Background Interferon (IFN)-α therapy for chronic hepatitis C virus infection is frequently associated with depression. The routine prophylaxis with antidepressants might expose patients to adverse ...effects, hence, the need for alternative preventive interventions. Omega-3 polyunsaturated fatty acids are safe and effective essential nutritional compounds used for the treatment of depression, putatively through an anti-inflammatory action. In addition, lower erythrocyte levels of omega-3 polyunsaturated fatty acids have been associated with an increased risk of IFN-induced depression. Methods We conducted a 2-week, double-blind, placebo-controlled trial comparing eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and placebo for the prevention of IFN-α-induced depression. A total of 162 patients consented to participate and were randomized to the study. All of the patients completed the 2-week trial; 152 participants were followed throughout the 24 weeks of IFN-α treatment and were included in the analysis. Results Compared with placebo, the incident rates of IFN-α-induced depression were significantly lower in EPA-treated but not in DHA-treated patients (10% and 28%, respectively, versus 30% for placebo, p = .037). Both EPA and DHA significantly delayed the onset of IFN-induced depression (week of onset: 12.0 and 11.7, respectively, versus 5.3 for placebo, p = .002). EPA and DHA were both well tolerated in this population. EPA treatment increased both EPA and DHA erythrocyte levels, but DHA only increased DHA erythrocyte levels. Conclusions EPA is effective in the prevention of depression in hepatitis C virus patients received IFN-α therapy. Our study confirms the notion that anti-inflammatory strategies are effective antidepressants in the context of depression associated with inflammation.
Studies on temporal changes in noninvasive fibrosis indices and liver stiffness measurement (LSM) in patients with chronic hepatitis C (CHC) treated with direct-acting antiviral agents (DAAs) are ...limited.
We retrospectively enrolled consecutive patients with CHC who had received DAAs.
In total, we recruited 395 consecutive patients, of which 388 (98.2%) achieved a sustained virologic response (SVR) at 12 weeks after therapy. In patients who received DAA therapy and achieved SVR 12 weeks after therapy (n = 388), the median aspartate aminotransferase/platelet ratio index (APRI) value decreased from 1.19 (0.62-2.44) at baseline to 0.50 (0.32-0.95), 0.51 (0.31-0.92), 0.48 (0.31-0.88), and 0.52 (0.33-0.92) at week 2, week 4, end of therapy, and PW12, respectively (all P < 0.001). The median FIB-4 value decreased from 2.88 (1.56-5.60) at baseline to 2.10 (1.30-3.65), 2.15 (1.30-3.65), 2.11 (1.37-3.76), and 2.22 (1.45-3.82) at week 2, week 4, end of therapy, and PW12, respectively (all P < 0.001). The median alanine aminotransferase level significantly decreased from week 2 until PW12 (all P < 0.001). The platelet count significantly increased from 2 weeks after DAA therapy initiation until PW12 (all P < 0.001); however, the magnitude of changes in the platelet count was low. In patients with paired LSMs obtained using acoustic radiation force impulse elastography at baseline and PW12 (n = 199), the median LSM decreased from 1.78 (1.25-2.30) m/s at baseline to 1.38 (1.14-1.88) m/s at PW12 (P < 0.001).
Noninvasive fibrosis indices, namely APRI and FIB-4, exhibited a rapid and sustained decline from week 2 until PW12 in patients with CHC who achieved SVR to DAA therapy. The rapid decline in APRI and FIB-4 values might mainly result from improvement in necroinflammation.
Patients with chronic hepatitis C (CHC) have a higher prevalence of hepatic steatosis and dyslipidaemia than healthy individuals. We analysed noninvasive fibrosis assessments, especially nonalcoholic ...fatty liver disease (NAFLD)‐related noninvasive fibrosis tests, for predicting liver‐related complications and hepatocellular carcinoma (HCC) occurrence in patients with CHC. This retrospective study enrolled 590 consecutive patients with CHC having a sustained virologic response (SVR) to direct‐acting antiviral agent (DAA) therapy. The NAFLD fibrosis score (NFS) exhibiting the highest value of area under the receiver operating characteristic curve (AUROC) was selected for comparison with the fibrosis‐4 index (FIB‐4). Of the 590 patients, 188 had metabolic syndrome. A multivariate Cox regression analysis identified total bilirubin at 3 or 6 months after DAA therapy (PW12), NFS at PW12 (hazard ratio HR: 2.125, 95% confidence interval CI: 1.058–4.267, p = .034) and alpha‐fetoprotein (AFP) at PW12 (HR: 1.071, 95% CI: 1.005–1.142, p = .034) as the independent predictors of liver‐related complications in all patients. In patients with metabolic syndrome, NFS and AFP values at PW12 were independent predictors of liver‐related complications and HCC occurrence. Time‐dependent NFS AUROC values at PW12 for 1‐, 2‐ and 3‐year liver‐related complications were higher than NFS values at baseline in patients with metabolic syndrome. NFS at baseline or PW12 is a more effective predictor of liver‐related complications than FIB‐4 values in all patients. NFS at PW12 may be a useful predictor of liver‐related complications and HCC development in patients with CHC with an SVR to DAA therapy, especially in those with metabolic syndrome.
We developed an optimal noninvasive index comprising routine laboratory parameters for predicting cirrhosis in chronic hepatitis B (CHB) and chronic hepatitis C (CHC) patients. This study included ...992 CHB patients and 1,284 CHC patients who received liver biopsy. We developed the new index, named modified Fibrosis-4 (mFIB-4) according to four independent variables of the model: age, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet count. The formula of the mFIB-4 index is 10 × Age(years) × AST(U/L)/Platelet count(10
/L) × AST(U/L). For predicting cirrhosis, the bootstrap areas under the receiver operating characteristic curve for platelet count, AST/ALT ratio (AAR), AAR/platelet ratio index (AARPRI), AST/platelet ratio index (APRI), FIB-4, Pohl score, age-platelet (AP) index, Lok index, fibrosis quotient (FibroQ), and mFIB-4 were 0.7680, 0.7400, 0.8070, 0.6090, 0.7690, 0.6990, 0.7850, 0.7960, 0.8110, and 0.8070 in CHB patients, and 0.8170, 0.7210, 0.8400, 0.7310, 0.8310, 0.6730, 0.8220, 0.8440, 0.8570, and 0.8480 in CHC patients, respectively. FibroQ and mFIB-4 exhibited the highest diagnostic performance levels for liver cirrhosis in CHB and CHC despite the inclusion of the international normalised ratio in the formulation of FibroQ. Thus, mFIB-4 is a simple, inexpensive, and readily available method for assessing the liver fibrosis stage of Asian patients with CHB or CHC.
To compare on-treatment and off-treatment parameters acquired using acoustic radiation force impulse elastography, the Fibrosis-4 (FIB-4) index, and aspartate aminotransferase-to-platelet ratio index ...(APRI) in patients with chronic hepatitis C (CHC).
Patients received therapies based on pegylated interferon or direct-acting antiviral agents. The changes in paired patient parameters, including liver stiffness (LS) values, the FIB-4 index, and APRI, from baseline to sustained virologic response (SVR) visit (24 weeks after the end of treatment) were compared. Multiple regression models were used to identify significant factors that explained the correlations with LS, FIB-4, and APRI values and SVR.
A total of 256 patients were included, of which 219 (85.5%) achieved SVR. The paired LS values declined significantly from baseline to SVR visit in all groups and subgroups except the nonresponder subgroup (n = 10). Body mass index (P = 0.0062) and baseline LS (P < 0.0001) were identified as independent factors that explained the LS declines. Likewise, the baseline FIB-4 (P < 0.0001) and APRI (P < 0.0001) values independently explained the declines in the FIB-4 index and APRI, respectively. Moreover, interleukin-28B polymorphisms, baseline LS, and rapid virologic response were identified as independent correlates with SVR.
Paired LS measurements in patients treated for CHC exhibited significant declines comparable to those in FIB-4 and APRI values. These declines may have correlated with the resolution of necroinflammation. Baseline LS values predicted SVR.
In the RESORCE study, regorafenib after sorafenib therapy improved survival in patients with advanced hepatocellular carcinoma (HCC). In total, 88 patients with unresectable HCC who received ...sorafenib–regorafenib sequential therapy were enrolled. The objective response rate and disease control rate were 19.3% and 48.9%, respectively, for regorafenib therapy (median duration: 8.1 months). Median progression-free survival (PFS) after regorafenib therapy was 4.2 months (95% CI: 3.2–5.1). The median overall survival (OS; from initiation of either sorafenib or regorafenib) was not reached in this cohort. According to multivariate Cox regression analyses, albumin-bilirubin (ALBI) grade at the initiation of regorafenib therapy is an independent predictor of disease control, PFS, and OS. Moreover, the combination of ALBI grade 2 and an alpha-fetoprotein (AFP) level of ≥20 ng/mL was an independent predictor of PFS (hazard ratio (HR): 3.088, 95% CI: 1.704–5.595; p < 0.001) for regorafenib therapy, and OS for both regorafenib (HR: 3.783, 95% CI: 1.316–10.88; p = 0.014) and sorafenib–regorafenib sequential (HR: 4.603, 95% CI: 1.386–15.29; p = 0.013) therapy. A combination of ALBI grade and AFP level can be used to stratify patients with unresectable HCC by PFS and OS probability for sorafenib–regorafenib sequential therapy.
Background and Aim
Noninvasive fibrosis indices can predict the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). Modified FIB‐4 (mFIB‐4) is a promising noninvasive ...index for predicting liver fibrosis. To investigate the predictive accuracy of several extant noninvasive fibrosis indices, including mFIB‐4, for HCC incidence in CHB patients receiving long‐term entecavir therapy.
Methods
We enrolled 1325 nucleos(t)ide analogue‐naïve CHB patients (noncirrhotic 844; cirrhotic 481) treated with entecavir. Baseline clinical features and fibrosis indices were collected and evaluated for predicting HCC risk through univariate and multivariate Cox regression analyses.
Results
Of the 1325 patients, 105 (7.9%) developed HCC during a median follow‐up period of 4.1 years. Age (hazard ratio HR, 1.039; 95% confidence interval CI, 1.020–1.059; P < 0.0001), diabetes mellitus (DM) (HR, 1.902; 95% CI, 1.185–3.052; P = 0.0077), and mFIB‐4 (HR, 4.619; 95% CI, 1.810–11.789; P = 0.0014) were independent predictors of HCC in all patients (mFIB‐4 ≥ 1.5 for the noncirrhotic cohort; DM and mFIB‐4 ≥ 2.0 for the cirrhotic cohort). A combination of mFIB‐4 and the DM status stratified the cumulative risk of HCC into three subgroups in all patients (high: mFIB‐4 ≥ 1.5/DM; intermediate: mFIB‐4 ≥ 1.5/non‐DM; and low: mFIB‐4 < 1.5, P < 0.0001) and in the cirrhotic cohort (high: mFIB‐4 ≥ 2.0/DM; intermediate: mFIB‐4 ≥ 2.0/non‐DM; and low: mFIB‐4 < 2.0, P = 0.0007). An mFIB‐4 cutoff value of 1.5 stratified the cumulative risk of HCC in the noncirrhotic cohort (P = 0.015).
Conclusions
The mFIB‐4 index alone or in combination with DM is the optimal noninvasive predictor of HCC risk in CHB patients receiving entecavir therapy.
Aims. Long-term risk stratification using combined liver stiffness (LS) and clinically relevant blood tests acquired at the baseline further beyond the sustained virologic response (SVR) visit for ...chronic hepatitis C (CHC) has not been thoroughly investigated. This study retrospectively investigated the prognostics of liver-related events (LREs) further beyond the SVR visit. Methods. Cox regression and random forest models identified the key factors, including longitudinal LS and noninvasive test results, that could predict LREs, including hepatocellular carcinoma, during prespecified follow-ups from 2010 to 2021. Kaplan–Meier survival analysis estimated the significance of between-group risk stratification. Results. Of the entire eligible cohort (n = 520) of CHC patients with SVR to antiviral therapy, 28 (5.4%) patients developed post-SVR LREs over a median follow-up period of 6.1 years (interquartile range = 3.5–8.7). The multivariate Cox regression analysis identified two significant predictors of LREs after the year 3 post-SVR (Y3PSVR) baseline (LRE, n = 15 of 28, 53.6%, median follow-up = 4.1 1.6–6.4 years after Y3PSVR): LS at Y3PSVR (adjusted hazard ratio aHR = 3.980, 95% confidence interval CI = 2.085–7.597, P<0.001), and α-fetoprotein (AFP) at Y3PSVR (aHR = 1.017, 95% CI = 1.001–1.034, P=0.034). LS ≥1.45 m/s and AFP ≥3.00 ng/mL for Y3PSVR yielded positive likelihood ratios of 4.24 and 2.62, respectively. Kaplan–Meier analysis revealed that among the stratified subgroups, the subgroup with concurrent LS ≥1.45 m/s and AFP ≥3.00 ng/mL at Y3PSVR exhibited the highest risk of LREs after Y3PSVR (log-rank P<0.001). Conclusion. We recommend the combined use of concurrent LS and AFP in future prediction models for LREs in CHC. Patients with concurrently high LS and AFP values further beyond the SVR visit may require a recall policy involving intense surveillance.
Background & Aims
This study investigates the long‐term incidences and predictors of developing hepatocellular carcinoma (HCC), cirrhotic events and mortality in cirrhotic patients receiving ...entecavir (ETV) therapy.
Methods
We enrolled 481 nucleos(t)ide analogue‐naïve chronic hepatitis B (CHB) patients who had compensated cirrhosis upon entry and had received ETV monotherapy for >12 months.
Results
The 8‐year cumulative incidences of developing HCC, cirrhotic events and liver‐related mortality were 26.5%, 8.62% and 10.03% respectively. Multivariate analysis revealed that diabetic mellitus (DM), higher fibrosis‐4 (FIB‐4) and alpha‐foetoprotein (AFP) levels at 12 months of treatment, and FIB‐4 increase from baseline to 12 months were independent factors of HCC. FIB‐4 and AFP levels at 12 months of treatment were also independent factors of cirrhotic events and mortality. FIB‐4 cut‐off values of 3, 3 and 5 as well as AFP cut‐offs of 5, 5, and 9 ng/mL at 12 months of treatment were optimal for predicting HCC, cirrhotic events and mortality during therapy respectively. The FIB‐4 and AFP levels at 12 months of treatment were assessed for the combined risk of developing clinical outcomes. The 8‐year incidences of HCC, cirrhotic events and liver‐related mortality in the subgroups with low FIB‐4 and AFP levels were only 5.95%, 1.03% and 2.43% respectively. DM was an independent predictor of HCC and mortality.
Conclusion
The combination of FIB‐4 and AFP levels at 12 months of treatment is a useful marker for predicting the development of HCC, cirrhotic events and mortality in compensated cirrhotic patients with CHB who are receiving ETV therapy.
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