B Fischler et al. JPGN 2016; 63: 288-94. This position paper by ESPGHAN suggests testing children with increased transaminases for hepatitis E virus (HEV) and notes that immunocompromised children with HEV may require treatment (with ribavirin or lowering immunosuppression). Best tests: serology for IgM and IgG and HEV RNA PCR.
F Huang et alHepatology 2016; 64: 350-59. This study from China showed frequent Hepatitis E excreted in milk from infected cows and that this milk is capable of transmit infection when given to rhesus macaques, even if pasteurized. Also, the article notes that seroprevalence of HEV in recent years has been higher than prior estimates (21% from 1988-94 and 6% from 2009-2010).
The August issue of Hepatology had several articles on Hepatitis C confirming the efficacy of newer agents:
LI Backus et al Hepatology 2016; 64: 405-14. This “real-world” observational study from the VA Clinical registry with 4,365 genotype 1 treatment-naive patients who received ledipasvir/sofosbuvir showed SVR rates of 91.3% (w/o ribavirin) and 92% (w ribavirin).
P Kwo et al. Hepatology 2016; 64: 370-80 (OPTIMIST-1) This study showed that 12 weeks of simeprevir+sofusbuvir for 12 weeks was highly effective (97% SVR) and that 8 weeks of this therapy was inferior (83% SVR). N=310 with genotype 1 (w/o cirrhosis). No patients stopped therapy due to adverse effects.
E Lawitz et al. Hepatology 2016; 64: 360-69 (OPTIMIST-2) This study showed that simeprevir+sofusbuvir for 12 weeks was effective in genotype 1 patients (n=103) with cirrhosis. For treatment-naive, the SVR was 88% and for treatment-experienced patients, the SVR was 79%.
Also in Hepatology:
S Heibani et alHepatology 2016; 64: 549-55. This study looked at 1-week versus 2-week intervals for endoscopic ligation. While 1-week ligation eradicated varices more quickly, neither approach was associated with differences in number of endoscopies, complications (including rebleeding) or other clinical outcomes.
In a recent study (Hepatology 2014; 60: 815-22), data from the National Health and Nutrition Evaluation Survery (NHANES) 1988-94 was compared with the NHANES 2009-2010 with regard to Hepatitis E virus (HEV) epidemiology. In addition, the most recent surgery coupled with a high performance HEV assay. A total of 8,814 individuals were included in the analysis.
The seroprevalence of HEV was estimated at 6.0% in the U.S. which is only one-third as high as previous estimates.
Birth outside the U.S., Hispanic race, and increasing age were all factors associated with increased HEV seroprevalence. The associations of hispanic origin and birth outside U.S. as risk factors disappear when age is taken into account.
Also noted: Hepatology 2014; 60: 1082-89. “Liver transplantation in the management of porphyria” –useful review.
Paracentesis is associated with reduced mortality in patients hospitalized with cirrhosis and ascites (Clin Gastroenterol Hepatol 2014: 496-503). This study relied on a 2009 Nationwide Inpatient Sample database with about 8 million discharges per year. Of the 17,771 eligible admissions, 61% underwent paracentesis, most (66%) within 1 day of admission. “In-hospital mortality was reduced by 24% among patients who underwent paracentesis.” The authors note that some providers may overestimate the risk of bleeding and that many have developed an increased reliance on interventional radiology. While the authors were not certain why this mortality benefit occurred, they note that patients who underwent paracentesis were probably at least as sick as those who did not. “Patients who underwent paracentesis were actually more likely to have sepsis or acute renal failure, both markers of illness severity.”
Sirolimus helps with hyperinsulinemic hypoglycemia (NEJM 2014; 370: 1131-37). This brief report showed that sirolimus can be an alternative to subtotal pancreatectomy. It enabled the authors “to discontinue intravenous infusions of dextrose and glucagon in all four patients and to halt octreotide in three of four. At 1 year of age, the four patients were continuing to receive sirolimus and were normoglycemic, without any apparent major adverse events.” Of interest, these findings parallel the findings in adults with insulinoma who were treated with mTOR inhibitors.
Ribavirin treatment for chronic hepatitis E infection in transplant recipients (NEJM 2014; 370: 1111-20). Retrospective uncontrolled study of 59 patients who had undergone solid-organ transplant had been treated with ribavirin at a mean dose of 600 mg for median of three months. Median time for HEV infection prior to therapy was nine months. HEV RNA level was undetectable in 46 of 59 patients (78%) after cessation of ribavirin.
Typically, Hepatitis E virus (HEV) is not considered a frequent pathogen in the U.S.; however, anti-HEV antibody has been detected in 21% of U.S. in population-based surveys between 1988-94 and the prevalence increases with age. It has been associated with acute-on-chronic liver disease and has been overlooked in some individuals labeled as having drug-induced liver disease. Thus, HEV is a significant cause of hepatitis and a useful review has been published (NEJM 2012; 367: 1237-44). As such, see if your knowledge is up to the test.
1. True or False: Worldwide, HEV is probably the second most common form of acute hepatitis
2. True or False: The autochthonous form is more common in developed countries and can be present in developing countries. Extra credit, what does “autochthonous” mean?
3. Best test to order to diagnose acute HEV?
4. Animal(s) most likely associated with the autochthonous form of HEV: shellfish, swine, or wild game
5. True or False: there are 4 genotypes
6. True or False: antibodies (IgG and IgM) appear at the time of clinical onset, just before elevations in serum aminotransferases and symptoms
7. How long do these antibodies remain detectable?
8. Which population is most prone to fulminant epidemic HEV? Pregnant women, immunocompromised hosts, or infants
9. Incubation period? a. 1-2 weeks b. 3-8 weeks c. 9-12 weeks
10. Case fatality rate? a. 1% b. 2-4% c. 5% d. 7-10%
11. Name extrahepatic manifestations
12. Best treatments for chronic HEV?
1. False, probably the most common cause of acute hepatitis
2. True. Autochthonous refers to locally-acquired or endemic HEV
3. IgM for anti-HEV
4, Swine, but the other two have been associated with cases as well
5. True. Types 1 and 2 are more common in developing countries and associated with waterborne outbreak/fecal-oral transmission
7. IgM anti-HEV for only 3-12 months, IgG anti-HEV persists for “years, if not for life”
8. Pregnant women. Nutritional and immunologic features may increase the risk of fulminant HEV in pregnant women. Rates of HEV are lower in many immunocompromised groups. Elderly patients are more at risk for mortality due to endemic form.