Summary
Hepatitis C is caused by infection with the hepatitis C virus (HCV) and represents a major global health burden. Persistent HCV infection can lead to progressive liver disease with the ...development of liver cirrhosis and hepatocellular carcinoma, possibly accounting for up to 0.5 million deaths every year. Treatment of HCV infection is undergoing a profound and radical change. As new treatments are extremely safe and effective, there are virtually no medical reasons to withhold therapy. Yet, the new therapies are expensive. As resources are limited, solid data to estimate the disease burden caused by HCV are urgently needed. Epidemiology data and disease burden analyses for 16 countries are presented. For almost all countries, the peak of HCV‐related cirrhosis, hepatocellular carcinoma and liver‐related death is a decade or more away. However, a surprising heterogeneity in country‐specific HCV‐associated disease burden exists. Also, HCV diagnosis and treatment uptake varied markedly between countries. A consistent finding was that a reduction of HCV liver‐related mortality is dependent on access to therapy. Increasing efficacy of therapy alone with a constant numbers of treatments will not have a major impact on the HCV‐related disease burden. The data presented here should inform public health policy and help drive advocacy for enhanced strategic investment and action. HCV kills patients, and the disease burden will continue to rise in most countries unless action is taken soon. Chronic HCV is a curable infection and a reversible liver disease. Fortunately, the tools to eliminate HCV are now available.
Summary
Hepatitis E virus (HEV) is the causative agent of hepatitis E in humans and a member of the genus Orthohepevirus in the family Hepeviridae. Infection usually leads to acute hepatitis that can ...become fulminant, particularly among pregnant women and in patients with preexisting liver disease, or may evolve to a chronic state, especially in immunosuppressed individuals. HEV has been shown to produce a range of extra‐hepatic manifestations including aplastic anaemia, acute thyroiditis, glomerulonephritis as well as neurological disorders such as Guillain‐Barré syndrome, neuralgic amyotrophy and encephalitis. The pathogenesis of these neurological injuries remains largely unknown, and it is also uncertain whether or not HEV can directly infect neuronal cells. In this study, we investigated whether HEV is capable of completing the viral life cycle in human neuronal‐derived cell lines such as neuroepithelioma (SK‐N‐MC), desmoplastic cerebellar medulloblastoma (DAOY), glioblastoma multiforme (DBTRG), glioblastoma astrocytoma (U‐373 MG) and oligodendrocytic (M03.13) cells. Following transfection of these cells with HEV Gaussia luciferase reporter virus, all tested cell lines supported HEV RNA replication. Furthermore, extra‐ and intracellular viral capsid was detected by an HEV antigen ELISA as a marker for virus assembly and release. Permissiveness for HEV cell entry could be demonstrated for the oligodendrocytic cell line M03.13. In conclusion, these results indicate that HEV tropism is not restricted to the liver and HEV can potentially complete the full viral life cycle in neuronal‐derived tissues explaining neurologic disorders during HEV infection.
The treatment of hepatitis C has dramatically improved over the past decade. Unlike any other chronic viral infection, a significant proportion of patients with chronic hepatitis C can be cured. ...However, the current standard therapy--pegylated interferon alpha and ribavirin--has its limitations. Limited efficacy in patients with hepatitis C virus (HCV) genotype 1 and the side effect profile will necessitate the development of new therapeutic approaches. This review describes the efficacy and optimisation of the current standard therapy of hepatitis C and its problems in special patient populations. New treatment directions beyond interferon alpha based therapies are on the horizon.
Summary
Background
Successful antiviral treatment of decompensated hepatitis B with HBV polymerase inhibitors is associated with improvement of liver function. To what extent liver function also ...improves in cirrhotic patients with chronic hepatitis C receiving novel interferon‐free (IFN‐free) therapies is unknown.
Aim
To study liver function in cirrhotic HCV patients receiving IFN‐free therapies.
Methods
We here studied 80 consecutive patients with advanced HCV associated liver cirrhosis including 34 patients (43%) with Child B/C cirrhosis and 42 patients (53%) with platelet counts of <90.000/μL receiving different combinations of direct acting antivirals without interferon sofosbuvir/ribavirin (n = 56), sofosbuvir/simeprevir ± ribavirin (n = 15) and sofosbuvir/daclatasvir ± ribavirin (n = 9). The majority of patients was infected with HCV genotype 1 (n = 50); HCV genotypes 2, 3 and 4 were present in 4, 24 and 2 patients, respectively.
Results
Liver function parameters including albumin, bilirubin, cholinesterase and prothrombin time all improved in the majority of patients during antiviral therapy irrespectively of the underlying HCV genotype, however, with different kinetics. MELD scores improved until post‐treatment week 12 in 44% of the patients but worsened in 15%. A sustained virological response was achieved in 63% of the patients. HCV RNA relapse led to moderate ALT increases in 15/23 patients but was not associated with hepatic decompensations.
Conclusion
This real‐world single centre study showed that interferon‐free treatment of hepatitis C patients with advanced liver cirrhosis restores liver function, and may thereby reduce the need for liver transplantations.
Background and Aims
Hepatitis delta virus (HDV) infection is associated with fast progression to liver cirrhosis and liver complications. Previous studies have, however, been mainly from tertiary ...care centers, with risk for referral bias toward patients with worse outcomes. Furthermore, the impact of HDV viremia per se on liver‐related outcomes is not really known outside the human immunodeficiency virus co‐infection setting. We have therefore evaluated the long‐term impact of HDV viremia on liver‐related outcomes in a nationwide cohort of patients with hepatitis B and D co‐infection, cared for at secondary care centers in Sweden.
Approach and Results
In total, 337 patients with anti‐HDV positivity, including 233 patients with HDV RNA viremia and 91 without HDV viremia at baseline, were retrospectively studied, with a mean follow‐up of 6.5 years (range, 0.5‐33.1). The long‐term risks for liver‐related events (i.e., hepatocellular carcinoma HCC, hepatic decompensation, or liver‐related death/transplantation) were assessed, using Cox regression analysis. The risk for liver‐related events and HCC was 3.8‐fold and 2.6‐fold higher, respectively, in patients with HDV viremia compared with those without viremia, although the latter was not statistically significant. Among patients with HDV viremia with no baseline cirrhosis, the cumulative risk of being free of liver cirrhosis or liver‐related events was 81.9% and 64.0% after 5 and 10 years of follow‐up, respectively. This corresponds to an incidence rate of 0.04 cases per person‐year.
Conclusions
HDV RNA viremia is associated with a 3.8‐fold higher risk for liver‐related outcomes. The prognosis was rather poor for patients with HDV viremia without cirrhosis at baseline, but it was nevertheless more benign than previous estimates from tertiary centers. Our findings may be of importance when making decisions about treatment and evaluating potential outcomes of upcoming antivirals against HDV.
Poor adherence to medication leads to worsening of the disease, increased mortality and substantial rise in health care costs.
It was our aim to evaluate drug adherence and influencing factors in a ...cohort of non-selected adult pharmacy customers with various chronic diseases and following long-term treatment.
We conducted an 8 week anonymized survey in 152 German pharmacies using the Morisky Medication Adherence Scale to measure medication adherence and a questionnaire comprising questions on multiple factors with potential impact on adherence. Depression was assessed applying the Patient Health Questionnaire-9.
In total, 1192 patients were included showing an overall adherence rate of 59.1%. A positive association to drug adherence was found in univariate analysis for non-smoking status, retirement, less disease related complaints, positive belief in drug effects, comprehensive knowledge about the disease and high quality of care by the physician and pharmacist. Multivariate regression analysis revealed that no or minimal depression (odds ratio (OR) 2.3, 95% confidence interval (CI) 1.7-3.0), higher patient age (>63 years) (OR 2.2, CI 1.7-2.8), high perceived importance of the medication (OR 2.0, CI 1.5-2.6), good tolerability of the medication (OR 2.0, CI 1.2-3.5) and drug effect as expected or better (OR 1.6, CI 1.1-2.3) were positively correlated with adherence.
Suboptimal adherence to medication is common in pharmacy customers with chronic diseases. The determined factors influencing adherence may help to identify patients at risk for nonadherence and support the need of improvement in physicians' communication with patients to achieve adequate adherence rates.
Linked Content
This article is linked to Mettke et al and Kao and Su papers. To view these articles visit https://doi.org/10.1111/apt.14427 and https://doi.org/10.1111/apt.14565.
Hepatitis B core-related antigen (HBcrAg) has been suggested as an additional marker of hepatitis B virus (HBV) infection. HBcrAg combines the antigenic reactivity resulting from denatured hepatitis ...B e antigen (HBeAg), HBV core antigen and an artificial core-related protein (p22cr). In Asian patients, high levels of HBcrAg have been suggested to be an independent risk factor for hepatocellular carcinoma, while low levels could guide safe cessation of treatment with nucleos(t)ide analogues. We here studied HBcrAg levels in different phases of HBV infection in a large European cohort predominantly infected with genotypes A and D: HBeAg-positive immune tolerance (n = 30), HBeAg-positive immune clearance (IC) (n = 60), HBeAg-negative hepatitis (ENH) (n = 50), HBeAg-negative inactive/quiescent carrier phase (c) (n = 109) and acute hepatitis B (n = 8). Median HBcrAg levels were high in the immune tolerance and immune clearance phases (8.41 and 8.11 log U/mL, respectively), lower in ENH subjects (4.82 log U/mL) but only 2.00 log U/mL in ENQ subjects. Correlation between HBcrAg and HBV DNA varied among the different phases of HBV infection, while HBcrAg moderately correlated with hepatitis B surface antigen in all phases. ENQ patients had HBcrAg levels <3 log U/mL in 79%, in contrast to only 12% in the ENH group. HBcrAg levels vary significantly during the different phases of HBV infection. HBcrAg may serve as valuable marker for virus replication and reflect the transcriptional activity of intrahepatic cccDNA. In HBeAg-negative patients, HBcrAg may help to distinguish between inactive carriers (ENQ) and those with active disease (ENH).
Chronic courses of hepatitis E virus (HEV) infections have been described in immunosuppressed patients. We aimed to study the role of HEV infections in heart transplant recipients (HTR). 274 HTR were ...prospectively screened for HEV infection using an anti‐HEV‐IgG ELISA and HEV‐PCR. In addition, 137 patients undergoing cardiac surgery (non‐HTR) and 537 healthy subjects were studied cross‐sectionally. The anti‐HEV‐IgG seroprevalence was 11% in HTR, 7% in non‐HTR and 2% in healthy controls (HTR vs. healthy controls p<0.0001; non‐HTR vs. healthy controls p<0.01). Anti‐HEV tested positive in 4.0% in control cohorts of other immunocompromised patients (n = 474). Four HTR (1.5%) were chronically infected with HEV as shown by HEV‐PCR and all four patients had liver transaminases of >200 IU/L and histological or clinical evidence of advanced liver disease. In three patients ribavirin treatment was successful with a sustained biochemical and virological response while treatment failed in one cirrhotic patient after ribavirin dose reduction. Heart transplant recipients and patients undergoing cardiac surgery have an increased risk for HEV infections. Chronic hepatitis E may explain elevated liver enzymes in heart transplant recipients. Treatment of HEV infection with ribavirin is effective but the optimal dose and duration of ribavirin therapy remains to be determined.
Heart transplant recipients have an increased risk for infections with the hepatitis E virus, leading to progressive chronic hepatitis in some patients, which can be treated with ribavirin.
Summary
Background
Hepatitis C virus (HCV) clearance with IFN‐based therapies reduces the incidence of hepatocellular carcinoma (HCC). There has been some debate if IFN‐free therapy with ...direct‐acting antivirals alters the risk for HCC.
Aim
To investigate the HCC incidence in cirrhotic HCV patients who cleared HCV with direct‐acting antivirals vs untreated controls.
Methods
We prospectively monitored 373 patients with chronic hepatitis C who received IFN‐free therapies with direct‐acting antiviral after January 2014. A retrospective control cohort of untreated cirrhotic patients was recruited out of 3715 HCV patients who were followed at our centre between 2007 and 2013, with similar HCC screening protocols.
Results
158 direct‐acting antiviral‐treated and 184 control patients with liver cirrhosis were included in this analysis. The groups did not differ in gender and genotype distribution, severity of liver disease and prevalence of diabetes mellitus. Patients were followed up for a median of 440 (range 91‐908) and 592 (range 90‐1000) days. HCCs developed in 6 and 14 patients during follow‐up, resulting in an incidence of 2.90 vs 4.48 HCCs per 100 person‐years. In the direct‐acting antiviral‐treated group, there was no new case of HCC later than 450 days after treatment initiation. In multivariate analysis, higher MELD‐Scores and AFP‐levels were independently associated with HCC development. Transplant‐free patient survival was similar in both groups.
Conclusions
IFN‐free direct‐acting antiviral therapy of chronic hepatitis C does not alter the short‐term risk for HCC in patients with liver cirrhosis. A reduced HCC incidence may become evident after more than 1.5 years of follow‐up.
Linked ContentThis article is linked to Kao and Su and Mettke and Wedemeyer papers. To view these articles visit https://doi.org/10.1111/apt.14565 and https://doi.org/10.1111/apt.14582.
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