Hepatitis B og C

Journal of Medical Virology, Accepted Article.

Objectives

Rural-to-urban migrant workers are susceptible to hepatitis B because of lack of self-protection awareness and social support. The aim of this study was to explore the factors influencing risk behaviours for hepatitis B among migrant workers based on the theory of planned behaviour (TPB).

Design

A cross-sectional survey.

Setting

Chongqing, China

Participant

Migrant workers

Primary and secondary outcome measures

The primary outcomes were the TPB variables. The secondary outcomes were factors explored by logistic regressions which were associated with hepatitis B related risk behaviours and behavioural intentions (BI).

Results

Of 1299 recruited migrant workers, 384 (29.56%) participants undertook risk behaviours related to hepatitis B virus infection in the 6 months prior to the survey, and 1111 (85.53%) migrant workers had the BI of doing so. Of 842 migrant workers who undertook sexual activities, 58.19% did not use condoms. Binary logistic regressions showed that migrant workers who were men (p<0.05), less educated (p<0.01), lacked hepatitis B knowledge (p<0.05) and of a young age (p<0.01), were more intent on conducting hepatitis B-related behaviours. Alcohol drinking (p<0.01) was also positively associated with hepatitis B risk. The scores of TPB variables, including attitude towards behaviour and subjective norms, were positively associated with BI when adjusted for sociodemographics (p<0.001). Meanwhile, experience of behaviour and regret feeling were positively associated with BI and actual behaviours (p<0.01 and p<0.05, respectively).

Conclusions

A considerable proportion of migrant workers undertake hepatitis B-related risk behaviours, and condoms are seldom used. Health education campaigns targeting the identified TPB variables may play a significant role in improving awareness of hepatitis B prevention among migrant workers, especially for those who are men, younger, alcohol drinkers, less educated and lacking hepatitis B knowledge.

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by Pinggui Wang, Lijie Zhang, Jian He, Guomin Zhang, Yvan Ma, Weimin Lv, Xiaoshu Zhang, Jin An

Hepatitis B is a major global public health threat. According to China’s National Notifiable Disease Reporting System (NNDRS), Gannan Tibetan Autonomous Prefecture (Gannan) had the highest incidence of hepatitis B in Gansu Province during 2004 to 2016. We evaluated NNDRS hepatitis B case reports from Gannan to determine accuracy of diagnosis and to understand factors associated with inaccuracy. We reviewed medical records with hepatitis B diagnosis hospitalized in seven county hospitals in Gannan between January 1, 2016 and July 31, 2017. Using national 'Classification and Diagnostic Procedures for Hepatitis B,' we independently reclassified the diagnoses. We determined the positive predictive value (PPV) of reported hepatitis B cases. We investigate clinicians’ understanding of the diagnostic and reporting criteria for hepatitis B by questionnaire. We reviewed and re-categorized 400 inpatients reported. Sixteen cases had been reported as acute hepatitis B, but on re-categorization, none were acute hepatitis B cases. PPVs for chronic hepatitis B and unclassified hepatitis B cases were 66% and 15% respectively; 327 (82%) of the reported hepatitis B cases were inaccurately classified; 261 were carriers, 59 were reported previously, and 7 did not have hepatitis B. The actual incidence of hepatitis B in Gannan in 2016 was estimated to be 19/100,000, significantly below the reported incidence of 106/100,000. Among reported cases, 81% had been tested for Alanine aminotransferase, 52% for hepatitis C antibody, 80% with liver ultrasound, 32% for hepatitis A antibody, and 7% for hepatitis B virus (HBV) DNA. Not all cases were tested for anti-HBc IgM or hepatitis E antibody or had a liver biopsy. In the knowledge test, 56% of clinicians accurately diagnosed three simulated cases of acute hepatitis B, and 17% correctly diagnosed two simulated cases chronic hepatitis B; 22% knew that “a client with only HBsAg positivity need not be reported.” The falsely high incidence in Gannan was due to diagnostic and reporting inaccuracies. We recommend that clinicians and laboratorians receive additional training in hepatitis B diagnostic criteria and reporting standards, including appropriate use of IgM anti-HBc tests. Hepatitis B surveillance data should be periodically reviewed and evaluated for accuracy.

AbstractBackground and AimsWe evaluated the patterns of peripheral TLR signalling activity and the expression of TLRs and NK cell activation in a cohort of patients experiencing severe hepatitis flares after stopping NA therapy.MethodsSamples were collected longitudinally from CHB patients enrolled in a prospective study of NA discontinuation. Patients experiencing hepatitis flares were compared to patients with normal ALT. PBMC were stimulated with TLR ligands and cytokine secretion in the cell culture supernatant measured. Expression of TLR2/4, NKG2D, NKp46 and TREM-1 on monocytes, NK and NK-T cells was measured.Results17 patients with severe reactivation hepatitis flares were compared to 12 non-flare patients. Hepatitis flares were associated with increased activity of TLR 2-8 and TLR 9 signalling in PBMC at the time of peak flare compared to baseline. Hepatitis flares were also associated with upregulation of TLR2, and TREM-1 receptor expression on NK. There were no differences at baseline between flare patients and non-flare patients.ConclusionHepatitis flares off NA therapy have a significant innate inflammatory response with upregulation of TLR signalling on peripheral monocytes and TLR-2 and TREM-1 expression on NK cells. This implicates the innate immune system in the immunopathogenesis of hepatitis B flares.

Hepatitis B virus (HBV) infection is considered one of the most critical public health problems worldwide, with an estimated 257 million people worldwide infected with HBV (https://www.who.int/hepatitis/publications/global-hepatitis-report2017/en/, 2017). More than 686,000 people die yearly from end-stage chronic hepatitis B (CHB) and CHB-related complications such as decompensated cirrhosis and hepatocellular carcinoma (http://www.who.int/mediacentre/factsheets/fs204/en/, 2017). Oral anti-viral drugs are regarded as first-line treatments for HBV considering the healthcare conditions, compliance, and cost.

Bulevirtide induced a significant decline in hepatitis D virus RNA over 24 weeks. After cessation of bulevirtide, hepatitis D virus RNA concentrations rebounded. Longer treatment durations and combination therapies should be investigated.

Hepatitis B virus (HBV) infection incurs a substantial burden worldwide due to the associated cost of prevention, diagnosis, and treatment (Zampino et al., 2015). Global HBV seroprevalence in 2016 was estimated to be 3.9%, with approximately 296 million people living with chronic HBV infection in 2019 and 1.5 million new infections annually (CDA Foundation Polaris Observatory, 2020; World Health Organization, 2021, 2017). In highly endemic countries, mother-to-child transmission (MTCT) accounts for most new cases (Gentile and Borgia, 2014).

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Abstract

Background

Oral daily preexposure prophylaxis (PrEP) using emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) is recommended as standard of care for prevention in individuals at high risk for HIV infection, including pregnant and postpartum cisgender women. FTC/TDF is also active against hepatitis B virus (HBV); however, concern has been raised that providing PrEP to individuals infected with HBV could lead to hepatitis flares and liver injury, especially in the setting of suboptimal PrEP use.

Methods

We conducted a cross-sectional analysis of baseline data from the PrEP in pregnant and postpartum women (PrEP-PP) cohort study from February 2020–March 2022 in one antenatal care clinic in Cape Town, South Africa (SA) to evaluate: (1) the field performance of a point of care test (POCT) (Determine II, Abbott Inc., Japan) for diagnosis of hepatitis B surface antigen (HBsAg) in a maternity setting, (2) the prevalence of HBV in a cohort of pregnant women not living with HIV.

Results

We enrolled 1194 HIV sero-negative pregnant women at their first antenatal visit. Median age was 26 years (IQR = 22–31 years); 52% were born before 1995 (before universal HBV vaccination had started in South Africa). Median gestational age was 22 weeks (IQR = 16–30 weeks). There were 8 POCT and laboratory confirmed HBV cases among 1194 women. The overall prevalence of 0.67% (95% CI = 0.34–1.32%). In women born before 1995, 8 of 622 women were diagnosed with HBsAg; the prevalence was 1.29% (95% CI = 0.65–2.52%), and in women born in 1995 or after (n = 572); the prevalence was 0% (95% CI = 0.0–0.67%). We confirmed the test results in 99.8% of the rapid HBsAg (Determine II). Sensitivity was 100% (95% CI = 68–100%). Specificity was 100% (95% CI = 99.67–100%).

Conclusion

The prevalence of HBV was very low in pregnant women not living with HIV and was only in women born before the HBV vaccine was included in the Expanded Program of Immunization. The Determine II POCT HBsAg showed excellent performance against the laboratory assay. HBV screening should not be a barrier to starting PrEP in the context of high HIV risk communities.

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Abstract

Background

Oral daily preexposure prophylaxis (PrEP) using emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) is recommended as standard of care for prevention in individuals at high risk for HIV infection, including pregnant and postpartum cisgender women. FTC/TDF is also active against hepatitis B virus (HBV); however, concern has been raised that providing PrEP to individuals infected with HBV could lead to hepatitis flares and liver injury, especially in the setting of suboptimal PrEP use.

Methods

We conducted a cross-sectional analysis of baseline data from the PrEP in pregnant and postpartum women (PrEP-PP) cohort study from February 2020–March 2022 in one antenatal care clinic in Cape Town, South Africa (SA) to evaluate: (1) the field performance of a point of care test (POCT) (Determine II, Abbott Inc., Japan) for diagnosis of hepatitis B surface antigen (HBsAg) in a maternity setting, (2) the prevalence of HBV in a cohort of pregnant women not living with HIV.

Results

We enrolled 1194 HIV sero-negative pregnant women at their first antenatal visit. Median age was 26 years (IQR = 22–31 years); 52% were born before 1995 (before universal HBV vaccination had started in South Africa). Median gestational age was 22 weeks (IQR = 16–30 weeks). There were 8 POCT and laboratory confirmed HBV cases among 1194 women. The overall prevalence of 0.67% (95% CI = 0.34–1.32%). In women born before 1995, 8 of 622 women were diagnosed with HBsAg; the prevalence was 1.29% (95% CI = 0.65–2.52%), and in women born in 1995 or after (n = 572); the prevalence was 0% (95% CI = 0.0–0.67%). We confirmed the test results in 99.8% of the rapid HBsAg (Determine II). Sensitivity was 100% (95% CI = 68–100%). Specificity was 100% (95% CI = 99.67–100%).

Conclusion

The prevalence of HBV was very low in pregnant women not living with HIV and was only in women born before the HBV vaccine was included in the Expanded Program of Immunization. The Determine II POCT HBsAg showed excellent performance against the laboratory assay. HBV screening should not be a barrier to starting PrEP in the context of high HIV risk communities.

…

Abstract

Background

Located in southwestern Indian Ocean, Mayotte is a French territory, with a very specific demographic, social and health context. To date, epidemiological data on infections by hepatitis B (HBV), C (HCV), and delta (HDV) viruses in Mayotte have been sparse. We aimed to estimate, in the 15–69-year-old general population living in Mayotte, the prevalence of infections by hepatitis B (HBV), C (HCV), and delta (HDV) viruses and the distribution of HBV status: current infection with positive HBs antigen (Ag); resolved infection with positive HBc antibodies and negative HBsAg; immunisation by vaccination with only positive HBs antibodies; and no infection/no immunisation with negative markers. We also described the characteristics of infected people and assessed the determinants of lifetime HBV infection.

Methods

The Unono Wa Maore survey, implemented in a random sample of the general population in 2018–2019, consisted of an at-home collection of epidemiological data and venous blood samples. Detection of hepatitis B, C, and delta serological and molecular markers was performed.

Results

Among 5207 eligible people, 4643 responded to the questionnaire (89.2%), with 2917 being tested for HBV and HCV (62.8%). Estimated HBV status was as follows: current infection 3.0% (95% confidence interval [CI]: 2.3–3.9%) (n = 76); resolved infection 27.8% (95% CI: 25.8–29.9); immunisation by vaccination 27.7% (95% CI: 25.9–29.7); and no infection/no immunisation 41.5% (95% CI: 39.3–43.7). One participant was positive for HDV antibodies (Ab) (0.65%) with a negative HDV-RNA viral load. The risk of lifetime HBV infection was higher in men (adjusted prevalence ratio (aPR): 1.55, 95% CI: 1.29–1.89); in people aged 30–49 years (aPR: 3.83, 95% CI: 1.49–9.81) or 50–69 years (aPR: 4.52, 95% CI: 1.77–11.53) compared to those under 20; in individuals who reported no condom use during their first sexual intercourse (aPR: 1.46, 95% CI: 1.01–2.14); and in those living in Dembeni-Mamoudzou (aPR: 1.40, 95% CI: 1.09–1.80) compared to the West-Centre of Mayotte. Finally, six individuals were positive for HCV antibodies (0.21%), including three positive for HCV RNA.

Conclusions

Mayotte is an area of intermediate endemicity for HBV and low endemicity for HCV and HDV. With a prevalence of HBsAg 10 times higher than in mainland France, a high proportion of people susceptible to HBV infection, and a demographic, health, and social context that may favour its transmission, hepatitis B is a major public health concern in Mayotte.

…

Abstract

Background

Located in southwestern Indian Ocean, Mayotte is a French territory, with a very specific demographic, social and health context. To date, epidemiological data on infections by hepatitis B (HBV), C (HCV), and delta (HDV) viruses in Mayotte have been sparse. We aimed to estimate, in the 15–69-year-old general population living in Mayotte, the prevalence of infections by hepatitis B (HBV), C (HCV), and delta (HDV) viruses and the distribution of HBV status: current infection with positive HBs antigen (Ag); resolved infection with positive HBc antibodies and negative HBsAg; immunisation by vaccination with only positive HBs antibodies; and no infection/no immunisation with negative markers. We also described the characteristics of infected people and assessed the determinants of lifetime HBV infection.

Methods

The Unono Wa Maore survey, implemented in a random sample of the general population in 2018–2019, consisted of an at-home collection of epidemiological data and venous blood samples. Detection of hepatitis B, C, and delta serological and molecular markers was performed.

Results

Among 5207 eligible people, 4643 responded to the questionnaire (89.2%), with 2917 being tested for HBV and HCV (62.8%). Estimated HBV status was as follows: current infection 3.0% (95% confidence interval [CI]: 2.3–3.9%) (n = 76); resolved infection 27.8% (95% CI: 25.8–29.9); immunisation by vaccination 27.7% (95% CI: 25.9–29.7); and no infection/no immunisation 41.5% (95% CI: 39.3–43.7). One participant was positive for HDV antibodies (Ab) (0.65%) with a negative HDV-RNA viral load. The risk of lifetime HBV infection was higher in men (adjusted prevalence ratio (aPR): 1.55, 95% CI: 1.29–1.89); in people aged 30–49 years (aPR: 3.83, 95% CI: 1.49–9.81) or 50–69 years (aPR: 4.52, 95% CI: 1.77–11.53) compared to those under 20; in individuals who reported no condom use during their first sexual intercourse (aPR: 1.46, 95% CI: 1.01–2.14); and in those living in Dembeni-Mamoudzou (aPR: 1.40, 95% CI: 1.09–1.80) compared to the West-Centre of Mayotte. Finally, six individuals were positive for HCV antibodies (0.21%), including three positive for HCV RNA.

Conclusions

Mayotte is an area of intermediate endemicity for HBV and low endemicity for HCV and HDV. With a prevalence of HBsAg 10 times higher than in mainland France, a high proportion of people susceptible to HBV infection, and a demographic, health, and social context that may favour its transmission, hepatitis B is a major public health concern in Mayotte.

…

Journal of Medical Virology, Accepted Article.

: Chronic hepatitis B (CHB) is associated with high morbidity and mortality. We aimed to investigate associations between hepatic histology and clinical characteristics in treatment-naïve children with CHB in Shanghai, China.

Journal of Medical Virology, Accepted Article.

Science Advances, Volume 8, Issue 31, August 2022. …

by Chun-Hsiang Wang, Ruey-Chang Lin, Hua-Yin Hsu, Yuan-Tsung Tseng

Postmenopausal women with hepatitis B virus (HBV) infection are more likely to have accelerated liver fibrosis, eventually advancing to liver cirrhosis or hepatocellular carcinoma (HCC). The association between sex hormones and HBV-related HCC risk is unclear. We investigated whether hormone replacement therapy (HRT) is beneficial to postmenopausal women with HBV infection. This retrospective study selected the data of 44,465patients with HBV infection between January 2000 and December 2018 from Taiwan’s National Health Insurance Research Database. After excluding patients with preexisting liver diseases, liver cirrhosis, or liver malignancies, we grouped the remaining 10,474 patients by whether they had undergone HRT for at least 3 months (n = 5,638) and whether they had not received HRT (n = 4,836). After propensity score matching, we assigned 3080 patients to an HRT cohort and matched them (1:1) with those in a non-HRT cohort. The incidence of HCC (P < 0.022) and all-cause mortality rate (P < 0.001) were lower in the HRT cohort than in the non-HRT cohort. The liver cirrhosis risk was not significantly higher in the HRT cohort (P = 0.355). HRT is associated with reduced HCC risk and improved survival outcomes but is unrelated to liver cirrhosis development in postmenopausal women.

Journal of Medical Virology, Accepted Article.

A major hurdle in the long-term treatment of chronic hepatitis B (CHB) patients is to maintain viral suppression in the absence of drug resistance. To date, no evidence of resistance to tenofovir disoproxil fumarate (TDF) has been observed. A cumulative evaluation of CHB patients who qualified for resistance surveillance over 8 years of TDF treatment was conducted. Patients in studies GS-US-174-0102 (HBeAg-) and GS-US-174-0103 (HBeAg+) were randomized 2:1 to receive TDF or adefovir dipivoxil (ADV) for 48 weeks followed by open-label TDF through year 8. Population sequencing of HBV pol/RT was attempted for all TDF-treated patients at baseline and, annually if viremic, at discontinuation, or with addition of emtricitabine. Overall, 88/641 (13.7%) patients qualified for sequence analysis at one or more time points. The percentage of patients qualifying for sequence analysis declined over time, from 9 to 11% in years 1-2 to <4% over years 3-8. Forty-one episodes of virologic breakthrough (VB) occurred throughout the study, with most (n=29, 70%) associated with nonadherence to study medication. Fifty-nine per cent of VB patients with an opportunity to resuppress HBV achieved HBV DNA resuppression. A minority of patients who qualified for sequencing had polymorphic (41/165, 24.8%) or conserved (17/165, 10.3%) site changes in pol/RT, with six patients developing lamivudine and/or ADV resistance-associated mutations. No accumulation of conserved site changes was detected. The long-term treatment of CHB with TDF monotherapy maintains effective suppression of HBV DNA through 8 years, with no evidence of TDF resistance or accumulation of conserved site changes.

In phase 2 trials, treatment with the combination of the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir resulted in high rates of sustained virologic response in patients chronically infected with hepatitis C virus (HCV) genotype 2 or 3.

A simple treatment regimen that is effective in a broad range of patients who are chronically infected with the hepatitis C virus (HCV) remains an unmet medical need.

Chronic hepatitis C virus (HCV) infection is associated with several extrahepatic manifestations. Patients with HCV may develop mixed cryoglobulinemia and its sequelae, ranging from cutaneous and visceral vasculitis to glomerulonephritis and B-cell non-Hodgkin lymphoma. HCV-infected patients have increased rates of insulin resistance, diabetes, and atherosclerosis, which may lead to increased cardiovascular morbidity and mortality. Neurological manifestations of HCV infection include fatigue and cognitive impairment. The mechanisms causing the extrahepatic effects of HCV infection are likely multifactorial and may include endocrine effects, HCV replication in extrahepatic cells, or a heightened immune reaction with systemic effects. Successful eradication of HCV with interferon alfa and ribavirin was shown to improve some of these extrahepatic effects; sustained virological response is associated with resolution of complications of cryoglobulinemia, reduced levels of insulin resistance, reduced incidence of diabetes and stroke, and improved fatigue and cognitive functioning. The availability of new interferon-free, well-tolerated anti-HCV treatment regimens is broadening the spectrum of patients available for therapy, including those in whom interferon was contraindicated, and will likely result in greater improvements in the extrahepatic manifestations of HCV. If these regimens are shown to confer significant benefit in the metabolic, cardiovascular, or neuropsychiatric conditions associated with HCV infection, extrahepatic manifestations of HCV may become a major indication for treatment even in the absence of liver disease.

Worldwide, although predominantly in low-income countries in the Middle East and Africa, up to 13% of hepatitis C virus (HCV) infections are caused by HCV genotype 4. For patients with HCV genotype 1, the combination of ledipasvir and sofosbuvir has been shown to cure high proportions of patients with excellent tolerability, but this regimen has not been assessed for the treatment of HCV genotype 4. We assessed the efficacy, safety, and tolerability of 12 weeks of combination therapy with ledipasvir and sofosbuvir for patients with chronic HCV genotype 4 infections.

Novel interferon- and ribavirin-free regimens are needed to treat hepatitis C virus (HCV) infection.

The Phase-2 C-SALVAGE study evaluated an investigational interferon-free combination of grazoprevir (a NS3/4A protease inhibitor) and elbasvir (a NS5A inhibitor) with ribavirin for patients with chronic HCV genotype-1 infection who had failed licensed DAA-containing therapy.

Hepatitis C virus (HCV) genotype 4 accounts for about 13% of global HCV infections. Because interferon-containing treatments for genotype 4 infection have low efficacy and poor tolerability, an unmet need exists for effective all-oral regimens. We examined the efficacy and safety of an all-oral interferon-free regimen of ombitasvir, an NS5A inhibitor, and paritaprevir (ABT-450), an NS3/4A protease inhibitor dosed with ritonavir (ombitasvir plus paritaprevir plus ritonavir), given with or without ribavirin.

Patients with cirrhosis resulting from chronic hepatitis C virus (HCV) infection are at risk of life-threatening complications, but consistently achieve lower sustained virological response (SVR) than patients without cirrhosis, especially if treatment has previously failed. We assessed the efficacy and safety of the NS5A inhibitor ledipasvir and the nucleotide polymerase inhibitor sofosbuvir, with and without ribavirin.

Interferon-free regimens are needed to treat hepatitis C virus (HCV) infections. We investigated the efficacy of combined simeprevir and sofosbuvir.

Effective treatment for hepatitis C virus (HCV) genotype 1 infection in patients who have not had a sustained virologic response to prior interferon-based therapy represents an unmet medical need.

In this phase 3 trial we evaluated the efficacy and safety of the interferon-free combination of ABT-450 with ritonavir (ABT-450/r), ombitasvir (also known as ABT-267), dasabuvir (also known as ABT-333), and ribavirin for the retreatment of HCV in patients who were previously treated with peginterferon-ribavirin.

No data are available about the prediction of long-term survival using repeated noninvasive tests of liver fibrosis in chronic hepatitis C (CHC). We aimed to assess the prognostic value of 3-year liver stiffness measurement (LSM), aspartate aminotransferase to platelet ratio index (APRI), and fibrosis 4 (FIB-4) evolution in CHC. CHC patients with two LSM (1,000-1,500 days interval) were prospectively included. Blood fibrosis tests APRI and FIB-4 were calculated the day of baseline (bLSM) and follow-up (fLSM) LSM. Evolution of fibrosis tests was expressed as delta: (follow-up-baseline results)/duration. Date and cause of death were recorded during follow-up that started the day of fLSM. In all, 1,025 patients were included. Median follow-up after fLSM was 38.0 months (interquartile range [IQR]: 27.7-46.1) during which 35 patients died (14 liver-related death) and seven had liver transplantation. Prognostic accuracy (Harrell C-index) of multivariate models including baseline and delta results was not significantly different between LSM and FIB-4 (P ≥ 0.24), whereas FIB-4 provided more accurate prognostic models than APRI (P = 0.03). By multivariate analysis including LSM variables, overall survival was independently predicted by bLSM, delta (dLSM), and sustained virological response (SVR). Prognosis was excellent in patients having bLSM <7 kPa, SVR, or no increase (<1 kPa/year) in 7-14 kPa bLSM. Prognosis was significantly impaired in patients with an increase (≥ 1 kPa/year) in 7-14 kPa bLSM, or decrease (≤ 0 kPa/year) in ≥ 14 kPa bLSM (P = 0.949 between these two groups). Patients with an increase (>0 kPa/year) in ≥ 14 kPa bLSM had the worst prognosis. Baseline and delta FIB-4 also identified patient subgroups with significantly different prognosis.

All-oral combination therapy is desirable for patients with chronic hepatitis C virus (HCV) infection. We evaluated daclatasvir (an HCV NS5A replication complex inhibitor) plus sofosbuvir (a nucleotide analogue HCV NS5B polymerase inhibitor) in patients infected with HCV genotype 1, 2, or 3.

Early treatment of acute hepatitis C virus (HCV) infection with interferon alfa monotherapy is very effective, with cure rates of greater than 85%. However, spontaneous clearance of HCV occurs in 10-50% of cases. We aimed to assess an alternative treatment strategy of delayed antiviral therapy in patients who do not eliminate the virus spontaneously compared with immediate treatment.

Earlier studies have suggested neurocognitive impairment in patients with chronic hepatitis C virus (HCV) infection even before liver cirrhosis has developed. Since these deficits might be reversible after successful antiviral therapy, we analyzed the long-term course of neurocognitive parameters in HCV patients with and without successful virus elimination by an interferon-based antiviral treatment. In a multicenter study including 168 HCV patients receiving antiviral therapy (peginterferon alpha-2b and ribavirin) we performed a long-term follow-up of neurocognitive performance before and after treatment. Neurocognitive function was psychometrically assessed using the computer-aided TAP (Test Battery of Attentional Performance). When tested at least 12 months after termination of antiviral treatment, patients with sustained virologic response (SVR) had improved significantly as compared to their pretreatment performance in three of five TAP subtasks (vigilance, P < 0.001; shared attention: optical task, P < 0.001; working memory, P < 0.001). Patients who failed to eradicate the virus, however, showed no significant long-term changes in neurocognitive performance in all five subtasks assessed (0.194 < P < 0.804). In the posttreatment evaluation, neurocognitive function was significantly better in responders to the antiviral therapy as compared to nonresponders.

A national survey for chronic hepatitis C has not been performed in Denmark and the prevalence is unknown. Our aim was to estimate the prevalence of chronic hepatitis C from public registers and the proportion of these patients who received specialized healthcare.

Since 2000 outbreaks of acute hepatitis C virus (HCV) among HIV-positive men who have sex with men (MSM) who denied injecting drug use have been reported from Europe, the United States, Canada and Australia. Given the burden of liver disease, in particular HCV, on the morbidity and mortality in HIV patients in the era of combination antiretroviral therapy, the rapid and significant rise in the incidence of HCV in the HIV-infected MSM population in high-income countries is alarming. This relates to a significant change in the epidemiology of HCV that has occurred, with HCV emerging as a sexually transmitted infection within this population. Work to date suggests that this permucosal HCV transmission results from high-risk sexual and noninjecting drug use behaviours, reopening the discussion on the importance of sexual transmission. Given this occurs almost exclusively in HIV-infected MSM, HIV probably has a critical role mediated either through behavioural and/or biological factors. Finally, the management of acute HCV in HIV infection is complicated by concomitant HIV infection and combination antiretroviral therapy. This review will synthesize the most recent epidemiological, immunological and management issues that have emerged as a result of the epidemic of acute HCV among HIV-infected MSM.

Tenofovir disoproxil fumarate (DF) is a nucleotide analogue and a potent inhibitor of human immunodeficiency virus type 1 reverse transcriptase and hepatitis B virus (HBV) polymerase.

The diagnosis and treatment of hepatocellular carcinoma (HCC) have witnessed major changes over the past decade. Until the early 1990s, HCC was a relatively rare malignancy, typically diagnosed at an advanced stage in a symptomatic patient, and there were no known effective palliative or therapeutic options. However, the rising incidence of HCC in several regions around the world coupled with emerging evidence for efficacy of screening in high-risk patients, liver transplantation as a curative option in select patients, ability to make definitive diagnosis using high-resolution imaging of the liver, less dependency on obtaining tissue diagnosis, and proven efficacy of transarterial chemoembolization and sorafenib as palliative therapy have improved the outlook for HCC patients. In this article, we present a summary of the most recent information on screening, diagnosis, staging, and different treatment modalities of HCC, as well as our recommended management approach.

Entecavir, a drug approved by the Food and Drug Administration for the treatment of chronic hepatitis B virus (HBV) infection, is not believed to inhibit replication of human immunodeficiency virus type 1 (HIV-1) at clinically relevant doses. We observed that entecavir led to a consistent 1-log(10) decrease in HIV-1 RNA in three persons with HIV-1 and HBV coinfection, and we obtained supportive in vitro evidence that entecavir is a potent partial inhibitor of HIV-1 replication. Detailed analysis showed that in one of these patients, entecavir monotherapy led to an accumulation of HIV-1 variants with the lamivudine-resistant mutation, M184V. In vitro experiments showed that M184V confers resistance to entecavir. Until more is known about HIV-1-resistance patterns and their selection by entecavir, caution is needed with the use of entecavir in persons with HIV-1 and HBV coinfection who are not receiving fully suppressive antiretroviral regimens.

Entecavir is a potent and selective guanosine analogue with significant activity against hepatitis B virus (HBV).

The natural history of hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-infected patients has never been studied according to the concept of liver fibrosis progression. The aim of this work was to assess the fibrosis progression rate in HIV-HCV coinfected patients and in patients infected by HCV only. A cohort of 122 HIV-HCV coinfected patients was compared with a control group of 122 HIV-negative HCV-infected patients. Groups were matched according to age, sex, daily alcohol consumption, age at HCV infection, and duration and route of HCV infection. The fibrosis progression rate was defined as the ratio between fibrosis stage (METAVIR scoring system) and the HCV duration. The prevalence of extensive liver fibrosis (METAVIR fibrosis scores 2, 3, and 4) and moderate or severe activity were higher in HIV-infected patients (60% and 54%, respectively) than in control patients (47% and 30%, respectively; P <.05 and P <.001, respectively). The median fibrosis progression rate in coinfected patients and in control patients was 0.153 (95% confidence interval [CI], 0.117-0.181) and 0.106 (95% CI, 0.084-0.125) fibrosis units per year, respectively (P <.0001). HIV seropositivity (P <.0001), alcohol consumption (>50 g/d, P =.0002), age at HCV infection (<25 years old, P <.0001), and severe immunosuppression (CD4 count 50 g/d), CD4 count ( PMID: 10498659

Our aim was to assess the natural history of liver fibrosis progression in hepatitis C and the factors associated with this progression.

Few data are available concerning the long-term prognosis of chronic liver disease associated with hepatitis C virus infection. This study examined the morbidity and survival of patients with compensated cirrhosis type C.

We measured antibody (anti-HCV) to hepatitis C virus, which causes non-A, non-B hepatitis, by radioimmunoassay in prospectively followed transfusion recipients and their donors. Of 15 patients with chronic non-A, non-B hepatitis documented by liver biopsy, all seroconverted for the antibody; of 5 with acute resolving non-A, non-B hepatitis, 3 (60 percent) seroconverted. The development of anti-HCV was delayed (mean delay, 21.9 weeks after transfusion, or 15 weeks after the onset of clinical hepatitis) and took approximately one year in one patient. Antibody has persisted in 14 of the 15 patients with chronic disease (mean follow-up, greater than or equal to 6.9 years; maximum, greater than or equal to 12), but has disappeared in the 3 with acute resolving disease after a mean of 4.1 years. Anti-HCV was detected in samples of donor serum given to 14 (88 percent) of the 16 anti-HCV-positive patients for whom all donor samples were available. Only 33 percent of the anti-HCV-positive donors tested had an elevated serum concentration of alanine aminotransferase; 54 percent were positive for antibody to the hepatitis B core antigen (anti-HBc). We conclude that hepatitis C virus is the predominant agent of transfusion-associated non-A, non-B hepatitis and that screening of donors for anti-HCV could prevent the majority of cases of the disease. "Surrogate" assays for anti-HBc and alanine aminotransferase would have detected approximately half the anti-HCV-positive donors involved in the transmission of hepatitis that we identified.