Among patients with chronic hepatitis B (CHB)-related decompensated cirrhosis receiving treatment with nucleos(t)ide analogues, baseline hepatitis flares were independently associated with improved long-term (≥3 months) outcomes compared with patients without baseline flares, according to a study published in Clinical Gastroenterology and Hepatology.

Hepatitis B flares in patients with CHB-related cirrhosis are common. Among patients with cirrhosis who developed hepatitis flares, 9% developed Treatment Response and Long-Term Prognosis Predicted by HBV pgRNA Status, and 32% of these patients died. Before the advent of nucleos(t)ide analogues, the lowest reported 5-year survival rate after development of hepatic decompensation was 35%. However, whether the outcomes of nucleos(t)ide analogues therapy differ between decompensated CHB-related cirrhosis patients with and without baseline hepatitis flares remains unknown.

This 16-year retrospective cohort study (January 2002 to March 2018) was designed to investigate the association of baseline hepatitis flares (defined as an abrupt increase in serum alanine transaminase [ALT] levels >5 times the upper limit of normal and associated hepatic decompensation) with CHB-related cirrhosis among adults treated with nucleos(t)ide analogues at a tertiary care center.

Nucleos(t)ide analogues investigated included adefovir, entecavir, lamivudine, and tenofovir. Decompensation was defined as a clinical presentation of jaundice with total serum bilirubin ≥2 mg/dL; an international normalized ratio >1.5 or a prolonged prothrombin time (PT) ≥3 seconds; and/or development of ascites/encephalopathy. Participants with other causes of liver disease were excluded.

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Of the 511 participants included, 300 (58.7%) had baseline flares. Of these, 287 (56.2%) were prescribed lamivudine, 200 (39.1%) were prescribed entecavir, and 24 (4.7%) were prescribed tenofovir.

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Compared with participants without baseline flares, participants with flares had higher baseline values of ALT, total serum bilirubin, platelet counts, PT, model for end-stage liver disease (MELD) and Child-Pugh scores, quantitative hepatitis B surface antigen, HBV DNA, and a higher genotype B HBV infection rate. In addition, patients with flares had lower rates of ascites, esophageal varice, hepatitis B e antigen positivity, and splenomegaly, as well as a lower neutrophil-to-lymphocyte ratio. Results found no statically significant difference between the specific nucleos(t)ide analogue used and a hepatic flare.

In total, 282 participants died or underwent liver transplants, 52.8% were treated with lamivudine, 42.9% with entecavir, and 4.2% with tenofovir. All deaths were due to decompensation-related complications (with 2 exceptions due to unrelated medical causes). At 1 year, all participants had significantly improved liver functioning compared with baseline (patients with baseline flares: MELD score [P <.001], Child-Pugh score [P =.01]; patients without baseline flares: MELD score [P <.001], Child-Pugh score [P =.02]), while participants with baseline flares had lower 1-year Child-Pugh scores and HBV DNA levels than those without.

The 16-year incidence of liver transplantation or cumulative mortality was lower in participants with baseline flares compared with those without (46.5% vs 73.2%; P <.001), but this difference was not significant until 3 months after antiviral therapy initiation. No between-group differences were seen in ALT normalization (48.5% vs 43.3%; P =.174), overall complete viral suppression (94.2% vs 91.4%; P =.463), and MELD improvement rates (90% vs 85.8%; P =.326), and the cumulative hepatocellular carcinoma incidences between the 2 groups were comparable.

Propensity score matching was used to match participants with and without baseline flares (n=182 for each) to find factors independently associated with cumulative incidence of liver transplantation or mortality. Baseline hepatitis flares were found to be negatively associated with the cumulative incidence of liver transplantation or mortality (hazard ratio [HR], 0.491; 95% CI, 0.317-0.76; P =.0014), while baseline levels of prolonged PT (HR, 1.223; 95% CI, 1.052-1.423; P =.009) and neutrophil-to-lymphocyte ratio (HR, 1.278; 95% CI, 1.027-1.591; P =.0279) were positively associated.

Study investigators conclude, “Altogether, in CHB-[related cirrhosis] patients treated with [nucleos(t)ide analogues] for decompensation, baseline hepatitis flares were associated with deteriorated baseline liver function but less severe portal hypertension, and these flares have a negligible impact on the outcomes within the first 3 months after the initiation of [nucleos(t)ide analogues] therapy. However, baseline hepatitis flares represent a favorable predictor of long-term outcomes in terms of mortality or transplantation after adjusting for the severity of hepatic decompensation and systemic inflammation.”


Chang ML, Cheng JS, Chien RN, Liaw YF. Hepatitis flare-related decompensation is associated with better outcomes in patients with chronic hepatitis B [published online January 23, 2020]. Clin Gastroenterol Hepatol. doi:10.1016/j.cgh.2020.01.018