Karin L. Andersson

Cost Effectiveness of Alternative Surveillance Strategies for Hepatocellular Carcinoma in Patients With Cirrhosis

BACKGROUND & AIMS The increasing incidence of hepatocellular carcinoma (HCC) in the United States has significant health and economic consequences. Ultrasound (US) surveillance is recommended for patients with cirrhosis because of their high risk of HCC and improving treatment outcomes for small tumors. We assessed the costs, clinical benefits, and cost effectiveness of US surveillance and alternative strategies for HCC in cirrhosis using a computer-based state transition model with parameters derived from available literature. METHODS Our model compared a policy of no surveillance with 6 surveillance strategies in cirrhotic patients ages 50 years and older in the United States: (1) annual US, (2) semiannual US, (3) semiannual US with alpha-fetoprotein, (4) annual computed tomography (CT), (5) semiannual CT, and (6) annual magnetic resonance imaging. The number of screening tests needed to detect one small HCC, cost per treated HCC, lifetime costs, quality-adjusted life expectancy, and incremental cost-effectiveness ratios were calculated. RESULTS Semiannual US surveillance for HCC in cirrhosis increased quality-adjusted life expectancy by 8.6 months on average, but extended it nearly 3.5 years in patients with small treated tumors. Semiannual US surveillance had an incremental cost-effectiveness ratio of

Prognostic Gene Expression Signature for Patients With Hepatitis C–Related Early-Stage Cirrhosis

30,700 per quality-adjusted life year (QALY) gained, and was more cost effective than the alternative surveillance strategies using a threshold of

Monitoring During and After Antiviral Therapy for Hepatitis B

50,000 per QALY gained. The incremental cost-effectiveness ratios for the combined alpha-fetoprotein/US and annual CT strategies exceeded

Non-high-density lipoprotein cholesterol as a biomarker for nonalcoholic steatohepatitis.

50,000/QALY unless the sensitivity and specificity of US decreased to less than 65% and 60%, respectively. CONCLUSIONS Semiannual US surveillance for HCC in cirrhotic patients improves clinical outcomes at a reasonable cost.

Prophylaxis of hepatitis B infection in solid organ transplant recipients

BACKGROUND & AIMS Cirrhosis affects 1% to 2% of the world population and is the major risk factor for hepatocellular carcinoma (HCC). Hepatitis C cirrhosis-related HCC is the most rapidly increasing cause of cancer death in the United States. Noninvasive methods have been developed to identify patients with asymptomatic early-stage cirrhosis, increasing the burden of HCC surveillance, but biomarkers are needed to identify patients with cirrhosis who are most in need of surveillance. We investigated whether a liver-derived 186-gene signature previously associated with outcomes of patients with HCC is prognostic for patients with newly diagnosed cirrhosis but without HCC. METHODS We performed gene expression profile analysis of formalin-fixed needle biopsy specimens from the livers of 216 patients with hepatitis C-related early-stage (Child-Pugh class A) cirrhosis who were prospectively followed up for a median of 10 years at an Italian center. We evaluated whether the 186-gene signature was associated with death, progression of cirrhosis, and development of HCC. RESULTS Fifty-five (25%), 101 (47%), and 60 (28%) patients were classified as having poor-, intermediate-, and good-prognosis signatures, respectively. In multivariable Cox regression modeling, the poor-prognosis signature was significantly associated with death (P = .004), progression to advanced cirrhosis (P < .001), and development of HCC (P = .009). The 10-year rates of survival were 63%, 74%, and 85% and the annual incidence of HCC was 5.8%, 2.2%, and 1.5% for patients with poor-, intermediate-, and good-prognosis signatures, respectively. CONCLUSIONS A 186-gene signature used to predict outcomes of patients with HCC is also associated with outcomes of patients with hepatitis C-related early-stage cirrhosis. This signature might be used to identify patients with cirrhosis in most need of surveillance and strategies to prevent the development of HCC.

Cost-Effectiveness of Risk Score–Stratified Hepatocellular Carcinoma Screening in Patients with Cirrhosis

Recent studies suggest that long‐term suppression of viral replication is critical to reducing the complications of chronic hepatitis B virus (HBV) infection. Monitoring for continued virological response during and after treatment is essential because current treatment options have limited success in achieving durable endpoints, and antiviral resistance may emerge during long‐term therapy. Methods of monitoring treatment response include tests for serum aminotransferase levels, HBV DNA level, hepatitis B e antigen (HBeAg) and antibody (anti‐HBe), hepatitis B surface antigen (HBsAg) or antibody (anti‐HBs), and liver histology. Virological suppression and loss of HBeAg or HBsAg with or without seroconversion play a prominent role in decision‐making regarding the success and duration of antiviral therapy. Guidelines recommend that testing for serum markers be repeated every 12‐24 weeks during antiviral therapy and every 6‐12 months afterward. Recent data also suggest that serum HBV DNA levels should be assessed at weeks 12 and 24 of therapy, because early viral response may predict the likelihood of sustained response and antiviral resistance. The use of serum HBV DNA levels for this purpose requires an assay with a wide range of quantification, such as real‐time polymerase chain reaction assays, which have a 7‐8 log10 dynamic range. Newer, investigational methods for monitoring treatment response include quantitative measurement of HBsAg, HBeAg, and intrahepatic covalently closed circular DNA. Conclusions: Better methods for defining durable treatment endpoints are needed. Other areas requiring further research include the optimal treatment duration and the establishment of the optimal use of early viral kinetics for decision‐making during antiviral therapy. (HEPATOLOGY 2009;49:S166–S173.)

Lupus-like Immune Complex-mediated Glomerulonephritis in Patients with Hepatitis C Virus Infection Treated with Oral, Interferon-free, Direct-acting Antiviral Therapy.

BACKGROUND & AIMS There are no clinically available biomarkers for nonalcoholic steatohepatitis (NASH); differentiating between steatosis and NASH requires histologic evaluation. Noninvasive methods are needed to replace liver biopsy and its associated risks. Production of very low density lipoprotein (VLDL) contributes to the development of NASH and might be used to distinguish steatosis from NASH. However, it is not possible to measure levels of VLDL directly in the clinic. Non-high-density lipoprotein-cholesterol (non-HDL-C) encompasses all apolipoprotein-B-containing lipoproteins, including VLDL, and can be calculated from standard lipid panels without additional cost. METHODS We evaluated the ability of non-HDL-C to differentiate steatosis from NASH in a prospective study of 218 patients with suspected NASH (steatosis, n = 100 and NASH, n = 118). RESULTS Patients with NASH had a trend toward increased levels of non-HDL-C, compared with those with steatosis (P = .08). However, among subjects not on lipid-lowering medications, those with NASH had significantly higher levels of non-HDL-C (144.6 mg/dL) than those with steatosis (129.3 mg/dL; P = .025). This difference remained significant when adjusted for levels of cholesterol and triglycerides, indicating that the difference results from increased levels of apolipoprotein B including VLDL. These findings were validated in a cohort of 40 patients with steatosis or NASH who were not taking lipid-lowering agents. The NASH group had significantly higher levels of non-HDL-C than the steatosis group (162.8 vs 145.9 mg/dL; P = .04). CONCLUSIONS NASH is associated with significantly higher levels of non-HDL-C than steatosis in patients who do not take lipid-lowering agents. This low-cost biomarker could be used in noninvasive differentiation between steatosis and NASH.

Postpartum Laboratory Follow-up in Women With Hepatitis B in Massachusetts From 2007 to 2012.

Rates of transmission of hepatitis B virus (HBV) infection from organ donors with HBV markers to recipients along with reactivation of HBV during immunosuppression following transplantation have fallen significantly with the advent of hepatitis B immune globulin (HBIg) and effective antiviral therapy. Although the availability of potent antiviral agents and HBIg has highly impacted the survival rate of HBV-infected patients after transplantation, the high cost associated with this practice represents a major financial burden. The availability of potent antivirals with high genetic barrier to resistance and minimal side effects have made it possible to recommend an HBIg-free prophylactic regimen in selected patients with low viral burden prior to transplant. Significant developments over the last two decades in the understanding and treatment of HBV infection necessitate a re-appraisal of the guidelines for prophylaxis of HBV infection in solid organ transplant recipients.

Peripartum Care for Mothers Diagnosed with Hepatitis B During Pregnancy: A Survey of Provider Practices

OBJECTIVES: Hepatocellular carcinoma (HCC) surveillance with biannual ultrasound is currently recommended for all patients with cirrhosis. However, clinical implementation of this “one‐size‐fits‐all” approach is challenging as evidenced by its low application rate. We aimed to evaluate the cost‐effectiveness of risk‐stratified HCC surveillance strategies in patients with cirrhosis. METHODS: A Markov decision‐analytic modeling was performed to simulate a cohort of 50‐year‐old subjects with compensated cirrhosis. Risk‐stratified HCC surveillance strategies was implemented, in which patients were stratified into high‐, intermediate‐, or low‐risk groups by HCC risk biomarker–based scores and assigned to surveillance modalities tailored to HCC risk (2 non‐risk‐stratified and 14 risk‐stratified strategies) and compared with non‐stratified biannual ultrasound. RESULTS: Quality‐adjusted life expectancy gains for biannual ultrasound in all patients and risk‐stratified strategies compared with no surveillance were 1.3 and 0.9–2.1 years, respectively. Compared with the current standard of biannual ultrasound in all cirrhosis patients, risk‐stratified strategies applying magnetic resonance imaging (MRI) and/or ultrasound only in high‐ and intermediate‐risk patients, without screening in low‐risk patients, were cost‐effective. Abbreviated MRI (AMRI) for high‐ and intermediate‐risk patients had the lowest incremental cost‐effectiveness ratio (ICER) of

Reactivation of a Vaccine Escape Hepatitis B Virus Mutant in a Cambodian Patient During Anti-Hepatitis C Virus Therapy

2,100 per quality‐adjusted life year gained. AMRI in intermediate‐ and high‐risk patients had ICERs <