Alaska Native and American Indian persons living in Alaska are eligible for health care in a prepaid managed healthcare system through the Alaska Native Tribal Health Consortium and Alaska Native Medical Center (ANMC), a tertiary referral hospital in Anchorage. Since 1995, the Alaska Native Tribal Health Consortium Liver Disease and Hepatitis Program has enrolled 1,234 people into a longitudinal outcomes cohort study of chronic HCV infection. All participants had a positive anti-HCV test confirmed either by recombinant immunoblot assay or HCV RNA by polymerase chain reaction. Of 986 persons in this study population living on June 1, 2010, most resided in urban areas, including 60% in Anchorage, 15% in Fairbanks and 11% in Juneau and Sitka. Details of this patient cohort have been previously described, including clinical outcomes through 2005 (6).

Approval for this study was obtained from the Institutional Review Boards of the Alaska Area Indian Health Service, the University of Washington Medical Center and the Centers for Disease Control and Prevention and appropriate Alaska Native Health Corporation boards. All patients provided written informed consent that included permission for chart review of previous records.

Medical records of all treatment naïve HCV RNA positive patients given appointments in the hepatology specialty clinic at ANMC over 2 specific 1-year periods (January 1–December 31, 2003, and January 1–December 31, 2007) were evaluated by a hepatology provider (physician or nurse practitioner) to examine treatment eligibility based on clinical guidelines, patient preference and patient attendance at appointments. These 1-year periods were selected 4 years apart in order to investigate differences in treatment eligibility over time. In addition to pertinent history, physical examination and laboratory testing, hepatology clinic providers routinely discussed the nature of HCV infection, including long-term prognosis, routine follow-up recommendations, the role of liver biopsy, indications for treatment and detailed discussions of the treatment regimen and potential side effects. Documented patient behaviours and responses were also used to establish patient acceptance of treatment.

The hepatology clinic was staffed by 2 physicians and 1 nurse practitioner for 5 half-day clinics weekly in 2003 and by 2 physicians and 2 nurse practitioners for 7 half-day clinics weekly in 2007. One of the 2 nurse practitioners was hired in 2006 and dedicated to hepatitis C management, including treatment. Beginning in 2002, all patients with chronic HCV infection living in the Anchorage area were sent a letter biannually recommending that they make a follow-up clinic appointment and have their liver function tests performed. Most follow-up appointments were made by clinic staff at the request of patients who contacted the clinic. Some patients who did not make clinic appointments or have liver function tests performed after receiving a reminder letter were contacted by clinic staff and offered an appointment, which was made with patient agreement. Likewise, patients referred by other providers for a new clinic appointment were contacted by clinic staff and offered an appointment, which was made with their agreement. Most patients seen in the ANMC hepatology clinic in Anchorage resided in the Anchorage area. Those referred from other areas of the state generally had travel to Anchorage provided free of charge to the patient.

Alanine aminotransferase (ALT) testing was performed at the ANMC laboratory (Anchorage, AK) on an Aeroset Chemistry analyzer (Abbott Laboratories, USA). An ALT level of lower than 40 U/L was defined as normal. Testing for HCV RNA and genotype was performed at the University of Washington as previously described (7). Liver biopsy was performed only for clinical reasons, primarily to evaluate for possible treatment. Liver biopsy slides were evaluated by at least 1 of the 2 physicians (SL or BM), both practicing hepatologists, for clinical purposes. In addition, biopsy slides were evaluated by a study pathologist (HD) who was blinded to patient identity and demographic, clinical and biological data. Fibrosis was evaluated using the Knodell system (8).

Patient data were analysed for characteristics that included gender, age, years since diagnosis, genotype, ALT level, Knodell fibrosis score, risk factors (injection drug use, blood transfusion and other) and alcohol consumption at the time of entry into the study (consumption of any alcohol and consumption of >50 g/day). Statistical analysis was performed to compare characteristics of persons with consistent hepatology clinic appointment attendance to those with inconsistent attendance for given appointments. Additionally, documented reasons for treatment eligibility were compared in 2003 and 2007 using the likelihood ratio chi-square statistic. We used the Cochran-Armitage test for trend to examine if the percentage of persons who attended their appointments varied with age, ALT level and time since diagnosis. All p-values were 2-sided and values <0.05 were considered statistically significant. The p-values were exact when sample size necessitated. All analyses were conducted by the use of SAS version 9.2 (SAS Institute, Cary, NC, USA).

Treatment with pegylated interferon and ribavirin was initiated in 4 of 94 patients (4%) in 2003 and 14 of 146 patients (10%) in 2007. Of the 4 patients started on treatment in 2003, 1 achieved a sustained virologic response; 1 discontinued treatment due to side effects; treatment failed in another, and the fourth relapsed after achieving an end of treatment response. Of the 14 patients started on treatment in 2007, 4 achieved a sustained virologic response; 8 discontinued treatment due to side effects; treatment failed in 1 and 1 relapsed.

In 2003, we identified 94 treatment naïve patients who were scheduled for 175 appointments in the ANMC hepatology clinic. Of 19 patients who were scheduled for multiple appointments, 14 did not attend any of the appointments and 5 attended at least one of the scheduled appointments; attendance at this appointment was used by the provider to evaluate for treatment eligibility. Thirty-two of the 94 patients (34%) did not attend any of the appointments and, thus, were considered not eligible for treatment during the study period by the provider. Of the 90 patients not treated, reasons for providers deferring treatment were inability to attend scheduled appointments, 32 (36%); documented alcohol or drug abuse within 6 months of evaluation, 16 (17%); patient decision to defer treatment despite being considered an eligible candidate, 16 (17%); liver biopsy without fibrosis or normal ALT, 8 (8%); documented uncontrolled psychiatric condition, 7 (7%); concurrent medical condition precluding treatment, 6 (6%); decompensated cirrhosis, 3 (3%), and age >65 years, 2 (2%) (Table I).

In 2007, we identified 146 treatment naïve patients who were scheduled for 278 appointments in the ANMC hepatology clinic. Of 45 patients who had multiple scheduled appointments, 2 attended none of them and 43 attended at least 1. Overall, 24 of the 146 patients (16%) did not attend any scheduled appointments. Of the 132 patients not treated, reasons for providers deferring treatment were patient decision to defer, 36 (27%); alcohol or drug abuse within 6 months of evaluation, 29 (22%); inability to attend scheduled appointments, 24 (18%); concurrent medical condition precluding treatment, 12 (9%); uncontrolled psychiatric condition, 9 (6%); decompensated cirrhosis, 7 (5%); patients considering or planning treatment but not yet started, 7 (5%); liver biopsy without fibrosis or normal ALT, 4 (3%); age >65 years, 2 (1%), and other, 2 (1%) (Table I).

The proportion of appointments attended increased significantly in 2007 versus 2003 (73% vs. 67%, respectively, p=0.04). Likewise, the percentage of patients who attended at least 1 scheduled appointment increased in 2007 versus 2003 (84% vs. 66%, p=0.002) (Table II). In 2003, persons with a history of intravenous drug use were significantly less likely to attend clinic appointments than those with other risk factors (p=0.04). In 2007, there was a significant difference in time since diagnosis among those who attended clinic appointments. Among persons diagnosed with HCV infection <3 years prior to the appointment, 93% attended at least 1 appointment compared to 86% and 73% for diagnosis 3–7 and ≥8 years prior, respectively (p=0.009). There was no significant difference in other characteristics in either year among those who attended scheduled appointments (Table III).