Non-cirrhotic Chronic Hepatitis Research Articles

Long-term hepatitis B surface antigen kinetics after nucleos(t)ide analog discontinuation in patients with noncirrhotic chronic hepatitis B

Background and aimFew studies have reported hepatitis B surface antigen (HBsAg) kinetics after nucleos(t)ide analog (NA) discontinuation in patients with noncirrhotic chronic hepatitis B (CHB). The study specifically investigated long-term HBsAg kinetics after NA discontinuation. MethodsBetween January 2014 to January 2024, this study prospectively enrolled 106 outpatients with noncirrhotic CHB who met the discontinuation criteria after NA consolidation treatment. Demographic, clinical, and laboratory data were collected and analyzed after NA discontinuation. ResultsNinety-six patients who finished 5 years of follow-up were included. HBsAg remained undetectable in 29 patients with end of treatment (EOT) HBsAg negativity. Among 67 patients with EOT HBsAg positivity, HBsAg seroclearance occurred in 12 (17.9%) patients with an estimated annual incidence of HBsAg seroclearance of 3.6%. Patients with EOT HBsAg levels of ≤1000 IU/mL had a higher HBsAg seroclearance rate than those with EOT HBsAg levels of >1000 IU/mL (33.3% vs. 5.4%). The proportion of patients with HBsAg ≤1000 IU/mL increased during follow-up. Logistic regression analysis indicated that the EOT HBsAg level was an independent factor for HBsAg seroclearance and an HBsAg level decline exceeding 1 log10 IU/mL. The optimal EOT HBsAg cutoff for both HBsAg seroclearance and an HBsAg level decline exceeding 1 log10 IU/mL was 359 IU/mL. ConclusionsPatients with EOT HBsAg negativity experienced no relapse and maintained HBsAg seroclearance during 5 years of follow-up after NA discontinuation. A higher HBsAg seroclearance rate can be obtained in patients with EOT HBsAg levels of ≤1000 IU/mL during 5 years of follow-up after NA discontinuation. Close monitoring and proper NA retreatment are recommended to guarantee the safety of NA discontinuation. Clinical trial numberClinicaltrials.gov number NCT02883647.

Discontinuation of Nucleos(t)ide Analog treatment in HBeAg-Negative Non-Cirrhotic Chronic Hepatitis B Patients: Real-Life Data of 20 Years.

Discontinuation of nucleos(t)ide analog is controversial in HBeAg-negative chronic hepatitis B patients not achieved HBsAg loss. We aimed to evaluate re-treatment rates and risk factors in non-cirrhotic HbeAg-negative chronic hepatitis B patients for whom nucleosi(t)ides analogs were discontinued. Demographic, clinical, and laboratory data before and at the end after discontinuation of nucleos(t)ide analogs were collected retrospectively. Seventy-two patients followed up between January 2000 and December 2019 were included; 43 were male, with a mean age of 46.3 (±10.8). Baseline median alanine aminotransferase (ALT) and hepatitis B virus DNA levels were 55.5 IU/L and 465 925 IU/mL, respectively. The median histologic activity index was 5.5 and the fibrosis score was 2. The median duration of treatment and consolidation therapy were 59 and 56 months, respectively. The median follow-up time after discontinuation of treatment was 55 months. Among 56 patients eligible for evaluation according to proposed re-treatment criteria, 29 (51.7%) patients were re-treated. The median time for relapse was 11 months. Re-treatment was significantly common in males (P = .034) and patients treated with tenofovir/entecavir (P = .04). Baseline hepatitis B virus DNA and levels of ALT, aspartate aminotransferase (AST) at the third and sixth months of treatment and at the end of treatment were statistically significantly higher in re-treated patients. A cutoff value of ≥405 000 IU/L for hepatitis B virus DNA discriminated patients for re-treatment. HBsAg was lost permanently in 2 non-re-treated patients. In resource-limited areas where follow-up of HBsAg or other markers is not possible, nucleos(t)ide analog discontinuation can be considered in patients in the early stage, with low baseline hepatitis B virus DNA and ALT levels, after a long consolidation therapy.

On-treatment risks of cirrhosis and hepatocellular carcinoma among a large cohort of predominantly non-Asian patients with non-cirrhotic chronic hepatitis B

The vast majority of studies evaluating differences in on-treatment risks of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) have been conducted in Asia. Data on the course of CHB on antiviral therapy among predominantly non-Asian populations is less well described. We aimed to evaluate overall risks of cirrhosis and HCC and the influence of baseline factors on this risk among a predominantly non-Asian cohort of patients with CHB in the US. Using longitudinal data from the national Veterans Affairs database, we evaluated the incidence of cirrhosis or HCC among adults with non-cirrhotic CHB on continuous antiviral therapy. Cumulative incidence functions and adjusted Cox proportional hazards models employed competing risks methods and evaluated overall risk and predictors of developing cirrhosis or HCC while on treatment. Among 2,496 patients with non-cirrhotic CHB (39.1% African American, 38.4% non-Hispanic White, 18.8% Asian, mean age 58.0 ± 13.4 years), the overall incidences of cirrhosis and HCC were 3.99 per 100 person-years (95% CI 3.66-4.35) and 0.43 per 100 person-years (95% CI 0.33-0.54), respectively. The highest incidences of cirrhosis and HCC were observed in non-Hispanic White patients (5.74 and 0.52 per 100 person-years, respectively), which were significantly higher than in Asian patients (1.93 and 0.17 per 100 person-years, respectively, p <0.0001). On multivariate regression, only baseline FIB-4 score was consistently associated with long-term risk of cirrhosis or HCC. Using a longitudinal cohort of predominantly non-Asian Veterans with non-cirrhotic CHB on antiviral therapy (an understudied population), we provide important epidemiological data to describe long-term risks of cirrhosis and HCC. In one of the largest studies to date of a predominantly non-Asian cohort of patients with non-cirrhotic chronic hepatitis B, we provide important epidemiological data describing the long-term risks of cirrhosis and hepatocellular carcinoma among patients on antiviral therapies. Among this understudied population, the overall incidence of cirrhosis was 3.99 per 100-person-years (95% CI 3.66-4.35) and of HCC was 0.43 per 100-person-years (95% CI 0.33-0.54). These data also emphasize the importance of continued monitoring and HCC surveillance among CHB patients who are maintained on antiviral therapies.

Evaluation of muscle strength and quality in North African patients with chronic hepatitis B: A pilot case control study

ABSTRACT Early detection of alteration of muscle strength, quantity, and quality, and sarcopenia is useful in non-cirrhotic chronic hepatitis B (NC-CHB) patients. Studies, which explored the handgrip strength (HGS) are scarce with questionable results, and no previous case-control study explored the presence of sarcopenia. The aim of this study was to assess the muscle strength [i.e.; HGS absolute (HGSA), HGSA/body mass index (BMI)], muscle quantity [i.e.; appendicular skeletal muscle (ASM), ASM/height2, ASM/total body weight (TBW), ASM/BMI], and muscle quality [i.e.; HGSA/total muscle mass (TMM), HGSA/ASM] of NC-CHB patients. This was a case-control study. Cases (n = 26) were untreated NC-CHB patients, and controls (n = 28) were ‘apparently’ healthy participants. Muscle mass was estimated via the TMM (kg) and ASM (kg). Muscle strength was evaluated via the HGS data [i.e.; HGSA (kg), HGSA/BMI (m2)]. Six variants of HGSA were determined: highest values for the dominant and non-dominant hands, highest value between the two hands, averages of the three measurements for the two hands, and the average of the highest values of the two hands. Muscle quantity was expressed in three relative variants (ASM/height2, ASM/TBW, and ASM/BMI). Muscle quality was evaluated via relative HGS data adjusted by muscle mass (i.e.; HGSA/TMM, HGSA/ASM). Probable and confirmed sarcopenia were retained in front of low muscle strength, and low muscle strength and muscle quantity or quality, respectively. There were no significant differences between controls and NC-CHB patients in values of muscle i) Strength whatever the HGS’ mode of expression (e.g.; HGSA/BMI: 1.59 ± 0.54 vs. 1.53 ± 0.54 m2, p = 0.622, respectively), ii) Quantity (e.g.; ASM/BMI: 0.79 ± 0.24 vs. 0.77 ± 0.23 m2, p = 0.883), and iii) Quality (e.g.; HGSA/ASM: 2.00 ± 0.25 vs. 2.01 ± 0.41, p = 0.952, respectively). One NC-CHB participant had a confirmed sarcopenia. To conclude, both controls and NC-CHB patients had similar HGS values. Only one NC-CHB patient had a confirmed sarcopenia.

Hepatocellular carcinoma surveillance based on the Australian Consensus Guidelines: a health economic modelling study

BackgroundHepatocellular carcinoma (HCC) is the fastest increasing cause of cancer death in Australia. A recent Australian consensus guidelines recommended HCC surveillance for cirrhotic patients and non-cirrhotic chronic hepatitis B (CHB) patients at gender and age specific cut-offs. A cost-effectiveness model was then developed to assess surveillance strategies in Australia.MethodsA microsimulation model was used to evaluate three strategies: biannual ultrasound, biannual ultrasound with alpha-fetoprotein (AFP) and no formal surveillance for patients having one of the conditions: non-cirrhotic CHB, compensated cirrhosis or decompensated cirrhosis. One-way and probabilistic sensitivity analyses as well as scenario and threshold analyses were conducted to account for uncertainties: including exclusive surveillance of CHB, compensated cirrhosis or decompensated cirrhosis populations; impact of obesity on ultrasound sensitivity; real-world adherence rate; and different cohort’s ranges of ages.ResultsSixty HCC surveillance scenarios were considered for the baseline population. The ultrasound + AFP strategy was the most cost-effective with incremental cost-effectiveness ratios (ICER) compared to no surveillance falling below the willingness-to-pay threshold of A$50,000 per quality-adjusted life year (QALY) at all age ranges. Ultrasound alone was also cost-effective, but the strategy was dominated by ultrasound + AFP. Surveillance was cost-effective in the compensated and decompensated cirrhosis populations alone (ICERs < $30,000), but not cost-effective in the CHB population (ICERs > $100,000). Obesity could decrease the diagnostic performance of ultrasound, which in turn, reduce the cost-effectiveness of ultrasound ± AFP, but the strategies remained cost-effective.ConclusionsHCC surveillance based on Australian recommendations using biannual ultrasound ± AFP was cost-effective.

HCV elimination in a Swiss opioid agonist therapy programme – a cohort study

In opioid agonist therapy (OAT) programmes, chronic hepatitis C is highly prevalent and directly observed therapy guarantees optimal adherence. Since 2017, all patients with chronic hepatitis C in Switzerland can be treated with pangenotypic direct-acting antivirals irrespective of liver fibrosis stage. Until the end of 2021, however, prescription was restricted to infectious disease specialists, gastroenterologists and certain addiction specialists. Difficult venous access after long-term intravenous drug use and, in the case of referral to a specialist, difficulties keeping appointments are barriers to HCV diagnosis and treatment. To assess whether minimally invasive point-of-care tests and a "test-and-treat / vaccinate on-site" approach can improve human immunodeficiency virus (HIV) / hepatitis C virus (HCV) screening, HCV treatment uptake and immunity against hepatitis A/B. Since September 2018, an infectious disease specialist and a study nurse performed 4-weekly visits in the OAT programme "HAG" (heroin dispensation of the canton Aargau), offering HIV/HCV antibody rapid testing (20 min) and HCV RNA quantification (GeneXpert®, 60 min) from capillary blood, noninvasive liver fibrosis assessment (Fibroscan®, 5-10 min) and HCV treatment prescription on-site. Recommended venous blood draws for HAV/HBV serology and HAV/HBV vaccinations were performed by the staff of the "HAG". Project performance was assessed by annual cross-sectional chart review. Of the 128 patients registered in April 2018, 79 (62%) were still present in May 2021. With 72 newly registered, a total of 200 patients could be assessed, of whom 129 (65%) were still present in May 2021. Between April 2018 and May 2021, the proportion ever tested for HIV antibodies increased from 79% (101/128) to 91% (117/129), the proportion ever tested for HCV antibodies from 83% (106/128) to 93% (120/129) and the proportion of those HCV antibody positive ever tested for HCV RNA tested from 89% (47/53) to 98% (56/57). The proportion with adequate HCV management (last HCV antibody test ≤1 year ago, if HCV antibody negative or last HCV RNA test ≤1 year ago, if HCV antibody-positive and RNA-negative) improved from 23% ([15 + 15]/128) to 80% ([55 + 48]/129). Overall, HCV treatment uptake increased from 60% (21/35) to 92% (55/60) and HCV RNA prevalence among the HCV antibody positives decreased from 38% (18/47) to 7% (6/84). Between 2018 and 2021, 19 non-cirrhotic chronic hepatitis C patients were successfully treated on-site (18 sustained virological responses [SVR] 12, 1 SVR4), with excellent adherence (≥93%) and, so far, no reinfection. The proportion with known HAV/HBV serostatus increased from 38%/51% to 64%/76%. Immunity against HAV/HBV improved from 19%/23% to 50%/57%. Capillary blood point-of-care tests and a "test-and-treat / vaccinate on-site" approach remove crucial barriers to diagnosis and treatment, making hepatitis elimination in OAT programmes achievable. A high fluctuation rate requires HIV/HCV/HAV/HBV testing at admission, but also allows more patients to be screened.

The neutrophil-to-lymphocyte ratio represents a systemic inflammation marker and reflects the relationship with 90-day mortality in non-cirrhotic chronic severe hepatitis.

Systemic inflammatory responses are common in patients with chronic severe hepatitis (CSH) and increase their risk of mortality. Knowledge regarding the impact of the systemic inflammatory response on short-term outcomes in noncirrhotic CSH patients is limited. We collected data from two prospective, multicenter cohorts from the CATCH-LIFE non-cirrhotic cohort. Cox regression was used to explore the association between systemic inflammation markers and 90-day liver transplant (LT)-free mortality. Generalized additive model (GAM) was used to illustrate the quantitative curve relationship between the neutrophil-to-lymphocyte ratio (NLR) and 90-day LT-free mortality. Kaplan-Meier methods were used to estimate the 90-year LT-free survival rates. The prevalence of CSH in the CATCH-LIFE study was 20.5% (226/1103). The 28-day and 90-day LT-free mortality rates were 17.7% and 26.1%, respectively. Noninfected patients accounted for 75% of CSH patients, and the NLR was independently associated with 90-day LT-free mortality. Quantitative analysis of the association between the NLR and 90-day LT-free mortality showed that an NLR of 2.9 may represent the starting point for disease deterioration in CSH patients without infection. This study identified the NLR as an independent risk factor for 90-day LT-free mortality in noncirrhotic CLD patients. The NLR can better indicate the systemic inflammatory response in noninfected CSH patients. An NLR of 2.9 may be the cutoff for disease aggravation onset in CSH patients without infection.

Systematic review and meta-analysis: impact of anti-viral therapy on portal hypertensive complications in HBV patients with advanced chronic liver disease.

The efficacy of nucleos(t)ide analogs (NAs) in non-cirrhotic chronic hepatitis B (CHB) patients is well-established. However, their impact on complications of portal hypertension in advanced chronic liver disease (ACLD) is less well characterized. MEDLINE/PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, and abstracts of major international hepatology meetings were searched for publications from Jan 1, 1995 to Nov 30, 2021. Randomized control trials and observational studies reporting the efficacy of NAs in ACLD patients were eligible. Pooled risk ratios (RRs) for outcomes of interest were calculated with a random-effect or fixed-effect model, as appropriate. Thirty-nine studies including 14,212 ACLD patients were included. NA treatment was associated with reduced risks of overall hepatic decompensation events (RR, 0.51; 95% confidence interval [CI]: 0.37-0.71), such as variceal bleeding (RR, 0.44; 95% CI: 0.26-0.74) and ascites (RR, 0.10; 95% CI: 0.01-1.59), on a trend-wise level. Moreover, the risks of hepatocellular carcinoma (HCC) (RR, 0.48; 95% CI: 0.30-0.75) and liver transplantation/death (RR, 0.36; 95% CI: 0.25-0.53) were also reduced by NA treatment and the first-line NAs were superior to non-first-line NAs in improving these outcomes (RR, 0.85; 95% CI: 0.75-0.97 and RR, 0.85; 95% CI: 0.73-0.99, respectively). NA therapy lowers the risk of portal hypertension-related complications, including variceal bleeding, HCC, and liver transplantation/death.

On-therapy HBsAg kinetics can predict HBsAg loss after nucleos(t)ide analogues interruption in HBeAg-negative patients. The cup is half full and half empty.

Nucleos(t)ide analogues withdrawal may improve HBsAg loss rates. However, conditions to select patients are not well established. to evaluate the impact of HBsAg kinetics before treatment interruption on post-treatment response. Longitudinal, ambispective study in non-cirrhotic chronic hepatitis B HBeAg-negative patients, analysing on-treatment and post-treatment HBsAg kinetics. On-treatment HBsAg kinetics diagnostic accuracy (AUROC) to identify HBsAg loss was evaluated. 52 HBeAg-negative patients stopped treatment after 8.2 years, and 6 (11.5%) achieved HBsAg loss one year after withdrawal. Multivariate analysis showed that on-treatment HBsAg kinetics was related to HBsAg loss (OR=0.10; 95%CI=0.016-0.632; p=0.014) with a high diagnostic accuracy (AUROC=0.935). A significant HBsAg decline ≥1 log10 IU/mL showed a positive and negative predictive value of 50% and of 97.6%, respectively. After treatment interruption, HBsAg decline speed (log10 IU/mL/year) accelerated in patients treated >6 years (from -0.06 to -0.20, p<0.05) and remained stable in treated <6 years (from -0.12 to -0.12 p=ns). On-treatment HBsAg kinetics can predict post-treatment HBsAg loss rate. Half of patients with a significant HBsAg decline can eliminate HBsAg the first year after withdrawal. Post-treatment HBsAg decline is faster not only in patients who lost the HBsAg but also in those who remain HBsAg-positive.

Potential impact of gut Lactobacillus acidophilus and Bifidobacterium bifidum on hepatic histopathological changes in non-cirrhotic hepatitis C virus patients with different viral load

BackgroundComposition of gut microbiota has recently been suggested as a key factor persuading the pathogenesis of numerous human diseases including hepatic cirrhosis.ObjectiveTo evaluate the potential impact of Lactobacillus acidophilus and Bifidobacterium bifidum microbiota on the progression of hepatic histopathological changes among patients with non-cirrhotic chronic hepatitis C (HCV) infection with different viral load. Additionally, to assess fecal composition of Lactobacillus acidophilus ATCC-4356 and Bifidobacterium bifidum ATCC-11863 microbiota genotypesMaterial and methodsThis study was carried out on 40 non-cirrhotic chronically infected HCV patients, and 10 healthy-controls. Liver biopsy and HCV genomic viral load were assessed for all patients after full clinical examination. Lactobacillus acidophilus ATCC-4356 and Bifidobacterium bifidum ATCC-11863 microbiota were assessed in all fecal samples using PCR assay, after counting total lactic acid bacteria.ResultsThere was a significantly higher difference between the count of both total lactic acid and Lactobacillus acidophilus of healthy controls compared to patients (P-value < 0.001). Though the count of total lactic acid bacteria, and Lactobacillus acidophilus were higher in the cases with early stage of fibrosis (score ≤ 1) compared to those with score > 1, there were no statistically significant differences with both the serum level of hepatitis C viremia (P = 0.850 and 0.977 respectively) and the score of fibrosis (P = 0.246 and 0.260 respectively). Genotypic analysis for the composition of the studied microbiota revealed that diversity was higher in healthy controls compared to patients.ConclusionsThe progression of hepatic fibrosis in HCV chronically infected patients seems to be plausible based on finding the altered Lactobacillus acidophilus and Bifidobacterium bifidum gut microbiota composition. Thus, modulation of these microbiota seems to be a promising target for prevention and control of HCV infection.

Progress in research of non-cirrhotic chronic viral hepatitis with osteoporosis

Progress in research of non-cirrhotic chronic viral hepatitis with osteoporosis

Serum HBsAg and ddPCR HBV-DNA as predictive parameters of HBsAg loss after nucleo(s)tide analogue (NA) treatment discontinuation in non-cirrhotic patients with Chronic Hepatitis B

Introduction: Stopping nucleo(s)tide analogue (NA) treatment in selected non-cirrhotic Chronic Hepatitis B (CHB) often leads to virus-induced flares, which may result to life-threatening liver failure.

The Impact of IL28B Gene Polymorphisms on Drug Responses

The Impact of IL28B Gene Polymorphisms on Drug Responses

HBV-related acute-on-chronic liver failure with underlying chronic hepatitis has superior survival compared to cirrhosis.

Acute-on-chronic liver failure (ACLF) is divided into three types according to the underlying liver disease: non-cirrhosis (type A), compensated cirrhosis (type B) and decompensated cirrhosis (type C). However, whether the underlying chronic liver diseases impact the ACLF prognosis is not clear. The present study aimed to compare the characteristics and outcomes of type A and type B hepatitis B virus (HBV)-ACLF patients. According to the European Association for the Study of Liver-Chronic Liver Failure (EASL-CLIF) diagnostic criteria, 86 type A HBV-ACLF and 71 type B HBV-ACLF were prospectively enrolled. The demography and laboratory data, organ failures, ACLF grades and prognosis were evaluated. Univariate and multivariate Cox regression analyses were performed to analyze the prognostic factors. The 28-day and 90-day mortality rates of type A and type B ACLF were 20.9 vs. 60.6% and 34.9 vs. 73.2%, respectively (both P < 0.001). Patients with type A ACLF were younger, had higher viral load and higher levels of alanine aminotransferase and aspartate aminotransferase, platelet count, serum albumin and sodium, international normalized ratio and alpha-fetoprotein, lower rate of ascites, lower Child-Pugh scores and CLIF sequential organ failure assessment scores, higher rate of coagulation failure. Type B ACLF had more renal and cerebral failure. Cirrhosis was one of the independent prognostic factors [hazard ratio, 2.4 (95% CI, 1.451-3.818) P < 0.001]. ACLF developing on noncirrhotic chronic hepatitis B had more serious liver inflammation but fewer extrahepatic organ failures and better outcome than ACLF developing from compensated HBV cirrhosis.

Identification of plasma lncRNA-ATB levels in hepatitis B virus-related cirrhosis and non-cirrhotic chronic hepatitis B patients

Long non-coding RNA-ATB (LncRNA-ATB) which is activated by transforming growth factor-β (TGF-β), is a key regulator of TGF-β signaling pathway. TGF-β plays an important role in various pathogenic processes, from inflammation and fibrosis to cirrhosis and cancer. In this study, we evaluated the plasma levels of lncRNA-ATB in patients with hepatitis B virus (HBV)-related cirrhosis and non-cirrhotic patients with chronic hepatitis B (CHB) and investigated the clinical values.Plasma samples were collected from 44 HBV-related cirrhosis patients, 45 non-cirrhotic CHB and 75 healthy controls. Briefly, after total RNA extraction and cDNA synthesis, quantitative real-time PCR (qPCR) was performed to detect plasma lncRNA-ATB levels.Results show the plasma levels of lncRNA-ATB in HBV-related cirrhosis patients were significantly higher in comparison to healthy controls (Fold change=2.60, p value=0.04). Also, we determined plasma levels of lncRNA-ATB as a specific biomarker of HBV-related cirrhosis (AUC=0.65, p value=0.03, Sensitivity 61.36%; Specificity 70.00%). In addition to, we investigated the plasma levels of lncRNA-ATB in non-cirrhotic CHB patients were significantly lower than healthy controls (Fold change= 0.33, p value=0.01). We also indicated plasma lncRNA-ATB levels were as a sensitive biomarker for diagnosis of non-cirrhotic CHB patients compared with healthy (AUC=0.66, p value=0.00, Sensitivity 71.11%; Specificity 57.78%).According to our results, circulating lncRNA-ATB has good specificity for diagnosing hepatitis B virus (HBV)-related cirrhosis and good sensitivity for diagnosis of non-cirrhotic chronic hepatitis B (CHB) patients.

EASL versus LI-RADS: Intra-individual comparison of MRI with extracellular contrast and gadoxetic acid for diagnosis of small HCC.

Liver Imaging Reporting and Data System (LI-RADS) and European Association for the Study (EASL) criteria for hepatocellular carcinoma (HCC) diagnosis have been updated in 2018. We aimed to compare the HCC diagnostic performance of LI-RADS and EASL criteria with extracellular contrast agents-MRI (ECA-MRI) and hepatobiliary agents-MRI (HBA-MRI). We prospectively evaluated 179 participants with cirrhosis (n=105) or non-cirrhotic chronic hepatitis B (CHB) (n=74) who underwent both ECA-MRI and HBA-MRI before surgery for de novo nodule(s) measuring 10-30mm. We compared the HCC diagnostic performance of EASL and LR-5 in both MRIs. In an analysis of 215 observations (175 HCCs, 17 non-HCC malignancies and 23 benign lesions) identified from cirrhotic or non-cirrhotic CHB participants, LR-5 with ECA-MRI provided the highest sensitivity (80.7%), followed by EASL with ECA-MRI (76.2%), LR-5 with HBA-MRI (67.3%) and EASL with HBA-MRI (63.0%, all P<.05). The specificities were comparable (89.4%-91.5%). When the analysis is limited to participants with pathological cirrhosis (123 observations), the sensitivity of LR-5 with ECA-MRI was similar to that of EASL with ECA-MRI (82.7% vs 80.2%, P=.156), but higher than LR-5 with HBA-MRI (65.1%) or EASL with HBA-MRI (62.8%, both P<.001), with comparable specificities (87.5%-91.7%). The LR-5 with ECA-MRI yielded the highest sensitivity with a similar specificity for HCC diagnosis in cirrhosis and non-cirrhotic CHB participants, while the sensitivities of LR-5 and EASL with ECA-MRI are similar for cirrhosis participants. This indicates non-invasive diagnosis criteria can differ by contrast agents and presence of cirrhosis.

Efficacy of Antiviral Treatment in Liver Biopsy-Proven Immune-Tolerant Chronic Hepatitis B Patients: A Retrospective Cohort Study.

The optimal timing of initiating antiviral treatment for immune-tolerant (IT) patients remains unknown. We conducted this study in liver biopsy-proven IT patients to compare the long-term outcomes of untreated and treated patients suffering non-cirrhotic chronic hepatitis B (CHB). This retrospective cohort study recruited 171 consecutive treatment-naïve CHB patients who completed liver biopsy test. Patients were stratified into IT (n = 60), mildly-active (MA; n = 31), immune-active (IA; n = 80), according to alanine aminotransferase (ALT) and liver biopsy data. One hundred and nine patients receiving antiviral treatment constituted the treated set, and 62 patients under close follow-up comprised the untreated set. Primary outcomes were virological response, HBeAg seroconversion, HBsAg loss, ALT normalization, and liver stiffness measurement normalization (NCT03740789). The study population was predominantly male (62.6%) with a mean age of 31 years. The proportion of virological response in treated patients in the MA phase was 57.1%, and the proportion of HBeAg seroconversion was 28.6%, which showed no difference with the 43.8% virological response and 31.5% HBeAg seroconversion in IA patients. The proportions of virological response and seroconversion were 18.2 and 9.1%, respectively, in the IT phase, which were lower than the rates in the MA and IA phases. However, 95.5% of IT patients persisted normal ALT, and 100% of IT patients persisted normal liver stiffness measurement in the treated group. Therefore, antiviral treatment should be considered for CHB patients with high viral load regardless of phase to minimize further damage to hepatocytes.

One-year Fibrosis-4 index helps identify minimal HCC risk in non-cirrhotic chronic hepatitis B patients with antiviral treatment.

Background and aimsFibrosis-4 (FIB-4) index is a HCC predictor in chronic hepatitis B (CHB) patients. However, little is known about whether FIB-4 helps identify non-cirrhotic CHB patients with minimal HCC risk after prolonged nucleos(t)ide analogue (NA) therapy.MethodsA total of 1936 ethnically diverse, non-cirrhotic CHB patients were enrolled in this retrospective multi-national study. All patients received prolonged NA treatment, including entecavir and tenofovir disoproxil fumarate. We explored whether FIB-4 cutoff of 1.30, a marker indicative of mild fibrosis severity, could stratify HCC risks in these patients.ResultsA total of 48 patients developed HCC after a mean follow-up of 6.98 years. FIB-4 level at 1 year after treatment (1-year FIB-4) was shown to be associated with HCC development and was superior to pre-treatment FIB-4 value. When patients were stratified by 1-year FIB-4 of 1.30, the high FIB-4 group was at an increased HCC risk compared to the low FIB-4 group, with a hazard ratio of 4.87 (95% confidence interval: 2.48–9.55). Multivariable analysis showed that sex and 1-year FIB-4 were independent predictors, with none of the 314 female patients with low 1-year FIB-4 developing HCC. Finally, 1-year FIB-4 of 1.30 consistently stratified HCC risks in patients with low PAGE-B score, a score composed of baseline age, sex and platelet count, and the annual incidence rate of HCC was 0.11% in those with PAGE-B < 10 + 1-year FIB-4 < 1.30.ConclusionsIn non-cirrhotic CHB patients receiving prolonged NA therapy, 1-year FIB-4 < 1.30 is useful for identifying those with minimal HCC risk by combining with female sex or low PAGE-B score.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12072-020-10124-z.

Once-daily tenofovir disoproxil fumarate in treatment-naive Taiwanese patients with chronic hepatitis B and minimally raised alanine aminotransferase (TORCH-B): a multicentre, double-blind, placebo-controlled, parallel-group, randomised trial

Antiviral therapy for patients with non-cirrhotic chronic hepatitis B and minimally raised alanine aminotransferase (ALT) is controversial. We aimed to investigate the efficacy and safety of tenofovir disoproxil fumarate in reducing the risk of disease progression in this patient population. TORCH-B is a multicentre, double-blind, placebo-controlled, parallel-group, randomised trial done at six teaching hospitals in Taiwan that enrolled patients with chronic hepatitis B. Eligible patients were aged 25-70 years and had substantial viraemia (viral DNA >2000 IU/mL) and minimally raised serum ALT concentrations more than one-fold but less than two-fold the upper limit of normal (ULN). Exclusion criteria included liver cirrhosis and previous antiviral treatment. Eligible participants were randomly assigned (1:1), stratified by site with a fixed block size of ten, to receive either 300 mg of oral tenofovir disoproxil fumarate or placebo once daily for 3 years. The participants, investigators, research coordinators, pathologists, laboratory personnel, and staff involved in patient care or assessment were masked to treatment assignment. 0·5 mg/day of oral entecavir was added to rescue acute hepatitis flare. The coprimary outcomes were change in necroinflammation severity on the Knodell scale and change in fibrosis stage on the Ishak scale and were evaluated in the modified intention-to-treat population, which comprised all patients with paired liver biopsies. Safety was evaluated in all patients who were randomly assigned. This trial is registered at ClinicalTrials.gov, NCT01522625, and is completed. From Jan 30, 2012, to Nov 10, 2015, 875 patients were screened and 160 were randomly assigned to receive either tenofovir disoproxil fumarate (n=79) or placebo (n=81). The coprimary outcomes were assessed in 146 patients (73 in each group). Liver fibrosis progressed (an increase of ≥1 stage) in 19 (26%, 95% CI 17-38) of 73 patients in the tenofovir disoproxil fumarate group and in 34 (47%, 35-59) of 73 patients in the placebo group (relative risk [RR] 0·56, 95% CI 0·35-0·88; p=0·013), whereas necroinflammation progressed (an increase of ≥2 points) in five (7%, 95% CI 2-15) patients in the tenofovir disoproxil fumarate group and in 12 (16%, 9-27) patients in the placebo group (RR 0·42, 95% CI 0·15-1·12; p=0·084). Two (3%) of 79 patients in the tenofovir disoproxil fumarate group and 13 (16%) of 81 patients in the placebo group had acute hepatitis flare requiring add-on entecavir (RR 0·16, 95% CI 0·04-0·68; p=0·013). The two groups were otherwise similar in occurrences of adverse events. No patients died. Tenofovir disoproxil fumarate reduces the risk of progression in liver fibrosis in patients with chronic hepatitis B and minimally raised ALT, but its effect on necroinflammation is non-significant. The Taiwan Ministry of Science and Technology, E-Da Hospital, the Taipei Institute of Pathology, Gilead Sciences.

Relationship between hepatosteatosis and histopathological and biochemical paramaters in patients with noncirrhotic chronic hepatitis B

Aim: Fatty liver is a common liver disease in the community. Mitochondrial dysfunction and oxidative process cause insulin resistance, causing fatty liver. Fatty liver diseases are higher in patients infected with chronic hepatitis B virus (HBV) than the normal population. We aimed to investigate the relationship between hepatosteatosis and biochemical and histopathological parameters in chronic HBV patients.Materials and Methods: Patients with follow-up between September/2017-November/2019 with chronic HBV diagnosis were included. Demographic and histopathological data of all patients were documented. Comorbid diseases, medications and previous operations were questioned. The presence of steatosis was determined by ultrasonography (USG) to all patients. Biochemical and histopathological data were compared with the presence of steatosis.Results: A total of 94 patients, 50(53.1%) women were included in the study. As a result of liver biopsy; while 20(21.2%) patients had no fibrosis (steage 0), 74(78.8%) patients had fibrosis (steage 1-3). In USG, 45(47.8%) patients were found to have hepatosteatosis and 49(52.2%) patients were not. In the comparison between the groups; there was no significant relationship between sex, age, liver function tests, HBV-DNA level, hepatic activity index and hepatosteatosis (p>0.05). A significant relation was found between the presence of fibrosis and hepatosteatosis (p=0.021).Conclusions: Chronic HBV is an inflammatory process that ends with cirrhosis and hepatocellular carcinoma, and in this process, fatty liver may increase disease and cause disease progression. In this context, it is important to prevent the development of steatosis in chronic HBV patients. However, this should be supported in prospective studies in larger populations.