The proportion of elderly people in the world population is constantly increasing. With age, the risk of numerous chronic diseases and their complications also rises. Research on the subject of cellular senescence date back to the middle of the last century, and today we know that senescent cells have different morphology, metabolism, phenotypes and many other characteristics. Their main feature is the development of senescence-associated secretory phenotype (SASP), whose pro-inflammatory components affect tissues and organs, and increases the possibility of age-related diseases. The liver is the main metabolic organ of our body, and the results of previous research indicate that its regenerative capacity is greater and that it ages more slowly compared to other organs. With age, liver cells change under the influence of various stressors and the risk of developing chronic liver diseases such as non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcoholic steatohepatitis (ASH) and hepatocellular carcinoma (HCC) increases. It has been proven that these diseases progress faster in the elderly population and in some cases lead to end-stage liver disease that requires transplantation. The treatment of elderly people with chronic liver diseases is a challenge and requires an individual approach as well as new research that will reveal other safe and effective therapeutic modalities.

Old people with chronic hepatitis C (HCV) were considered a difficult-to-treat category with more frequent adverse events until recently. Interferon-free direct-acting antivirals (DAAs) improved treatment adherence and quality of life of old patients. In this study, we aimed at reporting the real-world efficacy and safety of DAAs, in addition to predictors of sustained virological response (SVR) in old chronic HCV population.

This is a prospective observational intention-to-treat analysis that included old chronic hepatitis C genotype-4 patients (> 65 years) treated in a single specialized viral hepatitis treatment center in Egypt. Treatment regimens were allocated according to national guidelines for treatment of hepatitis C. Primary outcome was undetectable HCV-RNA at 12-week post-treatment by PCR. Secondary outcomes were identification of predictors of SVR and assessment of safety related issues.

Our study included 864 patients (64% females) with mean age of 67.7 ± 2.8 years. Overall SVR rate was 98.9% while SVR rates for sofosbuvir/daclatasvir/ribavirin, paritaprevir/ombitasvir/ritonavir/ribavirin, sofosbuvir/daclatasvir, sofosbuvir/ledipasvir/ribavirin, sofosbuvir/simeprevir/daclatasvir/ribavirin, sofosbuvir/simeprevir, interferon/sofosbuvir/ribavirin and sofosbuvir/ribavirin were 100%, 100%, 100%, 100%, 100%, 99.3%, 98% and 94.2%, respectively. DAAs were well tolerated. None of the patients discontinued the treatment due to adverse effects. Higher albumin, higher platelet count, lower bilirubin and lower stage of fibrosis were among predictors of favourable response.

Different DAAs regimens were safe and effective in old Egyptian patients with chronic HCV.

Hepatitis C virus (HCV) infection is considered as a major public health problem that, worldwide, chronically affects 170 million people. Elderly patients are more likely than younger patients to have increased duration of infection, increased rate of disease progression, and subsequently increased incidence of advanced liver disease. Natural history models predicted that the prevalence of HCV infection and its chronic sequelae as well as extrahepatic manifestations will eventually increase through the next decade and will mostly affect those who are greater than 60 years of age. Moreover, polytherapy and polypharmacy are frequent in elderly patients due to associated comorbidities. As advanced age is associated with increasing risk of development of cirrhosis and hepatocellular carcinoma, elderly patients are in special need of safe and effective antiviral therapies. Achievement of sustained viral responses (SVR) is associated with reduced liver-related complications and overall mortality in such patients with the advanced liver disease. With the recent introduction of interferon-free direct-acting antivirals, successful treatment for chronic HCV infection had dramatically improved, with overall cure rates that exceed 90% SVR. In our study, we aimed to study the efficacy and safety of combined sofosbuvir and daclatasvir, with or without ribavirin, in management of chronically infected HCV elderly patients who are more than 60 years old.

There is a lack of evidence-based data on aged patients with newer direct-acting antivirals (DAAs) and with shorter duration of treatment regimens involving DAAs with or without ribavirin (RBV) and pegylated interferon (Peg IFN).

Medical records of 240 patients treated with DAAs with or without Peg IFN and RBV between January 2013 and July 2015 were retrospectively analyzed. Patients were divided into two groups: patients aged 65 years and older (N=84) and patients aged younger than 65 years (N=156). Pretreatment baseline patient characteristics, treatment efficacy, factors affecting sustained virologic response at 12 weeks after treatment, and adverse reactions were compared between the groups.

No statistically significant difference was observed with end of treatment response (98.8 vs. 98%, P=0.667) and sustained virologic response at 12 weeks after treatment (93.1 vs. 94.1%, P=0.767) between patients aged 65 and older and those younger than 65 years of age. Fatigue was the most common adverse event recorded (32.5%), followed by anemia (19.6%), leukopenia (11.7%), thrombocytopenia (10%), skin rash (8.3%), and headache (7.9%). The RBV dose was reduced in eight (8%) patients and four patients discontinued the RBV treatment because of severe anemia. RBV dose reduction or discontinuation did not reach statistical significance (P=0.913). Increased fibrosis, cirrhosis, aspartate aminotransferase, alanine aminotransferase, hemoglobin, and platelet levels seem to affect the sustained virologic response in the elderly. Twelve (6.28%) patients failed to respond to treatment and the failure rate was not significant (P=0.767) between the groups.

DAAs with or without IFN and RBV in the standard recommended 12 or 24-week treatment regimens are effective, well tolerated, and may be safely extended to elderly patients infected with chronic hepatitis C.

Due to the progressive aging of the hepatitis C virus (HCV) population which have acquired the infection during its maximum spread after the Second World War, the management of the elderly HCV-infected patient is emerging as a hot topic. Unfortunately, although it is recognized that the progression of HCV-related liver disease gets faster with aging, and that even extra-hepatic manifestations of HCV infection are probably worse in the elderly, till now, treatment attempts in this population have been significantly limited by the well-known contraindications and side effects of interferon (IFN). The arrival of several new anti-HCV drugs, and the possibility to combine them in safe and effective anti-viral regimens, is relighting the hope of a cure for many elderly patients who had been cut out of IFN-based treatments. However, although these new regimens will be certainly more manageable, it should be underscored that IFN-free doesn't mean free from any contraindication or side-effect. Moreover, one issue which promises to become central is that of the possible interactions between antiviral therapy and the multiple drugs frequently assumed by elderly patients because of comorbidities. In this review, we will revise the epidemiology pointing to HCV as an infection of the elderly, the evidences that HCV harms the health of the aged patient more than that of the young one, and the available experiences of HCV treatment in the elderly with the "old" IFN-based regimens and with the newer drugs. We will conclude that the availability of IFN-free regimens should prompt us to change our mind and consider a significantly larger number of possible candidates among elderly patients, who would take significant advantage from viral eradication. Rather than the anagraphic age, drug-drug interactions and, mainly in case of economic restrictions, an evaluation of life expectancy dependent on liver disease with respect to that dependent on comorbidities, are likely to be the key issues guiding treatment indication in the next future. The sooner we will change our mind with respect to an a priori obstacle for anti-HCV treatment in the elderly, the sooner we will begin to spare many aged HCV patients from avoidable liver-related complications.

Studies up to August 30, 2012 of the efficacy and safety of peginterferon plus ribavirin therapy in CHC patients aged≥65 years were systematically identified in PubMed, Ovid, Web of Knowledge and Cochrane Library databases. A meta-analysis was performed using both fixed- and random-effects models based on heterogeneity across studies.

The overall sustained virological response (SVR) in CHC patients aged≥65 years was significantly lower than in patients aged<65 years on both intention-to-treat (ITT; 42.0% vs. 60.1%, respectively; P<0.00001) and per-protocol (PP; 54.4% vs. 67.4%, respectively; P=0.002) analyses, including treatment-naïve patients. Subgroup analysis showed that patients≥65 years with either hepatitis C virus (HCV) genotype 1/4 or 2/3 had lower SVR rates than younger patients. No statistically significant differences were observed between the two groups in terms of rapid virological response (RVR) and early virological response (EVR) rates (both P≥0.05). However, the end-of-treatment virological response (ETR) rate was lower in patients≥65 years, who also had a significantly higher risk of relapse than those aged<65 years (39.8% vs. 26.9%, respectively; P<0.00001). The discontinuation rate in the older patients was also significantly higher than in the younger patients (25.5% vs. 14.8%, respectively; P<0.00001). Ribavirin dose reduction in the older patients treated with peginterferon plus ribavirin was also significantly higher than in younger patients (44.5% vs. 32.8%, respectively; P<0.00001).

Peginterferon plus ribavirin therapy was effective for older patients with CHC, particularly those with HCV genotype 2/3. Response-guided therapy can be used for older patients with genotype 1/4, but such patients had poorer treatment adherence, leading to poorer treatment efficacy.

The recommended treatment for chronic hepatitis C is a combination of pegylated interferon (PEG IFN) plus ribavirin (RBV). However, the sustained virological response (SVR) rate of PEG IFN-RBV therapy was approximately 50% in patients with genotype 1b and a high viral load. Thus, we compared the efficiencies and side-effects of PEG IFN-RBV and self-injected low-dose natural (n) IFN-α in patients with hepatitis C virus (HCV).

A prospective, multicenter, open-label study was conducted in 12 Japanese institutions. A total of 129 patients with chronic hepatitis C and no detectable HCV after 24-72 weeks of PEG IFN-RBV treatment were assigned to the control (n = 82) or treated (n = 47) group. Treated patients received 3 million units of nIFN-α 2-3 times/week over 96 weeks. The groups were compared regarding treatment efficiency and side-effects.

Significant treatment success regarding virus negativation rates was found, with 89% and 73% for the treated and control groups, respectively (P = 0.039). In contrast, there was no difference in relapse rate between the groups 24 weeks after the 96-week nIFN-α treatment (P = 0.349). However, when early viral responders and late viral responders (LVR) were separated, LVR patients responded significantly to the treatment with 90% sustained virological response, compared to 53% for the control group (P = 0.044). The side-effects of nIFN-α were less than that of PEG IFN-RBV treatment.

Self-injected nIFN-α has larger benefits than prolonged PEG IFN-RBV for chronic hepatitis C patients with high viral loads of genotype 1b who fail to achieve early viral response during initial combination treatment.

To investigate the risk factors for liver-related mortality in chronic hepatitis C (CHC) patients.

All deceased CHC inpatient data were collected from the Beijing 302 Hospital clinical database, which includes more than 8250 CHC inpatients during the period from 2002 to 2012. The controls were matched to cases by age (± 2 years), sex and date of hospital admission (within the same year). Potential risk factors were included for the evaluation, and odds ratios (OR) and 95%CI were estimated using univariate (unadjusted) and multivariate (adjusted OR, AOR) conditional logistic regression. All statistical tests were two-sided. P values < 0.05 were considered statistically significant.

Based on examinations of 144 CHC-related deceased cases and 576 controls, we found that antiviral therapy with interferon-α was associated with a 47% decrease in the risk of hepatic mortality (AOR = 0.53, 95%CI: 0.28-0.99, P = 0.048). Additionally, the initial diagnostic stage of the disease (AOR = 2.89, 95%CI: 1.83-4.56 and P < 0.001 for liver cirrhosis/AOR = 8.82, 95%CI: 3.99-19.53 and P < 0.001 for HCC compared with CHC), diabetes (AOR = 2.35, 95%CI: 1.40-3.95, P = 0.001), hypertension (AOR = 1.76, 95%CI: 1.09-2.82, P = 0.020), alcohol consumption (AOR = 1.73, 95%CI: 1.03-2.81, P = 0.037) and HBsAg positivity (AOR = 22.28, 95%CI: 5.58-89.07, P < 0.001) were associated with a significant increase in the risk of liver-related mortality in CHC patients.

This study indicates that interferon-α treatment, the stage at the initial diagnosis of the disease and comorbidities are all independent risk factors for liver-related mortality in CHC patients.

Hepatitis C is a common infection worldwide. It is a major cause of cirrhosis and its complications, including hepatocellular carcinoma and liver transplantation. Treatment of hepatitis C has dramatically improved since its discovery. Current treatment includes pegylated interferon and ribavirin, and the addition of the protease inhibitors telaprevir, boceprevir, or simeprevir, or the polymerase inhibitor sofosbuvir. The rate of sustained viral response, considered a cure, now approaches 80 %. These treatments are complex, with multiple morbidities and drug interactions. The majority of patients with chronic hepatitis C are from the birth cohort of the 'baby boomer' years (1945-1965) with the oldest already 68 years old. In spite of this, most hepatitis C patients in clinical trials have been much younger and this is still the case in the ongoing studies. Thus, the group of patients most likely to require treatment in the future will have decisions made with a relative lack of evidence-based medicine. It is the purpose of this article to review the epidemiology, clinical manifestations, and treatment of hepatitis C with the data available in the aged population.

Elderly and/or cirrhotic patients with hepatitis C virus (HCV) are at high risk of adverse effects during interferon therapy. The aim of the present study was to evaluate the efficacy, safety and predictive factors for sustained virological response (SVR) of low-dose pegylated interferon-α-2a (PEG IFN-α-2a) monotherapy in elderly and/or cirrhotic patients with HCV genotype-2 or genotype-1 low level infection.

Sixty-four elderly (≥65 years) and/or cirrhotic patients with HCV genotype-2 or genotype-1 low level (<5 logIU/mL) infection underwent low-dose PEG IFN-α-2a (90 μg/week) monotherapy for 24 weeks. Sixty patients were available for efficacy assessment.

SVR was achieved in 78.3%. SVR rates according to genotype-1 low, genotype-2 low and genotype-2 high viral load were 90.0%, 87.1% and 57.9%, respectively. The discontinuation rate was 12.5%. PEG IFN-α-2a was interrupted or discontinued in four patients because of severe thrombocytopenia (<25 000/mm(3) ). The baseline platelet counts of all these patients were less than 70 000/mm(3) . On univariate analysis of factors contributing to SVR, significant differences were noted in viral load, platelet count, γ-glutamyltransferase, ferritin, α-fetoprotein level and rapid viral response (RVR). On multivariate analysis, RVR was the only independent factor (P = 0.010, odds ratio = 47.27). The positive and negative SVR-predictive values based on RVR were 95% and 82%, respectively.

Low-dose PEG IFN-α-2a monotherapy was effective and tolerable in elderly and/or cirrhotic patients with genotype-2 or genotype-1 low HCV level infection. However, a baseline platelet count of more than 70 000/mm(3) is needed for safety. RVR can predict SVR accurately.

Cancer patients were generally excluded from the therapeutic guidelines of antiviral therapy. We aimed to evaluate the efficacy and safety of antiviral therapy in patients with hepatitis C virus (HCV) infection concomitant with malignancy other than hepatocellular carcinoma (HCC).

Twenty-five HCV patients with curative malignancy other than HCC (group A) and 75 sex- and age-matched controls (group B) were recruited into a prospective and case-control analysis. All patients received peginterferon-alpha-2a (PegIFN-alpha-2a) and weight-based ribavirin according to the current treatment recommendations. The primary outcome measurement was sustained virological response (SVR). The safety issue between groups was also compared.

There were 22 (88.0 %) patients of group A and 59 (78.7 %) patients of group B who achieved an SVR (p = 0.39). The SVR rate was comparable between groups both in genotype-1 (HCV-1) (81.8 vs. 72.7 %, p = 0.70) and in genotype-2 (HCV-2) (92.9 vs. 83.3 %, p = 0.66) patients. Multivariate logistic regression analysis demonstrated that the achievement of a RVR (viral clearance during first 4 weeks of treatment) was the strongest predictor of an SVR (odds ratio/95 % confidence intervals [OR/CI]: 6.357/1.50 - 26.99, p = 0.01), followed by lower baseline viral loads (OR/CI: 0.403/0.174 - 0.936, p = 0.034) and higher dose of ribavirin exposure (OR/CI: 1.287/1.092 - 1.517, p = 0.003), whilst previous occurrence of cancer was not associated with SVR. Treatment adherence (76.0 vs. 72.0 %, p = 0.70) and the incidences of grade 3 or more adverse events (28.0 vs. 20.0 %, p = 0.40) were comparable between two groups.

Chronic hepatitis C patients with non-HCC malignancies receiving peginterferon/ribavirin combination therapy carried favorable efficacy and safety outcomes.

Limited data are available on the efficacy and safety of antiviral therapy in geriatric patients with chronic hepatitis C virus (HCV) infection.

To evaluate the efficacy and safety of pegylated interferon (pegIFN) plus ribavirin (RBV) therapy in geriatric HCV-infected patients.

Ninety-one geriatric patients (age ≥65 years; the elderly group) with HCV infection and 91 gender- and HCV genotype-matched middle-aged patients (age 50-64 years; the younger group) were assigned to receive weekly pegIFN injection plus weight-based oral RBV for 24 weeks. The on- and off-treatment virological responses were evaluated for treatment efficacy.

In intention-to-treat analysis, the sustained virological response (SVR) rate was substantially decreased in the elderly patients (elderly group vs. younger group, 40.7% vs. 61.5%, respectively; P = 0.005). The SVR rate was significantly lower in geriatric patients than in middle-aged patients with HCV genotype non-1 (54.3% vs. 82.9%; P = 0.01), but the difference was not significant with HCV genotype 1 (32.1% vs. 48.2%; P = 0.083). Furthermore, the older patients infected with HCV genotype non-1 who achieved a rapid virological response had a similar SVR rate to that of the younger patients. The withdrawal rate was 13.2% in the elderly group and 7.7% in the younger group.

Compared with middle-aged patients, the therapeutic efficacy of pegylated interferon plus ribavirin therapy is lower in hepatitis C virus-infected geriatric patients with an acceptable withdrawal rate. Considering prolonged lifespan in geriatric patients, we recommend treating geriatric hepatitis C virus-infected patients who have significant hepatic fibrosis and no other health problems.

Boceprevir was the first agent, along with telaprevir, of a novel class of direct-acting antivirals that entered clinical practice for the treatment of chronic hepatitis C. Boceprevir is an antiprotease that directly blocks hepatitis C virus (HCV) replication. Two studies in patients with HCV genotype 1 infection have shown that addition of boceprevir to the standard of care, ie, pegylated interferon-alfa (PEG-IFN-α) and ribavirin, markedly increased the rate of sustained virological response. A sustained virological response was obtained in about 70% of patients who had never been treated, as well as in 69%-75% and 40% of previous relapsers and nonresponders to PEG-IFN-α-ribavirin, respectively. Side effects were observed in almost all treated patients. Anemia, the most frequent adverse event related to administration of boceprevir, occurred in about 50% of patients. The decision to add boceprevir to the standard of care is made on an individual basis, and takes into account the prognosis of the liver disease, the efficacy of therapy, as it could be at best predicted, and the side effects that may arise, taking into account the comorbidities of the patient. Ultimately, the treatment must be accepted by the patient, who should fully understand the benefits and risks. Boceprevir trials were designed with the concept of individualized and response-guided therapy which establishes treatment decisions on how rapidly patients respond to treatment. Individualized therapy for chronic hepatitis C is based on patient and viral characteristics to make the best choice about whether a person will benefit from therapy and to evaluate on-treatment predictors of response to shorten therapy in patients with a rapid response as well as in patients who did not respond sufficiently to expect HCV eradication. This review focuses on the main results obtained so far, their impact on the treatment of patients with chronic hepatitis C, and potential therapeutic perspectives.

The prevalence of chronic hepatitis C virus (HCV) tends to be higher in the elderly in many countries. Aging is regarded as an unfavorable factor for liver disease progression and treatment outcome in HCV infection. The efficacy and safety of treating elderly patients remain a source of significant debate. Discrepancies in results may be attributed to dissimilarities in study design and treatment regimens. The long-term benefits of administering interferon-based therapy to elderly patients with HCV infection is a critical issue when taking the patient's remaining life expectancy into consideration. Rapid virological response is the most notable on-treatment response factor that is predictive of treatment success in elderly patients. A shortened treatment course may reduce drug-related side effects and promote treatment adherence, especially in the elderly. A regimen tailored towards super-responders might provide insights for treatment strategies in elderly patients.

A non-negligible percentage of the morbidity and mortality in older persons is due to liver disease. A discussion of the clinical presentation and proposed treatment of selected liver diseases in the elderly is therefore appropriate. Based on literature we will discuss the clinical course and treatment modalities of viral and autoimmune hepatitis, hepatocellular carcinoma and drug induced liver injury in the elderly.

Peginterferon (PEG-IFN) and ribavirin (RBV) combination treatment for patients with chronic hepatitis C (CHC), infected by genotype-1 hepatitis C virus with high viral loads, results in a sustained viral response (SVR) in ~50%. However, a trend of decreasing SVR in the older patients has been reported. In the present study, we verified this trend of treatment efficacy in older patients using the propensity score (PS).

We conducted a survey of 327 patients with CHC (genotype 1 and high viral loads) who were treated with PEG-IFN and RBV for 48 weeks. The SVR rate was compared between patients =60 and <60 years of age. Because backgrounds of these patients differed considerably, we verified this efficacy between the older (n = 102) and younger (n = 102) patients matched for gender, body weight, platelets (PLT), and red blood cell (RBC) counts using PS.

The total SVR rate was 42.9% (161/327); this rate decreased with increasing age and was lower in the older patients (≥60 years: 41.5%, <60 years: 54.3%, P = 0.0245). Moreover, younger age was a significant factor for SVR. After correction by PS, the SVR in older patients remained significantly lower (≥60 years: 43.1%, <60 years: 57.8%, P = 0.0497). In addition, RBC counts and hemoglobin (Hgb) concentrations, as well as RBV adherence in the older patients, decreased with this treatment, although there were no significant differences in pretreatment RBC and Hgb levels.

The analysis using PS indicated that RBV adherence in the older patients decreased even if they did not have lower pretreatment RBC and Hgb levels.

Which patients with hepatitis C virus (HCV) genotype 1 can benefit from extended treatment with pegylated interferon (Peg-IFN) plus ribavirin is unknown, although the overall sustained virologic response (SVR) rate has been shown to improve in patients with a late virologic response (LVR), defined as detectable serum HCV RNA at week 12 and undetectable at week 24.

Among 1163 chronic hepatitis C patients with genotype 1 treated with Peg-IFN plus ribavirin combination therapy, 213 patients with an LVR were examined in this study. In addition, we selected 81 patients of matched sex and age from each of the 48- and 72-week treatment groups, using the propensity score, to compare the efficacy of the two treatment durations.

With 72-week treatment, the timing of HCV RNA disappearance and the hemoglobin level at baseline showed a strong correlation with the SVR on multivariate analysis. Earlier HCV RNA disappearance was associated with a better SVR rate, regardless of the ribavirin dose (HCV RNA disappearance at week 16, 74%; at week 20, 52%; and at week 24, 31%, p = 0.01). The SVR rate with 72-week treatment was higher than that with 48-week treatment, irrespective of age, sex, or the platelet value, and, especially in aged patients (≥65 years old), the SVR rate increased markedly with 72-week treatment (48 weeks, 25% vs. 72 weeks, 56%; p < 0.05).

An earlier response predicts a higher SVR rate in patients with an LVR given 72-week treatment. Extended treatment with Peg-IFN plus ribavirin for patients with an LVR improved the treatment efficacy, even for aged patients.

This study investigated the efficacy and adverse effects of pegylated interferon (Peg-IFN) plus ribavirin therapy in aged patients with chronic hepatitis C (CH-C).

A total of 1040 naïve patients with CH-C (genotype 1, n=759; genotype 2, n=281), of whom 240 (23%) over 65 years old (y.o.), were treated with Peg-IFN alfa-2b plus ribavirin and assessed after being classified into five categories, according to age.

The discontinuance rate was higher for patients over 70 y.o. (36%), the most common reason being anemia. In the presence of genotype 1, the SVR rate was similar (42-46%) among patients under 65 y.o. and declined (26-29%) among patients over 65 y.o. For patients over 65 y.o., being male (Odds ratio, OR, 3.5, p=0.035) and EVR (OR, 83.3, p<0.001) were significant factors for SVR, in multivariate analysis. The Peg-IFN dose was related to EVR, and when EVR was attained, 76-86% of patients over 65 y.o. achieved SVR. SVR was not achieved (0/35, 0/38, respectively) if a 1-log decrease and a 2-log decrease were not attained at week 4 and week 8, respectively. In the presence of genotype 2, the SVR rate was similar (70-71%) among patients under 70 y.o. and declined among patients over 70 y.o. (43%).

Aged patients up to 65 y.o. with genotype 1 and 70 y.o. with genotype 2 can be candidates for Peg-IFN plus ribavirin therapy. The response-guided therapy can be applied for aged patients with genotype 1.

The issue of age in cases of chronic hepatitis C (HCV) in the West is a major problem; the average age of patients with HCV is increasing and its prevalence increases with advancing age.

This review is devoted to the analysis of the limited number of clinical studies performed to treat HCV in elderly patients.

The importance of the age factor is outlined in nearly all the studies done in the field. Advanced age is associated with a lower sustained virologic response (SVR) rate. Moreover, in elderly patients, these studies also tend to suggest that, before initiating an antiviral treatment, the physician should not only take into account the classical parameters associated with SVR but also the presence of co-morbidities and life expectancy. TAKE-HOME MESSAGES: Antiviral therapy should be used in selected elderly HCV patients with advanced fibrosis and more studies are required in this population to better define the parameters associated with SVR. As age is an important factor in the success of antiviral therapy, starting antiviral treatment at a young age should be favored.

The aim of this study was to evaluate the efficacy and indication of combination therapy with ribavirin plus peginterferon-alpha-2b in chronic hepatitis C virus (HCV) patients aged 65 years and older.

Five hundred and ninety-one consecutive HCV patients were treated with combination therapy. These patients were divided into elder patients (> or = 65 years) (n=115) and younger patients (< 65 years) (n=476). The clinical characteristics, sustained virological response (SVR) rates and discontinuation rates were compared between the two groups.

Compared with younger patients, baseline haemoglobin levels and baseline platelet counts were significantly lower (P<0.0001, P=0.013 respectively) and fibrosis was more advanced in elderly patients (P=0.0310). Moreover, the SVR rate was significantly lower (37.4 vs. 51.5%; P=0.0067) while the combination therapy discontinuation rate was significantly higher (32.2 vs. 17.0%; P=0.0003) in elderly patients. A multivariate analysis revealed that HCV load and genotype were significantly associated with an SVR in elderly patients. An SVR was achieved in over 50% of elderly male patients with genotype 1 and HCV RNA concentrations under 2,000,000 IU/ml. In contrast, the SVR rate was under 30% in elderly male patients with genotype 1 and with HCV RNA concentrations over 2,000,000 IU/ml and in all elderly female patients with genotype 1.

The SVR rate was lower in elderly patients than in younger patients. However, in elderly patients combination therapy was most beneficial for genotype 1 patients, male patients with HCV RNA concentrations < 2,000,000 IU/ml and patients with genotype 2.

The consensus meeting for the diagnosis, management and treatment for hepatitis C was held in 45(th) annual meeting for the Japan Society of Hepatology (JSH) in June 2009 where the recommendations and informative statements were discussed including organizers and presenters. The Several important informative statements and recommendations have been shown. This was the fourth JSH consensus meeting of hepatitis C, however, the recommendations have not been published in English previously. Thus, this is the first report of JSH consensus of hepatitis C. The rate of development of hepatocellular carcinoma (HCC) in HCV-infected patients in Japan is higher than in the USA, because the average age of the HCV-infected patients is greater and there are more patients with severe fibrosis of the liver than in the USA. In Japan, more than 60% of HCV-infected patients are genotype 1b infection, and they show lower response to perinterferon and ribavirin combination treatment. To improve the response rate is also an important issue in our country. To establish the original recommendations and informative statements to prevent the development of HCC is a very important issue in Japan.

This study was undertaken to investigate the effect of interferon (IFN) monotherapy on the risk of hepatocellular carcinoma (HCC) in aged-patients with chronic hepatitis C. Seven hundred and twenty-five patients with histologically proven chronic hepatitis C were enrolled in this retrospective cohort study; 531 received IFN monotherapy for 6 months between 1992 and 1995, and 157 were collected as a historical control. The effect of IFN therapy on the development of HCC was compared between the patients with chronic hepatitis C under 60 years old (non-aged group, n = 531) and those 60 and over (aged group, n = 194). A stepwise Cox proportional-hazards regression analysis in the non-aged group revealed that IFN therapy (risk ratio 0.52, 95% CI 0.33-0.81, P = 0.004), older age (P = 0.001), and higher histological stage (P < 0.001) were independent factors associated with the development of HCC. In the aged-group, only higher histological stage (P = 0.002) and male gender (P = 0.011), but not IFN therapy (risk ratio 0.77, 95% CI 0.42-1.40, P = 0.386), were identified as independent risk factors for HCC, although HCC was significantly reduced when sustained virological response (SVR) was obtained (risk ratio 0.23, 95% CI 0.08-0.64, P = 0.005). In conclusion, inhibitory effect of IFN on development of HCC in the patients with chronic hepatitis C aged 60 and over was limited to the patients achieving SVR when treated with 6 months-IFN monotherapy.

Chronic hepatitis C (CH-C) genotype 1 patients who achieved early virologic response have a high probability of sustained virologic response (SVR) following pegylated interferon (Peg-IFN) plus ribavirin therapy. This study was conducted to evaluate how reducing drug doses affects complete early virologic response (c-EVR) defined as hepatitis C virus (HCV) RNA negativity at week 12. Nine hundred eighty-four patients with CH-C genotype 1 were enrolled. Drug doses were evaluated independently on a body weight base from doses actually taken. From multivariate analysis, the mean dose of Peg-IFN alpha-2b during the first 12 weeks was the independent factor for c-EVR (P = 0.02), not ribavirin. The c-EVR rate was 55% in patients receiving > or = 1.2 microg/kg/week of Peg-IFN, and declined to 38% at 0.9-1.2 microg/kg/week, and 22% in patients given <0.9 microg/kg/week (P < 0.0001). Even with stratified analysis according to ribavirin dose, the dose-dependent effect of Peg-IFN on c-EVR was observed, and similar c-EVR rates were obtained if the dose categories of Peg-IFN were the same. Furthermore, the mean dose of Peg-IFN during the first 12 weeks affected HCV RNA negativity at week 24 (P < 0.0001) and SVR (P < 0.0001) in a dose-dependent manner. Our results suggest that Peg-IFN was dose-dependently correlated with c-EVR, independently of ribavirin dose. Thus, maintaining the Peg-IFN dose as high as possible during the first 12 weeks can yield HCV RNA negativity and higher c-EVR rates, leading to better SVR rates in patients with CH-C genotype 1.

Hepatitis C continues to be a major public health problem affecting approximately 3% of the global population. According to the World Health Organization, an estimated 170 million people have chronic hepatitis C. Ten percent to 20% of those who are chronically infected with hepatitis C will progress to cirrhosis and 5% will develop hepatocellular carcinoma. Although the safety and efficacy of hepatitis C therapies have been studied extensively in patients between the ages of 18 and 65, patients who are older than 65 still remain an understudied and difficult-to-treat population. This review discusses the epidemiology, natural history, and treatment of chronic hepatitis C in older adults.

The aim of this study was to elucidate the efficacy of interferon (IFN)-beta monotherapy for elderly patients of > or = 70 years with type C hepatitis (HCV) of genotype 2.

The present study was a retrospective cohort study. Inclusion criteria were type C hepatitis patients with HCV genotype 2a or 2b, > or = 70 years, and IFN-beta monotherapy of within 24 weeks. Thirty-one consecutive patients who satisfied the above criteria were enrolled in the present study. Independent factors that might have influenced the sustained virological response (SVR) were studied using logistic regression analysis.

Background of clinical profiles was as follows: median (range) age = 71 (70-76) years, male/female = 13/18, and median (range) HCV-RNA = 260 (< 5-3,800) KIU/mL. Out of 31, 16 patients (51.6%) had SVR by the intention-to-treat analysis. The SVR was significantly associated with the serum HCV RNA level. Logistic analysis showed that SVR occurred when HCV RNA level was < 100 KIU/mL (p=0.020). Based on the difference of the serum HCV RNA level, the SVR rate was 81.8% (9/11) in patients with a serum HCV RNA level of < 100 KIU/mL and 35.0% (7/20) in patients with a serum HCV RNA level of > or = 100 KIU/mL.

IFN-beta monotherapy of < or = 24 week is a possible therapy selection for elderly patients of > or = 70 years with type C hepatitis of genotype 2.

Interferon therapy is indicated for the treatment of chronic hepatitis C and prevention of hepatocellular carcinoma. We describe the case of a 66-year-old Italian woman who received pegylated interferon alpha-2a plus ribavirin combined therapy for HCV-related chronic liver disease. Preliminary hematochemical, ultrasound and bioptic investigations did not show liver cirrhosis or hepatocarcinoma. After 24 weeks of treatment transaminase serum levels were in the normal range and circulating HCVRNA was undetectable by PCR qualitative assay. On week 46 a serious adverse event occurred, with rapid transaminase increase, severe hyperpyrexia, and abdominal pain, leading to interruption of interferon and ribavirin. Liver biopsy was repeated and it revealed poorly differentiated hepatocellular carcinoma. Only palliative care could be performed and the patient died of liver failure within 2 months. The present case underlines that hepatocellular carcinoma can be misdiagnosed in spite of laboratory and instrumental follow-up. More sensitive tools are needed for tumor detection, to avoid IFN impairment of the liver, even though it eradicates HCV.

Hepatitis C virus (HCV) infection frequently occurs in elderly individuals, with a prevalence in individuals aged >60 years of up to approximately 40%. Although progression to cirrhosis is accelerated and occurs more frequently in patients who acquire the infection in old age, this outcome is often not seen because most elderly infected patients acquired HCV when they were young. Data on progression of HCV infection to cirrhosis and eventually to hepatocellular carcinoma are often derived from studies of HCV-infected individuals who present or are referred to hospitals, and which are therefore likely to overestimate the seriousness of the disease; indeed, population-based studies indicate that in many elderly individuals the disease is asymptomatic and runs a fairly benign course. Treatment is based on use of pegylated interferon-alpha and ribavirin, and is overall less effective and more toxic in the elderly. Therefore, treatment should be carefully considered on an individual basis and proposed only in patients up to the age of 75 years with a significant risk of progression of liver disease, no serious co-morbidities and good life expectancy. All treated patients should be followed long term in order to assess the influence of therapy on the evolution of liver disease (decompensated cirrhosis, hepatocellular carcinoma) and survival. It is hoped that liver biopsy, which is still required in order to assess prognosis appropriately, will be replaced in the future by less invasive methods based on combinations of biochemical markers of fibrosis and/or transient elastography, and that newer and less toxic orally administered drugs for HCV infection will become available.

Chronic liver disease and cirrhosis are the tenth leading causes of death in the United States and results in approximately 25,000 deaths annually. As life expectancy in developed countries has increased, so has the number of elderly patients who have liver disease. With an aging population and chronic liver disease becoming an increasingly significant cause of morbidity and mortality, the various causes for hepatitis will need to be evaluated and available treatments considered, even in elderly population. Common causes for hepatitis in elderly individuals include viral, autoimmune, and drug-induced hepatitis, but evidence for treatment of this population is limited. This article reviews the likely causes of hepatitis in elderly individuals and discusses evidence for treating this population.

Ribavirin, used to treat chronic hepatitis C, can induce hemolytic anemia, forcing the discontinuance of treatment. To establish a predictive measure to help circumvent this, we evaluated the relationship of hemoglobin (Hb) decline with the discontinuance of treatment during the progression of ribavirin-induced anemia.

One hundred and sixteen patients (71% male) with genotype 1 chronic hepatitis C were treated with pegylated interferon (PegIFN) alpha-2b and ribavirin. The mean age was 50.6 years and 55% were IFN naïve. A decline of Hb concentration by 2 g/dL at two weeks from the start of the treatment ("2 by 2" standard) was adopted as the predictive factor for the progression of anemia.

By applying the "2 by 2" standard, with DeltaHb >/= 2 g/dL (34%, n = 39), treatment was discontinued in 12 cases (31%), three of which (8%) because of severe anemia. ForDeltaHb < 2 g/dL (64%, n = 76), treatment was discontinued in 11 (14%) cases; none due to severe anemia. Ten percent (4/39) of patients showed the minimum Hb </= 8.5 g/dL in the DeltaHb >/= 2 g/dL group, with none in the DeltaHb < 2 g/dL group (P = 0.001). Furthermore, the patients with minimum Hb </= 8.5 g/dL were found only in the "2 by 2" standard-positive and low CL/F (<15) group (4/29, 14%).

Monitoring the Hb decline using the "2 by 2" standard can identify patients who are prone to developing severe anemia. Further prospective studies are needed using ribavirin reduction based on the "2 by 2" standard.

Recently, many diagnostic modalities have been developed for the detection of hepatocellular carcinoma (HCC). Of these, a less invasive and more accurate diagnostic procedure is desirable. This study was undertaken to compare combined dynamic multidetector row helical computerized tomography (MDCT) and superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging (MRI) with combined CT hepatic arteriography (CTHA) and CT during arterial portography (CTAP) for the detection of hypervascular HCC.

Forty-eight patients with 56 pathologically proved hypervascular HCCs (less than 5.0 cm in diameter) underwent dynamic MDCT and SPIO-enhanced MRI, as well as CTHA and CTAP. The images were reviewed by four independent and blinded readers on a tumor-by-tumor basis.

The mean areas under alternative-free response receiver operating characteristic curve (Az) for combined dynamic MDCT and SPIO-enhanced MRI (IV set) and combinedCTHA and CTAP (IA set) were comparable (0.948 and 0.969, respectively, P > 0.05), although the Az value of the IV set was significantly lower than that of the IA set in HCCs smaller than or equal to 1.5 cm (0.867 and 0.937, respectively, P = 0.033). The mean sensitivity and positive predictive value of the IV set were similar to those of the IA set.

Combined dynamic MDCT and SPIO-enhanced MRI showed a diagnostic accuracy comparable to intra-arterial contrast-enhanced CT (CTHA and CTAP) for hypervascular HCC, and may be a useful diagnostic option prior to curative treatments of hypervascular HCC, although a limitation exists in detecting HCCs smaller than or equal to 1.5 cm.

In Japan, patients with hepatitis C virus (HCV)-associated liver disease are getting older, and thus the number of deaths due to such disease is increasing. The efficacy of combination therapy with ribavirin and interferon for chronic HCV infection in elderly patients has not been fully clarified. The aim of the present study was to evaluate the efficacy and tolerability of combination therapy in such patients.

Two hundred and twenty consecutive patients with chronic hepatitis C were treated with combination therapy. These patients were divided into two groups according to age: patients >or= 60 years (n = 66) and patients < 60 years (n = 154). Clinical characteristics, the sustained virologic response (SVR) rate obtained by intention-to-treat analysis, and the rate of reduction or discontinuation of ribavirin were compared between the two groups.

The ribavirin discontinuation rate was significantly higher in the patients aged >or=60 years than in the patients aged <60 years. However, the SVR rates did not differ significantly between patients aged >or=60 years and those aged <60 years (31.8% vs 38.3% by intention-to-treat analysis). According to multivariate analysis, genotype and HCV viral load were significantly associated with SVR while patient age did not affect SVR.

Treatment of chronic hepatitis C with combination therapy was comparably effective between patients aged >or=60 years and those aged <60 years, although the ribavirin discontinuation rate was higher among the older patients than the younger patients.

The purpose of this study was to elucidate the long-term outcome after interferon (IFN) therapy in chronic hepatitis C elderly patients.

We studied the incidence of hepatocellular carcinoma (HCC) and survival probability after the initiation of IFN therapy in 500 Japanese chronic hepatitis C patients >60 years. The mean age of initiation of IFN was 63 years and the mean follow-up period was 7.4 years. Cox proportional hazard regression analysis was used to evaluate the long-term outcome after initiation of IFN therapy. Sustained virological response (SVR) was defined as negative HCV-RNA by RT-nested PCR 6 months after the completion of long-term IFN therapy. Non-response (NR) was applied to patients who did not show SVR. Hepatic fibrosis was defined as the fibrosis score (score 0-4) according to Knodell et al.

140 patients (28%) had an SVR and 360 patients (72%) had an NR. 71 of 500 patients developed HCC during follow-up. The cumulative incidence of HCC was 9.6% at the 5th year, 17.4% at the 10th year, and 31.3% at the 15th year. HCC developed with significance when: (1) HCV was not cleared after IFN therapy (p < 0.0001), (2) sex was male (p < 0.0001), and (3) staging of liver fibrosis was >2 (p = 0.008). 53 of the patients died. The cumulative survival probability was 95.7% at the 5th year, 86.4% at the 10th year, and 78% at the 15th year. Patients achieved a long survival with significance when: (1) staging of liver fibrosis was 1 (p < 0.0001), (2) HCV was cleared after IFN therapy (p = 0.034), and (3) sex was female (p = 0.015).

Chronic hepatitis C patients with clearance of HCV after IFN therapy had a significantly reduced risk of HCC appearance and achieved prolonged survival even if they are > or =60 years.

Few data are available on chronic hepatitis C (CHC) in elderly patients. The aim of this study was to compare the features and severity of CHC and the efficacy/safety of antiviral therapy in patients<65, between 65 and 80, and >80 yr old, and to determine the usefulness of biochemical markers (Fibrotest-Fibrosure/ActiTest [FT-AT]) in aged patients.

This was a retrospective study with two groups of patients: Group 1: prospective cohort including all hepatitis C virus patients from our institution (N=4,182); Group 2: all consecutive patients who had FT-AT performed in France between 2002 and 2004 (N=33,738).

A total of 6,865 patients>or=65 yr old was included (Group 1=881, Group 2=5,984). Group 1: patients>or=65 had a longer duration of and a higher age at infection, more genotype 1, and a history of transfusion (p<0.001). Among the 2,169 patients who underwent liver biopsy, bridging fibrosis (F2,F3,F4) was more frequent in patients>or=65 yr old, regardless of the duration of infection. In multivariate analysis, ages at biopsy and at infection were associated with F2,F3,F4. Discovery of CHC by a complication was more frequent in patients>or=65 yr (p<0.001). One hundred seventy patients>or=65 yr received antiviral therapy. A sustained virologic response was obtained in 45% of patients>or=65 yr treated with pegylated interferon/ribavirin. Group 2: At FT, 58% of patients>80 yr, 37% of patients between 65 and 80 yr, and 14% of patients<65 yr (p<0.001) had cirrhosis. Patients>80 yr (43%) with cirrhosis had nonelevated alanine amino transferase (ALT), compared with 31% of patients<65 yr (p<0.001).

In patients>or=65 yr, CHC is more severe and presents with lower ALT than in younger patients. Treatment is effective. Biochemical markers seem particularly useful as a noninvasive alternative to liver biopsy in this population.

Most of the older adults with chronic hepatitis C virus infection acquired the disease earlier in life. These patients often present with complications of liver disease, mainly cirrhosis and hepatocellular carcinoma. The burden of chronic hepatitis C virus infection in elderly persons is expected to increase significantly in the United States during the next 2 decades. It seems important that, for elderly patients with chronic hepatitis C, the risk-benefit of combination antiviral therapy consisting of pegylated interferon and ribavirin should be assessed on an individual basis. Assessment should be performed in all cases before considering treatment, and it should include evaluation of the degree of liver fibrosis by means of liver biopsy or, possibly, by means of noninvasive methods. Novel antiviral drugs that may have fewer adverse effects, such as protease inhibitors, may serve as potential alternatives. It is recommended that elderly patients (up to the age of 75 years) be included in randomized trials of chronic hepatitis C virus infection treatment.