Hepatitis C flare due to superinfection by genotype 4 in an HCV genotype 1b chronic carrier Daniele Accapezzato, Francesca Fravolini, Marco Antonio Casciaro and Marino Paroli We report here on a patient affected by chronic hepatitis C who developed acute hepatitis C virus (HCV) superinfection with replacement of genotype 1b by genotype 4. The history revealed no risk factors for a new exposure to HCV, with the exception of colonoscopy with mucosal biopsy performed about 3 months before. This report underlines the absence of an effective immune- mediated cross-protection against different HCV genotypes. Moreover, the possible relationship between HCV infection and colonoscopy points out the importance of strict adherence to international guidelines for disinfection and cleaning of invasive diagnostic tools for all subjects examined, including HCV chronic carriers. Eur J Gastroenterol Hepatol 14:879–881 & 2002 Lippincott Williams & Wilkins European Journal of Gastroenterology & Hepatology 2002, 14:879–881 Keywords: HCV genotype, HCV superinfection, endoscopy Department of Internal Medicine, La Sapienza University Hospital, Rome, Italy Correspondence to Marino Paroli, Dipartimento di Medicina Interna, Policlinico Umberto I, V.le del Policlinico 155, 00161, Rome, Italy Tel: +39 06 4997 2402; fax: +39 06 494 0594; e-mail: marino.paroli@uniroma1.it Received 16 January 2002 Revised 12 March 2002 Accepted 23 April 2002 Introduction Superinfection of a hepatitis C virus (HCV) chronic carrier with a new genotype is a rare event, and is generally limited to people at very high risk of infec- tion, including drug addicts, haemodialysis patients, and patients routinely receiving plasma derivatives. Although a certain degree of antibody cross-reactivity to the various genotypes has been reported in some patients, in particular haemophiliacs [1], it is not clear whether this could confer any kind of protection to the host. Data on cross-reactive HCV genotype-specific T- cells in chronic carriers are also lacking. We report here on a case of HCV superinfection apparently following colonoscopy in an HCV chronic carrier with develop- ment of severe acute liver disease and replacement of genotype 1b by genotype 4. Case report A 38-year-old woman was referred to our liver unit in 1996 because of elevated alanine aminotransferase (ALT) levels associated with the presence of anti-HCV antibodies. She had no identifiable risk factors, with the exception of a history of several dental treatments. HCV-RNA was detected in serum, and search for HCV genotype revealed the presence of genotype 1b, based on restriction fragment length polymorphism (RFLP) analysis. This test was repeated to avoid possible errors. Liver biopsy showed a moderately active chronic hepatitis with low-grade fibrosis. Laboratory tests and ultrasonography were performed, displaying a satisfac- tory liver function and no signs of cirrhosis. Institution of interferon-based antiviral therapy was excluded due to the presence of a major depressive disorder. The patient underwent periodical laboratory investigations of liver function and ultrasound imaging as an out- patient at our unit. ALT levels were constantly ele- vated, although they were less than 1.5 times normal values. The last check for the presence of serum HCV- RNA and genotype analysis before the subsequent HCV superinfection described here was performed in December 2000, revealing about 780 3 10 3 viral copies/ ml and confirming the presence of genotype 1b. In June 2001, the patient complained of the abrupt onset of abdominal pain. She was admitted urgently to the surgical department of the nearest hospital. During her stay, abdominal ultrasound, barium enema and colonoscopy with a mucosal biopsy were performed, without any pathological findings. Laboratory investiga- tion did not reveal any significant change as compared with previous tests. The patient was eventually dis- charged with a diagnosis of irritable bowel syndrome associated with mood disorders. In August, she com- plained of general malaise, easy fatigability, nausea and anorexia. Laboratory findings revealed a sharp increase of ALT levels (about 20 times normal values), so she was admitted to our unit as an in-patient. Physical examination revealed moderate hepatomegaly with minimal liver tenderness. HCV-RNA was detected in serum with 50 3 10 3 copies/ml. Unexpectedly, geno- type 4 rather than 1b was found. The accurate taking of her medical history over the past 6 months did not reveal any risk factor for HCV superinfection other than the colonoscopy performed about 10 weeks before. Case report 879 0954–691X & 2002 Lippincott Williams & Wilkins