Severe Fatigue and Age but Not Neurocognitive
Dysfunction or Liver Disease Significantly Impair
Quality of Life in HCV Patients,
Particularly among Women

By Ronald Baker, PhD

Fatigue has emerged as one of the most significantly disabling side effects of individuals with hepatitis C virus (HCV) infection. HCV patients complain of the debilitating effects of fatigue at all stages of hepatitis C [1]. Despite the high prevalence of fatigue and the repeated complaints about it from affected patients, there are scant data in the medical literature on this subject. As a result, the pathophysiology of fatigue in patients with hepatitis C is not well understood.

While chronic liver inflammation might be expected to be causally linked to fatigue, there is no correlation between cytokine concentrations and fatigue severity. [2] In addition, although often viewed as a result of the progression of liver disease, the severity of fatigue is not strongly linked to the biochemical and histological activity of hepatitis [3].

Recent research however shows clear associations between fatigue and female sex, age over 50 years, extrahepatic symptoms of HCV infection, and cirrhosis [4].

Ludwig Kramer, MD, and colleagues at the Department of Medicine IV, Medical University Vienna, in Vienna, Austria have demonstrated in earlier studies the potential neurocognitive aspects of HCV-related fatigue. The results of new research by these Austrian researchers appear in the October 2005 supplement of the journal AIDS [5]. Summarized and discussed here are the major findings of this new study and their implications for management of patients with chronic hepatitis C.

The Austrian researchers investigated the hypothesis that severity of fatigue rather than subclinical cognitive dysfunction has an independent effect on HCV-associated impairment of health-related quality of life (HRQL). To assess the severity of fatigue, the researchers utilized both the fatigue impact scale (FIS) [6] and the more recently developed brief fatigue inventory (BFI) [7], and compared their respective association with HRQL measures and clinical data.

The Austrian investigators evaluated 120 untreated patients referred to their liver clinic with chronic hepatitis C (aged 45 ± 12 years). Inclusion criteria were age between 18 and 80 years and presence of anti-HCV antibodies and HCV RNA in serum. Excluded from the study were individuals with decompensated cirrhosis, alcoholic liver disease, cryoglobulinemia, liver transplantation, other bacterial or viral infections, renal failure, insulin-treated diabetes, cerebrovascular disease and a current or past history of neurological or psychiatric illness including attention and learning deficits, medication with tranquillizers or antidepressants, or a history of alcohol or injection drug abuse within 6 months before the study.

Results

Relative to healthy controls, HCV-infected patients showed significant levels of fatigue (Fatigue Impact Scale, 49 versus 26 points, brief fatigue inventory, 3.0 versus 1.6 points, P < 0.001).

Fatigue impact scale and brief fatigue inventory scores were highly correlated (P < 0.001), demonstrating concurrent validity.

Severity of fatigue and age were the only factors independently associated with the impairment of HRQL (P < 0.001).

Fatigue was not related to the severity of hepatitis or the degree of subclinical brain dysfunction.

Based on the findings, the authors conclude, “In untreated patients with chronic HCV infection, fatigue severity and age but not neurocognitive dysfunction or hepatic function are independently associated with impaired HRQL.”

“Both the fatigue impact scale and the brief fatigue inventory are suitable tools to assess the subjective burden of fatigue.”

Discussion

This study demonstrates that fatigue severity and age are independently associated with impairment of HRQL in chronic HCV infection. It is arguably the first study to show that fatigue, not the severity of liver disease, sex or neurocognitive dysfunction, is a significant factor in the pathogenesis of HCV-associated HRQL reduction.

Because the severity of HCV-associated liver disease is only weakly associated with fatigue and effects on HRQL persisted even after liver transplantation [8], “psychological factors leading to fatigue clearly need to be identified,” note the study authors.

The authors also found that drug abuse was one of the main factors associated with HRQL impairment in patients co-infected with HIV and HCV. In addition, women, in particular, appeared to be significantly affected by fatigue.

The authors write, “Given that most patients with HCV infection, and particularly those with additional risk factors such as HIV infection, will exhibit some degree of fatigue [9], our findings have potential implications: The treatment of fatigue will probably become a therapeutic requirement for healthcare providers dealing with hepatitis C.”

Treatment to alleviate fatigue will probably eventually involve both pharmacological and non-pharmacological components. Unfortunately, the currently available psychostimulants have a high potential for dependency. “Modafinil needs to be investigated in patients with HCV infection,” they emphasize [10].

On a more hopeful note, the authors point out that structured exercise effectively improves HRQL in patients with the chronic fatigue syndrome, cancer, and AIDS, “and may be the best treatment option currently available [11,12] [for fatigue in chronic HCV patients].”

A randomized trial to investigate a structured exercise program in patients with HCV infection is ongoing.

In summary, the authors write, “Fatigue severity and age but not neurocognitive dysfunction or hepatic function are associated with impaired HRQL in patients with untreated chronic HCV infection.”

“Female patients were particularly affected by fatigue. These findings stress the need for effective therapeutic interventions to ameliorate the burden of fatigue in patients with HCV infection.”

11/04/05

Primary Source

L Kramer and others. Relative impact of fatigue and subclinical cognitive brain dysfunction on health-related quality of life in chronic hepatitis C infection. AIDS 19(Suppl 3): S85-S92. October 2005.

References

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