- Category: Approved HBV Drugs
- Published on Thursday, 09 July 2015 00:00
- Written by Liz Highleyman
Early treatment with antiviral therapy can restore liver function and increase survival in chronic hepatitis B patients with decompensated cirrhosis who might otherwise need a liver transplant, according to a Korean study published in the June 2015 issue of Hepatology.
Over years or decades chronic hepatitis B virus (HBV) infection can lead to advanced liver disease including cirrhosis, liver cancer, and end-stage liver failure that may require liver transplantation.
Antiviral therapy using nucleoside/nucleotide analogs such as lamivudine (Epivir), entecavir (Baraclude), adefovir (Hepsera), telbivudine (Tyzeka), tenofovir (Viread), or clevudine (not yet approved in the U.S.) is the mainstay of chronic hepatitis B treatment. But while antiviral drugs can effectively suppress HBV replication long-term during treatment, they usually do not lead to a cure.
Prior research has shown that antiviral therapy can slow liver disease progression, but outcomes among people who have already developed decompensated liver disease -- characterized by symptoms such as ascites (abdominal fluid accumulation), bleeding varices (enlarged veins in the esophagus or stomach), hepatic encephalopathy (brain impairment), or spontaneous bacterial peritonitis (abdominal infection) -- are not well understood
Jeong Won Jang from the Catholic University of Korea and colleagues evaluated the long-term effects of antiviral therapy for people with HBV-related decompensated cirrhosis.
This prospective cohort study included 707 adult hepatitis B patients with first-time complications of decompensation seen at 7 medical centers in Korea between 2005 and 2012. A majority were men and the mean age was 54 years. Everyone tested had HBV genotype C, the predominant type in Korea. People with liver cancer, hepatitis C, heavy alcohol use, or autoimmune liver disease were excluded.
The analysis included 284 untreated patients (40%) and 423 who received antiviral therapy (60%); in the latter group, 58 had been previously treated before study entry, 253 received early treatment (within 3 months of decompensation), and 112 had received delayed treatment (more than 3 months after decompensation). Most were treated with lamivudine or entecavir, with a small number receiving adefovir, clevudine, or telbivudine. At baseline the treated group had higher HBV activity levels and worse liver function than the untreated group.
Follow-up continued for 7 years after the onset of decompensation. The primary endpoint was 5-year transplant-free survival. Secondary endpoints included virological response (sustained undetectable HBV DNA during therapy), hepatitis B "e" antigen (HBeAg) seroconversion, and improvement in Child-Turcotte-Pugh (CPT) and MELD scores, 2 measures of liver disease severity.
- 320 patients were still alive at the end of the observation period, 260 had died, 64 had undergone liver transplantation, and 63 were lost to follow-up.
- Patients treated with antiviral therapy had significantly better transplant-free survival than untreated patients, despite having greater HBV activity and worse liver function.
- 5-year transplant-free survival rates were 60% for the early treated patients vs 46% for the untreated group.
- People with more severe liver impairment (CPT class B/C) and high HBV viral load appeared to benefit most from antiviral treatment.
- 245 patients (58%) were virological responders who maintained undetectable viral load, while 178 were classified as non-responders or not assessed due to early death, transplantation, or loss to follow-up.
- Virological responders had a higher 5-year transplant-free survival rate (73%) than either non-responders (43%) or untreated patients (46%).
- 13% and 49% of treated HBeAg-positive patients experienced HBeAg seroconversion at 12 and 60 months, respectively, compared with 11% and 35% in the untreated group.
- 64% of treated patients with elevated ALT liver enzymes at baseline experienced ALT normalization at 12 months.
- CTP and MELD scores decreased among all treated patients at 6 and 12 months, with the largest declines seen in those who received early treatment.
- One-third of treated patients improved enough to be removed from the liver transplant waiting list.
- 35% of treated patients and 29% in the untreated group developed hepatocellular carcinoma between 1 and 5 years -- not a significant difference.
"Patients with early treatment had better clinical outcomes than those with delayed treatment," the study authors wrote. "Survival was dependent on antiviral response, being significantly better in responders than in non-responders or untreated cases. The initial benefit of antiviral therapy was negated over time in non-responders." Furthermore, they continued, "Efficacy measures were significantly better in patients with early initiation of antivirals upon presentation of decompensation than in those with delayed therapy."
"Antiviral therapy significantly modifies the natural history of decompensated cirrhosis, improving liver function and increasing survival," the researchers concluded. "Liver function continued to improve and is maintained up to 5 years, delaying the need for liver transplantation, especially in responders."
They added that these results "underscore the importance of promptly administering potent antiviral drugs to patients under consideration for liver transplantation."
JW Jang, JY Choi, YS Kim, et al. Long-term effect of antiviral therapy on disease course after decompensation in patients with hepatitis B virus–related cirrhosis. Hepatology 61(6):1809-1820. June 2015.