Beat Muellhaupt

The natural history of pain in alcoholic chronic pancreatitis

BACKGROUND & AIMS The pain pattern of chronic pancreatitis (CP) and its surgical implications are discussed. The aim of this study was to (1) define typical pain patterns, (2) correlate pain patterns with the presumptive causes of the pain, and (3) compare the natural history of patients treated conservatively or surgically with respect to pain relief, pancreatic dysfunction, and clinical outcome. METHODS A cohort in this prospective long-term study included 207 patients with alcoholic CP (91 without and 116 with surgery for pain relief). A clinically based staging system was applied to characterize pain in the evolution from onset to end-stage CP. RESULTS Average duration of CP was 17 years. In early-stage CP, episodes of recurrent (acute) pancreatitis predominated. Chronic pain was typically associated with local complications (mainly pseudocysts, 84 of 155; 54%), relieved definitely by a single (drainage) procedure in approximately two thirds of patients. Additional surgery was required for late pain recurrence in 39 patients (34%), primarily symptomatic cholestasis (18 of 39; 46%). All patients achieved complete pain relief in advanced CP. CONCLUSIONS In our experience, relief of chronic pain regularly follows selective surgery tailored to the presumptive pain cause or occurs spontaneously in uncomplicated advanced CP.

Human Alveolar Echinococcosis after Fox Population Increase, Switzerland

An increase in fox population has led to an increase in incidence of human alveolar echinococcosis.

Association of Noncirrhotic Portal Hypertension in HIV-Infected Persons and Antiretroviral Therapy with Didanosine: A Nested Case-Control Study

BACKGROUND Noncirrhotic portal hypertension (NCPH) is a newly described life-threatening liver disease of unknown cause in human immunodeficiency virus (HIV)-infected persons. Postulated pathogenesis includes prolonged exposure to antiretroviral therapy, particularly didanosine. METHODS We performed a nested case-control study including 15 patients with NCPH and 75 matched control subjects of the Swiss HIV Cohort Study to investigate risk factors for the development of NCPH. Matching criteria were similar duration of HIV infection, absence of viral hepatitis, and follow-up to at least the date of NCPH diagnosis in the respective case. RESULTS All 15 case patients had endoscopically documented esophageal varices and absence of liver cirrhosis on biopsies; 4 died because of hepatic complications. At NCPH diagnosis, case patients and control subjects were similar concerning sex; race; Centers for Disease Control and Prevention stage; HIV-RNA level; CD4 cell count nadir; and lipids and lipodystrophy. Differences were found in age (conditional logistic regression odds ratio [OR] for 10 years older, 2.9; 95% confidence interval [CI], 1.4-6.1); homosexuality (OR, 4.5; 95% CI, 1.2-17); current CD4 cell count <200 cells/microL (OR, 34.3; 95% CI, 4.3-277); diabetes mellitus (OR, 8.8; 95% CI, 1.6-49); alanine aminotransferase level higher than normal (OR, 13.0; 95% CI, 2.7-63); alkaline phosphatase higher than normal (OR, 18.3; 95% CI, 4.0-85); and platelets lower than normal (OR, 20.5; 95% CI, 2.4-178). Cumulative exposure to antiretroviral therapy (OR per year, 1.3; 95% CI, 1.0-1.6), nucleoside reverse-transcriptase inhibitor (OR, 1.3; 95% CI, 1.1-1.7), didanosine (OR, 3.4; 95% CI, 1.5-8.1), ritonavir (OR, 1.4; 95% CI, 1.0-1.9), and nelfinavir (OR, 1.4; 95% CI, 1.0-1.9) were longer in case patients. Exposure to nonnucleoside reverse-transcriptase inhibitor and other protease inhibitors were not different between groups. In bivariable models, only the association of NCPH with didanosine exposure was robust; other covariables were not independent risk factors. CONCLUSIONS We found a strong association between prolonged exposure to didanosine and the development of NCPH.

Psychosocial Profiles After Transplantation : A 24-Month Follow-Up of Heart, Lung, Liver, Kidney and Allogeneic Bone-Marrow Patients

Objectives. Quality of life and psychosocial well-being usually improve after an organ transplant and remain stable for a minimum of several years. These findings, however, mainly apply to the “average” trend for transplant patients. This study aims to investigate whether transplant patients fall into different groups in good or poor psychosocial outcome after organ transplantation. Methods. One hundred thirty-one patients were assessed before and 6, 12, and 24 months after a heart, lung, liver, kidney, or bone-marrow transplant. Cluster analysis was applied to identify typical outcome profiles of the patients’ mental health (SF-36); differences between the clusters were investigated with regard to further psychosocial parameters (sense of coherence, optimism, psychosocial functioning, anxiety, depression, life/health satisfaction, medication experience). Results. The analysis revealed two clusters of transplant patients. Cluster A (n=78, 59.5%) showed a fairly good psychosocial outcome, improving over the posttransplant period of 2 years. Cluster B (n=53, 40.5%) included patients who reported a limited or poor outcome, deteriorating after the transplant. Furthermore, there are significant differences between clusters A and B in psychosocial parameters and physical functioning. Conclusions. These findings indicate that the experience of the transplant process may vary greatly from patient to patient, and that a considerable number of transplant recipients require psychosocial support, despite the majority of patients showing an unquestionable posttransplant improvement in psychosocial well-being.

Mutations of the cystic fibrosis gene in patients with chronic pancreatitis

OBJECTIVE: Several studies have reported an increased frequency of cystic fibrosis gene mutations in idiopathic but not in alcoholic chronic pancreatitis. The impact of cystic fibrosis gene mutations on the long-term course of chronic pancreatitis has not been analyzed. The aim of our study was to determine the frequency of cystic fibrosis gene mutations in patients with chronic pancreatitis with long-term follow-up and to see whether patients with mutations have a clinically different natural course compared to those without mutations. METHODS: Eighty two patients with chronic pancreatitis and 11 patients with recurrent acute pancreatitis of our well defined pancreatitis cohort were screened for the 31 most common cystic fibrosis gene mutations. The impact of cystic fibrosis gene mutations on the long-term course of chronic pancreatitis was assessed. RESULTS: A cystic fibrosis gene mutation was detected in five of 49 patients with alcoholic chronic pancreatitis (10.2%; 2.3 times the expected frequency) and in three of 14 patients with idiopathic-juvenile chronic pancreatitis (21.4%; 4.8 times the expected frequency). No mutations were found in the remaining patients with chronic pancreatitis of rare causes, hereditary pancreatitis, and recurrent acute pancreatitis. The frequency of pancreatic calcifications was significantly higher in patients with alcoholic chronic pancreatitis without mutations. This result was not confirmed in patients with idiopathic-juvenile chronic pancreatitis. The duration of pain and the frequency of exocrine and endocrine insufficiency was comparable in both subgroups irrespective of the mutation status. CONCLUSION: Our data indicate a significantly increased frequency of cystic fibrosis gene mutations both in patients with alcoholic and idiopathic-juvenile chronic pancreatitis. The natural course was similar in patients with mutations compared to those without mutations.

Connective tissue growth factor, steatosis and fibrosis in patients with chronic hepatitis C

Background/Aim: Both steatosis and insulin resistance have been linked to accelerated fibrosis in chronic hepatitis C. Connective tissue growth factor (CTGF) plays a major role in extracellular matrix production in fibrotic disorders including cirrhosis, and its expression is stimulated in vitro by insulin and glucose. We hypothesized that CTGF may link steatosis, insulin resistance and fibrosis.

Potential cellular receptors involved in hepatitis C virus entry into cells

Hepatitis C virus (HCV) infects hepatocytes and leads to permanent, severe liver damage. Since the genomic sequence of HCV was determined, progress has been made towards understanding the functions of the HCV-encoded proteins and identifying the cellular receptor(s) responsible for adsorption and penetration of the virus particle into the target cells. Several cellular receptors for HCV have been proposed, all of which are associated with lipid and lipoprotein metabolism. This article reviews the cellular receptors for HCV and suggests a general model for HCV entry into cells, in which lipoproteins play a crucial role.

Outcomes of liver transplantations from donation after circulatory death (DCD) treated by hypothermic oxygenated perfusion (HOPE) before implantation

BACKGROUND & AIMS Donation after circulatory death (DCD) liver transplantation is known for potentially worse outcomes because of higher rates of graft non-function or irreversible cholangiopathy. The impact of machine liver perfusion techniques on these complications remains elusive. We aimed to provide data on 5-year outcomes in patients receiving DCD liver transplants, after donor organs had been treated by hypothermic oxygenated perfusion (HOPE). METHODS Fifty HOPE-treated DCD liver transplants performed in Zurich between 2012 and 3/2017 were matched with 50 primary donation after brain death (DBD) liver transplants, and with 50 untreated DCD liver transplants in Birmingham. Match factors focussed on short cold ischaemia, comparable recipient age and low recipient laboratory model for end-stage liver disease scores. Primary endpoints were post-transplant complications, and non-tumour-related patient death or graft loss. RESULTS Despite extended donor warm ischaemia, HOPE-treated DCD liver transplants achieved similar overall graft survival, compared to standard DBD liver transplants. Particularly, graft loss due to any non-tumour-related causes occurred in 8% (4/50) of cases. In contrast, untreated DCD livers resulted in non-tumour-related graft failure in one-third (16/50) of cases (p = 0.005), despite significantly (p <0.001) shorter functional donor warm ischaemia. Five-year graft survival, censored for tumour death, was 94% for HOPE-treated DCD liver transplants vs. 78% in untreated DCD liver transplants (p = 0.024). CONCLUSIONS The 5-year outcomes of HOPE-treated DCD liver transplants were similar to those of DBD primary transplants and superior to those of untreated DCD liver transplants, despite much higher risk. These results suggest that a simple end-ischaemic perfusion approach is very effective and may open the field for safe utilisation of extended DCD liver grafts. LAY SUMMARY Machine perfusion techniques are currently being introduced into the clinic, with the aim of optimising injured grafts prior to implantation. While short-term effects of machine liver perfusion have been frequently reported in terms of hepatocellular enzyme release and early graft function, the long-term benefit on irreversible graft loss has been unclear. Herein, we report on 5-year graft survival in donation after cardiac death livers, treated either by conventional cold storage, or by 1-2 h of hypothermic oxygenated perfusion (HOPE) after cold storage. Graft loss was significantly less in HOPE-treated livers, despite longer donor warm ischaemia times. Therefore, HOPE after cold storage appears to be a simple and effective method to treat high-risk livers before implantation.Objectives: To provide 5-year outcome in human livers donated after circulatory death (DCD), treated by hypothermic oxygenated perfusion (HOPE). Background: DCD liver transplantation is known for potential worse outcome due to higher rates of graft non-function or irreversible cholangiopathy. The impact of machine liver perfusion techniques on these complications remains elusive. Methods: Fifty HOPE treated DCD liver transplants in Zurich between 2012 and 3/2017 were matched with 50 primary DBD liver transplants, and also with 50 un-treated DCD livers in Birmingham. Match factors focused on short cold ischemia, comparable recipient age and low recipient lab MELD. Primary endpoints were post-transplant complications, and non-tumor related patient death or graft loss. Results: Despite extended donor warm ischemia, HOPE treated DCD liver transplants achieved similar overall graft survival, compared to standard DBD liver transplants. Particularly, graft loss due to any non-tumor related causes occurred in 8% (4/50) of cases. In contrast, un-treated DCD livers resulted in non-tumor related graft failure in one-third (16/50) of cases (p=0.005), despite significant (p<0.001) shorter functional donor warm ischemia. Five-year graft survival, censored for tumor death, was consecutively 94% for HOPE treated vs 78% in un-treated DCD liver transplants (p=0.024). Conclusions: Outcome of HOPE treated human DCD liver transplants maintained over a period of five years, was comparable with DBD primary transplants, and also superior to un-treated DCD livers, despite much higher risk. These results suggest strong effectivity of a simple end-ischemic perfusion approach and may open the field for safe utilization of extended DCD liver grafts.