Unusual presentation of fatal disseminated varicella zoster virus infection in a patient with lupus nephritis: a case report.

BACKGROUND: The risk of life-threatening complications, such as visceral disseminated varicella zoster virus (VZV) infection, is greater in immunosuppressed individuals, such as systemic lupus erythematosus (SLE) patients. CASE PRESENTATION: Here, a case is reported of a Caucasian woman diagnosed with lupus nephritis and anti-phospholipid syndrome, who was subjected to mycophenolate mofetil and high-dose steroid remission-induction therapy. Two months later she developed abdominal pain followed by a fatal rapid multi-organ failure. As no typical skin rashes were evident, death was initially attributed to catastrophic anti-phospholipid syndrome. However, autopsy and virological examinations on archival material revealed a disseminated VZV infection. CONCLUSIONS: Overall, this case highlights the importance of having a high clinical suspicion of fatal VZV infections in heavily immunosuppressed SLE patients even when typical signs and symptoms are lacking.

Interplay of PNPLA3 and HSD17B13 Variants in Modulating the Risk of Hepatocellular Carcinoma among Hepatitis C Patients.

A single-nucleotide polymorphism causing a C to G change in the PNPLA3 gene (rs738409) is associated with disease severity and development of hepatocellular carcinoma (HCC) in nonalcoholic fatty liver disease; the insertion variant rs72613567:TA of the 17ß-hydroxysteroid dehydrogenase type 13 (HSD17B13) mitigates this detrimental effect. Our aim was to evaluate if the same holds true in chronic hepatitis C virus infection (HCV). With a case control retrospective study design, we selected 110 patients who developed HCC on a background of HCV infection, matching each patient for sex and age (±30 months) to three HCV-infected, non-HCC patients. All participants underwent genotyping for PNPLA3 and HSD17B13 gene variants. Both univariate and multivariate analyses of risk factors for advanced disease and HCC were performed. Carriage of PNPLA3 G∗ allele was associated with a trend of progressively more severe liver disease, from mild fibrosis to significant fibrosis, cirrhosis, and HCC (p = 0.007). When the HSD17B13:TA status of these patients was taken into account, the abovementioned trend was strengthened among HSD17B13 major allele homozygotes and completely blunted among carriers of the minor allele (p = 0.0003 and 0.953, respectively). In a conditional logistic regression model including diabetes and AST to platelet ratio index among predictor variables, the unfavourable genetic profile characterized by the coexistence of the PNPLA3 minor allele and HSD17B13 major allele (vs. all other possible combinations) was an independent risk factor for HCC (OR = 2.00, 95% CI: 1.23-3.26) together with a history of alcohol abuse. In conclusion, carriage of the combination PNPLA3 minor allele and HSD17B13 major allele may represent a risk factor for HCC among HCV-infected patients. The interplay between the two genes may explain some of the controversy on this topic and may be exploited to stratify HCC risk in hepatitis C.

IL-28B rs12979860 C/T allele distribution in patients with liver cirrhosis: role in the course of chronic viral hepatitis and the development of HCC.

BACKGROUND & AIMS: A single nucleotide polymorphism (rs12979860 C/T) 3kb upstream of the interleukin 28B (IL-28B) gene was shown to be associated with hepatitis C clearance. We verified whether this association also translates into a different genotype distribution at the end of the disease trajectory. METHODS: A RFLP-PCR technique was used to genotype 412 patients with cirrhosis due to hepatitis C (n=199), hepatitis B (n=75), alcohol (n=110), and other causes (n=28), of whom 256 underwent liver transplantation (OLT). Hepatocellular carcinoma (HCC) was demonstrated in the native liver of 85 OLT patients, 52 with viral cirrhosis, and 33 with non-viral cirrhosis respectively. A group of 292 patients (235 HCV and 57 HBV positive) with mild chronic hepatitis and 344 healthy subjects served as controls. RESULTS: A significant difference (p=0.0005) was observed in IL-28B rs12979860 genotype frequencies between patients with viral cirrhosis (C/C=99, C/T=137, T/T=38) and those with non-viral cirrhosis (C/C=72, C/T=58, T/T=8). Patients with HCV related cirrhosis carried more frequently the T/T genotype in comparison to mild hepatitis C or HBV-related cirrhosis. IL-28B rs12979860 genotype frequencies were C/C=23, C/T=50, T/T=12 among OLT patients with cirrhosis complicated by HCC, and C/C=79, C/T=78, T/T=14 among patients with cirrhosis not complicated by HCC (p<0.005). CONCLUSIONS: IL-28B rs12979860 C/T polymorphism T allele is more prevalent in patients with viral cirrhosis due to HCV in comparison to other aetiologies and to patients with mild chronic hepatitis C. Among OLT patients, carriage of this allele seems to augment the risk of developing HCC.

Influence of angiotensin-converting enzyme I/D gene polymorphism on clinical and histological correlates of chronic hepatitis C.

AIM: This study aimed to verify the relationship between the insertion-deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE) and clinical and histological correlates of chronic hepatitis C. METHODS: Two-hundred and fifty-eight, treatment naive, unselected hepatitis C virus (HCV) RNA-positive patients and 210 controls were studied. ACE allelic variants were determined by polymerase chain reaction. RESULTS: Mean staging scores adjusted for age, body mass index (BMI) and alcohol consumption were: men, D/* = 2.283; men, I/I = 2.092; women, D/* = 2.241; and women, I/I = 3.283 (P = 0.028). Age-adjusted mean BMI were: men, D/* = 25.01; men, I/I = 24.87; women, D/* = 23.73; and women, I/I = 22.50 (P = 0.006). Age and BMI-adjusted mean low-density lipoprotein (LDL)/ high-density lipoprotein (HDL) cholesterol ratios were: men, D/* = 2.344; men, I/I = 2.283; women, D/* = 1.916; and women, I/I = 1.903 (P = 0.004). Histological grading correlated positively with triglycerides and negatively with HDL and LDL cholesterol (P < 0.0001). CONCLUSION: Female ACE I/I homozygotes have higher liver fibrosis scores in comparison to D/* women and to men; moreover, they are leaner and have a lower LDL/HDL cholesterol ratio. These observations suggest a possible mutual influence between ACE polymorphism, serum lipid concentrations and outcome of chronic HCV infection.

ACE genotype, body weight changes and target organ damage in renal transplant recipients.

BACKGROUND: Carriage of the angiotensin-converting enzyme (ACE) D-allele favors weight gain in mid-life and, possibly, cardiovascular complications; we aimed to verify the relationship between these conditions and ACE polymorphisms in the renal transplant (RTx) setting. METHODS: ACE genotypes were evaluated in 169 RTx recipients (107 males, 62 females) and related to body mass index (BMI; kg/m2) changes 1 year after transplant, as well as to cardiovascular events and allograft loss. Allelic frequencies and body weights were compared with those of a control group (age- and sex-matched healthy blood donors). RESULTS: Allelic frequencies were 0.639 and 0.669 for the D-allele, and 0.361 and 0.331 for the I-allele, in recipients and controls, respectively (p=NS). In the patient population, carriage of the I/ allele was associated with a BMI >23 at the time of RTx (p<0.005). In contrast, in the control group, higher BMI values tended to occur in D/ carriers. Moreover, BMI values were higher in the control group (24.7 -/+ 3.5 vs. 23.6 -/+ 3.3, p=0.003) but, 1 year after RTx, this difference was nullified. At multivariate analysis, the factors associated with weight gain after RTx were ACE D/D (odds ratio [OR] = 2.35, 95% confidence interval [95% CI], 1.00-5.49) and age at RTx

Pancreatobiliary reflux resulting in pancreatic ascites and choleperitoneum after gallbladder perforation.

A 65-year-old man with chronic hepatitis C and no history of alcohol abuse was admitted to our liver unit for the recent development of massive ascites and presumed hepatorenal syndrome. In the preceding two weeks, he had received medical treatment for acute pancreatitis and cholecystitis. Abdominal paracentesis demonstrated a cloudy, orange peritoneal fluid, with total protein concentration 3.6 g/dl, serum-ascites albumin gradient 1.0 g/dl, and ratios of ascites-serum bilirubin and amylase approximately 8:1. Diagnostic imaging demonstrated no pancreatic pseudocysts. Ten days later, at laparotomy, acalculous perforation of the gallbladder was identified. After cholecystectomy, amylase concentration in the ascitic fluid dropped within a few days to 40% of serum values; ascites disappeared within a few weeks. We conclude that in the presence of a perforated gallbladder, pancreatobiliary reflux was responsible for this unusual combination of choleperitoneum and pancreatic ascites, which we propose to call pancreatobiliary ascites.