Improvement of hepatic fibrosis after tenofovir disoproxil fumarate switching to tenofovir alafenamide for three years.

BACKGROUND: Both tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) are the first-line treatments for chronic hepatitis B (CHB). We have showed switching from TDF to TAF for 96 weeks resulted in further alanine aminotransferase (ALT) improvement, but data remain lacking on the long-term benefits of TDF switching to TAF on hepatic fibrosis. AIM: To assess the benefits of TDF switching to TAF for 3 years on ALT, aspartate aminotransferase (AST), and hepatic fibrosis improvement in patients with CHB. METHODS: A single center retrospective study on 53 patients with CHB who were initially treated with TDF, then switched to TAF to determine dynamic patterns of ALT, AST, AST to platelet ratio index (APRI), fibrosis-4 (FIB-4) scores, and shear wave elastography (SWE) reading improvement at switching week 144, and the associated factors. RESULTS: The mean age was 55 (28-80); 45.3%, males; 15.1%, clinical cirrhosis; mean baseline ALT, 24.8; AST, 25.7 U/L; APRI, 0.37; and FIB-4, 1.66. After 144 weeks TDF switching to TAF, mean ALT and AST were reduced to 19.7 and 21, respectively. From baseline to switching week 144, the rates of ALT and AST < 35 (male)/25 (female) and < 30 (male)/19 (female) were persistently increased; hepatic fibrosis was also improved by APRI < 0.5, from 79.2% to 96.2%; FIB-4 < 1.45, from 52.8% to 58.5%, respectively; mean APRI was reduced to 0.27; FIB-4, to 1.38; and mean SWE reading, from 7.05 to 6.30 kPa after a mean of 109 weeks switching. The renal function was stable and the frequency of patients with glomerular filtration rate > 60 mL/min was increased from 86.5% at baseline to 88.2% at switching week 144. CONCLUSION: Our data confirmed that switching from TDF to TAF for 3 years results in not only persistent ALT/AST improvement, but also hepatic fibrosis improvement by APRI, FIB-4 scores, as well as SWE reading, the important clinical benefits of long-term hepatitis B virus antiviral treatment with TAF.

Performance of Endoscopic Ultrasound-Guided Versus Percutaneous Liver Biopsy in Diagnosing Stage 3-4 Fibrosis.

BACKGROUND: Percutaneous liver biopsy (P-bx) is the gold standard for diagnosing advanced fibrosis. Despite the proven technical feasibility of EUS-guided liver bx (EUS-bx) as a novel alternative way of liver biopsy, the clinical applicability remains to be determined. AIMS: The primary aim of this study is to evaluate if EUS-bx, compared to P-bx, can effectively and safely obtain adequate specimen and accurately predict hepatic fibrosis. METHODS: This is a single center, retrospective chart review among patients with liver diseases at a tertiary endoscopy center from February 2011 to March 2020. We assessed the EUS-bx versus P-bx outcomes by success rate, performance, and safety profile. The primary outcome was the association between EUS-bx clinical variables and the presence of histologic liver fibrosis stage ≥ 3. The secondary outcomes were the associations between EUS-bx and variables indicative of fibrosis. RESULTS: Fifty-nine patients underwent EUS-bx; and 59, P-bx. All EUS-bx procedures were successfully completed. All 56/56 (100%) of EUS-bx vs. 50/52 (96.2%) P-bx were considered adequate samples. Tissue lengths were significantly longer in the EUS-bx cohort (p < 0.0001) with a trend towards a greater number of portal tracts. 46/56 (82.1%) cases of EUS-bx vs. 32/52 (61.5%) of P-bx had > 10 portal tracts; 21/56 (37.5%) cases of EUS-bx vs. 14/52 (26.9%) of P-bx had > 15 portal tracts. There were 6 (10.2%) EUS-bx vs. 1 (1.7%) P-bx related complication leading to a phone call (p = 0.061). CONCLUSIONS: EUS-bx can safely performed and accurately predict liver fibrosis stage as the standard P-bx without being influenced by procedure-related factors.

Diagnosis and Management of Hepatitis Delta Virus Infection.

Hepatitis D virus (HDV) depends on hepatitis B virus (HBV) to enter and exit hepatocytes and to replicate. Despite this dependency, HDV can cause severe liver disease. HDV accelerates liver fibrosis, increases the risk of hepatocellular carcinoma, and hastens hepatic decompensation compared to chronic HBV monoinfection. The Chronic Liver Disease Foundation (CLDF) formed an expert panel to publish updated guidelines on the testing, diagnosis, and management of hepatitis delta virus. The panel group performed network data review on the transmission, epidemiology, natural history, and disease sequelae of acute and chronic HDV infection. Based on current available evidence, we provide recommendations for screening, testing, diagnosis, and treatment of hepatitis D infection and review upcoming novel agents that may expand treatment options. The CLDF recommends universal HDV screening for all patients who are Hepatitis B surface antigen-positive. Initial screening should be with an assay to detect antibodies generated against HDV (anti-HDV). Patients who are positive for anti-HDV IgG antibodies should then undergo quantitative HDV RNA testing. We also provide an algorithm that describes CLDF recommendations on the screening, diagnosis, testing, and initial management of Hepatitis D infection.

Mixed heavy metals exposure affects the renal function mediated by 8-OHG: A cross-sectional study in rural residents of China.

Heavy metals are important risk factors for kidney, but their co-exposure effect on kidney and related mechanism remain unclear. This study evaluated the relationship between heavy metals and renal function, and the feasible mediation effect of oxidative stress. Based on the Dongdagou-Xinglong cohort, participants were recruited and their information were collected through questionnaires and physical examinations. The urine concentration of heavy metals like Cobalt, Nickel, Molybdenum, Cadmium, Antimony, Copper, Zinc, Mercury, Lead, Manganese, and renal injury biomarkers like ß2-microglobulin, ß-N-Acetylglucosaminidase, retinol-binding protein, 8-hydroxyguanine (8-OHG) were measured and corrected by creatinine. Linear regression was conducted to analyze the relationship between metals and renal biomarkers. Bayesian kernel machine regression, weighted quantile sum and quantile-based g-computation were applied to analyze the association between metal mixtures and renal biomarkers. Finally, the mediating effect of 8-OHG was analyzed through the mediation model. We found that these metals were positively related with renal biomarkers, where copper showed the strongest relationship. The co-exposure models showed that renal biomarkers increased with the concentration of mixtures, particularly for cadmium, copper, mercury, manganese. In addition, the proportion of 8-OHG in mediating effect of metals on renal function ranged from 2.6% to 86.9%. Accordingly, the renal function damage is positively associated with metals, and 8-OHG may play an important mediating role.

HCV direct acting antiviral treatment leads to highly durable rates of ALT and AST lower than 30/19 criteria and improved APRI and FIB-4 scores.

Direct acting antiviral treatment (DAA) has been the standard of care for hepatitis C virus (HCV) infection, but its long-term benefits in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) improvement and hepatic fibrosis assessed by aspartate aminotransferase-to-platelet ratio index (APRI) and Fibrosis-4 index (FIB-4) scores remain unknown. The purpose of the present study was to assess DAA's long-term benefits, including frequencies of posttreatment week 96 ALT/AST < 30 (males)/19 (females) (<30/19), improvement of APRI and FIB-4 scores, and the associated factors. This was a single-center, retrospective study on 157 patients with HCV with DAA-mediated sustained virological response (SVR) 12. At posttreatment week (post-Rx wk) 96, 75.4% had ALT < 30/19; 62.7%, AST < 30/19; and 60.1%, both ALT/AST < 30/19. ALT/AST < 30/19 at post-Rx wk 96 was associated with ALT/AST < 30/19 at post-Rx wk 12 (p = 0.026), independently of Child-Turcotte-Pugh < 6 (p = 0.862), platelets ≤ 120 × 109 /L (p = 0.343). Improvement rates of APRI < 0.5 and FIB-4 < 1.45 from baseline to post-Rx wk 96 were from 30.9% to 80.5%, and from 23% to 37.8%, respectively. Both APRI and FIB-4 improvement was associated with both ALT/AST < 30 (males)/19 (females) at post-Rx wk 12 (p = 0.012 and 0.011, respectively). Conclusion: The present study showed that DAA-mediated SVR12 in patients with HCV resulted in (1) high and durable rates of ALT (75.4%), AST (62.7%), and both ALT/AST (60.1%) < 30/19, and (2) high rates of APRI < 0.5 (80.5%) and FIB-4 < 1.45 (37.8%) at post-Rx wk 96, demonstrated clinical value of ALT/AST < 30/19 and excellent long-term outcomes of DAA-mediated SVR12 in these patients.

Endoscopic ultrasound-guided portal pressure gradient with liver biopsy: 6 years of endo-hepatology in practice.

BACKGROUND AND AIM: The portal pressure gradient (PPG) is a useful predictor of portal hypertension (PH) related complications. We previously showed the feasibility and safety of endoscopic ultrasound guided PPG measurement (EUS-PPG). Now EUS-guided liver biopsy (EUS-bx) has been shown to be a safe and effective alternative to percutaneous or Interventional Radiology-guided liver biopsy for the diagnosis of chronic liver disease (CLD). We aimed to evaluate the correlation between PPG and clinical markers of PH, and assess the feasibility and safety of concomitant, single session EUS-PPG and EUS-bx. METHODS: This was a retrospective study of patients undergoing EUS-PPG for CLD at a single tertiary endoscopy center between February 2014 and March 2020. EUS-PPG was performed using a 25-gauge needle and compact manometer. Data analysis was performed with SAS version 9.4. RESULTS: Eighty-three patients underwent EUS-PPG with 100% technical success. The mean PPG was 7.06 mmHg (SD 6.09, range 0-27.3). PPG was higher in patients with (vs without) clinical features of cirrhosis (9.46 vs 3.61 mmHg, P < 0.0001), esophageal or gastric varices (13.88 vs 4.34 mmHg, P < 0.0001), and thrombocytopenia (9.25 vs 4.71 mmHg, P = 0.0022). In the 71 patients (85.5%) who underwent EUS-bx, 70 (98.6%) specimens were deemed adequate by the pathologist for histologic diagnosis. There were no early or late major adverse events. CONCLUSION: EUS-PPG correlates well with clinical markers of PH. EUS-bx can be performed safely during the same session as EUS-PPG, providing a comprehensive endoscopic evaluation of the patient with CLD.

A novel machine learning-based radiomic model for diagnosing high bleeding risk esophageal varices in cirrhotic patients.

BACKGROUND AND AIM: To develop and validate a novel machine learning-based radiomic model (RM) for diagnosing high bleeding risk esophageal varices (HREV) in patients with cirrhosis. METHODS: A total of 796 qualified participants were enrolled. In training cohort, 218 cirrhotic patients with mild esophageal varices (EV) and 240 with HREV RM were included to training and internal validation groups. Additionally, 159 and 340 cirrhotic patients with mild EV and HREV RM, respectively, were used for external validation. Interesting regions of liver, spleen, and esophagus were labeled on the portal venous-phase enhanced CT images. RM was assessed by area under the receiver operating characteristic curves (AUROC), sensitivity, specificity, calibration and decision curve analysis (DCA). RESULTS: The AUROCs for mild EV RM in training and internal validation were 0.943 and 0.732, sensitivity and specificity were 0.863, 0.773 and 0.763, 0.763, respectively. The AUROC, sensitivity, and specificity were 0.654, 0.773 and 0.632, respectively, in external validation. Interestingly, the AUROCs for HREV RM in training and internal validation were 0.983 and 0.834, sensitivity and specificity were 0.948, 0.916 and 0.977, 0.969, respectively. The related AUROC, sensitivity and specificity were 0.736, 0.690 and 0.762 in external validation. Calibration and DCA indicated RM had good performance. Compared with Baveno VI and its expanded criteria, HREV RM had a higher accuracy and net reclassification improvements that were as high as 49.0% and 32.8%. CONCLUSION: The present study developed a novel non-invasive RM for diagnosing HREV in cirrhotic patients with high accuracy. However, this RM still needs to be validated by a large multi-center cohort.

Endoscopic Ultrasound-Guided Porto-systemic Pressure Gradient Measurement Correlates with Histological Hepatic Fibrosis.

BACKGROUND AND AIMS: Endoscopic ultrasound is a novel diagnostic approach to chronic liver diseases (CLDs), and EUS-guided porto-systemic pressure gradient measurement (EUS-PPG) is an important expansion with a well-developed technique. However, the clinical value and applicability of EUS-PPG measurement in predicting histologically advanced hepatic fibrosis remain unknown. METHODS: This was a single-center retrospective study on patients with various CLDs undergoing EUS-PPG and EUS-guided liver biopsy (EUS-bx) to assess if EUS-PPG measurements correlate with histological fibrosis stage and various surrogate markers for severity of CLDs and its safety. Cases with EUS-PPG were identified at the University of California Irvine, a tertiary endoscopy center, between January 2014 and March 2020. RESULTS: In 64 patients, the mean age was 57.5; 40 (62.5%), males; mean Child-Turcotte-Pugh (CTP) and Model for End-Stage Liver Disease (MELD) scores, 5.9 and 10.4, respectively. The procedure success rate was 100%. Twenty-nine (45.3%) had EUS-PPG ≥ 5 mmHg that was associated with clinical cirrhosis (p < 0.0001), clinical portal hypertension (p = 0.002), hepatic decompensation (p = 0.013), MELD-Na > 10 (p = 0.036), PLTs ≤ 120 × 109/L (p = 0.001), INR ≥ 1.05 (p = 0.007), presence of EV, GV, or PHG (p < 0.0001), biopsy-proven fibrosis stage ≥ 3 (p = 0.002), APRI > 2 (p = 0.001), and FIB-4 > 3.25 (p = 0.001). Multivariable analysis confirmed that EUS-PPG ≥ 5 mmHg was significantly associated with liver biopsy-proven fibrosis stage ≥ 3 (LR 27.0, 95% CI = 1.653-360.597, p = 0.004), independent of C-cirrhosis, C-PHTN, thrombocytopenia, splenomegaly, and APRI score > 2, and FIB-4 score > 3.25. There were no serious complications related to EUS-PPG procedures. CONCLUSIONS: EUS-PPG measurements provide excellent correlation with histological hepatic fibrosis stage and various clinical, laboratory, endoscopic and imaging variables indicative of advanced liver disease without serious adverse events.

Synergistic Effect of Biejia-Ruangan on Fibrosis Regression in Patients With Chronic Hepatitis B Treated With Entecavir: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Long-term nucleos(t)ide analogue (NA) treatment can reverse liver fibrosis in chronic hepatitis B (CHB), but its effect on fibrosis regression remains limited. Biejia-Ruangan (BR) has been approved in China as an antifibrotic traditional Chinese medicine drug in patients with chronic liver diseases. A multicenter randomized controlled trial aims to evaluate the effect of BR on fibrosis regression in CHB patients treated with NAs. METHODS: CHB patients with histologically confirmed advanced fibrosis or cirrhosis were randomly assigned to receive entecavir (ETV) (0.5 mg per day) plus BR (2 g 3 times a day) or placebo for 72 weeks. Liver fibrosis regression was defined as a reduction of ≥ 1 point by the Ishak fibrosis stage (IFS). RESULTS: Overall, 500 patients were enrolled in each group as the intention-to-treat population. The rate of fibrosis regression after 72 weeks of treatment was significantly higher in the ETV + BR group (40% vs 31.8%; P = .0069). Among 388 patients with cirrhosis (ie, IFS ≥ 5) at baseline, the rate of cirrhosis reversal (ie, IFS ≤ 4) was significantly higher in the ETV + BR group (41.5% vs 30.7%; P = .0103). CONCLUSIONS: Addition of BR to the current standard treatment with NAs in CHB patients with advanced fibrosis or cirrhosis can improve liver fibrosis regression. CLINICAL TRIALS REGISTRATION: NCT01965418.

New Year's greeting and overview of World Journal of Hepatology in 2021.

The World Journal of Hepatology (WJH) was launched in October 2009. It mainly publishes articles reporting research findings in the field of hepatology, covering a wide range of topics, including viral hepatitis B and C, non-alcoholic fatty liver disease, alcoholic liver disease, autoimmune and chronic cholestatic liver disease, drug-induced liver injury, cirrhosis, liver failure, hepatocellular carcinoma, coronavirus disease 2019-related liver conditions, etc. As of December 31, 2020, the WJH has published 1349 articles, among which, the total cites is 18995 and the average cites per article is 14. In celebrating the New Year, we are pleased to share with you special a New Year's greeting from the WJH Editors-in-Chief, along with a detailed overview of the journal's submission, peer review and publishing metrics from 2020. In all, we are appreciative for the substantive support and submissions from authors worldwide, and the dedicated efforts and expertise provided by our invited reviewers and editorial board members.

Ultrasonographic (US) Two-Dimensional Measurement of Spleen Is Superior to Traditional Length Measurement Alone in Diagnosing Cirrhosis.

BACKGROUND: Splenomegaly measured by spleen length has been an imaging evidence for cirrhosis. However, data remains lacking on the value of other US findings for diagnosing cirrhosis. This study evaluated the value of spleen two-dimensional measurements (2D, i.e., length × thickness) in diagnosing cirrhosis by comparing with other US parameters. METHODS: A retrospective study on 297 cohort 1 patients with clinical/imaging diagnosis of cirrhosis was conducted. Spleen length and thickness were measured via US imaging and compared with other US parameters using statistical analysis to assess their value in diagnosing cirrhosis. A separate 161 cohort 2 patients with histological fibrosis staging was used to validate the findings from the cohort 1. RESULTS: Using 297 cohort 1 patients, US findings of spleen length > 12 cm (50.6% vs. 9.6%, p < 0.001); spleen thickness > 4 cm (78.2% vs. 21%, p < 0.001); and spleen 2D > 46 cm2 (81.6% vs. 15.3%, p < 0.001) were significantly associated with, but only spleen 2D > 46 cm2 (95% CI 7.9-92.8, p < 0.001) was independently associated with clinical/imaging evidence of cirrhosis on multivariate analysis. We further analyzed 161 cohort 2 patients and validated that US finding of spleen 2D > 46 cm2 carried the best sensitivity and specificity (93.5% and 95.3%) and was the only US parameter independently associated with histological stage 3-4 fibrosis, i.e., cirrhosis (95% CI 3.1-87, p = 0.006). CONCLUSION: Using both testing and validation cohorts, we demonstrated that spleen 2D > 46 cm2 carries 93.5% sensitivity and 95.3% specificity and is superior to other US parameters in diagnosing cirrhosis.

Excellent Safety and Sustained Virologic Response to Direct-Acting Antivirals Treatment in HCV-Infected Geriatric Patients: A Real-World Data.

BACKGROUND: Direct-acting antivirals (DAAs) are current standard of HCV treatment (Rx). However, data remain lacking on real-world safety, patterns of biochemical, virologic responses, and sustained virologic response (SVR12) rate in geriatric patients. AIMS: The present study assessed clinical presentation, safety, SVR12 rate, dynamic changes in HCV RNA, ALT, and AFP in geriatric patients (age ≥ 65 year old, G1) versus non-geriatric patients (G2) with chronic hepatitis C and received DAA treatment. METHODS: This was a single-center, retrospective study on 183 patients with DAA Rx and 12-week post-Rx follow-up. RESULTS: There were no significant differences in patterns of biochemical and virologic responses between the two groups. Undetectable HCV RNA rates were 67.2% versus 75.7% (p = 0.22) and 77.3% versus 84.3% (p = 0.24) at Rx week 2 and Rx week 4, respectively. The SVR12 rate was comparable in 2 groups, 94.1% (G1) versus 95.7% (G2, p = 0.64). ALT normalization rates were 91.2% versus 91.3% (p = 0.98), 92.6% versus 93.9% (p = 0.74), and 97.1% versus 97.4% (p = 0.89) at Rx week 2, post-Rx week12, and post-Rx week 24, respectively. AFP normalization was lower in G1 with 89.7% versus 95.7% (p = 0.12), 77.9% versus 87.8% (p = 0.08), and 79.4% versus 92.2% (p = 0.01), at Rx week 2, and post-Rx week 12, and post-Rx week 24, respectively. Both groups showed similar side effects profile including fatigue 11.8% versus 12.2% (p = 0.93) and headache 11.8% versus 13.9% (p = 0.68). CONCLUSION: Based on our real-world data, geriatric patients had excellent and comparable treatment outcomes with non-geriatric patients in safety and SVR12 rates to different DAA regimens.

Intestinal flora alterations in patients with early chronic kidney disease: a case-control study among the Han population in southwestern China.

OBJECTIVE: In this case-control study, we retrospectively analyzed the intestinal flora compositions of patients with early-stage chronic kidney disease (CKD). METHODS: Forty-seven patients with early CKD who were treated at the Traditional Chinese Medicine Hospital between March and October 2018 were enrolled, and 150 healthy volunteers were enrolled in the healthy control group. Fresh stool samples were collected. The V3-V4 region of the bacterial 16S rRNA was amplified via PCR. Biterminal sequencing was performed using the Illumina MiSeq platform. The flora compositions were compared between the two groups. RESULTS: The Chao1 and Shannon indices showed significantly lower intestinal flora diversity and abundances in the CKD group than in the healthy controls. Beta diversity analysis revealed notable differences in the intestinal flora compositions between the groups. At the phylum level, Actinobacteria and Proteobacteria abundances were significantly higher in the CKD group. Thirty-one species differed significantly between both groups, among which, differences in Ruminococcus and Roseburia displayed the highest diagnostic values for distinguishing CKD patients from healthy controls. CONCLUSIONS: Intestinal flora compositions are altered in early-stage CKD patients among the Han population in southwestern China.

Liver Cancer-Specific Serine Protease Inhibitor Kazal Is a Potentially Novel Biomarker for the Early Detection of Hepatocellular Carcinoma.

INTRODUCTION: Liver cancer-secreted serine protease inhibitor Kazal (LC-SPIK) is a protein that is specifically elevated in cases of hepatocellular carcinoma (HCC). We assessed the performance of LC-SPIK in detecting HCC, including its early stages, in patients with cirrhosis, hepatitis B virus (HBV), and hepatitis C virus (HCV). METHODS: We enrolled 488 patients, including 164 HCC patients (81 early HCC) and 324 controls in a blinded, prospective, case-control study. Serum LC-SPIK levels were determined by an enzyme-linked immunosorbent assay-based assay. The performance of serum LC-SPIK and α-fetoprotein (AFP), including area under the curve (AUC), sensitivity, and specificity, are compared. The performance of LC-SPIK was evaluated in an independent validation cohort with 102 patients. RESULTS: In distinguishing all HCC patients from those with cirrhosis and chronic HBV/HCV, LC-SPIK had an AUC of 0.87, with 80% sensitivity and 90% specificity using a cutoff of 21.5 ng/mL. This is significantly higher than AFP, which had an AUC of 0.70 and 52% sensitivity and 86% specificity using a standard cutoff value of 20.0 ng/mL. For early-stage HCC (Barcelona Clinic Liver Cancer stage 0 and A), LC-SPIK had an AUC of 0.85, with 72% sensitivity and 90% specificity, compared with AFP, which had an AUC of 0.61, with 42% sensitivity and 86% specificity. In addition, LC-SPIK accurately detected the presence of HCC in more than 70% of HCC patients with false-negative AFP results. DISCUSSION: The study provided strong evidence that LC-SPIK detects HCC, including early-stage HCC, with high sensitivity and specificity, and might be useful for surveillance in cirrhotic and chronic HBV/HCV patients, who are at an elevated risk of developing HCC.

Direct acting antiviral-induced dynamic reduction of serum α fetoprotein in hepatitis C patients without hepatocellular carcinoma.

Direct acting antiviral (DAA) treatments may reduce the elevated α fetoprotein (AFP), but data on how these treatments affect elevated AFP in patients with chronic hepatitis C (CHC) remain insufficient. In the present study, the frequency of baseline AFP elevations and their related factors, AFP dynamics during and after DAA treatment, and factors associated with AFP reduction was assessed. This retrospective study included 141 patients with CHC without hepatocellular carcinoma who received DAA and achieved sustained virological response. The details are as follows: mean post-treatment follow-up was 99 weeks (12-213); mean age, 57.8 years old; 52%, males; 79%, genotype (GT) 1; and 47%, cirrhosis. Pre-treatment AFP elevation (> 5.5 ng/mL) was seen in 48.2% patients. On multivariate analysis, baseline AFP > 5.5 was associated with the presence of cirrhosis (P =0.001), coexisting non-alcoholic steatohepatitis (NASH) (P = 0.035), and GT 1 (P = 0.029). AFP normalization was seen in 28.2% patients at treatment week 2, in 52% at the end of treatment, and in 73.4% at the end of follow-up. Post-treatment week 24 AFP normalization was associated with the absence of cirrhosis (P = 0.003), Child-Pugh score < 6 (P = 0.015), and baseline AFP < 10 (P = 0.015). AFP elevation is common in patients with CHC and independently associated with NASH, cirrhosis, and GT 1. DAA treatment resulted in AFP normalization as early as treatment week 2. Post-treatment week 24 AFP normalization is independently associated with the absence of cirrhosis, Child-Pugh score < 6, and baseline AFP < 10.

Hepatitis C virus antigens enzyme immunoassay for one-step diagnosis of hepatitis C virus coinfection in human immunodeficiency virus infected individuals.

BACKGROUND: Current diagnosis of hepatitis C virus (HCV) infection requires two sequential steps: testing for anti-HCV followed by HCV RNA PCR to confirm viremia. We have developed a highly sensitive and specific HCV-antigens enzyme immunoassay (HCV-Ags EIA) for one-step diagnosis of viremic HCV infection. AIM: To assess the clinical application of the HCV-Ags EIA in one-step diagnosis of viremic HCV infection in human immunodeficiency virus (HIV)-coinfected individuals. METHODS: The study blindly tested HCV-Ags EIA for its performance in one-step diagnosing viremic HCV infection in 147 sera: 10 without HCV or HIV infection; 54 with viremic HCV monoinfection; 38 with viremic HCV/HIV coinfection; and 45 with viremic HCV and non-viremic HIV coinfection. RESULTS: Upon decoding, it was 100% accordance of HCV-Ags EIA to HCV infection status by HCV RNA PCR test. In five sera with HCV infection, HCV RNA was as low as 50-59 IU/mL, and four out of five tested positive for HCV-Ags EIA. Likewise, it was also 100% accordance of HCV-Ags EIA to HCV infection status by HCV RNA PCR in 83 sera with HCV and HIV coinfection, regardless if HIV infection was active or not. CONCLUSION: The modified HCV-Ags EIA has a lower detection limit equivalent to serum HCV RNA levels of approximately 100 IU/mL. It is highly sensitive and specific in the setting of HIV coinfection, regardless of HIV infection status and CD4 count. These data support the clinical application of the HCV-Ags EIA in one-step diagnosis of HCV infection in HIV-infected individuals.

A Novel Noninvasive Program for Staging Liver Fibrosis in Untreated Patients With Chronic Hepatitis B.

OBJECTIVES: Chronic hepatitis B (CHB) can progress into liver fibrosis and cirrhosis with poor outcomes. Early and accurate diagnosis of liver fibrosis/cirrhosis is important to guide the preventive strategy of their related complications. METHODS: A Chinese multicenter cross-sectional study was conducted to develop and validate a novel noninvasive program for staging liver fibrosis in untreated patients with CHB. Liver histology was evaluated independently by 2 pathologists. The alanine aminotransferase ratio, Hepascore, and aspartate aminotransferase to platelet index values were calculated. Liver stiffness measurement (LSM) and diameter of the spleen were measured. Logistic regression with ℓ1 penalty of regression coefficients was used to select the optimal predictors. The diagnostic accuracy for the stage of liver fibrosis was assessed by the area under the receiver operator characteristic curve with 95% confidence interval (CI). RESULTS: A total of 1,200 patients with CHB were included, of whom 800 and 400 were in training and validation sets, respectively. LSM, platelets, age, hyaluronic acid, and diameter of the spleen were the top 5 predictors associated with any stage of liver fibrosis and integrated into a novel noninvasive program, named as the Chin-CHB score. The area under the receiver operator characteristic curve of the Chin-CHB score was 0.893 (95% CI: 0.77-0.92) for diagnosing significant fibrosis, 0.897 (95% CI: 0.85-0.95) for advanced fibrosis, and 0.909 (95% CI: 0.87-0.95) for cirrhosis. The diagnostic performance of the Chin-CHB score was similar between training and validation sets. The Chin-CHB score had better diagnostic performance than aspartate aminotransferase to platelet index, alanine aminotransferase ratio, LSM alone, and Hepascore for diagnosing any stage of liver fibrosis. CONCLUSIONS: The Chin-CHB score had good diagnostic performance for any stage of liver fibrosis.

Real-World Study on Sofosbuvir-based Therapies in Asian Americans With Chronic Hepatitis C.

BACKGROUND: Limited data exist with regard to treatment outcomes in Asian Americans with chronic hepatitis C (CHC). We evaluated sofosbuvir (SOF)-based regimens in a national cohort of Asian Americans. METHODS: Eligible Asian Americans patients with CHC who had posttreatment follow-up of 24 weeks for SOF -based therapies from December 2013 to June 2017 were enrolled from 11 sites across the United States. The primary endpoint was sustained virologic response (SVR) rates at posttreatment weeks 12 and 24. Secondary endpoints were to evaluate safety by tolerability and adverse events (AEs). RESULTS: Among 231 patients screened, 186 were enrolled. At baseline, 31% (57/186) patients were cirrhotic, 34% (63/186) were treatment experienced. Most of the subjects (42%, 79/186) received ledispavir/SOF therapy. The overall SVR12 was 95%, ranging from 86% in genotype (GT) 1b on SOF+ribavirin to 100% in GT 1b patients on ledipasvir/SOF at subgroup analyses. SVR12 was significantly lower in cirrhotic than in noncirrhotic patients [88% (50/57) vs. 98% (126/129), P<0.01]. Stratified by GT, SVR12 were: 96% (43/45) in GT 1a; 93% (67/72) in GT 1b; 100% (23/23) in GT 2; 90% (19/21) in GT 3; 100% (1/1) in GT 4; 83% (5/6) in GT 5; and 100% (16/16) in GT 6. Cirrhotic patients with treatment failure were primarily GT 1, (GT 1a, n=2; GT 1b, n=4) with 1 GT 5 (n=1). Patients tolerated the treatment without serious AEs. Late relapse occurred in 1 patient after achieving SVR12. CONCLUSIONS: In Asian Americans with CHC, SOF-based regimens were well tolerated without serious AEs and could achieve high SVR12 regardless of hepatitis C viral infection GT.