus (HCV) treatment response. We aim to determine the role of the IL28B genotype in Asian patients. METHODS: A total of 118 patients (all Korean, 55 patients with genotype 1 infection and 63 patients with genotype 2 infection) were consecutively enrolled and analyzed. RESULTS: The sustained virological response (SVR) rate was 74% (87/118), while 26 patients (22%) relapsed and five patients were non-responders (4%). For rs8099917, the frequencies of major homozygotes (TT), heterozygotes (GT), and minor homozygotes (GG) were 0.85, 0.14 and 0.01, respectively. Of the 55 patients with HCV genotype 1 infection, the SVR rate was 67% and 44% (P = 0.19) and the non-response rate was 2% and 22% (P = 0.015) for the major allele and minor or hetero allele, respectively. Of the 63 patients with HCV genotype 2 infection, the SVR rate was 80% and 100% (P = 0.13) and the non-response rate was 4% and 0% (P = 0.55) for major allele and hetero allele, respectively. CONCLUSIONS: The IL28B genotype may help identify non-responding patients in HCV genotype 1, but not in HCV genotype 2. Because of the high frequency of favorable alleles and the low frequency of non-response, the IL28B polymorphism may play a smaller role in Asian patients.