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1.  Late biliary complications in human alveolar echinococcosis are associated with high mortality 
AIM: To evaluate the incidence of late biliary complications in non-resectable alveolar echinococcosis (AE) under long-term chemotherapy with benzimidazoles.
METHODS: Retrospective analysis of AE patients with biliary complications occurring more than three years after the diagnosis of AE. We compared characteristics of patients with and without biliary complications, analyzed potential risk factor for biliary complications and performed survival analyses.
RESULTS: Ninety four of 148 patients with AE in Zurich had non-resectable AE requiring long-term benzimidazole chemotherapy, of which 26 (28%) patients developed late biliary complications. These patients had a median age of 55.5 (35.5-65) years at diagnosis of AE and developed biliary complications after 15 (8.25-19) years of chemotherapy. The most common biliary complications during long-term chemotherapy were late-onset cholangitis (n = 14), sclerosing cholangitis-like lesions (n = 8), hepatolithiasis (n = 5), affection of the common bile duct (n = 7) and secondary biliary cirrhosis (n = 7). Thirteen of the 26 patients had undergone surgery (including 12 resections) before chemotherapy. Previous surgery was a risk factor for late biliary complications in linear regression analysis (P = 0.012).
CONCLUSION: Late biliary complications can be observed in nearly one third of patients with non-resectable AE, with previous surgery being a potential risk factor. After the occurrence of late biliary complications, the median survival is only 3 years, suggesting that late biliary complications indicate a poor prognostic outcome.
PMCID: PMC4024798  PMID: 24914349
Alveolar echinococcosis; Biliary strictures; Biliary cirrhosis; Cholangitis; Cholestatic liver disease; Chronic liver disease; Complications; Echinococcal cysts; Prognosis
2.  A degradation-sensitive anionic trypsinogen (PRSS2) variant protects against chronic pancreatitis 
Nature genetics  2006;38(6):668-673.
Chronic pancreatitis (CP) is a common inflammatory disease of the pancreas. Mutations in the genes encoding cationic trypsinogen (PRSS1)1 and the pancreatic secretory trypsin inhibitor (SPINK1)2 are associated with CP. Since increased proteolytic activity due to mutated PRSS1 enhances the risk for CP, mutations in the gene encoding anionic trypsinogen (PRSS2) may also act disease predisposing. Here we analyzed PRSS2 in CP patients and controls and found, to our surprise, that a variant of codon 191 (G191R) is overrepresented in control subjects: G191R was present in 220/6,459 (3.4 %) controls but only in 32/2,466 (1.3 %) patients (odds ratio 0.37; P = 1.1 × 10-8). Upon activation by enterokinase or trypsin, purified recombinant G191R protein showed a complete loss of trypsin activity due to the introduction of a novel tryptic cleavage site that renders the enzyme hypersensitive to autocatalytic proteolysis. In conclusion, the G191R variant of PRSS2 mitigates intrapancreatic trypsin activity and thereby plays a protective role against chronic pancreatitis.
PMCID: PMC2746914  PMID: 16699518
3.  Human Alveolar Echinococcosis after Fox Population Increase, Switzerland 
Emerging Infectious Diseases  2007;13(6):878-882.
An increase in fox population has led to an increase in incidence of human alveolar echinococcosis.
We analyzed databases spanning 50 years, which included retrospective alveolar echinococcosis (AE) case-finding studies and databases of the 3 major centers for treatment of AE in Switzerland. A total of 494 cases were recorded. Annual incidence of AE per 100,000 population increased from 0.12– 0.15 during 1956–1992 and a mean of 0.10 during 1993–2000 to a mean of 0.26 during 2001–2005. Because the clinical stage of the disease did not change between observation periods, this increase cannot be explained by improved diagnosis. Swiss hunting statistics suggested that the fox population increased 4-fold from 1980 through 1995 and has persisted at these higher levels. Because the period between infection and development of clinical disease is long, the increase in the fox population and high Echinococcus multilocularis prevalence rates in foxes in rural and urban areas may have resulted in an emerging epidemic of AE 10–15 years later.
PMCID: PMC2792858  PMID: 17553227
Alveolar echinococcosis; Echinococcus multilocularis; epidemiology; fox (Vulpes vulpes); zoonosis; incidence; Switzerland; research
4.  European Echinococcosis Registry: Human Alveolar Echinococcosis, Europe, 1982–2000 
Emerging Infectious Diseases  2003;9(3):343-349.
Surveillance for alveolar echinococcosis in central Europe was initiated in 1998. On a voluntary basis, 559 patients were reported to the registry. Most cases originated from rural communities in regions from eastern France to western Austria; single cases were reported far away from the disease-“endemic” zone throughout central Europe. Of 210 patients, 61.4% were involved in vocational or part-time farming, gardening, forestry, or hunting. Patients were diagnosed at a mean age of 52.5 years; 78% had symptoms. Alveolar echinococcosis primarily manifested as a liver disease. Of the 559 patients, 190 (34%) were already affected by spread of the parasitic larval tissue. Of 408 (73%) patients alive in 2000, 4.9% were cured. The increasing prevalence of Echinococcus multilocularis in foxes in rural and urban areas of central Europe and the occurrence of cases outside the alveolar echinococcosis–endemic regions suggest that this disease deserves increased attention.
PMCID: PMC2958541  PMID: 12643830
alveolar echinococcosis; alveolar hydatid disease; Echinococcus multilocularis; epidemiology; geographic distribution; risk factors; clinical characteristics; case registry; research

Results 1-4 (4)