Concomitant diffuse large B-cell lymphoma and hepatocellular carcinoma in chronic hepatitis C virus liver disease: a study of two cases.

Chronic hepatitis C virus HCV infection progresses through liver fibrosis and cirrhosis to hepatocellular carcinoma HCC. It appears to be causally related to B-cell non-Hodgkin's lymphoma since regression after antiviral therapy has been described. Two cases are described of non-Hodgkin's lymphoma and HCC arising simultaneously in two patients. The first patient did not have cirrhosis on liver biopsy. HCV had been undetectable in plasma following successful therapy with interferon and ribavirin treatment 7 years earlier. The second patient developed an aggressive form of hepatocellular carcinoma HCC within weeks of stopping treatment with interferon and ribavirin. Therapy had induced complete viral suppression for over 40 weeks. The two cases suggest that non-Hodgkin's lymphoma and HCC can develop in the absence of detectable hepatitis C viremia and argues for continued surveillance even after sustained virological response to treatment.

Changing treatment paradigms: hepatitis C virus in HIV-infected patients.

The evaluation of hepatic histology and treatment of hepatitis C virus (HCV)/HIV-coinfected patients is rapidly changing. HCV has become an important cause of mortality in HIV-infected patients. Consequently, assessment of liver histology in all coinfected patients is particularly important. The evaluation of hepatic histology is shifting from reliance on the liver biopsy toward noninvasive modalities. Additionally, the importance of HCV-associated morbidity and mortality in HIV-infected patients has prompted increasing numbers of these patients to be HCV treatment candidates. Prospective trials in coinfected patients have reported lower sustained virologic responses compared to HCV-monoinfected patients. Consequently, the numbers of coinfected nonresponders to pegylated interferon/ribavirin continues to increase. Because none of the presently available treatment modalities for pegylated interferon/ribavirin nonresponders are clearly efficacious, management decisions must be individualized. The options include, HCV-specific medications, maintenance therapy, the use of alternative interferon formulations, and observation. HCV-specific agents, particularly protease and polymerase inhibitors, show early promise in HCV-monoinfected individuals. Their use in coinfected patients, however, is likely to be delayed for several years, and they are likely to be used in combination with interferon. Low-dose pegylated interferon, administered in an attempt to slow fibrosis progression (maintenance therapy), is being evaluated in several large prospective trials in monoinfected and coinfected patients. Observation may be best for nonresponders with relatively mild hepatic histology. In summary, HCV treatment will likely follow the example forged by HIV. In the near future, combinations of different drugs will likely be used simultaneously to result in durable viral suppression.

Prognostic significance of hepatitis C virus RNA detection by transcription-mediated amplification with negative polymerase chain reaction during therapy with peginterferon alpha and ribavirin.

The lower limit of detection of most polymerase chain reaction (PCR) assays for hepatitis C virus (HCV) RNA is 50 IU/ml, compared to 5 IU/ml for the transcription-mediated amplification (TMA) method. We retrospectively reviewed 57 patients to assess the predictive value of a positive TMA in the setting of a negative PCR during antiviral therapy. Patients were divided into (1) PCR-/TMA+ (discordant; n=21) and (2) PCR-/TMA-(concordant; n=36). Sustained virologic response (SVR) was decreased in the discordant group (48% vs. 75%; P=0.04). In discordant patients, SVR was more frequent in patients who had one positive TMA than in those who had two or more positive TMAs or one positive TMA and recurrent HCV RNA detectability by PCR during treatment (78% vs. 25%; P=0.03). Breakthrough occurred more frequently in discordant patients (24% vs. 3%; P=0.02). A positive TMA on two or more occasions in patients who have become PCR-negative on therapy indicates a high likelihood of treatment failure.