Excess liver-related morbidity of chronic hepatitis C patients, who achieve a sustained viral response, and are discharged from care.

The slides from the below ePOSTER along with other abstracts, webcasts, and video podcasts from the AASLD November meeting are available online@ the "LiverLearning" portal. Free registration is required, it's quick and painless folks, start the process by clicking here.Once that is accomplished, sign in and come back to this post and click this link, after landing on the page click on "VIEW ePOSTER" to view the 8 slides .

Topic: HCV: Treatment

The Liver Meeting® 2011 Selected Sessions

Excess liver-related morbidity of chronic hepatitis C patients, who achieve a sustained viral response, and are discharged from care.


Hamish A Innes1,2, Sharon J Hutchinson1,2, Samuel Allen3, Diptendu Bhattacharyya4, Peter Bramley5, Toby E S Delahooke6,7, John F Dillon8, Ewan Forrest9, Andrew Fraser10, Ruth Gillespie9, David J Goldberg2, Nicholas Kennedy11, Scott McDonald1,2, Allan McLeod2, Peter R Mills12, Judith Morris13 and Peter Hayes7, on behalf of the Hepatitis C Clinical Database Monitoring Committee.
1 Department of Mathematics and Statistics, University of Strathclyde, Glasgow G1 1XH, Scotland, UK; 2 Health Protection Scotland, Glasgow G2 6QE, Scotland, UK; 3 Crosshouse Hospital, Kilmarnock KA2 OBE, Scotland, UK; 4 Victoria Hospital, Kirkcaldy KY2 5AH, Scotland, UK; 5 Stirling Royal Infirmary, Stirling FK8 2AU, Scotland, UK; 6 Leicester Royal Infirmary, Leicester LE1 5EW,England, UK; 7 Royal Infirmary Edinburgh, Edinburgh, EH16 4SA, Scotland, UK ; 8 Ninewells Hospital & Medical School, Dundee DD 9SY, Scotland, UK; 9 Glasgow Royal Infirmary, Glasgow G4 0SF, Scotland, UK; 10 Aberdeen Royal Infirmary, Aberdeen AB25 2ZN, Scotland, UK; 11 Monklands Hospital, Airdrie ML6 0JS, Scotland, UK;
12 Gartnavel General Hospital, Glasgow G12 0YN, Scotland, UK; 13 Southern General Hospital, Glasgow G51 4TF, Scotland, UK

Premise

With an estimated worldwide prevalence of 2.35%1 the hepatitis C virus (HCV) presents a global public health challenge. In cohorts of HCV patients, up to 24% develop liver cirrhosis within 20 years of infection.2 Chronic HCV infection can however be treated (and the virus eradicated),through interferon based therapy. However, current treatment options are far from ideal,particularly with respect to frequent adverse effects,3 and substantial cost.4 Thus, when justifying the resourcing and widespread use of treatment, these drawbacks must be considered in the context of the improvement in prognosis that treatment induced viral eradication can confer.

Despite this, there is a lack of robust data in the literature quantifying the benefit of this improvement in prognosis, particularly in terms of all-cause, and non liver-related outcomes.

Further, although SVR patients without cirrhosis tend to be discharged from care without further follow-up (FU), liver-related morbidity in this population, relative to the general population, until now, remains entirely unexplored. In this study, we thus attempted to address these shortfalls in the HCV knowledge base.

Methods
A retrospective cohort of treatment naïve HCV patients commencing antiviral therapy (initiated 1996-2007, N=1215) was derived from clinical data bases installed in Scottish HCV treatment clinics. The records of these treatment patients were then linked to national hospital admission and mortality data(both current to December 2009).

The two outcomes of primary interest were liver-related mortality, and liver-related hospital episodes (outcomes determined on the basis of ICD 9/10 codes5, 6). The primary exposure variable of interest for treatment patients was a SVR (SVR is the optimum virological outcome of treatment).

Other exposure variables considered in these analyses were: gender, age at study entry, ethnicity, ever injected drugs, genotype, diagnosed cirrhotic at study entry, alcohol-related hospitalisation (alcohol-related hospitalisation determined on the basis of ICD 9/10 codes; according to previously documented methods6), and mean post-treatment alanine aminotransferase (ALT).Each treatment patients’ FU time began six months from being administered their final treatment dose(ensuring consistent comparability between SVR and non-SVR treatment groups) and ended at the dateof outcome, or censoring date.

FU time was censored for: (i) reaching the right censor date (December2009), or (ii) mortality (i.e. all-cause mortality for models with liver-related hospitalisation outcomes,and non liver-related mortality for models with liver-related mortality outcomes).

Cox regression was used to determine the association between a SVR and the risk of liver-related mortality and hospitalisation, after adjustment for confounders. Hospital episodes (unlike mortality data) can occur recurrently (i.e. can be experienced multiple times during FU). Thus, to account for within patient clustering in the likelihood of a hospital episode, an Andersen-Gill model for recurrent events, with robust variance estimation was used.

Further, we compared rates of: (a) liver-related hospital episodes, (b) non liver-related hospital episodes, (c) alcohol-related hospital episodes, and (d) all-cause hospital episodes, in subgroups of our treatment cohort (subgroups were: (i) non-cirrhotic SVR patients, (ii) all SVR patients, and (iii) all non-SVR patients), to that of the general population after adjustment for age, sex and calendar year, via the calculation of standardised morbidity ratios (N.B. only results relating to liver-related, and alcohol-related hospital episodes are presented in this poster).

In order to roughly gauge the contribution of chronic HCV per se (i.e. independent of lifestyle factors) on excess liver-related morbidity in our treatment subgroups, we chose a priori to similarly calculate SMRs for spontaneous resolvers of HCV; i.e. persons diagnosed with HCV antibodies in Scotland between 1 January 1996 and 31 December 2008, who were subsequently tested at least once for viral RNA (but never tested positive) and were never interferon treated. (N=3690).


Results
SVR was attained in 46% (650/1215) of persons in our cohort. Patients were followed-up for a total of 6,462 person years (mean duration of 5.3 years). During follow-up, 2,962 hospital episodes were observed. (Of these 1005 (34%) were liver-related), and 88 patients died (of which 55 deaths(63%) were liver-related). Fig 1-2 illustrates the results of Cox regression analyses, whilst Fig 3 presents standardised morbidity ratios for treatment subgroups (and spontaneous resolvers of HCV).


Conclusions

(1) Treatment naïve patients who attain a SVR, have a better prognosis than those who do not (i.e. SVR patients are more than four times less likely to die a liver related death, or be hospitalised for a liver-related cause).

(2) Despite this improved prognosis, SVR patients without cirrhosis (a group, who in the main tend to be discharged without further follow-up) still harbour an increased risk of liver-related morbidity (liver related hospitalisations are six times that of the general population).

(3) Further, liver-related morbidity in spontaneous resolvers of HCV is considerably higher (27 times) that of the general population. Because (i) spontaneous resolvers of HCV typically harbour viral RNA for less than 1 year,7 and (ii) the median duration of HCV infection for progression to cirrhosis is 30 years8, HCV induced liver damage in this population should be negligible, thus any liver damage that is apparent, should be largely attributable to lifestyle factors (and not past HCV infection).

Therefore our data suggests that lifestyle factors contribute substantially to liver disease in HCV infected patients, and could thus account for the excess liver-related morbidity observed in non-cirrhotic SVR patients.


References

1. Lavanchy D. Evolving epidemiology of hepatitis C virus. Clin Microbiol Infect 2011;17:107-115.
2. Freeman AJ, Dore GJ, Law MG, Thorpe M, Von Overbeck J, Lloyd AR, Marinos G, et al. Estimating progression to
cirrhosis in chronic hepatitis C virus infection. Hepatology 2001;34:809-816.
3. Tine F, Graviano D, Giannuoli G, Madonia S, Malizia G, Patti S, et al. An open-safety study of dual antiviral therapy
in real-world patients with chronic hepatitis C. Pharmacoepidemiol Drug Saf. 2010;19:1113-23.
4. Joint Formulary Committee; London: British Medical Association and Royal Pharamceutical Society of Great
Britain. British National Formulary;9AD. No.58.
5. McDonald SA, Hutchinson SJ, Bird SM, Mills PR, Hayes P, Dillon JF, Goldberg DJ. Excess morbidity in the hepatitis
C-diagnosed population in Scotland, 1991-2006. Epidemiol Infect;139:344-353.
6. McDonald SA, Hutchinson SJ, Bird SM, Graham L, Robertson C, Mills PR, Hayes P, et al. Association of selfreported
alcohol use and hospitalization for an alcohol-related cause in Scotland: a record-linkage study of
23,183 individuals. Addiction 2009;104:593-602.
Acknowledgements
We are grateful to the Scottish Government for funding the Scottish Hepatitis C Clinical Database.
7. Amin J, Law MG, Micallef J, Jauncey M, Van Beek I, Kaldor JM, et al. Potential biases in estimates of hepatitis C
RNA clearance in newly acquired hepatitis C infection among a cohort of injecting drug users. Epidemiol Infect
2007;135:144-150.
8. Poynard T, Bedossa P, Opolon P. Natural history of liver fibrosis progression in patients with chronic hepatitis C.
The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Lancet 1997;349:825-832.