EACS: Studies underline the need for better hepatitis C treatment

Gus Cairns
Published: 02 November 2007

A French study presented at the Eleventh European AIDS Conference drew a stark contrast between HIV/hepatitis C (HCV)-coinfected patients for whom hepatitis treatment works and those it doesn’t, and indicates that we should be offering treatment before significant liver damage has occurred – not because of it. And a Spanish study, which found a dismal prognosis for the HIV/HCV-coinfected with decompensated (end-stage) liver disease, reminds us why treatment (and better treatment) is needed.

Stéphanie Dominguez of Pitié Salpetrière Hospital in Paris presented a retrospective review of all patients with documented HIV/HCV coinfection and compared those who received interferon-based therapy with those who never received it.

The group comprised 437 patients, 75% of them men, who first presented to the hospital any time between 1980 and June 2006. The average length of follow-up was nearly ten years.

A reasonable proportion – 230 patients or 52.6% of the total – had received one or more courses of HCV treatment, most of it in recent years and most of it consisting of pegylated interferon plus ribavirin (peg-IFN/RBV).

Thirty-eight per cent of patients achieved the sustained viral response (SVR) which is tantamount to a cure, meaning that they had no detectable HCV in their blood 24 weeks after the end of therapy.

Liver decompensation (see more below) is what happens when the body gives up the struggle to force blood through a damaged liver and true liver failure begins; it is characterised by symptoms such as jaundice, ascites (fluid in the abdomen), varices (enlarged veins in the oesophagus, which can often cause life-threatening bleeds) and sometime encephalopathy caused by liver waste products.

There was a considerably higher risk of decompensation in patients who received HCV treatment than ones who didn’t – but this was because, as is common clinical practice, treatment was mainly offered to more advanced fibrosis, that is in whom significant liver damage had already occurred.

Liver decompensation occurred in 7.2% of the patient group overall, but in 14.3% of those who received treatment compared with 4.4% of those who didn’t.

When treatment worked, however, and an SVR was achieved, the risk of liver disease fell considerably: only 2.3% of patients who achieved an SVR got liver decompensation. The reason the figure wasn’t zero, Dominguez explained, was because in some patients treatment may have worked but the liver damage was already considerable.

The pattern in deaths was the same; 4.6% of the patient group overall died, 8.6% of those who received HCV treatment, but only 1.2% of those who achieved an SVR.

A Spanish study underlined the cost of liver decompensation. Maria López-Diéguez of La Paz University Hospital in Madrid presented findings from a national prospective cohort of 373 HIV/HCV coinfected patients who were already diagnosed with liver cirrhosis and compared those with and without decompensation for mortality and risk factors.

Patients with and without decompensation were similar in terms of age (44 years), gender (20% female), length of HCV infection (23 years) and HIV treatment status (82% on anti-HIV treatment). People with decompensation were much less likely to have received HCV treatment (28% versus 65%) and more likely to have had an AIDS-defining illness (54% versus 33%).

Their mortality was far worse. Nearly half (48.1%) of those with decompensation died during the follow-up period, compared with 6.7% of those without it. Their prognosis was very poor. The percentage either dying, developing liver cancer or having a liver transplant in patients with and without decompensation was 34% versus 5% after a year, 68% versus 8% after two years, and 100% versus 8% after three years. Median time to one of these events was 19 months in people with decompensation and 5.5 years in patients without. Eighteen per cent of patients with decompensation were dead within 18 months of being diagnosed with it.

The one piece of good news was that the incidence of new cases of decompensation was quite low. Four per cent developed it anew within a year, 6% by two years and 7% after three years.

“These results emphasise the critical importance of avoiding the development of end-stage liver disease in HIV/HCV-coinfected patients,” commented López-Diéguez.

Finally, a study of newly-acquired, acute HCV in patients already coinfected with HIV provided more evidence that there is an increasingly epidemic of sexually-transmitted HCV in gay men. Dr Alex Azwa presented data on cases of acute HCV from four European hospitals: the Chelsea and Westminster and Royal Free Hospitals in London, the Pitié-Salpetrière in Paris and the University of Bonn Hospital in Germany.

This was a retrospective analysis of HIV-positive patients presenting with acute hepatitis C between 1999 and 2006. One hundred and fifty patients were diagnosed with acute HCV during this period, two-thirds on the basis of abnormal liver function tests, 11% because they had hepatitis symptoms, and 15% because they’d been in contact with someone else with HCV.

Of these, 131 were gay men, five were injecting drug users and two had both risk factors. Twenty-one per cent showed any sign of hepatitis symptoms.Two-thirds of patients in Germany and the UK had HCV genotype 1 (HCV-1), but only 20% in France, where most cases were of HCV-4, which seems to have spread from Africa, where it is common.

One unexpected finding was that a much lower percentage of patients cleared HCV spontaneously from their systems than has previously been reported. By the end of 48 weeks only eleven patients (7%) had done so without the aid of treatment. However a number of patients who did receive treatment might have spontaneously cleared their HCV anyway. So the proportion who would have actually done so if peg-IFN/RBV was not available did so lay somewhere between 7% and 28% (eleven spontaneously cleared out of 39 who had not started treatment by 48 weeks).

What was striking was that only 26% of patients who had an undetectable HCV viral load twelve weeks after diagnosis were still undetectable at week 48; it may therefore take as long as a year to find out if someone genuinely has rid their body of HCV. Spontaneous clearance was linked to HCV baseline viral load and CD4 count; the average HCV viral load in those who cleared was 200,000 and in those who did not it was 1.1 million, and the average CD4 count in those who cleared was 623 compared with 426 in those who did not.

The low figures for spontaneous vial clearance, Azwa commented, may be due to re-infections as well as reactivations of HCV.

Finally, Dr Vincent Soriano of Hospital Carlos III in Madrid, giving a general introduction to HCV in Europe, said that there were 15 investigatory antiviral drugs in various stages of development for HCV as well as improved formulations of interferon. Although interferon will probably always be necessary for a complete cure, the treatment picture for HCV should be considerably better in three to four years’ time.

Reference

Dominguez S et al. Long-term impact of interferon (IFN)-based therapy on lever-related decompensation, hepato-cellular carcinoma (HCC) and liver death in HIV/HCV co-infected patients: a retrospective cohort study. Eleventh European AIDS Conference, Madrid, abstract PS8/3, 2007.

López-Diéguez M et al. Morbidity and mortality in HIV infected patients with compensated and decompensated cirrhosis: prospective cohort of 373 patients. Eleventh European AIDS Conference, Madrid, abstract PS8/4, 2007.

Azwa A et al. The Natural history of acute hepatitis C (AHC) in HIV co-infected individuals – a European collaborative study. Eleventh European AIDS Conference, Madrid, abstract PS8/5, 2007.

Soriano V. New drugs on the horizon for treatment of viral hepatitis. Eleventh European AIDS Conference, Madrid, opening presentation, session PS8, 2007.

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