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.

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.

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.

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.

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.

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.

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.

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.

Persistence of Circulating Hepatitis C Virus Antigens-Specific Immune Complexes in Patients with Resolved HCV Infection.

BACKGROUND: Our recent study indicated the possible presence of detectable hepatitis C virus antigens (HCV-Ags) after denaturation of sera with resolved HCV (R-HCV) infection. The present study determined and characterized persistent HCV-Ags-specific immune complexes (ICs) in these patients. METHODS: Sixty-eight sera with R-HCV and 34 with viremic HCV (V-HCV) infection were tested for free and IC-bound HCV-Ags using HCV-Ags enzyme immunoassay (EIA), the presence of HCV-Ags-specific ICs by immunoprecipitation and Western blot (IP-WB), HCV ICs containing HCV virions using IP and HCV RNA RT-PCR, and correlation of HCV ICs with clinical presentation in these patients. RESULTS: Using HCV-Ags EIA, we found 57.4% of sera with R-HCV infection were tested positive for bound, but not free HCV-Ags. Using pooled or individual anti-HCV E1/E2, cAg, NS3, NS4b, and/or NS5a to precipitate HCV-specific-Ags, we confirmed persistent HCV-Ags ICs specific to various HCV structural and non-structural proteins not only in V-HCV infection, but also in R-HCV infection. Using IP and HCV RNA PCR, we then confirmed the presence of HCV virions within circulating ICs in V-HCV, but not in R-HCV sera. Multivariable analysis indicated significant and independent associations of persistent circulating HCV-Ags-specific ICs with both age and the presence of cirrhosis in patients with R-HCV infection. CONCLUSIONS: Various HCV-Ag-specific ICs, but not virions, persist in 57.4% of patients who had spontaneous or treatment-induced HCV clearance for 6 months to 20 years. These findings enriched our knowledge on HCV pathogenesis and support further study on its long-term clinical relevance, such as extrahepatic manifestation, transfusion medicine, and hepatocarcinogenesis.

A highly specific and sensitive hepatitis C virus antigen enzyme immunoassay for One-step diagnosis of viremic hepatitis C virus infection.

UNLABELLED: The current standard in diagnosing hepatitis C virus (HCV) infection requires two sequential steps: anti-HCV test to screen, followed by HCV RNA reverse-transcription polymerase chain reaction to confirm viremic HCV (V-HCV) infection. HCV core antigen tests provided potential for possible one-step diagnosis. However, low sensitivity and specificity limit their clinical utility. The present study developed a novel HCV antigens enzyme immunoassay (HCV-Ags EIA) and assessed its sensitivity, specificity, and utility for one-step diagnosis of V-HCV infection using 365 serum specimens, including 176 without and 189 with V-HCV infection. First, we confirmed the presence of HCV nonstructural proteins 3, 4b, and 5a besides HCV core antigen during HCV infection and developed a novel HCV-Ags EIA through simultaneous detection of all four HCV proteins. For the first time, the present study demonstrated that serum sample denaturation decreases the test specificity due to release of HCV-Ags sequestered in HCV immune complexes and should not be used in any HCV-Ags, including all the current HCV core antigen assays. On the other hand, using sample nondenaturation, the HCV-Ags EIA results showed 98.9% specificity and 100% sensitivity compared to serum anti-HCV and HCV RNA reverse-transcription polymerase chain reaction results. Using serum sample dilution, and nondenaturation, the lowest limits of detection of the HCV-Ags EIA were equivalent to serum HCV RNA levels of approximate 150-250 IU/mL. CONCLUSIONS: The highly specific and sensitive HCV-Ags EIA developed in the present study has the lowest limit of detection equivalent to serum HCV RNA levels of 150-250 IU/mL; using nondenaturation of serum samples, our HCV-Ags EIA reliably differentiated V-HCV infection from resolved HCV infection, accomplishing screening and diagnosis of V-HCV infection in one step. (Hepatology 2016;64:415-424).

EUS-guided portal pressure gradient measurement with a simple novel device: a human pilot study.

BACKGROUND AND AIMS: Portal hypertension (PH) is a serious adverse event of liver cirrhosis. The hepatic venous pressure gradient or portal pressure gradient (PPG) accurately reflects the degree of PH and is the single best prognostic indicator in liver disease. This is usually obtained by interventional radiology (IR), although it is not routinely performed. Recently, we developed a simple novel technique for EUS-guided PPG measurement (PPGM). Our animal studies showed excellent correlation between EUS-PPGM and IR-PPGM. We present the first human pilot study of EUS-PPGM in patients with liver disease. METHODS: EUS-PPGM was performed by experienced endosonographers using a linear echoendoscope, a 25-gauge fine-needle aspiration needle, and a novel compact manometer. The portal vein and hepatic vein (or inferior vena cava) were targeted using a transgastric-transduodenal approach. Clinical parameters of PH were evaluated in each patient. Feasibility was defined as successful PPGM in each patient. Safety was based on adverse events captured in a postprocedural interview. RESULTS: Twenty-eight patients underwent EUS-PPGM with 100% technical success and no adverse events. PPG ranged from 1.5 to 19 mm Hg and had excellent correlation with clinical parameters of portal hypertension including the presence of varices (P = .0002), PH gastropathy (P = .007), and thrombocytopenia (P = .036). PPG was increased in patients with high clinical evidence of cirrhosis (P = .005). CONCLUSION: This novel technique of EUS-PPGM using a 25-gauge needle and compact manometer is feasible and appears safe. Given the availability of EUS and the simplicity of the manometry setup, EUS-guided PPG may represent a promising breakthrough for procuring indispensable information in the management of patients with liver disease.

Multicenter randomized controlled trial of percutaneous cryoablation versus radiofrequency ablation in hepatocellular carcinoma.

UNLABELLED: Radiofrequency ablation (RFA) is considered a curative treatment option for hepatocellular carcinoma (HCC). Growing data have demonstrated that cryoablation represents a safe and effective alternative therapy for HCC, but no randomized controlled trial (RCT) has been reported to compare cryoablation with RFA in HCC treatment. The present study was a multicenter RCT aimed to compare the outcomes of percutaneous cryoablation with RFA for the treatment of HCC. In all, 360 patients with Child-Pugh class A or B cirrhosis and one or two HCC lesions ≤ 4 cm, treatment-naïve, without metastasis were randomly assigned to cryoablation (n = 180) or RFA (n = 180). The primary endpoints were local tumor progression at 3 years after treatment and safety. Local tumor progression rates at 1, 2, and 3 years were 3%, 7%, and 7% for cryoablation and 9%, 11%, and 11% for RFA, respectively (P = 0.043). For lesions >3 cm in diameter, the local tumor progression rate was significantly lower in the cryoablation group versus the RFA group (7.7% versus 18.2%, P = 0.041). The 1-, 3-, and 5-year overall survival rates were 97%, 67%, and 40% for cryoablation and 97%, 66%, and 38% for RFA, respectively (P = 0.747). The 1-, 3-, and 5-year tumor-free survival rates were 89%, 54%, and 35% in the cryoablation group and 84%, 50%, and 34% in the RFA group, respectively (P = 0.628). Multivariate analyses demonstrated that Child-Pugh class B and distant intrahepatic recurrence were significant negative predictors for overall survival. Major complications occurred in seven patients (3.9%) following cryoablation and in six patients (3.3%) following RFA (P = 0.776). CONCLUSION: Cryoablation resulted in a significantly lower local tumor progression than RFA, although both cryoablation and RFA were equally safe and effective, with similar 5-year survival rates.

Rethinking the pathogenesis of hepatitis B virus (HBV) infection.

Chronic hepatitis B virus (HBV) infection affects approximately 375 million people worldwide. Current antiviral treatment effectively controls, but rarely clears chronic HBV infection. In addition, a significant portion of chronic HBV infected patients are not suitable for currently available antiviral therapy, and still face higher risk for cirrhosis and hepatocellular carcinoma. The poorly understood pathogenesis of HBV infection is the main barrier for developing more effective treatment strategies. HBV has long been viewed as non-cytopathic and the central hypothesis for HBV pathogenesis lies in the belief that hepatitis B is a host specific immunity-mediated liver disease. However, this view has been challenged by the accumulating experimental and clinical data that support a model of cytopathic HBV replication. In this article we systematically review the pathogenic role of HBV replication in hepatitis B and suggest possible HBV replication related mechanisms for HBV-mediated liver injury. We propose that a full understanding of HBV pathogenesis should consider the following elements. I. Liver injury can be caused by high levels of HBV replication and accumulation of viral products in the infected hepatocytes. II. HBV infection can be either directly cytopathic, non-cytopathic, or a mix of both in an individual patient depending upon accumulation levels of viral products that are usually associated with HBV replication activity in individual infected hepatocytes.

Advances in clinical application of cryoablation therapy for hepatocellular carcinoma and metastatic liver tumor.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Although surgical resection and liver transplantation are the curative treatments, many of HCC patients do not qualify for these curative therapies at the presentation. Thus, ablation therapies are currently important modalities in HCC treatment. Among currently available ablation therapies, cryoablation (ie, cryotherapy) is a novel local therapeutic modality. However, cryoablation has not been widely used as one of ablation therapies for HCC, because of historical concerns about risk of bleeding when cryotherapy is delivered by early generation of the argon-helium device. Nevertheless, with technological advances and increased clinical experience in the past decade, clinical application of cryoablation for HCC management has significantly increased. Accumulating data have demonstrated that cryoablation is highly effective in local tumor control with well-acceptable safety profile, and the overall survival is comparable with that of radiofrequency ablation in patients with tumors <5 cm. Compared with radiofrequency ablation and other thermal-based modalities, cryoablation has several advantages, such as the ability to produce larger and precise zones of ablation. This article systemically reviews the advances in clinical application of cryoablation therapy for HCC, including the related mechanisms and technology, clinical indications, efficacy and safety profiles, and future research directions.

Boceprevir plus peginterferon α-2b/ribavirin in chronic hepatitis C genotype 1: impact of baseline viral load on sustained virologic response.

BACKGROUND: Baseline viral load is a predictor of treatment outcome in patients with hepatitis C virus (HCV) infection receiving peginterferon and ribavirin. The impact of baseline viral load on sustained virologic response (SVR) after boceprevir-based therapy is unknown. METHODS: This retrospective analysis included patients with chronic HCV genotype 1 infection who were previously untreated or were previous treatment failures. Virologic response was assessed according to baseline viral load (≤1 million IU/mL, >1 to ≤5 million IU/mL, >5 to ≤10 million IU/mL, and >10 million IU/mL). RESULTS: SVR was higher in patients receiving boceprevir plus peginterferon and ribavirin than in those receiving peginterferon and ribavirin alone, regardless of baseline viral load. Patients with a baseline viral load ≤1 million IU/mL had the highest SVR (boceprevir plus peginterferon and ribavirin, 78% to 83%; peginterferon and ribavirin, 33% to 63%). Among patients with baseline viral load >1 million IU/mL, SVR rates were 57% to 68% in patients receiving boceprevir plus peginterferon and ribavirin, and 11% to 41% in patients receiving peginterferon and ribavirin. Relapse was higher in patients receiving peginterferon and ribavirin (previously untreated, 12% to 40%; previous treatment failures, 17% to 67%) than in those receiving boceprevir plus peginterferon and ribavirin (previously untreated, 3% to 12%; previous treatment failure, 9% to 16%), irrespective of baseline viral load. CONCLUSIONS: The efficacy of boceprevir plus peginterferon and ribavirin was unaffected by baseline viral loads >1 million IU/mL, whereas viral burden >1 million IU/mL was associated with lower SVR with peginterferon and ribavirin. Relapse rates were lower with boceprevir plus peginterferon and ribavirin than with peginterferon and ribavirin, and were unaffected by baseline viral load.

Clinical presentation and disease phases of chronic hepatitis B using conventional versus modified ALT criteria in Asian Americans.

BACKGROUND AND AIM: The modified normal alanine aminotransferase (ALT) value (i.e., males <30 and females <19 IU/L) is a better criteria associated with histological activity in chronic hepatitis B (CHB). This study was aimed to assess if the modified ALT criteria could be better associated with disease phases in a cohort of Asian Americans (AsAm) with CHB. METHODS: This two-center retrospective study evaluated 198 non-treated AsAm with CHB and a mean follow-up of 21 months. Both conventional and modified ALT criteria were used to determine the differences and clinical value using modified ALT criteria in classifying CHB phases. RESULTS: Among HBeAg (+) patients (29.3 %), HBV pre-core (PC) and basal core promoter (BCP) mutations were detected in 24.4 % and 31.3 %, respectively. Using baseline conventional ALT criteria, 97/153 (63.4 %) patients could be categorized into CHB phases 1 to 4, whereas 56/153 (36.6 %) were indeterminate. Using the modified ALT criteria, 43 (28.1 %) patients had phase changes of which 31/43 (72.1 %) were moved from phase 1 and indeterminate to phases 2 and 4, more active CHB phases. In 13/31 of these patients with liver biopsy, 6 (19.4 %) reported stage 2-4 fibrosis and 10 (32.3 %) reported grade 1-2 inflammation. Using modified ALT criteria to evaluate 48/153 patients with full data at baseline and the end of 1-year follow-up, we observed that 19/48 (39.6 %) changed their CHB phases; 5/48 (10.4 %) moved from phases 1 and 3 to phases 2 and 4; 2/48 (4.2 %) remained in the active phases; 10/48 (20.8 %) became indeterminate. CONCLUSIONS: HBV PC and BCP mutations were detectable in 24.4 % and 31.3 % of HBeAg (+) AsAm patients, respectively. Compared with conventional ALT criteria, modified ALT criteria is more sensitive in identifying CHB patients in active phases.

High intratumoral metastasis-associated in colon cancer-1 expression predicts poor outcomes of cryoablation therapy for advanced hepatocellular carcinoma.

BACKGROUND: Cryoablation is one of the local therapies for hepatocellular carcinoma (HCC), but its safety and effect has not been studied in patients with Child class A or B and Barcelona Clinic Liver Cancer (BCLC) stage C HCC. Metastasis-associated in colon cancer-1 (MACC1) overexpression has been associated with poor prognosis of HCC, but its predictive value to post-cryoablation outcomes remains unknown in patients with BCLC stage C HCC. METHODS: This study assessed the safety and outcomes of cryoablation measured by time to progression (TTP) and overall survival (OS), and predictive value of MACC1 mRNA and protein overexpression in tumorous tissue to post-cryoablation outcomes in 120 advanced HCC patients with child-pugh class A or B by quantitative polymerase chain reaction and immunohistochemical staining. The potenial correlation of MACC1 and c-Met expression to tumor cell proliferation and apoptosis was also analyzed. RESULTS: The cryoablation in patients with advanced unresectable HCC resulted in a median TTP and OS of 5.5 (4.2- 6.7) months and 10.5 (9.0-12.0) months, respectively and no significant complications, comparable to the historical report for RFA therapy. The MACC1 mRNA and nuclear protein expression was significantly increased in tumorous tissues in these patients than that in normal liver tissue controls. Higher expression of MACC1 mRNA and nuclear protein in tumorous tissues in these patients was associated with shorter post cryoablation median TTP and OS than that with lower MACC1 expression. CONCLUSIONS: Cryoablation is a safe and effective therapeutic option for patients with advanced HCC and Child-pugh class A or B cirrhosis; and a higher intratumoral expression of MACC1 or nuclear translocation predicts poor outcomes of cryotherapy in these patients.

High rates of viral suppression after long-term entecavir treatment of Asian patients with hepatitis B e antigen-positive chronic hepatitis B.

There are limited data on the effects of long-term entecavir therapy in Asian patients with chronic hepatitis B (CHB). We performed a post hoc analysis of 94 Asian hepatitis B e antigen-positive (HBeAg+), nucleos(t)ide analogue-naive patients who received 5 years of therapy with entecavir (up to 2 years in study ETV-022 and the remainder in study ETV-901). Among patients completing week 240, 95% (63 of 66) had levels of hepatitis B virus DNA <300 copies/mL, and 76% (50 of 66) had normalized levels of alanine aminotransferase. In addition to patients who achieved a serologic response during ETV-022, a further 40% (26 of 65) achieved HBeAg loss, and 18% (12 of 65) underwent HBeAg seroconversion through year 5 of entecavir therapy. No resistance to entecavir was detected, and the safety profile was consistent with previous reports. The long-term efficacy and safety of entecavir are therefore comparable between Asians and the overall population of HBeAg+ patients with CHB.