Monoterapi ribavirin untuk hepatitis C kronik
Abstract
Background
Hepatitis C is a major cause of liver‐related morbidity and mortality. A high proportion of patients never experience symptoms. Peginterferon plus ribavirin is the recommended treatment for chronic hepatitis C. However, ribavirin monotherapy may be considered for some patients.
Objectives
To assess the beneficial and harmful effects of ribavirin monotherapy for patients with chronic hepatitis C.
Search methods
We identified trials through electronic databases, manual searches of bibliographies and journals, authors of trials, and pharmaceutical companies until March 2009.
Selection criteria
We included all randomised trials irrespective of blinding, language, or publication status comparing ribavirin versus no intervention, placebo, or interferon for chronic hepatitis C.
Data collection and analysis
The primary outcome measures were serum sustained virological response (loss of hepatitis C virus RNA at least six months after treatment), liver‐related morbidity plus all‐cause mortality, and adverse events. Secondary outcome measures were end of treatment virological response, biochemical response (transaminase activity), and histological response. Randomisation methods, blinding, data handling, and funding were extracted as measures of bias control. Random‐effects and fixed‐effect meta‐analyses were performed for all outcomes. We only present the results of the fixed‐effect model if both models provide the same result regarding statistical significance. We present data as risk difference (RD) with 95% confidence intervals (CI).
Main results
We included 14 randomised trials with 657 patients. The majority of trials had unclear control of bias. Compared with placebo or no intervention, ribavirin had no significant effect on the sustained virological response (RD 0%, 95% CI ‐2% to 3%, five trials) or end of treatment virological response (RD 0% 95% CI ‐3% to 3%, ten trials). Ribavirin had no significant effect on liver‐related morbidity plus mortality (RD 0%, 95% CI ‐2% to 3%, 11 trials). Ribavirin significantly increased the risk of adverse reactions, including anaemia. Ribavirin significantly improved end of treatment biochemical and histological response but not the sustained biochemical response. Ribavirin was significantly inferior to interferon regarding virological and biochemical responses (five trials).
Authors' conclusions
Ribavirin seems without beneficial effects on serum virological response and liver‐related morbidity or mortality, and significantly increased the risk of adverse reactions. Ribavirin monotherapy seems significantly inferior to interferon monotherapy. The total number of included patients is small, and more trials are perhaps needed. The use of ribavirin monotherapy for chronic hepatitis C cannot be recommended outside randomised trials.
PICO
Plain language summary
Rawatan pesakit yang dijangkiti virus hepatitis C
Di seluruh dunia, kira‐kira 170 juta orang dijangkiti virus hepatitis C secara kronik. Hepatitis C adalah virus bawaan darah dan laluan transmisi termasuk penggunaan dadah intravena, transmisi ibu kepada bayi, amalan perubatan yang tidak selamat, tingkah laku seksual berisiko tinggi, dan transfusi darah. Hepatitis C kronik dalam kebanyakan pesakit adalah jangkitan virus yang tidak berbahaya, tetapi minoriti pesakit mendapat sirosis hati dan mungkin menderita komplikasi akibat sirosis atau mati akibatnya.
Rawatan dengan interferon membersihkan virus hepatitis C daripada darah dalam kira‐kira 15% pesakit. Menambah ribavirin kepada interferon (terapi kombinasi) meningkatkan dengan ketara kira‐kira 40% pembersihan hepatitis C dari darah. Tidak semua pesakit bertoleransi dengan interferon, dan juga interferon adalah mahal. Inilah sebabnya ribavirin diberi sebagai ubat tunggal yang mungkin dianggap pilihan bagi pesakit dengan hepatitis C kronik. Ulasan ini mengenal pasti 11 kajian rawak yang membandingkan ribavirin tanpa rawatan antiviral dalam kalangan pesakit hepatitis C kronik. Gabungan keputusan dari semua kajian tersebut menunjukkan ribavirin sahaja tiada kesan bermanfaat bagi pesakit dengan hepatitis C kronik. Tambahan pula, ribavirin yang diberi secara tunggal adalah kurang baik berbanding interferon untuk membersihkan hepatitis C dari darah dan mengenai pengurangan aktiviti enzim hati dalam darah. Lagipun, ribavirin sahaja meningkatkan risiko anemia. Oleh itu, pemberian ribavirin secara tunggal tidak boleh disyorkan, tetapi lebih banyak kajian diperlukan.
