Hepatitis C Virus Clearance in Older Adults

Antonio Massimo Ippolito, MD; Angelo Iacobellis, MD; Michele Milella, MD; Fabio Conti, MD; Vincenzo Messina, MD; Maria Rosa Valvano, PhD; Grazia Anna Niro, MD; Filomena Morisco, MD; Michele Barone, MD; Antonio Patrizio Termite, MD; Giuseppina Brancaccio, MD; Angelo Andriulli, MD

Disclosures

J Am Geriatr Soc. 2018;66(1):85-91. 

In This Article

Results

Two hundred fifty-three individuals aged 80 and older met the inclusion criteria; the mean age was 82.5 (range 80–88), and 132 (52%) were male. Forty had advanced fibrosis (16%), and the remaining 213 (94%) had liver cirrhosis. Thirty-three with cirrhosis recalled single or multiple events of liver decompensation (15.5%). At the pretreatment evaluation, 36 (17%) were staged in CPT Class B or C, 14 (7.5%) had a MELD score greater than 16, and 37 (17%) were D'Amico Stage 3 to 5. The distribution of HCV genotypes was as follows: 1A in 3 patients (1%), 1B in 164 (65%), 2 in 80 (32%), and 4 in 6 (2%). Ninety patients (35.6%) had no comorbidities at the baseline evaluation, 131 (54.9%) had one or two, and 24 (9.5%) had 3 or more. The most frequent comorbidities were diabetes mellitus, hypertension, and history of cardiovascular disease or cerebrovascular accidents.

Treatment Response

The overall SVR12 was 94.9%. Participant and virus characteristics that may have affected the outcome of therapy are shown in Table 1; no influence of sex, age, number of comorbidities, number of co-prescribed drugs, or failed previous antiviral treatment was seen. As to degree of liver impairment, participants in compensated (Stages 1 and 2) or decompensated (Stages 3 to 5) stages of the D'Amico system were equally responsive. A marginal lower response rate was documented in the 11 participants with CPT Class C. Response rates according to HCV genotype, presence of liver cirrhosis, and antiviral treatment schedule are given in Supplementary Table S1; no difference between the subgroups was noted.

Careful pretreatment evaluation of drug-drug interactions and good management of incipient side effects enabled treatment to be completed in all participants with multiple comorbidities. The most commonly used medications were angiotensin-converting enzyme inhibitors, beta-blockers, angiotensin II receptor blockers, and calcium antagonist receptors for individuals with hypertension; insulin or repaglinide in association or not with metformin for diabetes mellitus, and aldosterone blockers and furosemide for individuals with congestive heart failure. Sixty-two percent of participants with two or more comorbidities were undergoing platelet antiaggregant treatment with acetylsalicylic acid, and 2% of them were treated with dual antiplatelet therapy (clopidogrel plus acetylsalicylic acid); 2 participants were given vitamin K antagonists.

Treatment Safety

Two participants, one in CPT Class A5 and the other in D'Amico Stage 1,[20] withdrew from treatment because of dizziness or irritability. Twenty-seven participants (10.7%) complained of 51 side effects during treatment, which are listed in Supplementary Table S2; half of the side effects were classified as serious (Grades 3 and 4). The most frequent events were anemia (21.6%) and cutaneous rush and pruritus (17,6%), which were observed in participants who were administered ribavirin; reduction or withdrawal of ribavirin alleviated these complaints.

Posttherapy Follow-up Data

After completion of treatment, all participants, regardless of whether they had achieved SVR12, were regularly followed up for a mean of 14 ± 4 months (range 5–23 months). Comparing pre- and posttherapy parameters of liver function (Table 2), amelioration in serum albumin, creatinine, and platelet counts was seen. In addition, at the 3-month posttreatment evaluation, the number of individuals with cirrhosis in CPT Class A increased substantially, from 86% at baseline to 91%.

The time-course of adverse events during follow up is given in Figure 1; of the cohort of 253 individuals aged 80 and older, 27 (10.7%) manifested one or more events during the observation period, and the rest maintained compensated liver cirrhosis. Of 34 total events, 12 episodes were secondary to hepatic failure (9 ascites decompensation, 2 spontaneous bacterial peritonitis, 1 hepatic encephalopathy), 9 to extrahepatic disease (3 acute heart failure, 1 depression with an organic mental disorder, 1 hip fracture and immobilization syndrome, 1 cerebral hemorrhage, 1 breast cancer, 2 cases of severe anemia in participants with chronic kidney failure); in addition, there were 10 new cases of HCC and 3 deaths. The events occurred more frequently in individuals with D'Amico Stage 3 or 5 cirrhosis, with 17 events in 37 participants, versus 16 events in 176 participants in Stages 1 and 2; in those in CPT classes B and C, with 17 events in 36 participants, versus 16 events in 177 participants in Class A; in those with a MELD score of 16 or greater, with 8 events in 14 participants, versus 23 events in 239 participants with a score less than 16; in participants with baseline total bilirubin value of 2 mg/dL or greater, with 12 events in 17 participants, versus 22 events in 236 participants with baseline bilirubin of less than 2 mg/dL; in participants with serum albumin of 3.5 g/dL or less, with 23 events in 61 participants, versus 11 events in 192 participants with serum albumin greater than 3.5 g/dL. Only one participant with advanced fibrosis had an extrahepatic cardiopulmonary event associated with severe anemia; this participant had diabetes mellitus and hypertension and had a previous heart failure event (Supplementary Table S3). Supplementary Figure S1, Figure S2, Figure S3 and Figure S4 show the cumulative incidence of events according to liver impairment (D'Amico stage and CPT class), baseline albumin levels, and comorbidities. In the advanced stages of liver impairment, we observed events in 41% of participants with D'Amico Stages 4 and 5, in 42% of those with CPT Class C, in 27.8% of those with serum baseline albumin level of 3.5 g/dL and less, and in 37% of those with 3 of more comorbidities.

Figure 1.

Overall incidence of events in 253 individuals aged 80 and older with hepatitis C virus infection. H = hepatic events; NH = nonhepatic events; HCC = hepatocellular carcinoma; D = death.

Upon multivariate analysis, having 3 or more comorbidities (relative risk (RR) = 6.17, 95% CI = 2.51–14.52), a baseline albumin level of 3.5 g/dL or less (RR = 2.85, 95% CI = 1.12–7.04), and D'Amico Stage 4 or 5 liver impairment (RR = 3.77, 95% CI = 1.57–9.04) were independent risk factors for occurrence of events. We also considered the combination of baseline albumin level and number of comorbidities to provide clinicians with a simple, useful tool for antiviral treatment in individuals aged 80 and older. The combination of these two simple parameters allowed us to stratify the population into four subgroups of participants with different cumulative risks of incidence of events (6.2% 19.2%, 25.8%, 54.5%, respectively), so we can assume that the subgroup of participants with a lower cumulative incidence have a lower risk of experiencing an event, the subgroups with a risk of 19.2% and 25.8% have an intermediate risk, and the group with a risk of 54% have a higher risk of experiencing an event and concerns individuals aged 80 and older with cirrhosis and a baseline serum albumin level of 3.2 g/dL or less and 3 or more comorbidities (Figure 2, Supplementary Table S4).

Figure 2.

Overall incidence of events stratified according to baseline serum albumin level and number of comorbidities. (A) Low-risk group: baseline serum albumin level >3.5 g/dL and <3 comorbidities. Intermediate-risk group: (B) baseline serum albumin level >3.5 g/dL and ≥3 comorbidities and (C) baseline albumin serum level ≤3.5 g/dL and <3 comorbidities. (D) High-risk group: baseline serum albumin level ≤3.5 g/dL and ≥3 comorbidities.

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