HCV In Elderly Patients
Successful antiviral treatment for hepatitis C associated with reduction in risk of cirrhosis, HCC and overall mortality, regardless of age.
Harvoni effective for elderly with HCV genotype 1
Infectious Disease News, April 2016
Elderly adults with hepatitis C virus genotype 1 infection treated with Harvoni experienced high sustained virologic response, according to results…
Elderly veterans with chronic HCV at increased risk for cirrhosis, HCC
Elderly veterans with hepatitis C virus infection had a higher risk for developing cirrhosis or hepatocellular carcinoma compared with younger patients, according to results from a retrospective cohort study.
Hepatitis C Treatment and Cirrhosis
Cirrhosis is a serious medical condition, and although it can remain stable for a long time, it can also go south quickly. Patients with hep C-related cirrhosis clearly need to be treated, and treated soon. This article will discuss some of the risks and benefits of hepatitis C treatment in cirrhotic patients.
Clin Interv Aging. 2016; 11: 327–334.
Published online 2016 Mar 17. doi: 10.2147/CIA.S97242
Association of sustained virologic response with reduced progression to liver cirrhosis in elderly patients with chronic hepatitis C
Full Text, here.....
Patients older than 65 years are often excluded in clinical trials of HCV therapies because they often have significant comorbidities and experience adverse effects during or after treatment. Therefore, few studies have examined the progression of CHC in elderly patients.6,14,15,26–28
Previous research indicated that the progression of CHC to liver cirrhosis was associated with certain baseline host factors and time-dependent risk factors.2,3,29,30 The cumulative nature of fibrosis progression and the potential for more rapid progression in patients older than 40 years mean that cirrhosis is increasingly significant in elderly patients.2,5 In fact, previous research has documented that a longer duration of CHC infection and advanced patient age are associated with more rapid progression of CHC to liver cirrhosis.2,31 Our findings support the rapid progression of liver cirrhosis in patients aged 65 years and older. In particular, the 3-year cumulative risk of liver cirrhosis was 35.2% in our elderly patients who had persistent viremia.
Previous studies examined the efficacy of PEG-IFN plus RBV for treatment of CHC in elderly patients.4,15,26,28,32–35 Although such patients have higher rates of dose reduction and adverse effects, some of them achieve SVR.4,15,32,35 A recent meta-analysis indicated that the overall rate of SVR in elderly patients was significantly lower than in young patients based on intention-to-treat analysis (42.0% vs 60.1%, P<0.00001) and per-protocol analysis (54.4% vs 67.4%, P=0.002).15 The rates of drug discontinuation and RBV dose reduction in elderly patients were significantly higher than in younger patients.15 The poor SVR rate in elderly patients may be related to the high prevalence of liver cirrhosis and treatment intolerance.4,14,33 Our study demonstrated the efficacy of PEG-IFN plus RBV treatment in elderly patients. In particular, 65.5% of patients overall achieved SVR, and this included 50.6% of those with HCV genotype-1 and 89.3% of those with other HCV genotypes. These data support the use of our treatment regimen in elderly patients with CHC who do not have liver cirrhosis or HCC. Furthermore, there were no deaths or severe treatment-related complications, and most patients who could not tolerate treatment stopped treatment near the beginning of the regimen (mean treatment duration: 84 days). This suggests that the standard PEG-IFN plus RBV treatment is safe in elderly patients if they are closely monitored. From our previous study, the patients who had absence of liver cirrhosis, low baseline HCV RNA levels, high baseline ALT level, no HCV genotype-1, or were treated with PEG-IFN-α-2a were good responders to PEG-IFN plus RBV treatments.36 Thus, it seems that treatment will be effective in selected elderly patients with CHC, such as those with good response predictors (genotype 2/3, low viral load, IL28B-CC), good performance status, and without major concomitant diseases.
Previous long-term follow-up studies showed the benefits of SVR in patients with CHC.7–11 The achievement of an SVR through interferon-based therapy slows the progression from chronic hepatitis to liver fibrosis7–10 and reduces the subsequent development of HCC and liver-related mortality.11–13 These effects are universal and were stronger in patients with advanced fibrosis.11
A large-scale study that followed 1,386 patients with CHC but not liver cirrhosis over 5 years reported that the annual incidence of liver cirrhosis in untreated patients and patients treated with interferon-based therapy (n=892) was 2.26% and 1.11% (nonresponders: 1.99%, sustained responders: 0.74%), respectively.9 In addition, the 14.5-year cumulative incidence of cirrhosis was significantly lower in sustained responders (4.8%) than in nonresponders (21.6%, P=0.0007) and in untreated patients (36.6%, P<0.0001). The present study showed that cirrhosis progressed rapidly and that an SVR slowed the progression to fibrosis in elderly patients with CHC. In particular, patients without SVR had a significantly higher risk of liver cirrhosis than those with SVR, and a significantly higher 3-year cumulative incidence of liver cirrhosis than those with SVR. These results suggest that suppression of HCV RNA can dramatically reduce the risk of liver cirrhosis in elderly patients.
A previous study reported that high APRI score was associated with significant fibrosis or cirrhosis.22 Our patients also had elevated APRI scores (mean ± SD: 1.7±1.3), confirming the presence of advanced fibrosis at baseline and consistent with the rapid progression of fibrosis in elderly patients. In addition, there was a trend of a higher baseline APRI score in patients who progressed to liver cirrhosis than those who did not progress (2.1±1.2 vs 1.6±1.3, P=0.055). Nonetheless, after adjusting for APRI score by Cox regression, SVR remained the most important factor for progression to liver cirrhosis.
Antiviral treatments for CHC have evolved since 2011, and several new drugs, including direct-acting antivirals and host-targeted agents, are marketed or under clinical development. Interferon-free regimens are expected to cure >90% of patients with CHC,37 and the newly available drugs have fewer side effects than interferon-based regimens. This may improve compliance and reduce dropout rates. However, the new HCV therapies are very expensive and have not been thoroughly evaluated in elderly patients. Thus, additional research is needed to evaluate the cost-effectiveness of these new therapies in elderly patients. Before adoption of the new therapies in elderly patients, the PEG-IFN plus RBV regimen should continue to be used to prevent the rapid progression to cirrhosis.
There are several limitations in this study. First, this was a retrospective observational study. Some information such as age at infection, the number of patients who underwent therapy evaluation, the excluded patient number, and the reasons for excluding cannot be obtained from this study. However, it is difficult to perform a prospective controlled trial in elderly patients, so our findings nonetheless provide important information regarding treatment decisions in this population. Second, only 108 patients (74.5%) underwent liver biopsy at baseline, and we cannot provide paired biopsy data. Thus, most patients with cirrhosis were diagnosed using clinical criteria. However, our diagnostic criteria for cirrhosis included two documented ultrasonograms of liver cirrhosis with solid clinical end points (splenomegaly, ascites, hepatic encephalopathy, or varices).9 Although ultrasound is inaccurate in detecting the early stages of liver cirrhosis, combination of the morphologic finding can improve the performance of ultrasound to detect cirrhosis, reaching an accuracy of over 80%.38
In conclusion, liver fibrosis progressed rapidly in elderly patients. An SVR following PEG-IFN combination treatment can reduce the risk of liver cirrhosis in elderly CHC patients.
Full Text, here.....
Ledipasvir-sofosbuvir combo safe, effective for elderly hep C patients
The combination of ledipasvir and sofosbuvir (LDV/SOF) is safe, effective and well tolerated in people over 65 who have genotype 1 hepatitis C, researchers have found.
Hep C Treatments Can Cause Adverse Effects in Older Patients
Safety and Efficacy of Ledipasvir/Sofosbuvir for the Treatment of Genotype 1 Hepatitis C in Subjects Aged 65 Years or Older.
Hepatology. 2015 Dec 24. doi: 10.1002/hep.28425. [Epub ahead of print]
Saab S1, Park SH1, Mizokami M2, Omata M3, Mangia A4, Eggleton E5, Zhu Y5, Knox SJ5, Pang P5, Subramanian M5, Kowdley K6, Afdhal NH7.
BACKGROUND:Elderly subjects have been historically underrepresented in clinical trials involving antiviral hepatitis C therapies. The aim of this analysis is to retrospectively evaluate the safety and efficacy of ledipasvir/sofosbuvir (LDV/SOF) by age groups of less than 65 (< 65) of age vs. greater than or equal to 65 (≥ 65) years of age among subjects enrolled in phase 3 trials.
METHODS:Four open-label phase 3 clinical trials evaluated the safety and efficacy of LDV/SOF with or without ribavirin (RBV) for the treatment of genotype 1 chronic HCV. Sustained virological response at 12 weeks (SVR12), treatment-emergent adverse events (AEs), and graded laboratory abnormalities were analyzed according to age group.
RESULTS:Of the 2,293 subjects enrolled in four phase 3 trials, 264 (12%) were ≥ 65 years of age, of whom 24 subjects were aged ≥ 75 years. SVR12 was achieved by 97% (1965/2029) of subjects aged < 65 years and 98% (258/264) of subjects aged ≥ 65 years. The most common AEs in both LDV/SOF groups that occurred in ≥ 10% of subjects were headache and fatigue. The rate of study discontinuation due to AE was similar in the two age cohorts. The use of RBV in 1,042 (45%) subjects increased the number of AEs, treatment-related AEs, and AEs leading to study drug modification/interruption, particularly among elderly subjects.
CONCLUSIONS:LDV/SOF with or without RBV was highly effective for treatment of genotype 1 chronic HCV in subjects aged 65 and older. Addition of RBV did not increase SVR12 rates but led to higher rates of AEs, especially in elderly subjects. This article is protected by copyright. All rights reserved.
© 2015 by the American Association for the Study of Liver Diseases.
KEYWORDS:elderly; hepatitis C; ledipasvir/sofosbuvir
Daclatasvir/Asunaprevir Safe, Effective in Elderly With HCV GT1
By Bryant Furlow
November 12, 2015
Daclatasvir plus asunaprevir is effective and safe in elderly patients with hepatitis C virus (HCV) infection genotype (GT) 1, a population that was "left behind" when interferon-based therapy was introduced, according to authors of a study presented at The Liver Meeting® 2015.
Combo HCV Tx Efficacy Comparable in Elderly, Non-Elderly
By Bryant Furlow
November 16, 2015
At The Liver Meeting® 2015, researchers reported that the efficacy of dual oral therapy with asunaprevir + daclatasvir was comparable between elderly and non-elderly patients with chronic hepatitis C, including compensated cirrhosis.
Changes in Characteristics of HCV Patients in the Last Decade
Journal of Viral Hepatitis, June 5, 2015
In this study of 1348 patients with chronic hepatitis C newly referred to our liver centre, we found as expected patients seen in Era-2 (2011–2012) were older and more likely to have advanced liver disease compared to those seen a decade ago (Era-1, 1998–1999).
Hepatitis C Treatment for Older Adults
Occasionally I hear older adults with hepatitis C say, “I am too old for treatment.” This may have been true in the old interferon days, when treatment was fraught with side effects. It’s not true now. In honor of
Older Americans Month, let’s look at the current information pertaining to treating older adults with hepatitis C.
Gastroenterology & Hepatology Volume 11, Issue 5 May 2015
Antiviral Therapy in Elderly Patients With Hepatitis C Virus ...
The emergence of direct-acting antiviral (DAA) agents has revolutionized the treatment schema for hepatitis C virus (HCV) infection. From cure rates to tolerability, DAA agents have shown outstanding profiles compared with the prior therapy of pegylated interferon with ribavirin. However, the efficacy and safety profiles of DAA therapy in older patients, particularly the elderly, have been unclear, and patients in the 1945 to 1965 birth cohort constitute the largest proportion of the HCV population in the United States. Treating elderly patients with pegylated interferon and ribavirin has been challenging due to the frequent presence of multiple comorbidities in the elderly and high discontinuation rates caused by adverse events. Now, as more DAA agents have become widely studied and approved, subgroup analyses for the elderly population are being elucidated. Analysis of the current literature shows that these agents have been effective, well tolerated, and safe in the elderly population. This article highlights the efficacy and safety differences in interferon-based therapy and interferon-free regimens for elderly patients with HCV infection.
Age and Gender Effects on the Pharmacokinetics of HCV NS5A Inhibitor MK-8742
Preventing Mortality in Patients With Cirrhosis and HCV
Journal of Viral Hepatitis
July 4 2014
Webinar: Ageing with Chronic Hepatitis C
Hepatitis C Treatment and Aging
A reader wrote, “I have had hepatitis C since 1972. I am healthy, and I don’t have any symptoms...
Patients ineligible for HCV treatment due to age, comorbidities
Age and comorbid medical conditions are the most important reasons patients are ineligible for treatment of chronic hepatitis C virus infection, according to data presented at The International Liver Congress
Extrahepatic manifestations were common among Chinese patients with chronic hepatitis C virus infection, according to data from a recent study.
Extrahepatic manifestations - EMs were common in Chinese patients with chronic HCV infection, particularly fatigue, type 2 diabetes, renal impairment, lymphadenophy, fever, and thyroid dysfunction. Older age was associated with EMs...
Current HCV therapies may not benefit older patients
Innes H. J. Hepatol. 2014;doi:10.1016/j.jhep.2014.01.020.
A sustained virologic response to existing hepatitis C treatments — namely, pegylated interferon and ribavirin combined with a protease inhibitor — is less likely to benefit older patients with less advanced liver fibrosis, according to recent data. In light of these findings, older patients may opt to wait for future regimens with fewer adverse effects.
“The question of what value a [sustained virologic response], in itself, imparts on the patient is often left unstated,” researchers wrote in the Journal of Hepatology.” Given that many treatment candidates are without symptoms of their infection, patients must be well-informed regarding what, by way of prognosis improvement, [sustained virologic response] can offer. Yet, to date, this issue has received little attention despite being critical to informed consent.”
The researchers created the HCV Individualized Treatment-decision model to simulate the lifetime course of HCV-related liver disease according to two scenarios: the patient who achieves sustained virologic response (SVR) as a result of antiviral therapy and the patient who does not either because he or she does not accept therapy or fails to respond to treatment and the infection persists. The course of liver disease was compared for each model subject. The benefit of SVR was defined in the study as the likelihood of gaining additional life-years and “healthy” life-years spent avoiding liver failure.
Results indicated that the benefit of SVR varied widely. For example, the probability that a patient aged 60 years with mild liver fibrosis would gain life-years as a result of achieving SVR was just 1.6% (95% CI, 0.8-2.7) and 2.9% (95% CI, 1.5-4.7) for gaining healthy life-years. In comparison, the likelihood of a patient aged 30 years with compensated cirrhosis gaining life-years was 57.9% (95% CI, 46-69) and 67.1% (95% CI, 54.1-78.2) for healthy life-years.
“This benefit-disparity is equivalent to a clinician needing to clear infection in, on average, ~35 times as many persons of the former description, than persons of the latter, in order to avert the same number of HCV-related deaths,” the researchers wrote.
Severe liver disease is not necessarily an inevitable outcome in the absence of treatment, and because existing HCV therapies have well-documented adverse effects, clinicians and older patients face a difficult decision as to whether they should wait for future regimens that are more tolerable.
“In the short term, this work will inform the contemporary patient dilemma of immediate treatment with existing interferon-centered therapies, versus holding out for future regimens that promise higher SVR rates and improved tolerability,” the researchers concluded. “Longer term, it urges that broadened access to therapy be twinned with efforts to more objectively communicate, to the individual patient, the benefits of therapy.”
Disclosure: See the study for a full list of financial disclosures.
Hepatitis C viral infection and the risk of dementia
Chronic inflammation is an important cause of Alzheimer’s disease (AD). !Both infectious diseases and AD are characterized by the increased production of an array of immune mediators, cytokines, chemokines and complement proteins by the host cells and by changes in the lipid metabolism of the patient. !Patients with chronic Hepatitis C virus (HCV) infection may exhibit neuropsychological symptoms and cognitive impairment. !Recent evidence suggests that approximately one third of people with chronic HCV experience cognitive impairment. !In mild HCV disease, there is a beneficial effect on cerebral metabolism and an improvement in neurocognitive functions after HCV eradication following anti-viral therapy............
Liver physiology and liver diseases in the elderly
The liver experiences various changes with aging that could affect clinical characteristics and outcomes in patients with liver diseases. Both liver volume and blood flow decrease significantly with age. These changes and decreased cytochrome P450 activity can affect drug metabolism, increasing susceptibility to drug-induced liver injury. Immune responses against pathogens or neoplastic cells are lower in the elderly, although these individuals may be predisposed to autoimmunity through impairment of dendritic cell maturation and reduction of regulatory T cells. These changes in immune functions could alter the pathogenesis of viral hepatitis and autoimmune liver diseases, as well as the development of hepatocellular carcinoma. Moreover, elderly patients have significantly decreased reserve functions of various organs, reducing their tolerability to treatments for liver diseases. Collectively, aged patients show various changes of the liver and other organs that could affect the clinical characteristics and management of liver diseases in these patients
Bristol-Myers Squibb Submits First All-Oral, Interferon-Free and Ribavirin-Free Treatment Regimen for Regulatory Review in Japan for Patients with Chronic Hepatitis C Infection
**Study Design and Results For Elderly Patients Provided Only - View all results from the Phase III study with Daclatasvir (DCV) and Aasunaprevir (ASV) , here.
In this open-label, parallel group, Phase III study, interferon- ineligible/intolerant 135 patients and 87 interferon/ribavirin non-responder (NR) patients received daclatasvir 60 mg once daily plus asunaprevir 100 mg twice daily for 24 weeks. The primary endpoint was the percentage of patients with a sustained virologic response at 24 weeks after the end of treatment (SVR24).
Virologic Response - Elderly Only
Patients older then 65 years of age had SVR24 rates similar to those in patients less then 65 years and age did not appear to impact response rates. SVR24 rates for those more 65 years of age were 91.9% (57/62) in the interferon- ineligible/intolerant elderly patient population and 85.2% (23/27) in the non-responder elderly population.
Read the full press release here....
Chronic Hep C in Medicare beneficiaries
As baby boomers age, chronic hepatitis C (CHC) will become increasingly important in Medicare eligible group. Dr Younossi and colleagues from Virginia, USA evaluated trends in Medicare resource utilization for chronic hepatitis C. The team analyzed the Medicare in-patient and out-patient data from 2005 to 2010.
Telaprevir-based triple therapy for elderly patients with genotype 1 chronic hepatitis C
IDSA Oct 2-6 2013, San Francisco, CA
"TVR-based triple therapy can be used successfully and safely to treat elderly patients with genotype 1 chronic hepatitis C. IL28B genotyping and early virological response indicate effectiveness in these difficult-to-treat elderly patients."
Association of Visceral Obesity with High Viral Load and Histological Findings in Elderly Patients with Genotype 1 Chronic Hepatitis C
...visceral obesity was found to be associated with high viral load, steatosis , and age-dependent fibrosis progression in patients with genotype 1 chronic hepatitis C.....
Elderly age is not a negative predictive factor for virological response to therapy with pegylated interferon-α and ribavirin in chronic HCV patients
Age is not a significant predictive factor for achieving SVR, when relevant confounders are taken into account. Since life expectancy in Western Europe at age 60 is more than 20 yr, it is reasonable to treat chronic hepatitis C in selected elderly patients with relevant fibrosis or cirrhosis but without major concomitant diseases, as SVR improves survival and reduces carcinogenesis
Telaprevir safe, effective among older patients with chronic HCV
Furusyo N. J Hepatol. 2013;59:205-212.
Advanced age did not impact the efficacy of triple therapy with pegylated interferon, ribavirin and telaprevir among patients with hepatitis C genotype 1b in a recent study.
In a prospective study, researchers evaluated 120 patients with chronic hepatitis C genotype 1b, including 64 participants aged older than 60 years. All patients received peginterferon alfa-2b, ribavirin and telaprevir for 12 weeks, then 12 weeks of peginterferon and ribavirin.
During prior therapy 53.3% of participants had relapsed, 22.5% were treatment-naive, 20.8% were prior nonresponders and 3.3% had an unknown prior response.
Undetectable HCV RNA (rapid virological response) was observed at 4 weeks in 73.4% of older patients and 73.2% of patients aged younger than 60 years. Sustained virological response at 24 weeks post-treatment occurred similarly between groups: 76.6% of older patients vs. 83.9% of younger patients (P=.314 for difference). Investigators said SVR was more common among all patients with the IL28B TT allele (89.4% of older and 91.9% of younger patients vs. 41.2% and 68.4% among those without; P<.05 for both comparisons).
Multivariate analysis indicated associations between SVR and RVR (OR=7.498; 95% CI, 1.014-65.42) and IL28B TT genotype (OR=14.93; 95% CI, 1.6-142.9), as well as prior nonresponse (OR=8.403; 95% CI, 1.025-66.667), among
older patients. Independent associations with RVR and TT genotype also were noted among younger patients.
Treatment discontinuation for adverse events occurred in 12.5% of all cases. Hemoglobin decreases for levels of 100 g/L or more were observed in 41.1% of younger and 9.4% of older patients; between 85 g/L and 100 g/L in 25% and 40.6%,
and less than 85 g/L was present in 33.9% and 50% of younger and older patients, respectively (P=.0006).
“This study shows there is no impact by age on the virological outcome of TVR-based triple therapy for HCV genotype 1b chronic hepatitis C,” the researchers concluded. “We found that older patients achieve a better virological outcome by TVR-based triple therapy than with the traditional dual therapy. IL28B genotyping and EVR indicate the potential to achieve an
SVR in these difficult-to-treat older patients.”
Abstract: A pilot study of triple therapy with telaprevir, peginterferon and ribavirin for elderly patients with genotype 1 chronic hepatitis C.
Results suggest that 24-week triple therapy with telaprevir 1,500 mg seems
safe and efficacious for elderly Japanese patients infected with HCV genotype 1b.....
Abstract: Various Predictors of Sustained Virologic Response in Different
Age Groups of Patients With Genotype-1 Chronic Hepatitis C.
SVR rate was highest in patients younger than 45 years and lowest in patients older than 65 years even through propensity score matching analysis. As for the SVR predictors ....
May 19 2013
DDW 2013 - Patients with Medicaid less likely to receive HCV treatments
Although diagnosed hepatitis C infection was more common among people with Medicaid insurance, the treatment rates were lower compared with people who had commercial insurance, research presented here at Digestive Disease Week suggests.
Telaprevir can be successfully and safely used to treat older patients with genotype 1b chronic hepatitis C.
This prospective study enrolled 120 genotype 1b patients with chronic hepatitis C who received 12 weeks of triple therapy followed by a 12-week dual therapy that included pegylated interferon-α2b and ribavirin. Patients were categorized according to age: group A, 64 patients aged older then 60 and group B, 56 patients aged less then 60...
Interferon free regimens for the “difficult to treat”: are we there?
Excerpt - Older age is not an absolute contraindication for an interferon-based therapy. A French group showed good efficacy in a small group of patients older than 65 years treated with pegylated interferon and rivabirin (7). Nevertheless, other studies have demonstrated a trend towards lower SVR rates, as well as higher rates of dose reductions and discontinuations of therapy in this population as compared to younger individuals (6, 8). Currently, there are no data on the safety and efficacy of triple therapy in old patients. In the CUPIC French cohort, cirrhotic patients up to 83 years old have been included: though the number of severe adverse events using triple therapy seems clearly higher than those reported with peginterferon and ribavirin alone (9), a specific analysis in older patients has not been performed..continue reading..
Commentary: efficacy and safety of ribavirin plus pegylated interferon-alpha in geriatric patients with chronic hepatitis C
Hadziyannis, S. J. and Sevastianos, V.
The study of Hu et al. from Taiwan adds evidence on the safety and efficacy of treatment with pegylated interferon-alpha plus ribavirin (PR) in elderly patients with chronic hepatitis C virus (HCV) infection.
This topic is of clinical interest, as life expectancy is increasing both in developed and developing countries, anti-HCV positivity in the general population reaches peak prevalence in older age groups, the prevalence of cirrhosis in HCV-infected people above the age of 50 years is climbing and the yearly incidence of HCC reaches somewhere between 2% and 8%.[2, 3]
However, patients >65 years have been excluded from clinical trials of PR, because of a tendency towards lower sustained virological response (SVR) and a higher rate of treatment discontinuation.[4-8] At the same time clinical data encourages the effort of treating chronic HCV in advanced age.
In this context, the results of the present study support the view that treatment should not be denied to patients based on age, or other unfavourable factors, alone. However, because of the small number of cases in the age and HCV-genotype (HCV/G) subgroups, some differences may not have attained statistical significance. Thus, SVR rates were lower in older compared with middle-aged patients but the difference was significant only in HCV/G non-1 infections.
Moreover, the duration of treatment was limited to 24 weeks regardless of HCV/G with SVR rates in HCV/G1 similar, or even higher, in comparison with those in patients from Western countries treated for 48 weeks with PR. Race variations, IL28B genotypes or other factors may account for these differences. Therefore, the findings of this Asiatic study are not transferrable, as such, to Western populations either with G1 or non-1 infections. Possibly the development of new all oral HCV therapies with direct-acting antivirals will become the standard of care in the difficult to treat HCV patients, including the elderly.
Full Text - Efficacy and safety of ribavirin plus pegylated interferon alfa in geriatric patients with chronic hepatitis C
- 1 Hu C-C, Lin C-L, Kuo
Y-L, et al. Efficacy and safety of ribavirin plus pegylated interferon alfa in geriatric patients with chronic
hepatitis C. Aliment Pharmacol Ther 2013; 37: 81–90.
- 2 Fassio
E. Hepatitis C and hepatocellular carcinoma. Ann Hepatol 2010; 9(Suppl.): 119–22.
- 3 Colombo M, de Franchis R, Del
Ninno E, et al. Hepatocellular carcinoma in Italian patients with cirrhosis. New Engl J Med 1991;
- 4 Hiramatsu N, Oze T, Tsuda
N, et al. Should aged patients with chronic hepatitis C be treated with interferon and ribavirin combination
therapy? Hepatol Res 2006; 35: 185–9.
- 5 Iwasaki Y, Ikeda H, Araki
Y, et al. Limitation of combination therapy of interferon and ribavirin for older patients with chronic hepatitis
C. Hepatology (Baltimore, MD) 2006; 43: 54–63.
- 6 Nudo CG, Wong P, Hilzenrat
N, Deschenes M. Elderly patients are at greater risk of cytopenia during antiviral therapy for hepatitis C. Can J
Gastroenterol 2006; 20: 589–92.
- 7 Antonucci G, Longo MA, Angeletti
C, et al. The effect of age on
response to therapy with peginterferon alpha plus ribavirin in a cohort of patients with chronic HCV hepatitis including subjects older than 65 yr.
Am J Gastroenterol 2007; 102: 1383–91.
- 8 Yu JW, Sun LJ, Kang
P, Yan BZ, Zhao
YH. Efficacy and factors influencing treatment with peginterferon alpha-2a and ribavirin in elderly patients with chronic
hepatitis C. Hepatobiliary Pancreat Dis
Int 2012; 11: 185–92.
- 9 Lee SS, Roberts SK, Berak
H, et al. Safety of peginterferon
alfa-2a plus ribavirin in a large multinational cohort of chronic hepatitis C patients. Liver Int 2012;
- 10 Beinhardt S, Rutter K, Stattermayer AF, Ferenci P.
Revisiting the predictors of a sustained virologic response in the era of direct-acting antiviral therapy for hepatitis C
virus. Clin Infect Dis 2013; 56: 118–22.
Article first published online: 22 JAN 2013
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Characteristics of elderly hepatitis C virus-associated hepatocellular carcinoma patients.
Standard hep C treatment less effective in elderly
Efficacy and safety of ribavirin plus pegylated interferon alfa in geriatric patients with chronic hepatitis C
Causes, clinical features, outcomes of drug-induced liver
injury different for elderly patients
Common Antibiotics Pose a Risk of Severe Liver Injury in Older
Efficacy of pegylated interferon-alpha-2a plus ribavirin for patients aged at
least 60 years with chronic hepatitis C.
Viral Hepatitis in the Elderly
As life expectancy continues to rise, elderly adults represent a rapidly
growing proportion of the population. The likelihood of complications of
acute and chronic liver disease and overall mortality are higher in elderly populations. Several physiological changes associated with aging, greater prevalence of co-morbid conditions, and cumulative exposure to hepatotropic viruses and environmental hepatotoxins may contribute to worse outcomes of viral hepatitis in the elderly.
Although pharmacotherapy for hepatitis B and C continues to evolve, the efficacy, tolerability, and side effects of these agents have not been studied extensively in elderly adults. Immunization against hepatitis A and B in naïve elderly adults is an important public health intervention that needs to be revised and broadened.
New Antivirals Show Poor Safety in Hepatitis C With Cirrhosis
Two relatively new direct-acting antiviral drugs have poor safety profiles in
patients with hepatitis C virus (HCV) and cirrhosis, including a high rate of
serious adverse events leading to study discontinuation
The effect of pegylated interferon-alpha2b and ribavirin combination therapy for chronic hepatitis C infection in elderly patients
BMC Research Notes 2012, 5:135 doi:10.1186/1756-0500-5-135
Published: 10 March 2012
The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.
Hiroki Nishikawa, Eriko Iguchi, Yorimitsu Koshikawa, Soichiro Ako, Tadashi Inuzuka, Haruhiko Takeda, Jun Nakajima, Fumihiro Matsuda, Azusa Sakamoto, Sinichiro Henmi, Keiichi Hatamaru, Tetsuro Ishikawa, Sumio Saito, Ryuichi Kita, Toru Kimura and Yukio Osaki
The clearance of hepatitis C virus infection by interferon therapy significantly reduces the incidence of hepatocellular carcinoma and death in elderly chronic hepatitis patients. However, there are few reports concerning the efficacy and safety of pegylated interferon-alpha2b plus ribavirin combination therapy in elderly patients. The aims of the present study were to examine the effect and safety of pegylated interferon-alpha2b plus ribavirin combination therapy in 427 patients with chronic hepatitis C infection. We compared the rates of sustained virological response--defined as the absence of detectable hepatitis C virus in serum 24 weeks after the treatment ended--and the treatment discontinuation rate between 319 younger patients aged <65 years and 108 elderly patients aged [greater than or equal to]65 years. We also examined the factors contributing to a sustained virological response.
There was no significant difference in the sustained virological response rate between younger patients and elderly patients according to their hepatitis C virus genotype (41.5% (100/241) and 40.7% (35/86) for genotype 1; P = 0.899, 89.7% (70/78) and 86.4% (19/22) for genotype 2; P = 0.703, respectively). There was also no significant difference in the treatment discontinuation rate between the two age groups (10.3% (33/319) and 13.9% (15/108), respectively; P = 0.378). There were no serious adverse events requiring hospitalization. The factors contributing significantly to a sustained virological response in elderly patients were gender, hepatitis C virus genotype, platelet count, and the presence of a rapid or early virological response (undetectable hepatitis C virus in serum at weeks 4 or 12 of treatment, respectively). However, upon multivariate analysis, the presence of an early virological response was the only significant factor (odds ratio: 0.115, 95% confidence interval: 0.040-0.330, P < 0.001).
The efficacy and safety of pegylated interferon-alpha2b plus ribavirin combination therapy in elderly patients are not always inferior to those in younger patients. Obtaining an early virological response may be essential to achieve a sustained virological response in elderly patients with chronic hepatitis C infection.
Download Provisional PDF.
February 14, 2012
Resources Needed to Meet Needs of Seniors With Cirrhosis
As people living with cirrhosis age, they are more likely to become disabled, need hospitalization and require more caregiving from family members than seniors not living with liver disease, according to a study published in the January 2012 issue of Hepatology.
The need to provide and coordinate care for elderly people living with liver cirrhosis is expected to increase in the coming
years. In the United States, the number of older people with cirrhosis is growing, driven by an aging population of people living with chronic hepatitis C virus (HCV) infection and non-alcoholic fatty liver disease, a condition linked to obesity, type 2 diabetes, high blood pressure, elevated cholesterol and genetic factors.
Policy makers will need to allocate additional resources, while family members will be called upon to provide more informal
caregiving, according to Mina O. Rakoski MD, and her colleagues from the University of Michigan Medical School in Ann Arbor.
Rakoski and her colleagues used information from Health and Retirement Study (HRS) interviews, Medicare claims and patient records over a minimum of two years to assess measures of well-being among people older than 65. They compared 290 people living with cirrhosis to a matched group of 858 without signs of chronic liver disease.
Demographics were similar, with a few differences: People living with cirrhosis were less educated, more likely to be Hispanic, and had less income than the comparison group.
People living with cirrhosis were twice as likely to describe their health as poor, compared with those in the matched group. Other illnesses, including lung and heart disease, cancer, diabetes and cognitive impairment, were more common among people living with cirrhosis. They were also more likely to experience some degree of disability, and they reported more difficulty performing activities of everyday living (ADLs) such as bathing, toileting, dressing and eating, as well as instrumental activities of everyday living (IADLs), including grocery shopping, managing money, making phone calls and taking medication. In addition, almost 20 percent reported a significant decrease in their ability to perform ADLs and IADLs over a two-year period.
Not surprisingly, overall and out-of-pocket health care costs were much higher for elderly people living with cirrhosis. They had more medical appointments, were more likely to be hospitalized or cared for in a nursing home and received more care from family members than their non-cirrhotic counterparts. In fact, the yearly cost of informal caregiving by a family member ranged from $3,700 to $6,700 for people living with cirrhosis versus $1,600 to $2,900 for those without liver disease.
“It is important to emphasize this study compared subjects with cirrhosis to age-matched individuals, not healthy controls,” noted the authors.
They concluded by underscoring the opportunity to improve quality of care for elderly people living with cirrhosis
while lowering its cost. “Greater focus on a comprehensive delivery of care for patients with cirrhosis, including involvement of caregivers and improved care coordination, is necessary to optimize management of this frail population.”
Hepatitis C-Impact of age > 65 years on svr and relapse
Impact of age more then 65 years on svr and relapse in chronic hepatitis c (chc) patients (pts) treated with peginterferon alfa-2a (40kd) (pegifn?2a[40kd]) plus ribavirin (rbv): final analysis from the large multinational real-world prophesys cohorts
HCV In Elderly Patients
Journal of Viral Hepatitis
Hepatitis C Virus-related Chronic Liver Disease in Elderly Patients: An Italian Cross-sectional Study
A. Gramenzi; F. Conti; F. Felline; C. Cursaro; A. Riili; M. Salerno; S. Gitto; L. Micco; A. Scuteri; P. Andreone; M. Bernardi
Authors and Disclosures
Posted: 07/27/2010; J Viral Hepat. 2010;17(5):360-366.
Abstract and Introduction
Chronic hepatitis C virus (HCV ) infection has been poorly investigated in the elderly.
The Aim Of This Study Was ?
The aim of this study was to identify the age-specific characteristics of chronic hepatitis C by comparing patients more then 65 years with those less then 65 years of age.
Where Did This Study Take Place ?
A cross-sectional study was performed on data collected from consecutive outpatients referred for the first time to two tertiary outpatient clinics for liver diseases located in Bologna (Northern Italy) and Paola, Cosenza (Southern Italy) over a two-year period.
How Many Patients In The Study ?
A total of 560 anti-HCV and HCV -RNA positive patients were enrolled, of whom 174 (31%) were 65 years or older.
The proportion of older patients was significantly higher in the Southern Italy centre, accounting for more than 40%
Comparison Of liver Damage In Young And Older Groups Of Patients
Comparison of younger and older groups showed that 51% patients more then 65 years had advanced liver disease (liver cirrhosis or hepatocellular carcinoma) compared with 26% younger patients (Patients less then 0.0001).
About half of the patients more then 65 years were not aware of their anti-HCV positive status, even if they tended to be more symptomatic than the younger group. By multivariate analysis, patients more then 65 years of age, the alcohol consumption and diabetes were independently associated with advanced liver disease.
Overall, 34 out of 174 patients (20%) in the more then 65 years had received antiviral treatment compared with 122 out of 386 (32%) younger patients (Patients = 0.003).
Our results further emphasize the notion that chronic hepatitis C is becoming a disease of the elderly and that elderly patients with chronic HCV infection often have severe and underestimated disease.
Click Here To See The Full Study , Below Is Only The Summary/Discussion
This study provides a picture of the age-specific differences of patients with HCV-related chronic hepatitis attending tertiary outpatient clinics for liver disease. As a recent Italian population-based survey indicated thatHCV infection seems to follow two different transmission patterns according to a North–South gradient, we conducted our study in two clinical centres located in Northern and Southern Italy.
In our study as a whole, in a two-year period, nearly a third of HCV -RNA positive referred outpatients were 65 years or older. However, when the two recruitment centres were compared, this proportion was significantly higher in the Southern Centre, accounting for more than 40%. Even though a selection bias cannot be excluded, age distribution and mode of infection in the two areas reflect what is known in the general population. These data show that in Northern Italy HCV infection is mainly found in the 31–60 year age group, consistent with intravenous drug use, whereas in Central and Southern Italy the highest HCV seroprevalence rates are detected in patients older than 60 years consistent with health care-related practices in the past. In spite of the different epidemiological pattern, the main virological and clinical features of older patients in the two recruitment areas tended to be homogeneous.
About half of the patients more the 65 years of age in our study were not aware of their anti HCVpositive status, even if they tended to be more symptomatic than their younger counterparts. In addition, the prevalence of laboratory features of chronic liver disease, namely elevated serum ALT, did not differ between the two patient groups. This observation is at variance with previous data showing that most elderly patients with chronic HCV infection have normal ALT, even in the presence of advanced liver disease.[4,16] This difference might simply reflect a referral bias, since a study conducted in outpatient clinics for liver disease tends to enrol sicker patients, transaminase elevation being the main reason for referral.
Even though we do not have hard data on liver fibrosis, such as those deriving from eitherliver biopsy or surrogate markers, we can confirm that patients more the 65 years with chronic HCV infection have more severe liver disease than younger patients.
More than 50% of patients aged 65 years or older had cirrhosis and/or HCC, and the occurrence of liver-related complications as the presenting symptom of HCV -related liver disease was significantly more frequent in patients more then 65 years.
These findings could result from the high selection of the patients we enrolled who were recruited because they had HCV infection. Nevertheless, our results are consistent with those obtained in a large French study in patients referred for chronic HCV infection where the prevalence of cirrhosis, as assessed by biochemical markers of fibrosis, was above 50% in the elderly, and liver-related complications more often heralded the liver disease in patients over 65 years.
Age more then 65 years also emerged as an independent variable associated with advanced liver disease (cirrhosis and/or HCC) on multivariate analysis, together with excessive alcohol consumption and diabetes. However, because of the poor reliability of the information we had on age at infection, we did not include disease duration.
Thus, it cannot be established whether the observed association between age and advanced liver disease was related to an old age at infection or to a longer duration of the disease. Indeed, previous studies have demonstrated that the rate of liver disease progression inHCV chronic infection is more rapid in patients infected at an older age. Nevertheless, in our study the higher prevalence of advanced liver disease among elderly patients could also reflect a selection bias since elderly patients tended not to be screened for HCV unless they had clinically manifest liver disease.
As previously reported, older patients in our study were less frequently treated than their younger counterparts and the proportion of those treated after 65 years was negligible. This is not surprising since elderly patients with HCV infection are considered difficult-to-treat and no standard treatment guidelines are currently available for these particular patients. Indeed, elderly patients with chronic HCV infection are generally excluded from randomized controlled trials and often have comorbidities that contraindicate antiviral treatment.
Nevertheless, a study conducted in Veterans Affairs Medical Centres throughout the United States showed older age to be a strong predictor of not being a treatment candidate, even after adjusting for comorbidities.
Taken together, our results further emphasize the notion that chronic hepatitis C is becoming a disease of the elderly and that elderly patients with chronic HCV infection often have severe and underestimated Liver disease. Therefore, clinicians need to be aware of the importance of ageing when considering either treatment to prevent disease progression or surveillance programs for HCC. However, as it is likely that more and more elderly HCV-positive patients will be identified and brought to care, the current lack of specific guidelines for managing these patients will represent a major challenge for clinicians.
Also See: Cryoglobulinemia in elderly patients with HCV-related chronic hepatitis c
Older Genotype 3 Chronic Hepatitis C Patients Do Not Respond as Well to Interferon-based Therapy
Hepatitis C Virus Infection in the Elderly Population
Older Article/2004 = Seniors and Hepatitis C