Response-guided therapy for hepatitis C genotype 2 and 3 in those with HIV coinfection.

BACKGROUND: Current guidelines recommend that interferon-based treatment of hepatitis C (HCV) genotype 2 or 3 in those with HIV coinfection should be for 48 weeks, especially if HCV PCR remains positive after 4 weeks of treatment. AIM: To examine a single-center experience using response-guided therapy (RGT) using pegylated interferon (PegIFN) and weight-based ribavirin (RBV) for treating HCV genotype 2 or 3 in those with HIV coinfection. METHODS: Electronic medical records were used to identify patients with HCV genotype 2 or 3 HIV coinfection seen at the Toronto General Hospital Immunodeficiency Clinic from February 2003 to December 2012. HCV PCR was tested after every 4 weeks of treatment until it was negative (<50 IU/mL). RGT protocol was as follows: Those with HCV PCR first negative after 4 weeks (VR4) were treated 24 weeks; first negative after 8 weeks (VR8) treated 36 weeks and VR12 treated 48 weeks. RESULT: Database search identified 35 individuals with HCV genotype 2 or 3. Twelve were excluded. Total 23 patients completed the treatment and were included for data analysis. Eleven of 23 (48 %) achieved VR4 and eleven of 23 (48 %) achieved VR8. Only one individual had detectable viremia to week 12 and required 48 weeks of treatment. The majority (96 %) were successfully treated with <48 weeks of PegIFN-RBV therapy. One hundred percent achieved SVR with a response-guided HCV therapy. CONCLUSION: The use of response-guided therapy allows therapy to be shortened in the majority of individuals. HCV PCR testing should be performed every 4 weeks during the first 12 weeks of therapy until HCV PCR is negative.

The phenotypic expression of inflammatory bowel disease in patients with primary sclerosing cholangitis differs in the distribution of colitis.

BACKGROUND: Inflammatory bowel disease (IBD) associated with primary sclerosing cholangitis (PSC) is reported to be mild and prone to right-side predominance with rectal sparing. However, no dedicated studies evaluating patterns of presentation of liver disease with respect to IBD are available. METHODS: We performed a detailed histological examination of the colonic biopsies in the context of PSC, identifying 97 patients [89 with ulcerative colitis and ten with Crohn's disease (CD)] stratified into two groups, based on their initial disease presentation: hepatic/biliary (group 1-PSC-IBD; n=56) versus colonic (group 2-IBD-PSC; n=41). RESULTS: Inflammatory bowel disease that preceded PSC had a tendency to have a "pan-colitis" distribution; this group included all patients with CD. Inflammatory bowel disease diagnosis that followed PSC presentation was more likely to be right-sided, sparing the descending, sigmoid and rectal regions (p=0.002). In both groups, colitis was mild with focal deep plasmacytosis and occasional mild cryptitis. Active cryptitis with crypt abscesses, surface erosion and ulceration were not identified in any of the patients. CONCLUSION: Colitis associated with PSC shows mild disease activity and the colitis pattern is associated with disease presentation, i.e. colitis preceding PSC (IBD-PSC cohort) typically have a pancolitic distribution, while colitis following PSC (PSC-IBD cohort) demonstrates right-sided predominance. Awareness by pathologists and clinicians of these patterns of inflammatory bowel disease is important and of use in directing appropriate investigations for patients.

Death from Liver Failure despite Lamivudine Prophylaxis during R-CHOP Chemotherapy due to Rapid Emergence M204 Mutations.

Background. Rapid and early emergence of clinically significant LAM resistance is thought to be unlikely during the first year of treatment, and as a result LAM is thought to be a reasonable choice as a first line agent for prophylaxis during chemotherapy. Aim. To report fatal HBV reactivation despite appropriate LAM prophylaxis in two previously treatment-naive individuals undergoing R-CHOP chemotherapy. Case Presentation. Case 1 is a 65-year-old man with chronic HBV infection: HBeAg-negative, HBV DNA 6.65E5 IU/mL, ALT 43 IU/L, and Fibroscan 4.4 kPa, consistent with F0, who was diagnosed with lymphoma that was treated with R-CHOP and LAM prophylaxis. HBV DNA fell to 2.18E1 IU/mL within 2 months of starting LAM. Four months after chemotherapy, despite ongoing LAM of 7-month duration with confirmed adherence, severe asymptomatic hepatitis was noted during routine monitoring with ALT 1019 IU/L, HBeAg negative, HBV DNA 1.43E7 IU/mL, and genotyping confirmed L80I and M204I mutations. He died 14 days after flare diagnosis despite a switch to tenofovir (HBV DNA had fallen to 1.94E5 IU/mL 2 weeks after starting tenofovir). Case 2 is a 50-year-old man who was found to have HBeAg-negative hepatitis B, ALT 37 IU/L, and no clinical features of cirrhosis (platelets 283, APRI 0.19) after lymphoma diagnosis. Lymphoma was treated with R-CHOP and LAM prophylaxis. Pretreatment HBV DNA was not done but was 8.90E4 IU/mL 3 weeks after starting LAM and 3.96E3 IU/mL 3 months after starting LAM. Two months after chemotherapy, despite ongoing LAM of 7-month duration with confirmed adherence, severe symptomatic hepatitis presenting with jaundice, abdominal pain, and confusion was noted. ALT 902 IU/L, HBeAg negative, HBV DNA 1.02E8 IU/mL, and genotyping confirmed L80I, M80V, and M204V/S mutations. He died 3 days after flare diagnosis despite the addition of tenofovir. Conclusion. Lamivudine should not be used for prophylaxis of patients with chronic hepatitis B with detectable HBV DNA undergoing chemotherapy with rituximab containing cytotoxic chemotherapy even if they have never had exposure to lamivudine in the past. In this setting, lamivudine failure due to resistance can develop quickly leading to liver failure that cannot be salvaged with tenofovir. Whether LAM is safe for prophylaxis with rituximab-based cytotoxic chemotherapy for patients with undetectable HBV DNA is unknown, but agents with a high barrier to resistance may be preferable.