Background: Hepatitis B vaccine is an effective measure to prevent hepatitis B virus infection. Whether chronic hepatitis C virus (HCV) infection decreases humoral and cell-mediated immunity responses to hepatitis B vaccination is still controversial.
Methods: Patients with chronic HCV infection who were not in treatment and healthy controls, matched at a 1:2 ratio for community, sex, and age (within 5 years), were identified from a community-based screening. All participants received 3 doses of hepatitis B vaccine. Antibody to hepatitis B surface antigen was tested 1 month after the third vaccine dose and was compared between 2 groups. Spot-forming cells (SFCs) of interferon γ and interleukin 2, 4, 5, and 6 were counted by means of enzyme-linked immunospot, and SFC counts were compared between the 2 groups.
Results: The rates of nonresponse and low, normal, and high response were 3.80%, 10.13%, 45.57%, and 40.50% respectively, in the HCV group, and the corresponding rates in the healthy control group were 1.26%, 10.13%, 39.24%, and 49.37% (all P > .05). There were no significant differences in SFC counts between the 2 groups for interferon γ or interleukin 2, 4, or 5 (all P > .05).
Conclusions: This study provided preliminary evidence of the good immunogenicity and safety of hepatitis B vaccination among patients in China with chronic hepatitis C who are not in treatment.
Clinical Trials Registration: NCT 02898922.
Infectious Diseases (17), Vaccines (6) Hepatitis B (12), Chronic Hepatitis C (4), Infections (3), more mentions
RATIONALE: Hepatitis A viral infection is a well-known cause of subclinical or acute self-limited hepatitis. Few cases of hepatitis A virus (HAV)-associated acute liver failure (ALF) have been reported in low HAV endemic countries annually.
PATIENTS CONCERNS: To investigate the possible factors that affected the severity of HAV infection, a family cluster infected with the HAV subgenotype IB strain, which is not common in Japan, was described.
DIAGNOSES: This family consisted of five members who all were infected with HAV.
INTERVENTIONS: Four of the five patients hospitalized except for an asymptomatic patient.
OUTCOMES: Two of the five patients, men in their 50s and 60s, developed ALF, and one patient died. Various host factors, including sex (male), age, and a high bilirubin level, may affect the outcomes. Based on viral factors, HAV RNA was higher in the fatal case compared with others, and it decreased within a short period of time. The similarity of the nucleotide sequences was 99.9% among the HAV isolates based on an entire genomic sequence. Deletions and/or insertions on the HAV protein-coding sequences that caused a frameshift were found in surviving cases but not in the fatal case.
LESSONS: The rapid clearance of increased HAV and the absence of defective HAV might be closely associated with the onset of liver failure.
Infectious Diseases (6) Hepatitis A (5), Liver Failure (3), Infections (2), more mentions
AIMS: To estimate the effects of needle syringe programmes (NSP) and opioid substitution therapy (OST), alone or in combination, for preventing acquisition of Hepatitis C virus (HCV) in people who inject drugs (PWID).
METHODS: Systematic review and meta-analysis. Bibliographic databases were searched for studies measuring concurrent exposure to current OST (within last 6 months) and/or NSP and HCV incidence among PWID. High NSP coverage was defined as regular NSP attendance or ≥100% coverage (receiving sufficient or greater number of needles/syringes per reported injecting frequency). Studies were assessed using the Cochrane risk of bias in non-randomised studies tool. Random effects models were used in meta-analysis.
RESULTS: We identified 28 studies (n=6279) in North America (13), UK (5), Europe (4), Australia (5), and China (1). Studies were at moderate (2), serious (17) critical (7) and non-assessable risk of bias (2). Current OST is associated with 50% (risk ratio (RR) 0.50 95% CI 0.40-0.63) reduction in HCV acquisition risk, consistent across region and with low heterogeneity (I(2) =0, p=0.889). Weaker evidence was found for high NSP coverage (RR=0.79 95% CI 0.39-1.61) with high heterogeneity (I(2) =77%, p=0.002). After stratifying by region, high NSP coverage in Europe was associated with a 56% reduction in HCV acquisition risk (RR=0.44, 95% CI 0.24-0.80) with low heterogeneity (I(2) =12.3%, p=0.337) but not in North America (RR=1.58, I(2) =89.5%, p=<0.001). Combined OST/NSP is associated with a 76% reduction in HCV acquisition risk (RR=0.24 95% CI=0.07-0.89, I(2) =80% p=0.007). According to GRADE criteria, the evidence on OST and combined OST/NSP is low quality while NSP is very low.
CONCLUSIONS: Opioid substitution therapy reduces risk of hepatitis C acquisition and is strengthened in combination with needle syringe programmes. There is weaker evidence for the impact of needle syringe programmes alone, although stronger evidence that high coverage is associated with reduced risk in Europe.
Hepatitis A virus (HAV) infection is an ancient disease and likely to have afflicted mankind since humans first began to live in groups large enough to sustain transmission of the causative agent, HAV. In reviewing what was known as 'catarrhal jaundice' in 1912, Cockayne noted descriptions of epidemic jaundice extending back to antiquity1. The infectious nature of the disease was proven several decades later in deliberate human transmission studies2. Such experiments led to a clear distinction between hepatitis A ('infectious hepatitis') and hepatitis B ('homologous serum jaundice') and recognition of the lack of cross immunity between these two forms of transmissible hepatitis as early as 19453. However, the responsible virus was not identified until almost 30 years later, when small, round viral particles were discovered by immune electron microscopy in the feces of an experimentally-infected human subject by Feinstone et al. in 19734. This review provides an up-to-date in in-depth overview of HAV and the acute inflammatory hepatic infection it causes in humans, including recently recognized aspects of its molecular virology, evolution, natural history, pathogenesis, epidemiology and prevention.
Infectious Diseases (7), Vaccines (1) Hepatitis A (4), Jaundice (3), Infections (2), more mentions
BACKGROUND AND AIMS: It is unclear whether direct-acting antiviral (DAA) treatment-induced sustained virologic response (SVR) reduces the risk of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV) infection. We aimed to determine the impact of DAA-induced SVR on HCC risk.
METHODS: We identified 62,354 patients who initiated antiviral treatment in the Veterans Affairs (VA) national healthcare system from 1/1/1999 to 12/31/2015, including 35,871 (58%) interferon-only regimens, 4535 (7.2%) DAA+interferon regimens and 21,948 (35%) DAA-only regimens. We retrospectively followed patients until 6/15/2017 to identify incident cases of HCC. We used Cox proportional hazards regression to determine the association between SVR and HCC risk or between type of antiviral regimen (DAA-only vs DAA+interferon vs Interferon-only) and HCC risk.
RESULTS: We identified 3271 incident cases of HCC diagnosed at least 180 days after initiation of antiviral treatment during a mean follow-up of 6.1 years. The incidence of HCC was highest in patients with cirrhosis and treatment failure (3.25 per 100 patient-years), followed by cirrhosis and SVR (1.97), no cirrhosis and treatment failure (0.87) and no cirrhosis and SVR (0.24). SVR was associated with a significantly decreased risk of HCC in multivariable models irrespective of whether the antiviral treatment was DAA-only (adjusted hazard ratio [AHR] 0.29, 95% CI 0.23-0.37), DAA+interferon (AHR 0.48, 95% CI 0.32-0.73) or interferon-only (AHR 0.32, 95% CI 0.28-0.37). Receipt of a DAA-only or DAA+interferon regimen was not associated with increased HCC risk compared to receipt of an interferon-only regimen.
CONCLUSIONS: DAA-induced SVR is associated with a 71% reduction in HCC risk. Treatment with DAAs is not associated with increased HCC risk compared to treatment with interferon.
LAY SUMMARY: Eradication of hepatitis C infection with direct-acting antiviral agents reduces the risk of liver cancer dramatically.
Immune System Diseases (7), Infectious Diseases (3), Oncology (2) Cirrhosis (4), Hepatitis C (3), Hepatocellular Carcinoma (2), more mentions
BACKGROUND: Liver fibrosis stage determines risk of morbidity and mortality from chronic hepatitis C virus (HCV) infection. Prior data have shown long-term reversal of liver fibrosis, measured by vibration-controlled transient elastography (VCTE), in patients successfully treated with interferon-based therapies.
AIM: Our study sought to determine the effect of treatment with modern HCV direct-acting antiviral (DAA) therapy on noninvasive liver fibrosis measurements.
METHODS: A total of 70 patients had VCTE-based liver stiffness measurement (LSM) taken before treatment, directly after treatment completion, and at least 12 months after completion of DAA therapy. Our primary outcome was a >30% improvement in VCTE score at the end of follow-up, relative to baseline.
RESULTS: The sustained virologic response rate in our cohort was 95.7%. In our cohort, 34 (48.6%) met the primary outcome. Those who had baseline elevated alanine aminotransferase (OR 3.27; 95% CI 1.13-9.47) and genotype 1 (OR 14.63; 95% CI 1.70-125.83) had higher odds of meeting that outcome, and this remained significant after adjusting for age, baseline body mass index, gender, baseline elevated alkaline phosphatase levels, treatment experience, liver transplant status, smoking, and baseline liver stiffness.
CONCLUSION: Treatment of chronic HCV with modern DAA therapy was associated with a significant improvement in LSM by VCTE measurement, suggesting possible early improvement in liver fibrosis along with resolution of inflammation over the first year after treatment completion.
Immune System Diseases (3), Infectious Diseases (2), Anti-Obesity and Weight Loss (1) Liver Fibrosis (5), Infections (2), Chronic Hepatitis C (2), more mentions
BACKGROUND: Suppressive activity of recurrence by interferon-free direct-acting antivirals (DAA) is not elucidated after curative treatment of hepatocellular carcinoma (HCC).
PATIENTS AND METHODS: A total of 177 patients received DAA after curative manners of HCC: 89 patients underwent DAA therapy after initial HCC treatment, and the other 88 patients after repeated therapy of 2-10 times. Among a cohort of HCC patients with surgery and radiofrequency ablation, 89 patients were chosen adjusting age, gender, and Barcelona Clinic Liver Cancer (BCLC) staging with 89 patients with initial HCC therapy.
RESULTS: HCC recurrence rates at the end of first and second year were 18.1 and 22.1% in patients with once of HCC therapy, 28.2 and 41.6% in those with 2-3 times of therapy, and 60.2 and 74.5% in those with 4 or more times of therapy, respectively (P < 0.0001). Recurrence rates were compared between 89 patients with DAA therapy after initial HCC therapy and 89 age-, gender-, and BCLC staging-matched patients without antiviral therapy after initial HCC therapy. HCC recurrence rates at first and second year were 18.1 and 25.0% in patients with DAA therapy and 21.8 and 46.5% in those without DAA therapy, respectively (P = 0.003). Multivariate analysis showed DAA therapy significantly decreased recurrence rate with a hazard ratio of 0.353 (confidence interval: 0.191-0.651) after adjustment with covariates of tumor multiplicity, alpha-fetoprotein value, and prothrombin time.
CONCLUSIONS: DAA therapy significantly decreased recurrence rate when it was performed after initial HCC therapy.
Infectious Diseases (1), Oncology (1), Immune System Diseases (1) Hepatocellular Carcinoma (3), Neoplasms (2), Liver Neoplasms (1), more mentions
After an initial exposure, subjects can develop test-taking/learning strategies called the "test sophistication effect. Cirrhotics wth prior overt hepatic encephalopathy (OHE) could have persistent learning impairments.
AIM: To define learning/test-sophistication on EncephalApp (downloadable Application) in OHE patients compared to no-OHE patients and controls cross-sectionally and longitudinally.
METHODS: The EncephalApp Stroop App consists of 2 sections; the easier "Off" run assesses psychomotor speed while the difficult "On" run assesses cognitive flexibility. Cross-sectional Analysis: Cirrhotic outpatients with/without controlled OHE and healthy controls underwent EncephalApp testing, which requires 5 "off" and 5 "on" runs. We studied the difference in time required between completing trial 1 compared with trial 5 (delta 1-5) in the both the "On" and "Off" runs in controls, all cirrhotics; and between prior OHE/no-OHE cirrhotics. Longitudinal Analyses: Two groups of cirrhotics were studied; one was administered EncephalApp, ≥ 2 weeks apart and the second before, and 6 months post-liver transplantation.
RESULTS: 89 controls and 230 cirrhotics (85 prior OHE, MELD 11) with similar age (64 vs 61, p=0.9) were included. Cirrhotic patients had impaired EncephalApp total times and impaired learning on the On runs compared to controls. OHE patients had worse EncephalApp times and learning with the On runs compared to no-OHE patients, which persisted in the longitudinal cohort. No differences in learning were seen in the Off runs. After transplant there was restoration of learning capability with the On runs in the OHE patients.
CONCLUSION: Cognitive flexibility tested by the EncephalApp On runs improves over time in healthy controls and no-OHE but not prior OHE. Psychomotor speed remains similar over time. The learning Impairment manifested by cirrhotics with OHE is restored post-transplant. This article is protected by copyright. All rights reserved.
BACKGROUND: Living donor liver transplantation (LDLT) has been reported to have high rates of hepatocellular carcinoma (HCC) recurrence compared to deceased donor liver transplant (DDLT). This has been assumed to be due to the frequent use of small-for-size grafts (SFSG) in LDLT rather than DDLT, but the relationship between graft size and prognosis remains controversial. This study aimed to clarify the effect of SFSG on the oncologic outcomes of patients with HCC who underwent LDLT.
METHODS: Between January 2005 and December 2015, 597 consecutive patients underwent LDLT. Among these patients, those with HCC who underwent LDLT were randomly matched to 1 (graft-to-recipient body weight ratio [GRWR] <0.8%): 3 (GRWR≥0.8%) ratio according to propensity score. HCC recurrence and patient survival were analyzed using the Kaplan-Meier method and log-rank test. In addition, stratified subgroup analysis based on the Milan criteria was performed. SFSG was defined as a GRWR<0.8%.
RESULTS: Using propensity score matching, 82 patients with GRWR<0.8% and 246 patients with GRWR≥0.8% were selected. For patients with HCC within the Milan criteria, no significant difference of HCC recurrence (P=0.82) and patient survival (P=0.95) was found based on GRWR. However, for patients with HCC beyond the Milan criteria, 1-, 3-, and 5-year recurrence free survival rates were 52.4%, 49.3%, and 49.3%, respectively, for patients with GRWR<0.8%, and 76.5%, 68.3%, and 64.3%, respectively, for patients with GRWR≥0.8% (P=0.049). The former group exhibited poor patient survival rates (P=0.047).
CONCLUSIONS: For patients with HCC within the Milan criteria, no significant difference in oncologic outcomes was found based on liver graft size. However, among the patients with HCC beyond the Milan criteria, SFSG recipients showed poor oncologic outcomes. Since extended criteria are frequently used in LDLT for HCC, recipients' prognosis can be improved if liver grafts of appropriate size are carefully selected during donor selection. This article is protected by copyright. All rights reserved.
BACKGROUND AND OBJECTIVES: Hepatitis C virus infection is common in patients with CKD and leads to accelerated progression to ESRD. Sofosbuvir is a potent direct-acting antiviral therapy against hepatitis C virus; however, there are concerns about its safety in patients with CKD. The objective of our study was to determine the safety and efficacy of sofosbuvir in patients with CKD.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We studied a retrospective observational cohort of patients with CKD defined by eGFR<60 ml/min per 1.73 m(2), ≥30 mg albuminuria per 1 g creatinine, or ≥200 mg proteinuria per 1 g creatinine who received sofosbuvir-based therapy in a large health care system. Regression models were constructed to predict likelihood of sustained virologic response, detect adverse events, and examine changes in eGFR from baseline to follow-up.
RESULTS: Ninety-eight patients with CKD (42% stage 1 or 2 CKD and 58% stage 3 CKD) were included. Mean age was 62 years old, 78% were men, and 65% were white. Additionally, 49% of patients had diabetes, 38% of patients had cirrhosis, and 33% of patients had prior solid organ transplant. Overall sustained virologic response was 81% and varied by regimen used and viral genotype. Average baseline eGFR was equivalent to average on-treatment eGFR, but seven patients experienced a rise in creatinine ≥1.5 times baseline while taking sofosbuvir; all but one recovered. In patients with eGFR<60 ml/min per 1.73 m(2) at baseline (stage 3 CKD), regression models showed that hepatitis C cure was associated with a 9.3 (95% confidence interval, 0.44 to 18) ml/min per 1.73 m(2) improvement in eGFR during the 6-month post-treatment follow-up period. Adverse events were common (81%), but serious adverse events (17%) and treatment discontinuations (8%) were uncommon.
CONCLUSIONS: Sofosbuvir-based direct-acting antiviral therapy is safe and effective in a cohort of patients with CKD infected with hepatitis C.
Infectious Diseases (6), Endocrine Disorders (3), Immune System Diseases (3) Hepatitis C (6), Diabetes Mellitus (3), Cirrhosis (2), more mentions
BACKGROUND: Research suggests depression and alcohol misuse are highly prevalent among chronic hepatitis C (CHC) patients, which is of clinical concern.
AIMS: To compare ICD-9 codes for depression and alcohol misuse to validated survey instruments.
METHODS: Among CHC patients, we assessed how well electronic ICD-9 codes for depression and alcohol misuse predicted these disorders using validated instruments.
RESULTS: Of 4874 patients surveyed, 56% were male and 52% had a history of injection drug use. Based on the PHQ-8, the prevalence of depression was 30% compared to 14% based on ICD-9 codes within 12 months of survey, 37% from ICD-9 codes any time before or within 12 months after survey, and 48% from ICD-9 codes any time before or within 24 months after survey. ICD-9 codes predicting PHQ-8 depression had a sensitivity ranging from 59 to 88% and a specificity ranging from 33 to 65%. Based on the AUDIT-C, the prevalence of alcohol misuse was 21% compared to 3-23% using ICD-9 codes. The sensitivity of ICD-9 codes to predict AUDIT-C score ranged from 9 to 35% and specificity from 80 to 98%. Overall 39% of patients reported ever binge drinking, with a sensitivity of ICD-9 to predict binge drinking ranging from 7 to 33% and a specificity from 84 to 98%. More than half of patients had either an ICD-9 code for depression, a survey score indicating depression, or both (59%); more than one-third had the same patterns for alcohol misuse (36%).
CONCLUSIONS: ICD-9 codes were limited in predicting current depression and alcohol misuse, suggesting that caution should be exercised when using ICD-9 codes to assess depression or alcohol misuse among CHC patients.
Neuroscience (11), Infectious Diseases (2) Depressive Disorder (11), Chronic Hepatitis C (1), Hepatitis C (1), more mentions
Patients with end-stage renal disease who are undergoing dialysis may be at high risk of developing hepatocellular carcinoma (HCC). We investigated the characteristics and prognosis of HCC in patients undergoing dialysis in Japan. Patients characteristics, progression of HCC at diagnosis, and survival rates after diagnosis were compared between 108 HCC patients undergoing dialysis and 526 non-dialysis patients followed up at liver center. The comparisons were also performed after adjusting for patient age, gender, platelet count, and etiology using propensity-score matching. HCC was more advanced in patients undergoing dialysis than in non-dialysis controls. The 3- and 5-year survival rates of patients undergoing dialysis were 56.3% and 38.3%, respectively, which were lower than those of non-dialysis controls (66.5% and 52.7%, respectively, P = 0.0026). The results were the same after propensity score matching (P = 0.0014). In Japan, HCC was more advanced at diagnosis in patients undergoing dialysis in comparison to HCC in patients at liver centers, resulting in a lower survival rate after diagnosis.
AIMS: This study aims to investigate the kinetics of serum HBsAg levels in chronic hepatitis B patients with long-term nucleos(t)ide analogs (NAs) therapy.
METHODS: This was a retrospective clinical study. Serum HBsAg in serial samples of 94 patients, who received at least 8 years of NAs therapy, were measured using Elecsys(®) HBsAg II Quant Assay.
RESULTS: In this cohort, serum HBsAg levels reduced from 3.80 log10 IU/mL at baseline to 2.72 log10 IU/mL at year 8 (p < .001), and the percentage of patients with HBsAg <1000 IU/mL increased from 14.9% at baseline to 55.3% at year 8 (p < .001). The reduction of serum HBsAg did not differ significantly between patients stratified by baseline virological parameters and type of antiviral agents. But as compared to patients without HBeAg seroconversion, HBsAg levels were significant lower in patients with HBeAg seroconversion (3.19 vs. 2.47 log10 IU/mL at year 8, p = .001). As compared to patients with slow (0-1 log10 IU/mL) or steady HBsAg(≤0 log10 IU/mL) decline at year 1, patients with a rapid HBsAg (≥1 log10 IU/mL) decline had a significantly lower HBsAg levels from year 2 to 8. However, Cox regression analysis showed that only absolute HBsAg levels at year 1 was an independent predictor of subsequent HBsAg <1000 IU/mL at year 8 of antiviral therapy(HR 0.242, p = .004).
CONCLUSION: Pronounced HBsAg declines could be achieved in patients after long-term effective therapy with NAs, and on-treatment low serum HBsAg level at year 1 might be a predictor of serum HBsAg <1000 IU/mL at year 8.
Infectious Diseases (4), Immune System Diseases (3) Chronic Hepatitis B (3), Hepatitis B (1), more mentions
OBJECTIVE: Infections are common and associated with complications and mortality in acute liver failure (ALF). The temporal relationship between ammonia and infection in ALF patients is unclear. We aimed to evaluate the predictors of infection and its relationship with arterial ammonia levels.
MATERIALS AND METHODS: Consecutive ALF patients hospitalized between January 2004 and December 2015, without signs of infection at/within 48 h of admission, were included. Occurrence of infection after 48 h was documented and ammonia levels were estimated for five consecutive days. Multivariate logistic regression analysis was used to assess factors associated with development of infection. Generalized estimating equations (GEE) were used to evaluate five-day time trend of ammonia in patients with and without infection.
RESULTS: Of 540 consecutive patients, 120 were infected at admission/within 48 h and were excluded. Of the rest 420 patients, 144 (34.3%) developed infection after 48 h and 276 (65.7%) remained non-infected. Infected patients had higher mortality than non-infected patients (61.8% vs 40.0%, p < .001). On multivariate analysis, presence of cerebral edema(HR 2.049; 95%CI, 1.30-3.23), ammonia level on day 3 of admission (HR 1.006; 95%CI, 1.003-1.008), and model for end stage liver disease (MELD) score (HR 1.051; 95%CI, 1.026-1.078) were associated with development of infection. GEE showed group difference in serial ammonia values between infected and non-infected patients indicating lack of ammonia decline in infected patients.
CONCLUSIONS: Cerebral edema, elevated ammonia on day 3, and higher MELD score predict the development of infection in ALF. Ammonia persists at high levels in infected patients, and elevated ammonia on day 3 is associated with complications and death.
BACKGROUND: & Aims: Hepatocellular (HCC) surveillance guidelines for patients with chronic hepatitis B virus (HBV) infection are based on race- and age-specific estimates of HCC risk, derived from studies conducted in areas in which HBV is endemic.
METHODS: We conducted a retrospective cohort study using the national Veterans Administration data to identify patients with chronic HBV infection from 2001 through 2013. We examined the effect of race and age on HCC risk while adjusting for baseline clinical characteristics.
RESULTS: The study cohort had 8329 patients; 3498 patients (42.0%) were white, 3248 (39%) were African Americans (AAs), and 659 (7.9%) were Asian Pacific Islanders (APIs). The annual HCC incidence was highest in APIs (0.65%), followed by whites (0.57%) and AAs (0.40%). After adjusting for clinical and viral factors, the risk of HCC was significantly higher in APIs compared with whites (adjusted hazard ratio [HR]=2.04; 95% CI, 1.31-3.17). There was no difference in HCC risk between AAs and whites (adjusted HR, 0.77; 95% CI, 0.58-1.02). HCC risk increased with age: adjusted HR=1.97 (95% CI, 0.99-3.87) for 40-49 years; adjusted HR= 3.00 (95% CI, 1.55-5.81) for 50-59 years; and adjusted HR=4.02 (95% CI, 2.03-7.94) for more than 60 years vs less than 40 years. Patients with cirrhosis had higher risk of HCC than patients without cirrhosis (adjusted HR=3.69; 95% CI, 2.82-4.83). However, even among patients without cirrhosis, the annual incidence of HCC was more than 0.2% for all patients older than 40 years with high levels of alanine aminotransferase-regardless of race.
CONCLUSION: In a sample of male veterans with chronic HBV infection, risk of HCC is highest among APIs, followed by whites and AAs. Cirrhosis increased HCC risk. Among patients without cirrhosis, male patients who are older than 40 years and have increased levels of alanine aminotransferase might benefit from HCC surveillance, regardless of race.
Tenofovir disoproxil fumarate (TDF) is a recommended first-line therapy for both naïve and experienced chronic hepatitis B (CHB) patients although reduced estimated glomerular filtration rate (eGFR), hypophosphatemia, hyperphosphaturia and Fanconi syndrome have been reported in some patients. Entecavir (ETV) could be considered as a rescue therapy for TDF treated patients developing renal dysfunction, though patients with prior history of treatment with Lamivudine (LAM) can develop ETV resistance strains which can lead to potentially severe hepatitis flares. Tenofovir alafenamide (TAF), a new prodrug of tenofovir, has been recently developed with the aim to improve the renal and bone safety profile compared to TDF, while maintaining the same virological efficacy. The recently published 48-week phase III TAF registration studies confirmed the superior safety profile. Here we describe a case of a 75-year old woman with compensated HBV cirrhosis who developed ETV resistant strains and grade 3 chronic kidney disease after many years of LAM and Adefovir (ADV) treatment and a TDF-induced Fanconi syndrome. The administration of 25 mg/day of TAF, granted as part of a compassionate use program, rapidly suppressed viral replication to undetectable levels without worsening renal function or side effects.
Infectious Diseases (3), Kidney Disease (1) Fanconi Syndrome (3), Cirrhosis (1), Hepatitis B (1), more mentions
BACKGROUND: In diagnostics, serum hepatitis B virus (HBV)-RNA levels are valuable when the HBV-DNA load in circulation is effectively suppressed by nucleos(t)ide analogue (NUC) therapy. This study aimed to determine the intrahepatic viral replication activity reflected in serum HBV-RNA and whether HBV-RNA contributes to liver histological changes in NUC-treated patients.
METHODS: A cross-sectional set of serum and liver biopsy samples was obtained from entecavir-treated patients with undetectable levels of serum HBV-DNA. The correlations between HBV-RNA concentration in serum and levels of peripheral and intrahepatic viral replicative forms and histological scores were analyzed. Quasispecies of serum HBV-RNA and intrahepatic viral replicative forms were examined by deep sequencing. HBV-RNA-positive hepatocytes were visualized by in situ hybridization.
RESULTS: Serum HBV-RNA was detected in 35 of 47 patients (74.47%, 2.33-4.80 log10 copies/mL). These levels correlated not only with the intrahepatic HBV-RNA level and the ratio of intrahepatic HBV-RNA to covalently closed circular DNA (cccDNA), but also with the histological scores for grading and staging. From the view of quasispecies, serum HBV-RNA was more genetically homogenous with contemporaneously sampled intrahepatic HBV-RNA relative to cccDNA pool and dynamically changed over time in consecutive samples. In situ histology study revealed that HBV-RNA-positive hepatocytes were clustered in foci, sporadically distributed across the lobules, and co-localized with hepatitis B surface antigen.
CONCLUSION: Serum HBV-RNA levels reflect intrahepatic viral transcriptional activity and are associated with liver histopathology in patients receiving NUC therapy. Our study sheds light on the nature of HBV-RNA in the pathogenesis of chronic HBV infection and has implications for the management of chronic hepatitis B during NUC therapy.
LAY SUMMARY: Serum HBV-RNA levels are indicative of the intrahepatic transcriptional activity of covalently closed circular DNA and are associated with liver histological changes in patients with chronic B hepatitis who are receiving nucleos(t)ide analogue therapy.
Infectious Diseases (5) Hepatitis B (2), Chronic Hepatitis B (2), Hepatitis (1), more mentions
BACKGROUND/AIMS: The clinical course of chronic hepatitis B (CHB) patients with partial virologic response (PVR) during tenofovir disoproxil fumarate (TDF) therapy remains unclear.
METHODS: We retrospectively investigated the long-term clinical outcomes of TDF treatment in nucleos(t)ides-naïve CHB patients, particularly in those with PVR.
RESULTS: A total of 391 patients treated with TDF therapy for more than 12 months were included. Virologic response (VR) was achieved in 341 patients (87.2%). PVR was evident in 127 (45.3%) of the 391 patients. Multivariate logistic regression analysis using selected baseline factors identified absolute HBV DNA levels at baseline (OR 0.496; 95% CI 1.369-1.969) and HBeAg positivity (OR 0.622; 95% CI 1.096-3.167) as factors significantly associated with PVR. During continuous prolonged TDF therapy, 127 (71.8%) of 177 patients with PVR achieved VR. The cumulative rates of VR in patients with PVR at 12, 24, and 36 months were 42.4, 79.7, and 90.2%, respectively. Serum HBV DNA level at week 24 was significantly associated with VR in patients with PVR.
CONCLUSIONS: The vast majority of CHB patients with PVR achieved VR through prolonged TDF therapy, although the time to achieve VR was delayed in those with PVR. This suggests that adjustment of TDF therapy in patients with PVR is unnecessary.