Varicella-Zoster Virus-Induced Hepatitis in a Liver Transplant Recipient: A Case Report.

Infections after solid organ transplantation are a major cause of mortality and morbidity. Varicella-zoster virus (VZV) infection after solid organ transplantation is rare. Here we present a case presenting with acute hepatitis and shingles after a liver transplantation (LT). A 36-year-old male patient underwent a liver transplantation; 7 months later his liver function tests increased. An examination and test results revealed that he had VZV-induced hepatitis. After VZV treatment, his test results returned to normal levels. Hepatic involvement of VZV infection is rare, but it may be fatal in immunocompromised individuals. Early diagnosis and early initiation of antiviral therapy is important in the control of hepatitis and rare hepatotropic viruses in immunocompromised individuals.

Kidney biopsy reveals metastatic adenocarcinoma of the appendix simulating nephrotic syndrome.

Membranous glomerulonephritis (MGN) is among the most common causes of nephrotic syndrome in adults. The malignancy in presumed tumor-induced MGN has usually been diagnosed at the time the proteinuria is discovered. Here we report a 57-year-old male patient with a history of refractory pyuria and nephrotic syndrome. The kidney biopsy confirmed the diagnosis of not only MGN, but also metastasis of appendix adenocarcinoma. To our knowledge this is the first case report diagnosed as a metastatic malignancy from a kidney biopsy which no other imaging techniques were able to display.

Biliary complications in 106 consecutive duct-to-duct biliary reconstruction in right-lobe living donor liver transplantation performed in 1 year in a single center: a new surgical technique.

OBJECTIVE: Biliary complications remain a major source of morbidity after living donor liver transplantation (LDLT). Of 109 consecutive right lobe (RL)-LDLTs performed in 1 year in our institution, we present the biliary complications among 106 patients who underwent a new duct-to-duct anastomosis technique known as University of Inonu. METHODS: Of 153 liver transplantations performed in 1 year from January to December of 2008, 128 were LDLTs including 109 RL-LDLTs. The others were left or left lateral grafts. All RL-LDLT patients were adults, all of whom except three included a duct-to-duct anastomosis. RESULTS: All, but three, biliary reconstructions were completed with a surgical technique, so called UI, in which 6-0 prolene sutures were used. Nine bile leaks were seen in 106 recipients (8.49%) performed in a duct-to-duct fashion in a time period of 1 to 4 weeks. Seventeen patients (16.03%) posed bile duct stricture (BDS). Five patients had both. Although endoscopic stent placement and percutaneous balloon dilatation, 4 patients continued to suffer from BDS on whom a permanent access hepatico-jejunostomy (PAHJ) procedures were performed. CONCLUSION: We recommend a duct-to-duct biliary reconstruction because of its de facto advantages over other types of anastomosis provided the native duct is not diseased. After almost 2 years, the bile tract complication rate was 22.64%.

Expression of matrix metalloproteinases 2 and 9 in donor liver, cirrhotic liver, and acute rejection after human liver transplantation.

Matrix proteinases are known to play an important role in the cell migration during cancer invasion, in organ development, and in tissue damage during inflammatory process. Among the matrix proteinases, matrix metalloproteinases (MMP) are the most powerful proteinases. Changes at the extracellular matrix components play an essential role in acute rejection after orthotopic liver transplantation (OLT). This prospective clinical study investigated the alterations in the expression of MMP-2 (72-kd gelatinase type IV collagenase [gelatinase A]) and MMP-9 (92-kd gelatinase type IV collagenase [gelatinase B]) in patients with acute cellular rejection (ACR) compared with the biopsies of cirrhotic livers (CL) of patients who underwent OLT, and with healthy livers (HL) of the donors. Although MMP-2 expression was not present in the hepatocytes of the HL, it was in the endothelium; it was moderate in CL and severe in the livers suffering from ACR. MMP-9 expression, on the other hand, is found to be present only in the inflammatory cells, with an increasing intensity in HL, CL, and in livers suffering from ACR. The results suggest that MMP-2 and MMP-9, beside their roles in liver injury with tissue remodeling and fibrosis as mentioned in the previous studies, can be a marker of acute rejection.

Effect of resveratrol and melatonin on oxidative stress enzymes, regeneration, and hepatocyte ultrastructure in rats subjected to 70% partial hepatectomy.

AIM: We sought to compare the antioxidant effects of resveratrol (R) and melatonin (M) after 70% partial hepatectomy (PH) as evidenced by ultrastructural alterations and effects on hepatocyte proliferation and apoptosis. METHODS: Twenty-six male Wistar albino rats were randomized into four groups: group A (n = 8) resveratrol (R); group B (n = 8) melatonin (M); group C (n = 5) control PH; group D (n = 5) sham operated animals. The rats that received either R or M were sacrificed a week after PH. The malondialdehyde, glutathione, glutathione S-transferase, and nitric oxide levels were estimated in liver homogenates. The morphological changes were investigated using light and electron microscopy (EM). Cell proliferation was detected by immunohistochemical staining with monoclonal antibodies to Ki-67. Apoptosis was detected by the transferase-mediated dUTP nick end-labeling method. RESULTS: PH induced hepatic LP, decreased GSH and NO, and inhibited GST activity (P < .05). R and M completely prevented PH-induced lipid peroxidation, decreased hepatic GSH and NO levels (P < .05). The inhibition of GST activity was prevented by R (P < .05), but not with M (P > .05). In the PH group EM showed severe morphological changes: mitochondrial degeneration, vacuoles, lipid droplets, and myelin-like figures. In both the R and M groups, morphological alterations repaired protective effects more prominently in the R group. Ki-67 indices (KI) were increased in the PH group and decreased in both R and M groups (P < .001). In the M group, KI was the lowest, but the difference compared with R was not significant (P > .05). Apoptosis was slightly increased in PH, but in either the R or M groups, apoptosis was intensively increased (P < .001). Increased apoptosis was greatest in the M group and the difference compared with the R group was statistically significant (P < .05). CONCLUSION: R and M suppressed PH-induced oxidative damage, attenuated proliferation, and stimulated apoptosis. When we compared R and M, R showed more potent antioxidative effects and was morphologically more protective to hepatocytes. Antiproliferative effects of M were more potent. Because of their potent antioxidative effects, R and M can be effective for oxidative damage like ischemia-reperfusion injury; however, because of the adverse effects on proliferation and apoptosis more studies are needed in states in which regeneration is critical.

Resveratrol attenuates inflammation and stricture formation in experimental caustic esophageal burns.

The purpose of medical treatment in the caustic esophageal burns (CEB) is to decrease inflammatory reaction and to prevent stricture formation. Resveratrol has anti-inflammatory and antifibrotic properties. The aim of this study is to investigate potential therapeutic effects of resveratrol in experimental CEB. We divided 42 male Wistar albino rats into five groups: a control group, caustic groups 4 and 28 (esophageal burns were created), and resveratrol groups 4 and 28 (esophageal burns were created and resveratrol was administered). We used 25% NaOH to form CEB following the method of Gehanno and Guedon as modified by Liu and Richardson. Animals were killed on the 4th and 28th days for biochemical and histopathological examinations. We found that the mean malondialdehyde and nitric oxide assays of the caustic groups were significantly higher than that of the resveratrol groups (P < 0.05). On the other hand, glutathione assay of the resveratrol groups was significantly higher than that of the caustic groups (P < 0.05). Histologically, edema, inflammation and necrosis were found to be significantly lower in the resveratrol 4 group compared with the caustic 4 group (P < 0.05). Submucosal and muscular collagen accumulation were found significantly lower in the resveratrol 28 group compared with the caustic 28 group (P < 0.05). We conclude that resveratrol decreased both the inflammatory reaction and the stricture formation in experimental CEB.

Partial hepatectomy is curative for the localized type of Caroli's disease: a case report and review of the literature.

The case of a 58-year-old woman who was diagnosed with the localized type of Caroli's disease is presented. This disease involves the whole of the left half of the liver. A left hepatectomy was followed by complete resolution of symptoms. The current article suggests that hepatic resection may be aggressively performed in selected patients with the localized form of Caroli's disease.

Protective effects of resveratrol on spleen and ileum in rats subjected to ischemia-reperfusion.

Resveratrol is as an antioxidant with free radical-scavenging activity and finds its clinical application in the prevention of postischemic tissue injury following solid organ transplantation. This study investigates the effect of Resveratrol on spleen and ileum tissues subjected to hepatic ischemia-reperfusion (I/R) in rats. Twenty-four rats were recruited in the study as follows: group A: I/R (n = 8), group B: I/R + Resveratrol (n = 8), and group C: sham operation (n = 8). After intraperitonealy pretreatment of eight rats with resveratrol (15 mg/kg/d) for 5 days, 16 rats were subjected to 45 minutes of hepatic ischemia followed by 30 minutes reperfusion period. Resveratrol was given 15 minutes prior to ischemia and just before the reperfusion in rats. After reperfusion period all rats were sacrificed. Spleen and ileum tissues were examined spectrophotometrically to measure malondialdehyde (MDA), glutathione (GSH), and total nitrite, nitrate as an end product of nitric oxide (NO) levels. Concerning the spleen, statistically significant decrease of GSH and increase of MDA and NO levels were found group A when compared to groups B and C (P = .040, P = .004, and P = .001 group A vs group B; P = .05, P = .003, and P = .001 group A vs group C, respectively). Parallel results were obtained in ileum. A statistically significant decrease in GSH and an increase in MDA and NO levels in group A in respect to group B and group C was obtained (P = .048, P = .034, and P = .001 group A vs group B; P = .004, P = .001, and P = .003 group A vs group C, respectively). The result of this study shows that resveratrol has a protective effect on spleen and ileal mitochondrial oxidative stress in rats subjected to I/R.

Effect of steroid on mitochondrial oxidative stress enzymes, intestinal microflora, and bacterial translocation in rats subjected to temporary liver inflow occlusion.

Protective effects of steroids against ischemia-reperfusion (I/R) injury are well known, but there is little information about the influence of temporary inflow occlusion on intestinal barrier function or bacterial translocation. The aim of this experimental study was to investigate the effects on liver, kidney, spleen, ileal mitochondrial stress enzymes, and bacterial translocation of methylprednisolone (MP) in rats undergoing temporary liver inflow occlusion. Twenty-seven pathogen-free Wistar albino rats were randomized into three groups: group A: I/R (n = 10); group B: I/R + MP (n = 10); and group C: sham (n = 7). Rats in groups A and B were subjected to 20 minutes of portal vein and hepatic artery occlusion with 3 mg/kg MP injected into group B animals intraperitoneally during the occlusion. Twenty-two hours later, all rats were sacrificed to measure mitochondrial oxidative stress enzymes in liver, kidney, spleen, and ileum. We evaluated intestinal bacterial counts, intestinal mucosal histopathology, bacterial translocation to mesenteric lymph nodes (MLN), liver, spleen, and kidney. Decreased levels of malondialdehyde and increased levels of glutathione were observed in all examined tissues of group B compared to those of group A rats. Statistically significant increases in the intestinal counts of Klebsiella spp and Proteus spp and of bacterial translocation to liver, kidney, spleen, and MLN were measured in group B with respect to group A.

Effect of fish oil, olive oil, and vitamin E on liver pathology, cell proliferation, and antioxidant defense system in rats subjected to partial hepatectomy.

The high capacity of liver regeneration after partial hepatectomy (PH) is well known. This study investigated the role of the antioxidant defense system in regeneration among Wistar-albino male rats subjected to 70% partial hepatectomy after a pretreatment period of 2 weeks with eicosapentanoic acid (EPA) rich fish oil (FO), first pressed virgin olive oil (OO), or vitamin E. The control group of 10 rats underwent PH only. On postoperative day 3, all rats were humanely killed. Liver sections of animals treated with FO or vitamin E showed significant increases in regeneration within both liver parenchyma and cut surface compared with the control group (P < .05). Liver sections of OO displayed an insignificant increase in liver regeneration (P > .05), with less increase in parenchyma than of the cut surface. The enhancement of the liver parenchymal regeneration in the FO group was significantly greater than that of the vitamin E group. Concerning liver function tests (LFT), there was no significant difference among the groups. When the treatment groups were compared to the control group glutathione (GSH) levels were increased and content of malondialdehyde (MDA), nitric oxide (NO), and superoxide dismutase (SOD) were decreased. Based on these results, we concluded that after 70% PH in rats, the liver parenchyma and cut surface regeneration were greatest with FO and least with OO treatment. Both FO and vitamin E served to improve the antioxidant defense system more than OO treatment.

Effects of nucleoside analogues on liver regeneration 70% partially hepatectomized rats.

The alternatives for prophlaxis and treatment of recurrent hepatitis B virus infection have increased since new oral nucleoside analogues have become available. We conducted this experimental study to investigate the effect in the liver of these agents on the expression of transforming growth factor alpha (TGF-alpha) and on proliferation index, estimated by Ki-67. Thirty male Wistar albino rats were randomized into three groups: group A (n = 10) received adefovir dipivoxil (40 mg/kg/d per gavage); group B (n = 10), lamivudine (L; 30 mg/kg/d per gavage); and group C (n = 10) did not receive any treatment and were the control group. Groups A and B were treated for 3 days. Animal treatment began on day -1. After performing 70% partial hepatectomy on day 0, all rats were sacrificed on postoperative day 2 to harvest liver tissues for histopathological examination. We stained and indexed Ki-67 and TGF-alpha immunohistochemically on the hepatectomy surface and in the parenchyma, Ki-67 and TGF-alpha indices were significantly higher in group A compared with group B (P = .001 and P = .004, respectively, and P = .003 and P = .001, respectively). When the L group was compared with the control group for results on the hepatectomy surface and the parenchyma, Ki-67 and TGF-alpha indexes were insignificantly different (P = .6 and P = .3, respectively, and P = .1 and P = .6, respectively). Based on the results of this experimental study, we concluded that Adefovir dipivoxil has greater proliferative effect on liver parenchyma and in the cut surface than does lamivudine.

Liver pathology and cell proliferation after calcineurin inhibitors and antiproliferative drugs following partial hepatectomy in rats.

Immunosuppressants are the cornerstones of treatment after solid organ transplantation. This study investigated the pathology and cell proliferation following partial hepatectomy (PH) in rats undergoing immunosuppressive treatment. After 1 day, all rats were subjected to 70% PH. Groups A and B (n = 10) received calcineurin inhibitors subcutaneously: either FK506 or cyclosporine (CyA). Groups C and D (n = 10) received antiproliferative drugs: either mycophenolate mofetil (MMF) or sirolimus (SRL) by gavage. A control group (n = 5) received 1 mL of tap water daily. On postoperative day 2, all rats were sacrificed to obtain liver tissue for pathologic examination. Using immunohistochemistry we separately examined the hepatectomy surface and the liver parenchyma. In the parenchyma, the Ki-67 indices were higher in the CyA and FK506 groups and lower in the SRL and MMF groups compared with controls (P < .01). CyA had the highest and MMF the lowest values. On the hepatectomy surface, Ki-67 indices and TGF-alpha expressions were higher in the CyA group and lower in the SRL and MMF groups compared with the control group (P < .01). Slightly higher values in the FK506 group were not significantly different compared with the control group (P > .05). All groups other than FK506 showed prominent cholangiolar epithelial phenotypes compared with the control group. In the CyA and SRL groups, the number of cholangiolar cells was higher (P < .01), and in the MMF group lower than in the control group (P < .01). Among all groups, SRL had the highest values.

Proton magnetic resonance spectroscopy findings of a sacrococcygeal schwannoma.

Schwannoma is tumor of peripheral nerves, originating from Schwann cells. It is a rare nerve sheath tumor, which frequently occurs in the intracranial acoustic nerve and spinal nerves. We report on a 28-year-old woman who suffered from a large pelvic mass that was diagnosed to be sacrococcygeal schwannoma. The features of proton magnetic resonance spectroscopy (MRS) study are discussed. The magnetic resonance imaging instrument was a 1.5 T, Gyroscan Intera with a body coil as a radiofrequency transmitter and a signal receiver. T2-weighted images were obtained under the following conditions-turbo spin echo (TSE) T2: turbo spin echo repeat time (TR) = 4500 msec, echo time (TE) = 96 msec. Single voxel MRS was performed by the point-resolved spectroscopy technique with a long TE (136 msec). MRS measurement was performed on two different parts of the tumor. As well as strongly elevated choline and lipid signals, the tumor spectrum showed increased N-acetylaspartate resonances. MRS can be used effectively in the preoperative diagnosis of retroperitoneal and pelvic masses, which demonstrate unusual clinical features.

Hepatocellular carcinomas in native livers from patients treated with orthotopic liver transplantation: biologic and therapeutic implications.

The gross and histopathologic characteristics of 212 nonfibrolamellar hepatocellular carcinomas (HCCs) discovered in native livers removed at the time of liver transplantation were correlated with features of invasive growth and tumor-free survival. The results show that most HCCs begin as small well-differentiated tumors that have an increased proliferation rate and induce neovascularization, compared with the surrounding liver. But at this stage, they maintain a near-normal apoptosis/mitosis ratio and uncommonly show vascular invasion. As tumors enlarge, foci of dedifferentiation appear within the neoplastic nodules, which have a higher proliferation rate and show more pleomorphism than surrounding better-differentiated areas. Vascular invasion, which is the strongest predictor of disease recurrence, correlates significantly with tumor number and size, tumor giant cells and necrosis, the predominant and worst degree of differentiation, and the apoptosis/mitosis ratio. In the absence of macroscopic or large vessel invasion, largest tumor size (P <.006), apoptosis/mitosis ratio (P <.03), and number of tumors (P <.04) were independent predictors of tumor-free survival and none of 24 patients with tumors having an apoptosis/mitosis ratio greater than 7.2 had recurrence. A minority of HCCs (<15%) quickly develop aggressive features (moderate or poor differentiation, low apoptosis/mitosis ratio, and vascular invasion) while still small, similar to flat carcinomas of the bladder and colon. In conclusion, hepatic carcinogenesis in humans is a multistep and multifocal process. As in experimental animal studies, aggressive biologic behavior (vascular invasion and recurrence) correlates significantly with profound alterations in the apoptosis/mitosis ratio and with architectural and cytologic alterations that suggest a progressive accumulation of multiple genetic abnormalities.