What Do We Know about the Difficult-to-Treat Patient with Chronic Hepatitis C Infection ?

Hepatitis C is a worldwide infection that affects more than 170 million individuals. The lifetime risk of cirrhosis remains around 20% and approximately 20% of those patients who develop cirrhosis will develop liver cancer. The only management for hepatitis C patients with end-stage liver disease with liver failure with or without liver cancer remains liver transplantation. In today’s afternoon, Professor Robert G. Gish，who came from California Pacific Medical Center, San Francisco, United States, given us a report which focuses on the difficult-to-treat patient with chronic hepatitis C infection. He said that the ultimate goal of management of hepatitis C is to cure patients, preferably, before they develop cirrhosis or cancer and before they develop the need for liver transplantation. Unfortunately, there are a large number of patients who have failed interferon or who are not candidates for this complex treatment. The patients who are “difficult to treat include patients with the profile of a low response and low cure rate to interferon-based antiviral therapy include: 1. Patients with HIV co- infection. 2. Patients who have advanced fibrosis or cirrhosis. 3. Patients with fatty liver (NASH) disease, especially those patients with documented insulin resistance. 4. Patients with defective immune systems such as patients with organ transplants. 5. Specific ethnic groups including African Americans. 6. Patients with medical or psychological contraindications to interferon-based therapies who may need dose reductions during treatment. 7. Patients with contraindications to ribavirin-based therapy such as anemia or cardiovascular disease who may not be able to receive full dose ribavirin therapy. 8. Patients without adequate health care resources who may be noncompliant or non adherent to a therapeutic regimen.

The major focus of his report is patients with advanced fibrosis and cirrhosis, and patients with fatty liver with insulin resistance as well as patients with ethnic backgrounds that have low response rates due to changes in intracellular responses to interferon and or ribavirin. The viral and immune mechanistic explanations for low cure rates in patients with cirrhosis or insulin-resistance have not been clearly defined. Immune responses, both intra- and extracellular, are probably modified in each of these important clinical conditions. Cirrhosis is a relative condition of immunosuppression. T cell dysfunction has been reported in this clinical setting as well. Insulin resistance appears to interfere with intracellular mechanisms to suppress or clear HCV infection. Attempts to override these inhibitory pathways have not yet been clearly or fully established; yet, patients with fatty liver who undergo weight loss appear to have a higher response rate to Interferon-based therapies. Changes in response to interferon that are based on genetic and ethnic backgrounds are being investigated and are not fully understood.

Finally Professor Robert G. Gish pointed out that the difficult-to-treat patient with hepatitis C continues to be a dominant portion of hepatologists and other clinicians’ practice profiles. Additional information is needed and additional therapeutic options are required to increase the cure rate in this patient population.

Robert G. Gish 教授认为慢性丙型肝炎治疗的最终目标为在进展为肝硬化或肝细胞癌，在需要进行肝移植之前将患者治愈。但不幸的是，目前还存在相当一部分对以干扰素为基础的抗病毒治疗反应差、治愈率低的难治患者，包括合并进展期肝纤维化和肝硬化患者、胰岛素抵抗的脂肪肝患者以及特殊种族背景的患者。他指出肝硬化或胰岛素抵抗导致应答率低的病毒学和免疫学机制尚不明确，基因和特殊种族背景的不同导致对干扰素反应不同的机制也并不完全清楚。因此，这些难治性慢性丙型肝炎患者仍将成为肝病专家关注和研究的主要对象，以尽早提高这部分患者的治愈率。