Hepatitis C Reactivation with Chemotherapy

There are a lot of reports describing the potential of adverse outcomes due to hepatitis B reactivation with chemotherapy as well as with treatment of hepatitis C; in addition, there are recommendations to prevent this occurrence (see below). With hepatitis C virus (HCV), the issue of reactivation has not garnered the same type of concern.  A recent study (HA Torres et al. Hepatology 2018; 67: 36-47) indicates that HCV can reactivate with chemotherapy, though this may not result in adverse outcomes. The authors prospectively followed HCV-infected patients receiving cancer therapy from 2012-16.  Reactivation was defined as HCV RNA increase >1 log over baseline and hepatic flare as an increase in ALT >3 times ULN.

Key finding:

  • “Reactivation occurred in 23 (23%)…No patient with reactivation experienced liver failure or liver-related death within 36 weeks after initiation of cancer treatment…most had an unremarkable clinical course.”

Related articleM Persico et al. Hepatology 2018; 67: 48-55.  In the Persico study, the authors examined the association of HCV with non-Hodgkin’s lymphoma. In this observational study, all patients underwent antiviral therapy with sofosbuvir/ledipasvir and chemotherapy.  Compared to a historical control group, the antiviral treatment group had similar overall survival but a significantly higher disease-free survival after 52 weeks.  Thus, the authors note that antiviral treatment combined with chemotherapy, “was shown to be safe and effective in influencing remission of aggressive lymphomas in HCV patients.”

Related blog posts:

View from Bright Angel Trail

Cancers Complicating Inflammatory Bowel Disease

In several prior posts, the issue of cancer and inflammatory bowel disease (IBD) has been discussed.  In my view, even the word “cancer” is so scary that it can make people make bad choices (related: Facts, “Misfearing” and Women’s Health | gutsandgrowth).  An up-to-date succinct summary (Laurent Beaugerie, M.D., Ph.D., and Steven H. Itzkowitz, M.D. N Engl J Med 2015; 372:1441-1452) provides a fairly good overview of “Cancers Complicating Inflammatory Bowel Disease.”

Key points:

  • “Smokers are overrepresented among the patients with Crohn’s disease…results in an excess rate of smoking related cancers.” (Smoking also is associated with more aggressive Crohn’s)
  • Colorectal cancers risk factors (Table 1), specific to IBD, include coexisting primary sclerosing cholangitis (PSC), and increasing duration & extent of colonic IBD.
  • A “progressive decrease in the excess risk of colorectal cancer in patients with IBD has been noted over time.”  This may be due to better control of inflammation, surveillance, and colectomy.  Still, the risk of colorectal cancer in patients with IBD is 1.5 to 2 times greater than the general population risk.
  • Small-bowel adenocarcinoma –risk is 20-30 times that of the general population, typically arises more than 8 years after diagnosis.  Absolute risk in those with disease more than 8 years is estimated at “0.5 per 1000 patient-years.”
  • Intestinal lymphomas –absolute risk is about 0.1 per 1000 patient-years.
  • Cholangiocarcinoma (CCA)–absolute risk is approximately “0.08 per 1000 patient-years.” CCA is mainly evident in patients with PSC who have a risk ~160 times the general population and lifelong risk of 5-10%.
  • Non-Hodgkin’s lymphoma –“whether TNF-alpha antagonists promote lymphomas by themselves in patients with IBD is difficult to assess…” A recent study found no excess risk in patients receiving TNF-alpha antagonists after adjustments for cotreatments.
  • Skin Cancers –nonmelanoma skin cancer, though not life-threatening, occur more often in those with current thiopurine usage.
  • HPV-Related Cervical Cancer –“it is still unclear whether the risk of HPV-related cervical cancer is intrinsically increased in woman with IBD or independently worsened by exposure to an immunosuppressant.”
  • Thiopurines: “after adjustment for confounders, current use of thiopurines for IBD has been shown to be associated with an overall relative risk of cancer of 1.3 to 1.7.”
  • TNF-alpha antagonists: “There is no overall excess risk of cancer in patients treated with TNF-alpha antagonists for IBD.”  However, more long-term data are needed.

Recommendations:

  • Figure 2 provides recommendations for colorectal cancer surveillance based on the American Gastroenterological Association (AGA), British Society of Gastroenterology (BSG) and European Crohn’s and Colitis Organisation (ECCO) recommendations. Typically, 8-10 years after diagnosis of colitis, starting surveillance (with chromoendoscopy if available) is recommended.  In patients with Crohn’s disease, “the excess risk appears when more than 30 to 50% of the colonic surface is ever involved.” However, with PSC, the excess risk of colorectal cancer is significant at the time of diagnosis.
  • For cholangiocarcinoma screening in those with PSC, “most experts recommend noninvasive annual imaging of the biliary tract (MRCP or ultrasound) and serum CA 19-9.”
  • For HPV, vaccination is recommended and regular Papanicolaou tests

Take-home message: Some cancers are increased in association with IBD.  However, the medications, particularly immunosuppressants, may reduce the incidence of inflammation-related cancers…or promote immunosuppression-related cancers.

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Sandy Springs

Sandy Springs

Anti-Tumor Necrosis Factor Therapies and Cochrane Reviews

A recent article (Inflamm Bowel Dis 2014; 20: 2132-41) reviews the best available evidence on anti-TNF therapies.  This article emerged from a Cochrane collaboration session at Digestive Diseases Week (DDW) in 2013.

Key points:

  • “There is insufficient evidence to recommend ECI (early combined immunosuppression)) for every newly diagnosed patient, although it may be justifiable in some “high-risk” patients.”
  • With Crohn’s disease, combination of infliximab and azathioprine significantly improved remission, steroid-free remission, and mucosal healing rates compared with infliximab alone.
  • “A recent Cochrane review has shown that infliximab, adalimumab, and certolizumab are all effective…The choice of TNF-α antagonist depends on adherence, patient preference, mode of delivery, and cost.
  • Elective switching of TNF-α antagonists: in patients who are doing well, elective switching “may be associated with loss of both tolerance and efficacy.”  “Dose intensification or early treatment termination was observed in 47% of patients who switched to adalimumab after an ongoing response to scheduled maintenance infliximab therapy compared with 16% of patients who remained on infliximab maintenance therapy.” 28% of ADA patients discontinued therapy compared with 2% of IFX patients.
  • When to stop therapy: among patients in deep remission >6 months who stopped, relapse occurred in 43.9% over 1 year.
  • Patients who take thiopurines or biologics (IFX or ADA) have an increased risk of nonmelanoma skin cancer. Odds ratio, compared to controls, as high as 6.75 for combination therapy (>365 days).
  • Lymphoma: the Cochrane review “found no statistically significant difference in the incidence of lymphoma between biologics and control treatment…and data from the TREAT registry also demonstrated no apparent signal for TNF-α antagonist (i.e. infliximab)-related lymphoma or overall malignancy.”
  • There has been incremental risk of Non-Hodgkin’s lymphoma and hepatosplenic T-cell lymphoma with azathioprine (thiopurines).

Related blog posts:

Other articles briefly noted:

Inflamm Bowel Dis 2014; 20: 2142-50. “Approach and management of patients with chronic hepatitis B and hepatitis C during the course of inflammatory bowel disease.”

Inflamm Bowel Dis 2014; 20: 2151-56.  Use of cyclosporin and tacrolimus in inflammatory bowel disease.  Checking hepatitis B surface antigen, surface antibody, and core antibody are recommended at the time of diagnosis of IBD. Algorithm for managing hepatitis B serology is given in Figure 1.

Another life-threatening complication of HCV

Epidemiological studies have shown a causal relationship between B-cell non-Hodgkin lymphoma (B-NHL) and hepatitis C virus (HCV) (Hepatology 2012; 55: 634-641).  This is not simply an association but a cause and effect.

The cited reference reviews several aspects of this relationship including the mechanisms of lymphoproliferation, the epidemiology, the clinical manifestations, the treatment, the prognosis, and preventive measures.

  • With regard to epidemiology, the odds ratios are between 2.4 and 5.2.  This is a small risk compared to hepatocellular carcinoma.
  • Management: Lymphoma may regress with HCV treatment, indicating a role for HCV in pathogenesis.   HCV treatment may prevent the occurrence of B-NHLs as well.  For aggressive lymphomas, patients require systemic treatment with rituximab-based regimens (1st line treatment).
B-NHLs are not nearly as important as cirrhosis and hepatocellular carcinoma in terms of mortality and morbidity in patients with HCV.  It is nevertheless quite significant considering the number of infected persons worldwide.
Other related posts on HCV:

Additional references:

  • -Gastroenterology 2011; 140: 1182. Increasing HCC/Cirrhosis in HCV pts.
  • -Clinical Gastro & Hep 2008; 6: 451. HCV associated with increased risk of non-Hodgkins lymphoma. OR was 1.8 among n=4784 cases of NHL/n=6269 controls
  • -Clinical Gastro & Hep 2008; 6: 459. Overweight & obesity increase risk of HCC. n=1431 chronic HCV patients; 36% developed HCC over 10 year f/u. OR 1.9 of HCC if overweight & 3.1 OR of HCC if obese.
  • -NEJM 2002; 347: 89-95. regression of splenic lymphoma w HCV treatment.