Chronic Hepatitis C virus infection in Swiss primary care practices: Low case loads—high barriers to treatment?

Abstract

Background: The primary care physician (PCP) diagnoses chronic Hepatitis C virus (HCV) infection in most patients. He serves as gatekeeper and plays a key role in counselling and treatment guidance. Objectives: To calculate the approximate HCV caseload per practice and characterize PCPs management of the disease; in particular, to determine antiviral treatment rates and reasons for PCPs for withholding treatment. The ultimate objective was to identify potentially modifiable barriers to treatment. Methods: A confidential self-administered questionnaire centred on the above-mentioned questions was distributed to 2371 Swiss primary care physicians. All respondents of the main questionnaire received an additional small questionnaire focussed on the initial disease workup. Descriptive statistics were used to describe questionnaire responses and PCP demographics. Results: The response rate was 53.1%. Of all participating PCPs (n = 1084), 86.2% reported having patients with chronic HCV, with an average number of 4 patients per practice; 18.6% (n = 142) of PCPs did not monitor their chronic HCV patients. Two-thirds (66.8%) of the sample chronic HCV patient population (n = 4626) never received antiviral therapy. The main reasons given by PCPs for withholding treatment were HCV-specialist advice, patient preference, normal liver enzymes and patient related factors like substance abuse or psychiatric co morbidity.

Conclusions: Most PCPs follow patients with chronic hepatitis C, but practice caseloads are low, which may account for insecurity in managing this complex disease.

Key words::

• Hepatitis C
• primary care physician
• disease workup
• patient monitoring
• barriers to treatment

Introduction

The World Health Organization (WHO) has described chronic hepatitis C virus (HCV) infection as a ‘viral time bomb’ (1). The disease affects some 170 million persons worldwide (2). In Switzerland, accurate prevalence data are unavailable but estimates range from 50 000 to 70 000 anti-HCV positive persons (0.7–1% of the total population) and 7 to 14 new infections per 100 000 persons annually (3). A simulation model based on data from 2002 predicts an increase in HCV morbidity and mortality of 70–90%, reaching a maximum between 2015 and 2020 (3).

Chronic Hepatitis C infection leads to liver cirrhosis in 5–20% of patients (2) and is a major factor in 50–70% of hepatocellular carcinomas and two thirds of liver transplants (1). The current standard of care, pegylated interferon-ribavirin based antiviral therapy (4), lowers the risk of cirrhosis and hepatocellular carcinoma (4,5). Yet, many chronic HCV patients remain untreated (6), for reasons that include the physician's level of knowledge and experience, patient preference, medical or psychiatric co morbidity and substance abuse (6–8). However, various feasibility studies in patients often considered too difficult to treat, such as active injecting drug users, participants in methadone maintenance programs or psychiatric patients, have reported compliance rates and treatment outcomes similar to those in other patients (9–11). Considering these findings, the latest US National Institutes of Health (NIH) and French Consensus Conference guidelines, both issued in the year 2002, advocate increased availability of the best current treatment for all chronic HCV patients (12,13). Both conferences recommend incorporating into the disease workup liver function parameters, viral load, genotype and fibrosis staging whether by liver biopsy or non-invasive methods. The general treatment indication is based on fibrosis stage ≥ F2 according to the Metavir score. This is a system to qualify the degree of fibrosis of a liver biopsy. Fibrosis is graded on a 5-point scale from 0 to 4: F0 = no fibrosis, F1 = portal fibrosis without septa, F2 = portal fibrosis with few septa, F3 = numerous septa without cirrhosis, F4 = cirrhosis. In genotypes 2 and 3, though, due to high-sustained virological response rates, treatment may be started at any time with no need for prior liver biopsy.

Since all Swiss residents have compulsory health insurance, they have ready access to medical consultation and HCV treatment. Most chronic HCV infections are diagnosed by PCPs. In Switzerland, there are mainly two types of PCPs: general practitioners (five years specialization in total, rotation in internal medicine, surgery and elective specialities) or specialists in internal medicine (six years of specialization in internal medicine). As gatekeepers to the health care system, PCPs play a key role in disease assessment, monitoring and specialist referral.

The aims of this survey were to calculate the approximate HCV caseload per primary care practice and characterize PCP management of the disease, in particular to determine treatment rates and the reasons for withholding antiviral treatment. The ultimate objective was to identify potentially modifiable barriers to treatment.

Methods

Questionnaire

We developed a confidential self-administered physician-only questionnaire to determine the number of chronic HCV patients per practice, the number of patients receiving antiviral treatment, reasons for non-treatment, disease monitoring and patient referral to HCV-specialists (i.e. gastroenterologist or hepatologist).

All respondents of our main questionnaire received an additional small self-administered questionnaire focussed on the initial disease workup, i.e. liver function tests, viral load, genotype, and liver biopsy.

After review by HCV-specialists, the questionnaires were pilot tested with three primary care physicians for content validity, clarity, comprehensiveness and appropriateness of items and response categories. Since all replies were fully anonymous and contained no individual patient data, ethical approval for the survey was not required.

Participating physicians

We used the Roche™ database of Swiss PCPs who, regardless of their medical specialization or geographical setting, accept visits by Roche™ representatives (n = 2522). We excluded those with a particular interest or speciality in HCV and/or gastroenterology or hepatology (n = 351). The remaining PCPs (n = 2171) were visited personally by Roche™ representatives in their practices between September 2005 and December 2006 and were invited to fill out and fax back the questionnaire. Demographic information on the participating physicians (sex, age, years of post-graduate medical activity, medical specialization, additional hospital activity, geographic distribution) was also collected.

Statistical analysis

Descriptive statistics were used to describe questionnaire responses and PCP demographics. Differences between PCPs (> 10 HCV patients versus < 10 HCV patients per practice) were assessed using Pearson chi-square test for categorical variables. All data were analysed using STATA (version 9, Stata Corp LP, College Station, TX, USA).

Results

Primary care physicians

Questionnaires were completed by 1258 PCPs (response rate 53.1%), which equates to around 20% of the estimated 7000 Swiss PCP population (14). 1084 PCPs (86.2%) had chronic HCV patients in their practice. Demographic data, available for 1039 (95.8%) participating PCPs, showed that most were male (n = 889, 85.6%) and averaged 25 years post-qualification. 673 (68.4%) were general practitioners, 239 (24.3%) specialized in internal medicine and 72 (7.3%) reported other specialities. Most (n = 903; 88.4%) worked exclusively in private practice, while the remaining 11.6% had additional hospital duties. In their demography and geographical distribution, the participating PCPs were a representative sample of the Swiss PCP population (9).

Monitoring of HCV patients

On average, there were 4.3 chronic HCV patients per practice. 116 PCPs (9.2%) had ≥ 10 HCV positive patients. Monitoring data on treatment naïve patients were available from 887 practices: 246 PCPs (27.7%) referred patients for monitoring to an HCV-specialist, 494 PCPs (55.7%) measured liver enzymes annually in their practice, while 147 PCPs (16.6%) neither provided nor organized any monitoring at all. Division of PCPs into two groups of total chronic HCV patients per practice (878 PCPs; ≥ 10 patients: 116 PCPs (13.1%); < 10 patients: n = 762 (86.9%); 9 PCPs did not mention the number of patients they followed) showed significantly higher monitoring rates in practices with ≥ 10 patients (n = 111 (95.7%) versus n = 620 (81.4%), P < 0.001) (Figure 1.).

Figure 1. Chronic Hepatitis C monitoring organized by primary care physicians.

Few PCPs (n = 110; 10.3%) felt confident enough to offer antiviral treatment entirely within their practice. The remaining 89.7% preferred to refer their patients for antiviral treatment to an HCV-specialist (private or hospital gastroenterologist or hepatologist).

Treatment of HCV patients

Participating PCPs cared for a total of 4626 chronic HCV patients, 2625 (66.8%) had not received antiviral therapy by the time of the survey; 133 (12.3%) PCPs reported all their chronic HCV patients as having received antiviral treatment.

Table I details PCPs’ reasons for non-treatment. The questionnaire allowed multiple answers.

Table I. Primary care physicians’ reasons for withholding antiviral treatment.

Patient related reasons:	n	%	HCV related reasons:	n	%
Patient preference	295	26.2	Normal liver enzymes	284	25.3
Drug problem	131	11.6	Previously non-responder	59	5.3
Old age	125	11.1	Biopsy result	35	3.1
Alcohol problem	53	4.7	Difficult-to-treat genotype	18	1.6
Compliance problem	48	4.3	Patient asymptomatic	7	0.6
Depression	28	2.5	Spontaneous clearance	4	0.3
HIV co-infection	19	1.7	Organizational issues:
Patient ‘not stable’	9	0.8	Ongoing investigations	14	1.3
Medical comorbidities	8	0.7	Financial issues	5	0.4
Transplantation	2	0.2	Other:
Pregnancy	2	0.2	Specialist advice	313	27.8
Financial issues	5	0.4	No information	94	8.4

The three predominant reasons for non-treatment were HCV specialist advice (n = 313), patient preference (n = 295) and normal liver enzymes (n = 284). The next most important were intravenous drug use (n = 131) and advanced age (n = 125). These were followed by a miscellany, including included non-response to previous antiviral treatment, alcoholism, non-compliance, liver biopsy result, depression, HIV co-infection, difficult-to-treat genotype and ongoing investigations.

Diagnostic work-up

The response rate to our sub-survey of PCPs’ HCV workup was 16% (n = 176). PCPs measured alanin-aminotransferase (ALT) in 454 (95.9%) patients, gamma-glutamyl-transferase (GGT) in 453 (95.7%) patients and viral load was determined in 367 (77.6%). Genotypes were available for 255 (53.91%) patients and 179 (37.8%) patients had undergone liver biopsy (Figure 2).

Figure 2. Complementary exams ordered by primary care physicians in the workup of chronic Hepatitis C patients.

Discussion

Prevalence of chronic HCV patients in primary care practices

Around 20% of all Swiss PCPs participated in our survey. The vast majority (86.2%) have chronic HCV patients, but caseloads are relatively low, averaging four chronic HCV patients per practice. Other European countries report similarly low figures (15,16). However, given the predicted increase in HCV-related morbidity and mortality until 2015–2020 (3), PCPs are likely to face HCV-related issues more frequently soon.

Disease assessment and monitoring

Most PCPs organize regular follow-up for their treatment-naïve chronic HCV patients, but 16.6% see no need for monitoring at all, which could expose their patients to a serious health risk. Under a third of PCPs (27.7%) refer their patients to a specialist for monitoring, although the great majority (89.7%) opt for specialist referral to initiate treatment. These findings comply with Swiss HCV expert recommendations (17) that PCPs be responsible for general monitoring and that specialist referral be reserved for initiating treatment and for patients with hepatic impairment.

Diagnostic work-up

The disease workup substudy showed frequent neglect of the investigations required for appropriate treatment decisions: viral load was performed in 77.6%, genotype in 53.9% and biopsy in 37.8%. However, these results need to be interpreted with caution due to the low response rate (16%, n = 176). They may well reflect a best-case scenario of physicians interested in the subject, with real numbers being possibly even lower. If so, this would represent a major barrier to treatment. Alternatively, it is also possible that in some cases there was a clear need from the start for withholding or deferring treatment, so that no further workup was planned. Simple cause-and effect conclusions, therefore, cannot be drawn: the relationship between inadequate workup and treatment decision is difficult to determine in this cross-sectional design. We did not find any other studies on HCV-disease work-up in primary care.

Treatment rates—barriers to treatment

Two-thirds (66.8%) of chronic HCV patients in the participating primary care practices had not undergone antiviral therapy. This rate is alarmingly high but in line with studies in various settings and countries (6–8). However, the rate is significantly lower (48.8%) among patients attending the specialist consultations of the Swiss Hepatitis C Cohort Study (SCCS) (18). However, comparisons have to be interpreted with caution as patient populations differ greatly between primary and specialist care.

Patient preference was one of the main reasons for non-treatment, possibly because HCV infection is largely asymptomatic (19), discouraging patients from embarking on a therapy with often significant adverse effects (20,21). It is essential for PCPs to provide reliable basic information on the importance and modalities of antiviral treatment to help lower such patient-related barriers to treatment. They should not hesitate to refer reluctant patients to an HCV-specialist for expert consultation.

The presence of normal liver enzymes was one of the most frequently cited reasons for non-treatment. However, this attitude needs reviewing in the light of poor correlation between transaminase levels and the stage of liver fibrosis (22,23).

Many PCPs considered several patient related factors, such as intravenous drug use, alcohol abuse or psychiatric conditions (i.e. depression) as insurmountable barriers to successful antiviral therapy and hence withheld treatment for the patients concerned. However, various feasibility studies have shown that antiviral treatment can be successful with similar compliance rates and treatment outcomes provided it is conducted by HCV specialists embedded in a multidisciplinary team including the PCP and often a psychiatrist and/or addiction specialist (9–11). Hence, PCPs should be encouraged to involve HCV-specialists when developing treatment strategies in patients who appear ‘too difficult to treat.’

Survey limitations

The study has the limitations implicit in its cross-sectional design. We are aware of the limited testing of internal validity and reliability of the questionnaire. Our data were self-reported: differences between self-reported and actual practice are well-documented (24). The responses received, therefore, may represent a best-case scenario featuring PCPs with a special interest in the subject. This might, especially apply to our substudy on disease workup with a low response rate of only 16%.

However, our main survey (n = 1084, response rate 53.1%), covered a representative PCP sample and their chronic HCV patients. It may thus help to optimize treatment access and minimize the future burden of HCV-related liver disease.

Practical implications

In summary, we found

• The HCV caseload to be relatively low, in line with reports from other European countries;

• A frequent neglect of investigations required for appropriate treatment decisions;

• That two thirds of chronic HCV patients in primary care had not received antiviral therapy, which is in line with other studies in various settings and countries;

• That the presence of normal liver enzymes, patient preferences, and other patient related factors (e.g. intravenous drug use, alcohol abuse or psychiatric conditions) were regarded to be important barriers for appropriate treatment.

Therefore, in line with expert recommendations that specialist referral be reserved for initiating treatment and for patients with hepatic impairment and that PCPs be responsible for general monitoring, we propose a set of practical guidelines for primary care physicians, as shown in Table II.

Table II. Practical implications for primary care physicians.

Specialist referral for:

Workup completion: a full workup to all HCV patients: viral load, genotype, and biopsy or non-invasive staging of fibrosis

Treatment should not be deferred before these items are determined

Evaluating treatment indication and treatability, especially in seemingly ‘too difficult to treat patients’

Support in conducting treatment and managing adverse effects

Monitoring of HCV patients:

Non-cirrhotic patients: annual transaminases

Cirrhotic patients: six-monthly HCC screening and liver function tests

Conclusion

In conclusion, we found those most Swiss primary care physicians’ follow patients with chronic Hepatitis C, but caseloads per practice are relatively small, that might lead to insecurities in the management of this complex disease. As most PCPs provide regular disease monitoring, disease assessment often seems to be incomplete and treatment rates are low. We can only encourage network collaborations between PCPs and HCV-specialists to provide the best possible care for the individual patient.

Declaration of interest: This study was supported by Roche Pharma Schweiz AG. Dr Helbling has received a grant from Essex Chemie AG, Lucerne and served as a consultant and advisory board member for Roche Pharma Schweiz AG. Dr Bruggmann has served as speaker, consultant and advisory board member for Roche Pharma Schweiz AG, Essex Chemie AG, Lucerne and Schering Plough.