The aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4) are commonly used compound surrogates for advanced fibrosis in chronic hepatitis C (CHC) patients. ...However, the use of APRI and FIB-4 entails a risk of overestimating the fibrosis stage due to the impact of necroinflammatory activity on transaminases. We sought to investigate the optimal cutoff values of the two compound surrogates for predicting cirrhosis stratified by AST level.
This retrospective study enrolled 1716 treatment-naive CHC patients who underwent liver biopsy prior to interferon therapy from 1997-2010. Fibrosis was scored according to the modified Knodell classification. The upper limit for normal AST in our hospital is 37 IU/L. We stratified the enrolled patients into the categories of AST≤37 IU/L (N = 132), 37<AST≤74, (N = 501), 74<AST≤148 IU/L (N = 737), and AST>148 IU/L (N = 346).
436 patients had cirrhosis (F4). The area under receiver operating characteristic (AUROC) analysis results distinguishing cirrhosis (F4) from non-cirrhosis (F0-F3) were 0.81 for APRI and 0.85 for FIB-4 in patients with AST≤37 IU/L; 0.71 for APRI and 0.72 for FIB-4 in patients with 37<AST≤74IU/L; 0.72 for APRI and 0.73 for FIB-4 in patients with 74<AST≤148 IU/L; and 0.68 for APRI and 0.70 for FIB-4 in patients with AST>148 IU/L. The optimal cutoff values of APRI and FIB-4 for the diagnosis of cirrhosis were 0.6 and 1.4, respectively, in patients with AST≤37 IU/L; 1.1 and 2.2, respectively, in patients with 37<AST≤74 IU/L; 2.2 and 3.4, respectively, in patients with 74<AST≤148 IU/L; and 3.4 and 5.5, respectively, in patients with AST>148 IU/L.
We provide optimal cutoff values of both APRI and FIB-4 to predict cirrhosis stratified by AST levels, which should be more feasible compared with the single cutoff values proposed in previous studies.
Summary
Background
Comparative long‐term efficacy of entecavir (ETV) and tenofovir disoproxil fumarate (TDF) for prevention of disease progression to hepatocellular carcinoma (HCC) among high‐risk ...patients with chronic hepatitis B (CHB)‐related compensated cirrhosis is controversial.
Aims
To compare the long‐term efficacy of ETV and TDF in HCC prevention in patients with CHB‐related cirrhosis, and to evaluate predictive risk factors for HCC development.
Methods
From January 2008 to March 2018, 894 treatment‐naïve patients with CHB‐related compensated cirrhosis on ETV or TDF were enrolled based on the longitudinal cohort study. Data were originally collected for 7.3 years of follow‐up or after the launch of TDF in 2011. Only the 5‐year cumulative incidence and risk factors of HCC were assessed.
Result
Total 678 and 216 patients received ETV and TDF, respectively. The cumulative risk of HCC at 1, 3 and 5 years of follow‐up was 1.6%, 11.3% and 18.7%, respectively, in the ETV group; and 0.9%, 6.7% and 10.7%, respectively, in the TDF group (P = 0.0305). Univariate and adjusted‐multivariable models revealed that platelet count, alpha‐fetoprotein (AFP) levels and upper gastrointestinal (UGI) varices were independent risk factors for HCC development. TDF resulted in risk of HCC development compared to ETV with adjusted hazard ratios (aHRs) of 0.66 (95% confidence interval CI:0.40, 1.08; P = 0.0971), 0.69 (95% CI: 0.42, 1.14; P = 0.1488) and 0.66 (95% CI: 0.38, 1.14; P = 0.1407) under stepwise selection, propensity score adjustment, and propensity score matching multivariable models, respectively.
Conclusions
For treatment‐naïve patients with CHB‐related compensated cirrhosis with 5‐year follow‐up, after variable adjustments, propensity score approaches and subgroup analyses, TDF showed a lower rate of HCC development that did not reach statistical significance, compared to the ETV.
Summary
Background
The impact of metabolic syndrome (MetS) on hepatitis is an interesting issue.
Aim
To evaluate the association of MetS and chronic viral hepatitis including hepatitis B virus (HBV) ...and hepatitis C virus (HCV) infection in southern Taiwan.
Methods
From 2004 to 2013, a series of community‐based health screenings for residents aged 40 and older were held in Tainan city. MetS was defined according to the Joint Scientific Statement. Cut‐offs of body‐mass index measures of 24 kg/m2 and 27 kg/m2 were used to stratify lean, overweight and obese subjects.
Results
We enrolled 180 359 participants; the prevalence of MetS was 30.1%, which was significantly associated with advanced age and female sex. There were 18 726 (10.4%) HBV, 13 428 (7.4%) HCV, 1337 (0.7%) HBV plus HCV (B+C) and 146 868 (81.5%) non‐HBV non‐HCV participants (NBNC). Prevalence rates of MetS in subjects with HBV, HCV, B+C and NBNC were 25.2%, 31.5%, 28.9% and 30.7% respectively (P < 0.001). There were 18.8% lean body, 35.4% overweight and 45.8% obese participants among 54 361 MetS subjects. Lean MetS subjects were older, had more diabetes, and had higher metabolic component levels, but lower alanine transaminase and aspartate transaminase‐platelet ratio index levels compared with obese MetS subjects. HCV infection was positively associated with MetS (P < 0.001). However, HBV infection was inversely associated with MetS only among lean subjects (P = 0.002), but not among the general population.
Conclusions
This large population‐based study indicated that HCV infection was positively associated with MetS. However, HBV infection was inversely associated with MetS only among lean subjects.
Intrahepatic distant recurrence (IDR) is a significant problem for patients who have undergone radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). The objective of the study was to ...investigate risk factors and to predict outcomes of recurrent IDR within Milan criteria after complete RFA for primary early-stage HCC.
This retrospective study reviewed 449 patients with intrahepatic distant recurrent HCC after complete RFA for early-stage HCC. After excluding 100 patients who were beyond Milan criteria, with incomplete lab data, or had follow-up less than three months, a total of 349 patient cases were compiled and their baseline characteristics, further treatment modalities after tumor recurrence and survival were analyzed.
After a median follow-up of 36.2 months, 92 patients had expired. The majority of patients were male (59.9%) with a median age of 64.3 years (range:38-88). The cumulative 5-year overall survival (OS) rates after treatment for recurrent HCC was 67.2%. On multivariate analysis, end-stage renal disease(Hazard ratio (H.R.) = 2.33, p = 0.021), m-ALBI grade 2a (H.R. = 2.86, p = 0.003) and m-ALBI grades 2b or 3 (H.R. = 2.30, p = 0.009), APRI greater than 1 (H.R. = 1.92, p = 0.036) and 2nd recurrence occurring within 1 year (H.R. = 2.69, p<0.001) were significantly associated with worse survival. The cumulative 5-year 2nd recurrence rate was 87.4%. On multivariate analysis, male gender (H.R. = 1.47, p = 0.01), age greater than 65 years (H.R. = 1.72, p<0.001), an alpha fetoprotein level greater than 20ng/ml (H.R. = 1.41, p = 0.016), surgical treatment for recurrent HCC (H.R. = 0.25, p = 0.007), tumor number greater than 1 (H.R. = 1.35, p = 0.046), and IDR developing within 2 years (H.R. = 1.67, p = 0.001) were prognostic factors for 2nd recurrence.
Our study suggested that presence of end-stage renal disease, m-ALBI grades 2 and 3, APRI >1 and time to 2nd HCC recurrence were all associated with overall survival while the 2nd HCC recurrence was associated with male gender, age ≥65 years, α-fetoprotein level >20 ng/mL, non-surgical therapy, time to IDR, and tumor number> 1.
Background and Aim
The Albumin‐Bilirubin (ALBI) grade is a new index to assess objectively liver function and prognosis in patients with hepatocellular carcinoma (HCC). This study aimed to elucidate ...the application of ALBI grade in baseline and sorafenib‐end in advanced HCC patients who received sorafenib.
Methods
A total of 415 consecutive advanced HCC patients in Child–Pugh A received sorafenib in our hospital. Sorafenib was terminated when radiologic tumor progression or clinical liver function deterioration (LD) occurred in the reassessment bimonthly. Patients who failed with sorafenib monotherapy were retrospectively analyzed.
Results
A total of 260 (62.6%) patients were enrolled, including 98 (37.7%) ALBI grade I and 162 (62.3%) grade II in baseline. More patients in ALBI grade II stopped sorafenib because of LD than in grade I (33.3% vs 14.3%, P < 0.001). Those who in baseline ALBI grade I had a superior overall survival than in grade II (8.5 months vs 4.4 months, P = 0.003). Cox regression analysis confirmed that baseline ALBI grade II (P < 0.001) and ALBI grade increase during treatment (P < 0.001) strongly contributed to the mortality of HCC patients who received sorafenib. After sorafenib failure, those with post‐sorafenib treatment had a better post‐sorafenib survival than those without (9.3 vs 1.6 months, P < 0.001). Logistic regression analysis indicated that sorafenib‐end ALBI grade and LD occurrence were the only two predictors of post‐sorafenib treatment after sorafenib failure.
Conclusions
In clinical practice, we firstly demonstrated that not only ALBI grade in baseline but also ALBI grade change during treatment could predict the prognosis of advanced HCC patients who received sorafenib.
Whether the etiology of chronic liver disease (CLD) impacts the overall survival (OS) of patients with hepatocellular carcinoma (HCC) remains unclear. We aim to clarify this issue.
Between 2011 and ...2020, 3941 patients who were newly diagnosed with HCC at our institution were enrolled in this study. In patients with multiple CLD etiologies, etiology was classified using the following hierarchy: hepatitis C virus (HCV) > hepatitis B virus (HBV) > alcohol-related > all negative. All negative was defined as negative for HCV, HBV, and alcohol use disorder.
Among 3941 patients, 1407 patients were classified with HCV-related HCC, 1677 patients had HBV-related HCC, 145 patients had alcohol-related HCC, and 712 patients had all-negative HCC. Using the all-negative group as the reference group, multivariate analysis showed that HBV is an independent predictor of mortality (hazard ratio: 0.856; 95% confidence interval: 0.745-0.983; p = 0.027). Patients with HBV-related HCC had superior OS compared with patients with other CLD etiologies (p<0.001). Subgroup analyses were performed, for Barcelona Clinic Liver Cancer (BCLC) stages 0-A (p<0.001); serum alpha-fetoprotein (AFP) levels≧20 ng/ml (p<0.001); AFP levels < 20 ng/ml (p<0.001); age > 65 years (p<0.001); and the use of curative treatments (p = 0.002). No significant difference in OS between HBV and other etiologies was observed among patients aged ≤ 65 years (p = 0.304); with BCLC stages B-D (p = 0.973); or who underwent non-curative treatments (p = 0.1).
Patients with HBV-related HCC had superior OS than patients with other HCC etiologies.
Atezolizumab plus bevacizumab has been approved as the first-line systemic treatment for patients with unresectable hepatocellular carcinoma (uHCC). This study was designed to assess the clinical ...impact of atezolizumab plus bevacizumab in uHCC patients. A total of 48 uHCC patients receiving atezolizumab plus bevacizumab were identified, including first-line, second-line, third-line, and later-line settings. In these patients, the median progression-free survival (PFS) was 5.0 months, including 5.0 months for the first-line treatment, not reached for the second-line treatment, and 2.5 months for the third line and later line treatment. The objective response rate and disease control rate to atezolizumab plus bevacizumab were 27.1% and 68.8%, respectively. The severity of most adverse events was predominantly grade 1-2, and most patients tolerated the toxicities. The ratios of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte (PLR) were used to predict PFS in these patients. The optimal cutoff values of NLR and PLR were 3 and 230, and NLR and PLR were independent prognostic factors for superior PFS in the univariate and multivariate analyses. Our study confirms the efficacy and safety of atezolizumab plus bevacizumab in uHCC patients in clinical practice and demonstrates the prognostic role of NLR and PLR for PFS in these patients.
Previous studies from western countries have reported that active hepatocellular carcinoma (HCC) was associated with direct-acting antiviral (DAA) treatment failure. We sought to examine this issue ...in an Asian cohort.
A retrospective cohort study was conducted on hepatitis C virus (HCV)-infected patients with advanced fibrosis who were treated with DAAs at our hospital between January 2017 and June 2018.
We treated 1021 HCV-infected patients during this period. A total of 976 of those patients were enrolled in a per-protocol analysis, including 556 (57.2%) who had genotype 1b infections, and 314 (32.3%) who had genotype 2 infections. The mean age of all 976 patients was 65.5 years, and 44.5% were male. 781 of the patients had no HCC, 172 had inactive HCC, and 23 had active HCC. Non-sustained virologic response (SVR) was noted in 10 (1.3%) patients without HCC, 5 (2.9%) patients with inactive HCC, and 4 (13.0%) patients with active HCC. After adjustment for confounders, active HCC (versus inactive HCC and non-HCC) was associated with non-SVR (adjusted odds ratio AOR = 24.5 (95% confidence interval CI = 4.4-136.9), P<0.001). Next, we excluded the 23 patients with active HCC from the multivariate analysis. After adjustment for confounders, inactive HCC (versus non-HCC) was not associated with non-SVR (AOR = 3.1 (95% CI = 0.94-9.95), P = 0.06).
Active HCC was associated with non-SVR, while inactive HCC was not. We thus suggest the deferral of DAA treatment until after the complete radiological response of HCCs to treatment.
To investigate the incidence of gastric cancer (GC) attributed to gastric intestinal metaplasia (IM), and validate the Operative Link on Gastric Intestinal Metaplasia (OLGIM) for targeted endoscopic ...surveillance in regions with low-intermediate incidence of GC.
A prospective, longitudinal and multicentre study was carried out in Singapore. The study participants comprised 2980 patients undergoing screening gastroscopy with standardised gastric mucosal sampling, from January 2004 and December 2010, with scheduled surveillance endoscopies at year 3 and 5. Participants were also matched against the National Registry of Diseases Office for missed diagnoses of early gastric neoplasia (EGN).
There were 21 participants diagnosed with EGN. IM was a significant risk factor for EGN (adjusted-HR 5.36; 95% CI 1.51 to 19.0; p<0.01). The age-adjusted EGN incidence rates for patients with and without IM were 133.9 and 12.5 per 100 000 person-years. Participants with OLGIM stages III-IV were at greatest risk (adjusted-HR 20.7; 95% CI 5.04 to 85.6; p<0.01). More than half of the EGNs (n=4/7) attributed to baseline OLGIM III-IV developed within 2 years (range: 12.7-44.8 months). Serum trefoil factor 3 distinguishes (Area Under the Receiver Operating Characteristics 0.749) patients with OLGIM III-IV if they are negative for
. Participants with OLGIM II were also at significant risk of EGN (adjusted-HR 7.34; 95% CI 1.60 to 33.7; p=0.02). A significant smoking history further increases the risk of EGN among patients with OLGIM stages II-IV.
We suggest a risk-stratified approach and recommend that high-risk patients (OLGIM III-IV) have endoscopic surveillance in 2 years, intermediate-risk patients (OLGIM II) in 5 years.
Our objective was to develop a predictive nomogram that could estimate the long-term survival of patients with very early/early-stage hepatocellular carcinoma (HCC) undergoing radiofrequency ablation ...(RFA). For this retrospective study, we enrolled 950 patients who initially received curative RFA for HCC at Barcelona Clinic Liver Cancer (BCLC) stages 0 and A between 2002 and 2016. Factors predicting poor survival after RFA were investigated through a Cox proportional hazard model. The nomogram was constructed using the investigated variables influencing overall survival (OS). After a median follow-up time of 6.25 years, 400 patients had died, and 17 patients had received liver transplantation. The 1-,3-,5-,7-, and 10-year OS rates were 94.5%, 73.5%, 57.9%, 45.7%, and 35.8%, respectively. Multivariate analysis showed that age greater than 65 years, albumin-bilirubin (ALBI) grades 2 and 3, AST-to-platelet ratio index (APRI) greater than 1, tumor size larger than 3 cm, diabetes mellitus, end-stage renal disease, and tumor number greater than 1 were significantly associated with poor OS. The nomogram was constructed using these seven variables. The validation results showed a good concordance index of 0.683. When comparing discriminative ability to tumor, node, and metastasis (TNM), BCLC, and Cancer of the Liver Italian Program (CLIP) staging systems, our nomogram had the highest C-index for predicting mortality. This nomogram provides useful information on prognosis post-RFA as a primary treatment and aids physicians in decision-making.
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