News Articles 101 - 110 of 160

09
May
Myrcludex B - an effective novel HBV/HDV treatment
News Type: Hepatology News

Myrcludex B is a new drug to treat HBV and HDV. In a multi-centre German first-in-human study (1), single ascending doses of myrcludex B were administered up to 20 mg intravenously and 10 mg subcutaneously in 36 healthy volunteers.

Myrcludex B was well tolerated and no serious or relevant adverse events representing off-target effects, and no immunogenic effects were observed up to the highest applied dose. The pharmacokinetic model suggested that subcutaneous doses of 10 mg and above reach a target saturation of over 80% for at least 15 hours.

In a pilot trial conducted at centres in Russia and Germany, 24 patients with chronic HDV were equally randomized to myrcludex B, or pegylated interferon alpha (pegIFNα-2a) or their combination (2).

Interim results showed that, after 24 weeks of treatment, HDV RNA, a relevant marker for HDV infection, decreased in all patients. Two of eight patients who received either myrcludex B or pegINF2a became negative for HDV RNA, and five of seven patients who received both drugs at the same time became negative. The drug was well tolerated.

References

1. Myrcludex B: a first-in-human clinical study with a first-in-class hepatitis B and hepatitis D virus entry inhibitor. Blank A, Markert C, Hohmann N et al. J Hepatol. 2016 Apr 27 [Epub ahead of print] 

 

2. Interim results of a Phase Ib/IIa study of the entry inhibitor myrcludex B in chronic hepatitis D infected patients. Bogomolov P, Alexandrov A, Voronkova N et al. J Hepatol. 2016 Apr 27 [Epub ahead of print]

09
May
Stool could be a source of HCV infection
News Type: Hepatology News

A new German study shows, for the first time, that HCV can often be detected in stool samples of chronically infected patients irrespective of occult bleeding. This, say the study authors, suggests that stool could be a potential source for HCV infection.

Researchers at Hannover Medical School retrospectively collected stool samples of 98 HCV patients. Specific HCV primers were used to identify samples positive for HCV RNA. HCV RNA-positive samples were tested for HCVcoreAg with the Architect HCVAg assay. Presence of occult blood was investigated by the hemoCARE guajak test. Viral stability and infectivity of recombinant HCV particles was investigated in vitro by incubation of genotype 2a chimeric virus Jc1 with bile and stool suspensions.

HCV RNA could be detected in 68 out of the 98 stool samples and and 16 samples also tested positive for HCVcoreAg. Presence of HCV RNA in stool was more frequent in male than in female and in patients with low platelet counts but was not associated with the detection of occult blood. Stool suspensions and to a lesser extent bile reduced the in vitro infectivity of genotype 2a chimeric Jc1 virus even though infection of Huh7 cells was not completely abrogated.

The researchers suggest that stool can be a potential source for HCV infection and thus unprotected anal intercourse should be avoided.

Reference

Frequent detection of HCV RNA and HCVcoreAg in stool of patients with chronic hepatitis C. Heidrich B, Steinmann E, Plumeier I et al. J Clin Virol. 2016 Apr 14;80:1-7 [Epub ahead of print]

09
May
Elastin fibre accumulation predicts hepatocellular carcinoma
News Type: Hepatology News

Using a novel computational analysis, researchers found that elastin fibre was a predictor for the development of hepatocellular carcinoma (HCC), independently of collagen fibre and F stage.

The researchers, at Musashino Red Cross Hospital, Tokyo, enrolled 189 consecutive patients with HCV and advanced fibrosis. Using Elastica van Gieson-stained whole-slide images of pretreatment liver biopsies, collagen and elastin fibres were evaluated pixel by pixel (0.46 μm/pixel) and the cumulative incidences of HCC within three years were analyzed.

There was a significant correlation between collagen and elastin fibres, whereas variation in elastin fibre was greater than in collagen fibre. Both collagen fibre and elastin fibre were significantly correlated with F stage.

In total, 30 patients developed HCC during follow-up. Patients who had higher elastin fibre in addition to higher collagen fibre showed significantly higher incidences of HCC. With regard to elastin fibre, this difference remained significant in F3 patients. Furthermore, for patients with a higher collagen fibre amount, higher elastin was a significant predictor for HCC development.

Reference 

Elastin fibre accumulation in liver correlates with the development of hepatocellular carcinoma. Yasui Y, Abe T, Kurosaki M et al. PLoS One. 2016 Apr 29;11(4):e0154558 

03
May
HCV/HIV co-infection increases transplant waiting list mortality
News Type: Hepatology News

HCV/HIV co-infection is a factor in mortality prior to liver transplantation and is associated with higher mortality on the waiting list, new evidence shows.

In a study at University Hospital Lozano Blesa, Zaragoza, Spain, among 199 patients with HCV enrolled for liver transplants between 1998 and 2015, 17 were also infected with HIV.

The patients with HCV/HIV co-infection had higher mortality on the waiting list than those with HCV monoinfection (35.3% versus 4.6%). The intention-to-treat survival analysis (ITTA) at one, three and five years was 75%, 64%, and 57% for HCV monoinfection and 52%, 47%, and 39% for HCV/HIV co-infection, respectively. The ITTA at one, three, six and 12 months was 96%, 91%, 87%, and 75% for HCV monoinfection and 76%, 70%, 64%, and 52% for HCV/HIV co-infection, respectively.

A Cox regression analysis was carried out including all variables with predictive value in the univariate analysis, showing that only donor age > 70 years (hazard ratio 3.12), UNOS 1 status (hazard ratio 10.1), MELD (hazard ratio 1.13), and HIV co-infection (hazard ratio 2.65) had independent negative predictive value for survival.

Reference

Intention-to-treat survival analysis of HCV/HIV co-infected liver transplant: Is it the waiting list? Araiz JJ, Serrano MT, García-Gil FA et al. Liver Transpl. 2016 Apr 26 [Epub ahead of print]

03
May
Prednisone/azathioprine effective in paediatric autoimmune hepatitis
News Type: Hepatology News

In a new study, prednisone and azathioprine produced biochemical remission and significantly improved the prognosis of most children with autoimmune hepatitis (AIH), although there were significant side effects.

This was a retrospective analysis of the medical records of 15 patients with AIH, diagnosed before 18 years of age, treated in the Provincial Infectious Diseases Hospital in Bydgoszcz, Poland, between 2002 and 2013.

Biochemical remission of the disease was achieved on average after 36 days of treatment. Histopathological regression in the control liver biopsy was found in seven patients and progression in two patients.

Ten of the 15 patients experienced exacerbation of the disease from one to three times during observation, with an increase of ALT activity to greater than three norm, and the remaining five patients had no increase of ALT activity. In total, 10 patients in the study group experienced 17 exacerbations. In 13 cases of exacerbations, these were associated with a reduction in the dose of immunosuppressive drugs. There was no correlation between the biochemical exacerbation and changes in the histopathological image. Steroidside effects occurred in 14 patients.

The researchers suggest the significant side effects of treatment indicate the need for further exploration of effective and safe therapy, especially in the paediatric population.

Reference

Evaluation of the effectiveness of treatment with prednisone and azathioprine of autoimmune hepatitis in children. Pniewska A, Sobolewska-Pilarczyk M, Pawłowska M. Prz Gastroenterol. 2016;11(1):18-23 

03
May
Growth impairment warning for children treated with PEG/INF/R
News Type: Hepatology News

Impairment of growth should be considered as part of the risk-benefit profile of peg-interferon/ribavirin therapy in children with HCV, say researchers.

In a global open-label study, the team assessed the five-year follow-up of 107 children and adolescents with HCV who received peg-interferon and ribavirin for 24 or 48 weeks. Ninety-four patients were enrolled in the long-term follow-up part of the study and the median duration of follow-up was 287 weeks.

Of 63 with sustained virologic response enrolled on the study, 54 completed five years of follow-up and none relapsed in this time. Significant decreases in height Z scores were observed during treatment. The impact of treatment on height Z score was larger in patients treated for 48 weeks compared with those treated for 24 weeks (mean change from baseline to the end of treatment was -0.13 and -0.44 in the 24-week and 48-week treatment groups, respectively).

Among patients treated for 24 weeks, full recovery of height Z scores to baseline was observed by year one of follow-up, whereas only partial recovery was observed during five years of follow up in patients treated for 48 weeks (mean change from baseline to the final follow-up visit was -0.16 and -0.32 in the 24-week and 48-week treatment groups, respectively). Similar patterns were observed for weight and body mass index Z scores.

The researchers concluded that considerations should include both deferring treatment in patients during optimal growth periods, and the possibility of interferon-free regimens being available to children in the next five to 10 years. 

Reference

Long-term follow-up of children treated with peginterferon and ribavirin for Hepatitis C virus infection. Haber B, Alonso E, Pedreira A et al. J Pediatr Gastroenterol Nutr. 2016 Apr 21 [Epub ahead of print]

 

25
Apr
Patients with autoimmune hepatitis may be at risk of diabetes
News Type: Hepatology News

A new study suggests that many people with autoimmune hepatitis (AIH) may be at risk of diabetes mellitus (DM).

Researchers retrospectively analyzed 118 Japanese patients diagnosed with AIH from 1990 to 2014 at Nihon University School of Medicine. The prognosis of patients with and without DM was also compared.

Twenty-nine patients had DM and 21 received corticosteroids. The annual cumulative incidence rate of newly diagnosed DM was 1.2%. Multivariate analysis showed that DM occurred in older patients (odds ratio 6.290) and  with higher serum immunoglobulin G levels (odds ratio 12.400).

A Cox hazard regression analysis revealed that predictive factors for DM were absence of other autoimmune diseases (odds ratio 0.171), use of corticosteroids (odds ratio 6.693) and lower platelet counts (odds ratio 1.873).

The 10-year survival rates of the DM and non-DM groups were 94.1% and 94.6%, respectively. There was no significant difference between these groups.

Reference

Prevalence and risk factors of diabetes mellitus in patients with autoimmune hepatitis. Matsumoto N, Ogawa M, Matsuoka S et al. Intern Med. 2016;55(8):879-85 

25
Apr
Obesity epidemic linked to more childhood NAFLD
News Type: Hepatology News

As a probable result of obesity, non-alcoholic fatty liver disease (NAFLD)  is the most common form of chronic liver disease seen in children today, say US reviewers.

The reviewers, from Alfred I duPont Hospital for Children, Wilmington and the Thomas Jefferson University, write that childhood obesity has reached epidemic proportions, and by 2012, more than one third of American children were overweight or obese. As a result, increasingly children are developing complications of obesity including liver disease. In fact, NAFLD disease is the most common form of chronic liver disease seen in children today.

Recently, there has been a burgeoning literature examining the pathogenesis, genetic markers, and role of the microbiome in this disease.

On the clinical front, new modalities of diagnosing hepatic steatosis and hepatic fibrosis are being developed to provide non-invasive methods of surveillance in children. Lastly, the mainstay of treatment of paediatric NAFLD has been largely through lifestyle interventions, namely, dieting and exercise. Currently, there are a number of clinical trials examining novel lifestyle and drug therapies for NAFLD that are registered with the US National Institutes of Health ClinicalTrials.gov website.

Reference 

Paediatric non-alcoholic fatty liver disease. Uppal V, Mansoor S, Furuya KN.Curr Gastroenterol Rep. 2016 May;18(5):24

25
Apr
Telbivudine versus entecavir in HBV patients receiving chemotherapy
News Type: Hepatology News

In chronic HBV patients receiving cytotoxic chemotherapy, telbivudine (LdT) showed lower clinical efficacy in viral suppression than entecavir (ETV) but was associated with greater extent of improvement in liver and renal functions, a new study found.

A total of 290 treatment-naïve chronic HBV patients undergoing intense chemotherapy at Tuen Mun Hospital, Hong Kong received daily 600 mg of LdT or 0.5 mg of ETV as pre-emptive antiviral chemoprophylaxis.

The ETV group had significantly higher proportion of patients with undetectable HBV DNA load compared to LdTat week 24 (72.99% compared to 50.33%). The cumulative rates of virological breakthrough in the LdT and ETV groups were 9.15% and 3.65% at the second year, respectively; this was associated with undetectable HBV DNA at week 24.

Compared with the ETV group, Model for End-stage Liver Disease score (year one: 4.53 versus 7.53) and estimated glomerular filtration rates (eGFRs) (year one: 118.17 versus 91.79 mL/min; year two: 111.14 versus 76.45 ml/min) in the LdT group were significantly improved from baseline after the first year. Moreover, a significant number of patients with impaired renal function had improved eGFRs after LdT than ETV treatment (32.68% versus 8.76%).

Reference

Comparison of clinical efficacy and renal safety of telbivudine and entecavir in chronic hepatitis B patients receiving cytotoxic chemotherapy. Law ST, Lee MK, Lee AS et al. J Dig Dis. 2016 Apr 16 [Epub ahead of print]

25
Apr
Metabolic disorders biggest risk for hepatocellular carcinoma
News Type: Hepatology News

Metabolic disorders appear to be the biggest risk factors for hepatocellular carcinoma (HCC) and have increased in the last decade, new US evidence suggests.

Researchers at the National Cancer Institute, Bethesda, used data from the Surveillance, Epidemiology, and End Results-Medicare linkage to calculate population attributable fractions (PAFs) for each risk factor over time. A total of 10, 708 patients with HCC who were diagnosed between 2000 and 2011 were compared with 332,107 cancer-free controls residing in the Surveillance, Epidemiology, and End Results areas.

Overall, the PAF was greatest for metabolic disorders (32%), followed by HCV (20.5%), alcohol (13.4%), smoking (9%), HBV (4.3%), and genetic disorders (1.5%). The PAF for all factors combined was 59.5%. PAFs differed by race/ethnicity and sex. Metabolic disorders had the largest PAF among Hispanics (PAF, 39.3%) and whites (PAF, 34.8%), whereas HCV had the largest PAF among blacks (PAF, 36.1%) and Asians (PAF, 29.7%).

Between 2000 and 2011, the PAF of metabolic disorders increased from 25.8% to 36%. In contrast, the PAFs of alcohol-related disorders and HCV remained stable. 

Reference

Population attributable fractions of risk factors for hepatocellular carcinoma in the United States. Makarova-Rusher OV, Altekruse SF, McNeel TS et al. Cancer.