Genetic test predicts cirrhosis outcomes

CHICAGO – Cirrhosis patients with the rs738409 CG/GG genotype experienced worse outcomes, including a slower recovery of encephalopathy, ascites, and bilirubin, compared with those without this CG/GG genotype, based on data from a prospective study. The findings were presented at the annual Digestive Disease Week.

Most patients with hepatitis C virus–associated cirrhosis do well after treatment with direct-acting antiviral agents to achieve a sustained virologic response, according to Winston Dunn, MD, of Kansas University Medical Center, Kansas City, and his colleagues.

However, patients with decompensated cirrhosis may have a range of outcomes, and, to help predict treatment success, Dr. Dunn and his colleagues examined the possible genetic role of the rs738409 Single Nucleotide Polymorphism of Patatin-like Phospholipase Domain Containing 3 gene.

The researchers assessed 30 adults with Child-Pugh (CPT) Class B or C cirrhosis caused by HCV infection who underwent interferon-free, direct-acting antiviral therapy and achieved sustained virologic response. They collected DNA from each patient using a cheek swab. The study population included 16 patients with a CC genotype, 11 with CG, and 3 with GG.

They measured changes in CPT scores and Model for End-Stage Liver Disease (MELD) scores from before DAA treatment to 12 weeks after treatment. Baseline scores were similar among all patients, as were demographic characteristics, although patients with the rs738409 CC genotype averaged a higher body-mass index 35 kg/m2, vs. 29 kg/m2 (P = 0.03).

After 12 weeks, 13 of 16 patients with the CC genotype (81 %) had improved CPT scores, and 8 patients (50%) had improved MELD scores by at least 1 point. None had worsened CPT or MELD scores. By contrast, 5 of 14 patients with CG/GG genotype (36%) had improved CPT scores, and 4 (29%) had improved MELD scores by at least 1 point; 3 patients (21%) had worsened CPT scores and 4 (29%) had worsened MELD scores by at least 1 point.

Overall, patients in the CG/GG groups showed a 1.7-point higher delta CPT score and a 2.3-point higher delta MELD score after adjusting for confounding variables, compared with patients with CC after adjusting for confounding variables.

The study findings were limited by small numbers and prospective design, and the genetic test is not yet widely available, Dr. Dunn said. However, “Our results will help target patients for liver transplant evaluation based on individual genetic risk factors,” the researchers said.

The study was funded by the Frontiers Pilot and Collaborative Studies Funding Program. Dr. Dunn had no relevant financial conflicts to disclose.

Digestive Disease Week^® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).

CHICAGO – Cirrhosis patients with the rs738409 CG/GG genotype experienced worse outcomes, including a slower recovery of encephalopathy, ascites, and bilirubin, compared with those without this CG/GG genotype, based on data from a prospective study. The findings were presented at the annual Digestive Disease Week.

Most patients with hepatitis C virus–associated cirrhosis do well after treatment with direct-acting antiviral agents to achieve a sustained virologic response, according to Winston Dunn, MD, of Kansas University Medical Center, Kansas City, and his colleagues.

However, patients with decompensated cirrhosis may have a range of outcomes, and, to help predict treatment success, Dr. Dunn and his colleagues examined the possible genetic role of the rs738409 Single Nucleotide Polymorphism of Patatin-like Phospholipase Domain Containing 3 gene.

The researchers assessed 30 adults with Child-Pugh (CPT) Class B or C cirrhosis caused by HCV infection who underwent interferon-free, direct-acting antiviral therapy and achieved sustained virologic response. They collected DNA from each patient using a cheek swab. The study population included 16 patients with a CC genotype, 11 with CG, and 3 with GG.

They measured changes in CPT scores and Model for End-Stage Liver Disease (MELD) scores from before DAA treatment to 12 weeks after treatment. Baseline scores were similar among all patients, as were demographic characteristics, although patients with the rs738409 CC genotype averaged a higher body-mass index 35 kg/m2, vs. 29 kg/m2 (P = 0.03).

After 12 weeks, 13 of 16 patients with the CC genotype (81 %) had improved CPT scores, and 8 patients (50%) had improved MELD scores by at least 1 point. None had worsened CPT or MELD scores. By contrast, 5 of 14 patients with CG/GG genotype (36%) had improved CPT scores, and 4 (29%) had improved MELD scores by at least 1 point; 3 patients (21%) had worsened CPT scores and 4 (29%) had worsened MELD scores by at least 1 point.

Overall, patients in the CG/GG groups showed a 1.7-point higher delta CPT score and a 2.3-point higher delta MELD score after adjusting for confounding variables, compared with patients with CC after adjusting for confounding variables.

The study findings were limited by small numbers and prospective design, and the genetic test is not yet widely available, Dr. Dunn said. However, “Our results will help target patients for liver transplant evaluation based on individual genetic risk factors,” the researchers said.

The study was funded by the Frontiers Pilot and Collaborative Studies Funding Program. Dr. Dunn had no relevant financial conflicts to disclose.

Digestive Disease Week^® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).

CHICAGO – Cirrhosis patients with the rs738409 CG/GG genotype experienced worse outcomes, including a slower recovery of encephalopathy, ascites, and bilirubin, compared with those without this CG/GG genotype, based on data from a prospective study. The findings were presented at the annual Digestive Disease Week.

Most patients with hepatitis C virus–associated cirrhosis do well after treatment with direct-acting antiviral agents to achieve a sustained virologic response, according to Winston Dunn, MD, of Kansas University Medical Center, Kansas City, and his colleagues.

However, patients with decompensated cirrhosis may have a range of outcomes, and, to help predict treatment success, Dr. Dunn and his colleagues examined the possible genetic role of the rs738409 Single Nucleotide Polymorphism of Patatin-like Phospholipase Domain Containing 3 gene.

The researchers assessed 30 adults with Child-Pugh (CPT) Class B or C cirrhosis caused by HCV infection who underwent interferon-free, direct-acting antiviral therapy and achieved sustained virologic response. They collected DNA from each patient using a cheek swab. The study population included 16 patients with a CC genotype, 11 with CG, and 3 with GG.

They measured changes in CPT scores and Model for End-Stage Liver Disease (MELD) scores from before DAA treatment to 12 weeks after treatment. Baseline scores were similar among all patients, as were demographic characteristics, although patients with the rs738409 CC genotype averaged a higher body-mass index 35 kg/m2, vs. 29 kg/m2 (P = 0.03).

After 12 weeks, 13 of 16 patients with the CC genotype (81 %) had improved CPT scores, and 8 patients (50%) had improved MELD scores by at least 1 point. None had worsened CPT or MELD scores. By contrast, 5 of 14 patients with CG/GG genotype (36%) had improved CPT scores, and 4 (29%) had improved MELD scores by at least 1 point; 3 patients (21%) had worsened CPT scores and 4 (29%) had worsened MELD scores by at least 1 point.

Overall, patients in the CG/GG groups showed a 1.7-point higher delta CPT score and a 2.3-point higher delta MELD score after adjusting for confounding variables, compared with patients with CC after adjusting for confounding variables.

The study findings were limited by small numbers and prospective design, and the genetic test is not yet widely available, Dr. Dunn said. However, “Our results will help target patients for liver transplant evaluation based on individual genetic risk factors,” the researchers said.

The study was funded by the Frontiers Pilot and Collaborative Studies Funding Program. Dr. Dunn had no relevant financial conflicts to disclose.

Digestive Disease Week^® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).