Liver transplantation is the gold standard of care in patients with end-stage liver disease and those with tumors of hepatic origin in the setting of liver dysfunction. From 1988 to 2009, liver transplantation in the United States grew 3.7-fold from 1713 to 6320 transplants annually. The expansion of liver transplantation is chiefly driven by scientific breakthroughs that have extended patient and graft survival well beyond those expected 50 years ago. The success of liver transplantation is now its primary obstacle, as the pool of donor livers fails to keep pace with the growing number of patients added to the national liver transplant waiting list. This review focuses on three major challenges facing liver transplantation in the United States and discusses new areas of investigation that address each issue: 1) the need for an expanded number of useable donor organs, 2) the need for improved therapies to treat recurrent hepatitis C after transplantation and 3) the need for improved detection, risk stratification based upon tumor biology and molecular inhibitors to combat hepatocellular carcinoma.

In this retrospective study of hepatitis C virus (HCV)–infected transplant recipients in the 9-center Adult to Adult Living Donor Liver Transplantation Cohort Study, graft and patient survival and the development of advanced fibrosis were compared among 181 living donor liver transplant (LDLT) recipients and 94 deceased donor liver transplant (DDLT) recipients. Overall 3-year graft and patient survival were 68% and 74% in LDLT, and 80% and 82% in DDLT, respectively. Graft survival, but not patient survival, was significantly lower for LDLT compared to DDLT (P = 0.04 and P = 0.20, respectively). Further analyses demonstrated lower graft and patient survival among the first 20 LDLT cases at each center (LDLT ≤20) compared to later cases (LDLT > 20; P = 0.002 and P = 0.002, respectively) and DDLT recipients (P < 0.001 and P = 0.008, respectively). Graft and patient survival in LDLT >20 and DDLT were not significantly different (P = 0.66 and P = 0.74, respectively). Overall, 3-year graft survival for DDLT, LDLT >20, and LDLT ≤20 were 80%, 79% and 55%, with similar results conditional on survival to 90 days (84%, 87% and 68%, respectively). Predictors of graft loss beyond 90 days included LDLT ≤20 vs. DDLT (hazard ratio [HR] = 2.1, P = 0.04), pretransplant hepatocellular carcinoma (HCC) (HR = 2.21, P = 0.03) and model for end-stage liver disease (MELD) at transplantation (HR = 1.24, P = 0.04). In conclusion, 3-year graft and patient survival in HCV-infected recipients of DDLT and LDLT >20 were not significantly different. Important predictors of graft loss in HCV-infected patients were limited LDLT experience, pretransplant HCC, and higher MELD at transplantation.

Background

Hepatitis B virus (HBV) infection constitutes a major health problem for homeless persons. Ability to complete an HBV vaccination series is complicated by the need to prioritize competing needs, such as addiction issues, safe places to sleep, and food, over health concerns.

Objectives

The objectives of this study were to evaluate the effectiveness of a nurse-case-managed intervention compared with that of two standard programs on completion of the combined hepatitis A virus (HAV) and HBV vaccine series among homeless adults and to assess socio-demographic factors and risk behaviors related to the vaccine completion.

Methods

A randomized, three-group, prospective, quasi-experimental design was conducted with 865 homeless adults residing in homeless shelters, drug rehabilitation sites, and outdoor areas in the Skid Row area of Los Angeles. The programs included (a) nurse-case-managed sessions plus targeted hepatitis education, incentives, and tracking (NCMIT); (b) standard targeted hepatitis education plus incentives and tracking (SIT); and (c) standard targeted hepatitis education and incentives only (SI).

Results

Sixty-eight percent of the NCMIT participants completed the three-series vaccine at 6 months, compared with 61% of SIT participants and 54% of SI participants. NCMIT participants had almost 2 times greater odds of completing vaccination than those of participants in the SI program. Completers were more likely to be older, to be female, to report fair or poor health, and not to have participated in a self-help drug treatment program. Newly homeless White adults were significantly less likely than were African Americans to complete the vaccine series.

Discussion

The use of vaccination programs incorporating nurse case management and tracking is critical in supporting adherence to completion of a 6-month HAV/HBV vaccine. The finding that White homeless persons were the least likely to complete the vaccine series suggests that programs tailored to address their unique cultural issues are needed.

Hepatitis C is one of the leading causes of liver disease in the United States, affecting more than 4 million individuals. The current treatment regimen involves pegylated interferon in combination with ribavirin. Although antiviral treatment has been associated with a greater than 50% sustained viral response rate, the adverse effects have proven to be detrimental to quality of life and therapy adherence, and consequently lead to lower sustained viral response rates. This article identifies the most frequently described complications associated with pegylated interferon and ribavirin. The active management of these complications is discussed, including both preventive and empiric treatments.

Hepatitis C virus (HCV) affects about 170 million people worldwide and is the most common chronic blood borne infection in the United States. Since the advent of blood screening protocols in the early 1990s, injection drug use has become the leading cause of infection. Hepatitis C can have both hepatic and nonhepatic manifestations of infection. Hepatic manifestations include hepatic fibrosis, cirrhosis, liver cancer, and liver failure. The standard treatment for chronic HCV is combination therapy with pegylated interferon-α and ribavirin. Although pegylated interferon and ribavirin has been used against HCV for close to a decade, advances in therapy have centered on doses and treatment durations. There has been increasing interest in applying on-treatment response or viral kinetics to predict antiviral response rates and shape therapeutic intervention. Protease inhibitors are a promising adjuvant to combination therapy, but their efficacy and safety are still under investigation.

Purpose

Hepatitis B viral markers may be useful for predicting outcomes such as liver-related deaths or development of hepatocellular carcinoma. We determined the frequency of these markers in different clinical stages of chronic hepatitis B infection.

Methods

We compared baseline hepatitis B viral markers in 317 patients who were enrolled in a prospective study and identified the frequency of these tests in immune-tolerant (IT) patients, in inactive carriers, and in patients with either hepatitis B e antigen (HBeAg)-positive or HBeAg-negative chronic hepatitis or cirrhosis.

Results

IT patients were youngest (median age 27 years) and HBeAg-negative patients with cirrhosis were oldest (median age 58 years) (p = 0.03 to <0.0001). The male to female ratio was similar both in IT patients and in inactive carriers, but there was a male preponderance both in patients with chronic hepatitis and in patients with cirrhosis (p < 0.0001). The A1896 precore mutants were most prevalent in inactive carriers (36.4%) and HBeAg-negative patients with chronic hepatitis (38.8%; p < 0.0001), and the T1762/A1764 basal core promoter mutants were most often detected in HBeAg-negative patients with cirrhosis (65.1%; p = 0.02). Genotype A was detected only in 5.3% of IT patients, and genotype B was least often detected in both HBeAg-Positive patients with chronic hepatitis and cirrhosis (p = 0.03). The hepatitis B viral DNA levels were lowest in inactive carriers (2.69 log10 IU/mL) and highest in IT patients (6.80 log10 IU/mL; p = 0.02 to <0.0001). At follow-up, HBeAg-positive and HBeAg-negative patients with cirrhosis accounted for 57 of 64 (89.1%) liver-related deaths (p < 0.0001).

Conclusion

Differences in baseline hepatitis B viral markers were detected in patients in various clinical stages of hepatitis B virus infection. HBeAg-positive and HBeAg-negative patients with cirrhosis accounted for the majority of the liver-related fatalities.

Purpose

Hepatitis B viral markers may be useful for predicting outcomes such as liver-related deaths or development of hepatocellular carcinoma. We determined the frequency of these markers in different clinical stages of chronic hepatitis B infection.

Methods

We compared baseline hepatitis B viral markers in 317 patients who were enrolled in a prospective study and identified the frequency of these tests in immune-tolerant (IT) patients, in inactive carriers, and in patients with either hepatitis B e antigen (HBeAg)-positive or HBeAg-negative chronic hepatitis or cirrhosis.

Results

IT patients were youngest (median age 27 years) and HBeAg-negative patients with cirrhosis were oldest (median age 58 years) (p = 0.03 to <0.0001). The male to female ratio was similar both in IT patients and in inactive carriers, but there was a male preponderance both in patients with chronic hepatitis and in patients with cirrhosis (p < 0.0001). The A1896 precore mutants were most prevalent in inactive carriers (36.4%) and HBeAg-negative patients with chronic hepatitis (38.8%; p < 0.0001), and the T1762/A1764 basal core promoter mutants were most often detected in HBeAg-negative patients with cirrhosis (65.1%; p = 0.02). Genotype A was detected only in 5.3% of IT patients, and genotype B was least often detected in both HBeAg-Positive patients with chronic hepatitis and cirrhosis (p = 0.03). The hepatitis B viral DNA levels were lowest in inactive carriers (2.69 log10 IU/mL) and highest in IT patients (6.80 log10 IU/mL; p = 0.02 to <0.0001). At follow-up, HBeAg-positive and HBeAg-negative patients with cirrhosis accounted for 57 of 64 (89.1%) liver-related deaths (p < 0.0001).

Conclusion

Differences in baseline hepatitis B viral markers were detected in patients in various clinical stages of hepatitis B virus infection. HBeAg-positive and HBeAg-negative patients with cirrhosis accounted for the majority of the liver-related fatalities.

Refractory ascites is defined as ascites that does not recede or that recurs shortly after therapeutic paracentesis, despite sodium restriction and diuretic treatment. To date, there is no approved medical therapy specifically for refractory ascites. Management of these patients is based upon procedures such as large-volume paracentesis and transjugular intrahepatic portosystemic shunts (TIPS), which temporarily alleviate symptoms but are not curative. These patients have a poor prognosis and are at risk for a series of complications that are associated with the condition or are secondary to therapy. The most common complications include spontaneous bacterial peritonitis, hepatic hydrothorax, spontaneous bacterial empyema, and umbilical hernia. The predicted survival rate is as low as 50% at 1 year, and prognosis worsens as patients present with comorbidities such as hepatorenal syndrome, renal failure, and hepatocellular carcinoma. The only curative treatment is liver transplantation, though current studies have shown that TIPS also increases survival.

OBJECTIVE: The availability of a single vaccine active against hepatitis A and B may facilitate prevention of both infections, but complicates the question of whether to conduct pre-vaccination screening. The authors examined the cost-effectiveness of pre-vaccination screening for several populations: first-year college students, military recruits, travelers to hepatitis A-endemic areas, patients at sexually transmitted disease clinics, and prison inmates. METHODS: Three prevention protocols were examined: (1) screen and defer vaccination until serology results are known; (2) screen and begin vaccination immediately to avoid a missed vaccination opportunity; and (3) vaccinate without screening. Data describing pre-vaccination immunity, vaccine effectiveness, and prevention costs borne by the health system (i.e., serology, vaccine acquisition, and administration) were derived from published literature and U.S. government websites. Using spreadsheet models, the authors calculated the ratio of prevention costs to the number of vaccine protections conferred. RESULTS: The vaccinate without screening protocol was most cost-effective in nine of 10 analyses conducted under baseline assumptions, and in 69 of 80 sensitivity analyses. In each population considered, vaccinate without screening was less costly than and at least equally as effective as screen and begin vaccination. The screen and defer vaccination protocol would reduce costs in seven populations, but effectiveness would also be lower. CONCLUSIONS: Unless directed at vaccination candidates with the highest probability of immunity, pre-vaccination screening for hepatitis A and B immunity is not cost-effective. Balancing cost reduction with reduced effectiveness, screen and defer may be preferred for older travelers and prison inmates.