Protease Inhibitor–Based DAAs Appear Safe in Decompensated Patients

Jim Kling

May 24, 2022

SAN DIEGO – An analysis of a large, international cohort suggests that treatment with protease-inhibitor (PI)–based direct-acting antivirals (DAAs) may be safe for patients with hepatitis C virus (HCV) with cirrhosis and early-stage liver decompensation.

The study relied on data from the REAL-C registry, including 935 patients treated with oral DAAs at 27 centers in the U.S., Europe, and Asia Pacific countries. The researchers compared efficacy and tolerability outcomes from PI-based and non PI-based DAA regimens in patients deemed to have decompensated HCV cirrhosis.

The findings were encouraging. "It is something important because currently we are short of treatments for decompensated HCV patients. If the tolerability is similar, we perhaps should not withhold [PI] treatment for these patients that sometimes need them the most," said Yu Jun Wong, MD, who presented the study at the annual Digestive Disease Week® (DDW). Wong is a second-year consultant at Changchi General Hospital in Singapore.

"I think it was a very interesting study and something that needed to be done. It was encouraging that patients who did have some level of decompensated cirrhosis did not worsen compared to those who were on a non PI-based therapy," said Meena Bansal, MD, who comoderated the session where the research was presented.

However, the study was limited by some uncertainty around the definition of decompensation among the study participants. During the Q&A session, audience members questioned whether patients categorized as decompensated were truly decompensated at the time of treatment initiation. Bansal noted, for example, that a patient might experience a variceal bleed in the context of heavy alcohol consumption, and therefore be considered decompensated, but might stop drinking afterward with a reduction in portal hypertension and recovery of liver function. "So it would be important to know if they were still decompensated at the time they initiated therapy. If that was the case, then these results are more promising," said Bansal.

Despite these limitations, the study is good news. "If you do not have access to non-PI based therapy, you might feel a little bit more secure starting a PI-based therapy, particularly the second generation PI-based therapies, if they're at least on the earlier side of that decompensation scale. But it's still unclear in true decompensated Child's B or C whether or not PI-based therapy would have the same results," said Bansal.

Wong acknowledged the limitation that the study doesn't apply to more severely decompensated patients. "Whether it remains safe in patients with higher Child-Pugh scores is hard to extrapolate at this point of time. We still need to look further into the data," said Wong.

Still, the results offer hope to physicians and patients who might find themselves in difficult circumstances. "If you're resource limited, and you don't even have access to transplant, these findings suggest that early decompensated patients may benefit from PI-based therapy. If I say to the patient, there's a chance this could make you worse, but there's a chance this could make you better, [this is an option] as long as the patient is aware of the possible outcomes," said Bansal.

The study included patients with a history of ascites, variceal bleeding, jaundice, or hepatic encephalopathy 6 months before treatment with DAA, or baseline measures of Child-Turcotte-Pugh (CTP) score ≥7 or Model of End-Stage Liver Disease (MELD) score >10. The analysis included data between 2014 and 2021.

The mean age was 64, and 59.6% of participants were male. Overall, 70.8% had genotype 1, and 32% were treatment experienced. In total, 45.2% were treated with PI-based DAAs.

The PI cohort was older (64.6 versus 62.7; P = .01), and more likely to have genotype 1 (87.2% versus 56.3%; P < .001) and chronic renal disease (64.0% vs. 53.9%; P = .001).

The two groups had similar rates of sustained virologic response at 12 and 24 weeks, as well as similar rates of significant improvement or significant worsening, suggesting similar tolerability. There was a lower frequency of liver decompensation in the PI group at 12 weeks (4.4% vs. 7.9%; P = .04) and a trend at 24 weeks (8.8% versus 12.6%; P = .08).

Another limitation of the study is the potential for bias due to its retrospective nature.

Wong has been an invited speaker for AbbVie and Gilead. Bansal has no relevant financial disclosures.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.

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