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Jan
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The use of single agent, tenofovir disoproxil fumarate (TDF), failed to prevent HIV acquisition or the establishment of a viral reservoir in two men who have sex with men.
The World Health Organization recently recommended Truvada (tenofovir disoproxil/emtricitabine) or TDF for high-risk individuals, with limited data for single-agent TDF pre-exposure prophylaxis in men who have sex with men.
Researchers from Guys and St Thomas' NHS Trust, London, reported two cases of TDF pre-exposure prophylaxis failure in men who had sex with men and who had received long-term TDF for HBV infection and who had therapeutic levels of drug immediately after HIV acquisition.
Rapid antiretroviral intensification at the diagnosis of acute HIV infection failed to limit immune dysfunction or prevent the establishment of a viral reservoir.
Reference
Tenofovir disoproxil fumarate fails to prevent HIV acquisition or the establishment of a viral reservoir: two case reports. Fox J, Brady M, Alexander H et al. Infect Dis Ther. 2016 Jan 9. [Epub ahead of print]
Jan
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Prophylactic antiviral therapy could be withdrawn six months after ending chemotherapy in HBsAg-negative/anti-HBc-positive patients with diffuse large B cell lymphoma (DLBCL).
This was the conclusion of researchers at Peking University Cancer Hospital and Institute who retrospectively analysed 107 newly diagnosed DLBCL patients with HBV who received chemotherapy.
The median time from the cessation of anti-tumor therapy to the withdrawal of prophylactic antiviral therapy was 6.1 months. The incidence of delayed HBV reactivation was 21.7% in the HBsAg-positive group and none in the HBsAg-negative/anti-HBc-positive group. No HBV-related fulminant hepatitis or hepatitis-related deaths occurred.
The multivariate analysis showed that female gender and more than eight cycles of chemotherapy were independent risk factors of HBV reactivation in HBsAg-positive patients.
The researchers suggest a longer course (i.e. over six months) of prophylactic antiviral drug administration may be an optimal option to prevent delayed HBV reactivation for HBsAg-positive patients.
Reference
Hepatitis B virus reactivation after withdrawal of prophylactic antiviral therapy in patients with diffuse large B cell lymphoma. Liu WP, Wang XP, Zheng W et al. Leuk Lymphoma. 2016 Jan 4:1-8. [Epub ahead of print]
Jan
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Second generation direct-acting antiviral agents (DAAs) with pegylated interferon and ribavirin (PR) and dual DAA regimens should become first line treatments for naïve HCV genotype 1.
Authors from Mahidol University, Bangkok, have performed a literature review and network meta-analysis and concluded the DAAs offer significant clinical benefits over PR alone.
They compared the treatment efficacy of the second generation DAAs, simeprevir (SMV), sofosbuvir (SOF), daclatasvir (DCV), ledipasvir (LDV), and paritaprevir/ritonavir/ombitasvir plus dasabuvir (PrOD) for naïve HCV genotype 1. Primary outcomes were sustained virological response at weeks 12 (SVR12) and 24 (SVR24) after the end of treatment and adverse drug events. Sixteen studies were included in the analysis.
Compared with the PR regimen, SOF plus PR, SMV plus PR, and DVC plus PR regimens yielded significantly higher probability of SVR24 with pooled risk ratios of 1.98, 1.46 and 1.68, respectively.
Pooled incidence rates of SVR12 and SVR24 in all treatment regimens without PR (pooled incidence of SVR12 ranging from 93% to 100%, and pooled incidence of SVR24 ranging from 89% to 96%) were much higher than the pooled incidence rates of SVR12 (51%) and SVR24 (48%) in PR alone.
In comparing SOF plus LDV with ribavirin and SOF plus LDV without ribavirin, the chance of SVR12 was not significantly different between these two regimens, with the pooled risk ratio of 0.99.
The risks of serious adverse drug events, anaemia and fatigue were relatively higher in treatment regimens with PR than in the treatment regimens without PR.
Reference
Efficacy of second generation direct-acting antiviral agents for treatment naïve hepatitis C genotype 1: a systematic review and network meta-analysis. Suwanthawornkul T, Anothaisintawee T, Sobhonslidsuk A et al. PLoS One. 2015 Dec 31;10(12):e0145953
Jan
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HBV patients with liver cirrhosis may be at an increased risk of insulin resistance and abnormal glucose metabolism, new evidence suggests.
In a study at China’s Affiliated Jiangyin Hospital of Southeast University Medical College, 106 HBV positive subjects with liver cirrhosis as well as with different grade of Child-Pugh and 37 healthy subjects had the oral glucose tolerance test (OGTT), C-peptide and insulin release test. Plasma glucose and insulin levels were analysed periodically for two hours after oral glucose loading.
There was no significant difference in the level of fasting plasma glucose and C-peptide between the two groups. However, the levels of OGTT two-hour glucose, insulin and C peptide were significantly higher in the cirrhosis group than in the controls.
The peak insulin and C-peptide response occurred at 60 minutes in the controls but was delayed to 120 minutes in the cirrhosis group. There was a significant difference between the two groups in the pattern of plasma glucose levels at corresponding time points. The OGTT two hour glucose and insulin levels were positively correlated with Child-Pugh Scores.
Reference
The investigation of glucose metabolism and insulin secretion in subjects of chronic hepatitis B with cirrhosis. Guo CH, Sun TT, Weng XD et al. Int J Clin Exp Pathol. 2015 Oct 1; 8(10): 13381-6
Jan
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BASL has welcomed new Government guidelines, which state there is no safe level of drinking.
In a report published today (Friday, 8 January), the UK’s Chief Medical Officer warns any level of alcohol consumption increases the risk of a range of cancers. It also states men should have no more than 14 units a week, bringing the limit in line with the recommended maximum for women.
It says the oft-reported heart health benefits of alcohol only apply for women 55 and over, and concluded that there is no justification for drinking for health reasons. It also recommends pregnant women avoid alcohol altogether.
A BASL spokesman said it was an important report that enabled the public to make informed choices about the graduated risks of drinking alcohol.
“It tackles the increasingly tenuous myth that alcohol could be in any way beneficial for cardiovascular health, and reverses the unhelpful 'daily drinking' guideline in favour of a sensible weekly total - the equivalent of two bottles of wine shared with a partner plus a couple of pints at the weekend,” he added.
Dame Sally Davies, Chief Medical Officer for England, said any level of regular drinking carried a health risk, but sticking to the weekly limit would keep the risk of cancer and liver disease low.
“I want pregnant women to be very clear that they should avoid alcohol as a precaution. Although the risk of harm to the baby is low if they have drunk small amounts of alcohol before becoming aware of the pregnancy, there is no ‘safe’ level of alcohol to drink when you are pregnant,” she added.
“What we are aiming to do with these guidelines is give the public the latest and most up to date scientific information so that they can make informed decisions about their own drinking and the level of risk they are prepared to take.”
Jan
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In a Belgian study, patients with HCV genotype 4 (HCV-4) were more frequently of black African origin than of any other origin.
This multicentre study selected 473 HCV-4 patients from seven Belgian hospital databases and compared them according to ethnic origin, i.e., black African (331) or not (142), for epidemiological, clinical, biological and histological characteristics. Interleukin 28B polymorphism (CC-genotype) was evaluated in a second cohort of 69 black African and 30 non-black African patients.
Compared to other patients, the black African patients were more likely to be female and were older, commonly overweight, frequently had abnormal glucose metabolism and arterial hypertension. They were less likely to have dyslipidemia, a history of alcohol consumption or ALT elevation. The route of infection was more frequently unknown in these patients.
Black African patients had more HCV-4 subtypes, were less frequently of IL28B CC-genotype and had less severe liver fibrosis. The proportion of patients who received antiviral treatment was similar in the two groups.
Reference
Ethnic epidemiological profiles and antiviral therapy among patients infected with hepatitis C virus genotype 4: a multicentre study from Belgium. Nkuize M, Mulkay JP, Moreno C et al. Acta Gastroenterol Belg. 2015 Oct-Dec; 78(4):365-72
Jan
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A new review summarises our current knowledge regarding chronic HBV with severe spontaneous acute exacerbation.
The reviewers, from Kaohsiung Veterans General Hospital in Taiwan, explain that spontaneous acute exacerbation is not uncommon in the natural history of chronic HBV, with a cumulative incidence of 10% to 30% every year. While exacerbations can be mild, some patients may develop hepatic decompensation and even die.
The underlying pathogenesis is possibly related to the activation of cytotoxic T lymphocyte-mediated immune response against HBV. An upsurge of serum HBV DNA usually precedes the rise of alanine aminotransferase and bilirubin.
Whether antiviral treatment can benefit in this condition remains controversial, early nucleos(t)ide analogue (NA) treatment seemed to be associated with an improved outcome. There has been no randomized study that has compared the effects of different NAs in this setting. However, potent NAs with good resistance profiles are recommended.
Reference
Chronic hepatitis B with spontaneous severe acute exacerbation. Tsai WL, Sun WC, Cheng JS. Int J Mol Sci. 2015 Nov 26; 16(12):28126-28145
Jan
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Ledipasvir/sofosbuvir (LDV/SOF), with or without ribavirin (RBV) has been shown to be highly effective for the treatment of genotype 1 chronic HCV in patients aged 65-plus.
Among 2,293 patients with genotype 1 chronic HCV enrolled in four multi-national phase three trials, 264 were aged 65 or older and 24 were over 75. All were treated with LDV/SOF, and 1,042 also received RBV.
Sustained virological response at 12 weeks (SVR12) was achieved by 97% of 2,029 patients aged under 65, and 98% of the 264 aged 65 or older.
The most common adverse events (AEs) in both LDV/SOF groups, occurring in ≥ 10% of subjects, were headache and fatigue. The rate of study discontinuation due to AE was similar in the two age cohorts. The addition of RBV increased the number of AEs, treatment-related AEs, and AEs leading to study drug modification/interruption, particularly among elderly subjects.
Reference
Safety and efficacy of ledipasvir/sofosbuvir for the treatment of genotype 1 hepatitis C in subjects aged 65 years or older. Saab S, Park SH, Mizokami M et al. Hepatology. 2015 Dec 24 [Epub ahead of print]
Jan
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HEV genotype 3 (HEV-3) viremia mainly presents in patients with underlying chronic liver diseases or an impaired immune system, Dutch investigators reported.
The investigators, from the Erasmus MC, University Medical Centre Rotterdam studied 79 patients with HEV-3 infections diagnosed by means of quantitative real-time reverse transcription-polymerase chain reaction test (RT-PCR).
Sixty-one patients were immunocompromised. Three had only transient viremia, 43 cleared the infection within six months and 26 developed chronic infection. Five patients were lost to follow-up.
All patients developing chronic infection were immunocompromised. Overall, 13 patients within this cohort died. Three patients had pre-existent liver diseases and died of liver-related causes. Time between diagnosis and death was shorter for patients with pre-existent liver diseases
Twenty-eight per cent of patients on immunosuppressive medication achieved viral clearance after reducing the dose of immunosuppressive therapy. Thirty patients were treated with off-label ribavirin, of whom 25 demonstrated a sustained viral response was documented.
Reference
Hepatitis E virus genotype 3 infection in a tertiary referral centre in the Netherlands: Clinical relevance and impact on patient morbidity. Nijskens CM, Pas SD, Cornelissen J et al. J Clin Virol. 2015 Dec 2; 74:82-87 [Epub ahead of print]
Jan
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People with HBV are at an increased risk of osteoporosis, a new Taiwanese study shows.
Using a nationwide Longitudinal Health Insurance Database 2000, the study compared 36,146 adult HBV patients with 144,584 patients without advanced liver disease
Compared with the comparison cohort, the HBV patients had a higher risk of osteoporosis (adjusted hazard ratio 1.14) after adjusting for age, sex, frequency of medical visits, and comorbidities of diabetes, hypertension, hyperlipidemia, heart failure, cirrhosis, chronic kidney disease, thyroid diseases, medication of steroid, PPI, warfarin, aspirin, and oestrogen replacement therapy.
The HBV patients exhibited a 1.13-fold higher risk of developing osteoporosis, but the risk of osteoporotic fracture was comparable between patients with HBV and the comparison cohort (adjusted hazard ratio 1.20). The incidence of osteoporosis increased with the increment of age (age ≤ 49, adjusted hazard ratio 1; age 50-64, 5.67,age ≧ 65, 13.3) and coexisting cirrhosis (adjusted hazard ratio 1.62).
However, the osteoporosis risk contributed by HBV decreased with age and the age-specific risk analyses showed that patients with HBV exhibited the highest risk of osteoporosis than patients without HBV for the patients aged ≤49 (adjusted hazard ratio 1.42). Furthermore, the osteoporosis risk contributed by HBV decreased with the presence of comorbidities (adjusted hazard ratio 1.27 versus 1.04).
Reference
Association between chronic hepatitis B virus infection and risk of osteoporosis: a nationwide population-based study. Chen CH, Lin CL, Kao CH. Medicine (Baltimore). 2015 Dec; 94(50): e2276
