Differentially Expressed Proteins in Chronic Active Hepatitis, Cirrhosis, and HCC Related to HCV Infection in Comparison With HBV Infection: A proteomics study.

BACKGROUND: Hepatocellular carcinoma is a highly progressive cancer in the case of late diagnosis which is frequently associated with HBV and HCV viral infections. OBJECTIVES: To identify differentially expressed serum proteins among three main stages of HCV infection and healthy individuals, and their comparisons with sera from patients with the same stage of HBV infection. PATIENTS AND METHODS: Two-dimensional polyacrylamide gel electrophoresis combined with liquid chromatography-tandem mass spectrometry was performed on 47 sera from healthy volunteers, those with chronic active hepatitis, cirrhosis and HCC patients associated with HBV and HCV infections. RESULTS: Among these, 62 spots were differentially expressed (≥ 1.5 fold; P < 0.05), of which 42 spots that corresponded to 15 proteins were identified by liquid chromatography-tandem mass spectrometry. CD5-like antigen (CD5L) was differentially expressed between cirrhosis and HCC patients with HCV infection. Leucine-rich α2-glycoprotein (LRG) and haptoglobin (HP) α2 isoforms differed in the HCC that was associated with either HCV or HBV infections. CONCLUSIONS: CD5L might be a useful biomarker for early diagnosis of HCC in HCV cirrhotic patients. LRG and HP α2 isoforms could be potential markers for distinguishing viral HCC. Our results also further support the presence of varying molecules involved in hepatocarcinogenesis in HBV when compared with HCV infection.

Hepatitis B recurrence after liver transplantation: a single center experiences and review the literature.

BACKGROUND: Despite the advances in the treatment of chronic hepatitis B virus (HBV) infection, liver transplantation (LT) remains the only hope for many patients with end-stage liver diseases resulting from HBV. OBJECTIVES: The aim of this study was to investigate the rate of HBV recurrence in cases that had undergone LT due to the HBV related liver cirrhosis. PATIENTS AND METHODS: Forty-nine patients who underwent LT due to HBV related cirrhosis since 2001 to 2009 in Shiraz Organ Transplantation Center were enrolled in the present study. They were asked to complete the planned questionnaire and also to sign the informed consent in order to take part in this study. Post-transplant prophylaxis protocol against HBV recurrence was based on a hundred milligrams of lamivudine daily plus intramuscular injections of hepatitis B immune globulin (HBIG) with appropriate dosage to keep anti-HBs antibody titer above 300 IU/L and 100 IU/L in the first six months and afterwards, respectively. Blood samples were obtained and checked for HBsAg, HBeAg, and the titers of Anti -HBsAb as well as Anti- HBeAb with ELISA. A quantitative HBV DNA assay was also done on all samples (GENE-RAD® Real-time PCR). RESULTS: There were 91.8% males and 8.2% females enrolled in the study. The duration of post-transplant prophylaxis ranged from 3 months to 8 years (mean 18.9 ± 19.3 months). HBsAg and HBeAg were positive in 24.5% and 2% of cases, respectively. Real-time PCR for HBV DNA were zero copies/mL in 91.8% of patients, none of which represented a positive value for HBV recurrence (Positive > 10,000 copies/mL). The mean Anti-HBs Ab titer was 231.7 ± 135.9 IU/L; it was above 100 IU/L in 71.4% of patients. Thirty-seven (75.5%) of the patients were taking tacrolimus plus mycophenolate mofetil, 6 (12.2%) were on cyclosporine plus mycophenolate mofetil, and 6 (12.2%) were taking sirolimus plus mycophenolate mofetil. HBsAg was detectable in seven patients taking tacrolimus plus mycophenolate mofetil (18.9%), in four patients taking cyclosporine plus mycophenolate mofetil (66.7%), and in one patient among the six who were taking sirolimus plus mycophenolate mofetil (16.7%). There was no significant statistical correlation between the presence of a positive value for HBsAg and the immunosuppression regimen or Anti HBsAb titer (P ˃ 0.05). Presence of a positive value for HBsAg was not predictive of a positive HBV DNA or its level in blood (P ˃ 0.05). CONCLUSIONS: Post-transplant HBV prophylaxis with lamivudine and intramuscular HBIG with appropriate dosage to keep anti-HBs antibody titer above 300 IU/L in the first six months and above 100 IU/L afterwards is effective for prevention of HBV recurrence after LT.

Prevalence and risk factors of renal dysfunction after liver transplant: a single-center experience.

OBJECTIVES: Renal dysfunction is one of the most significant complications after liver transplant. It is attributed mainly to nephrotoxicity caused by calcineurin inhibitors. We evaluated the renal functioning in liver transplant recipients alive for at least 6 months after liver transplant. MATERIALS AND METHODS: One hundred seventy patients (108 male [63.5%], 62 female [36.5%]; mean age, 31.4 +/- 13.3 years; age range, 13-61 years) were included in this study. Patients who had undergone a liver transplant between 1994 and 2006 at the Organ Transplantation Center of the Shiraz University of Medical Sciences in Shiraz, Iran, and had been alive for at least 6 months after surgery were included. Data were collected regarding age, sex, body mass index, underlying liver disease, graft type, immunosuppressive medications, serum creatinine levels, and glomerular filtration rate before, 1, and 6 months after liver transplant. Renal dysfunction was defined as a serum creatinine level above 132.6 micromol/L or a glomerular filtration rate less than 60 mL/min/1.73 m2, based on our reference range. Glomerular filtration rate was calculated using the Schwartz formula (glomerular filtration rate mL/min/1.73 m2 = K x Ht (cm) / Cr mg/dL). Data were analyzed with SPSS software. RESULTS: The mean follow-up was 25.9 +/- 23.5 months (range, 6-156 months). The main indications for liver transplant were cryptogenic cirrhosis (n=42), hepatitis B infection (n=34), autoimmune cirrhosis (n=30), Wilson's disease (n=21), and primary sclerosing cholangitis (n=18). The mean pretransplant glomerular filtration rate was 93.7 +/- 35.6 mL/min/1.73 m2. The mean glomerular filtration rates in the first and sixth months after liver transplant were 81.6 +/- 29.3 mL/min/1.73 m2 and 83.6 +/- 32.9 mL/min/1.73 m2. Sex, body mass index, type of immunosuppressive medication, and underlying liver disease were not predictors of renal dysfunction (P > .05). Posttransplant renal dysfunction was significantly more common in older patients (ie, those aged 38.8 years and older) (P = .0001) and those with a family history of renal disease (P < .05). CONCLUSIONS: Renal dysfunction may be a significant problem for patients after liver transplant, and early detection of renal dysfunction in patients after liver transplant is important. Of all the risk factors studied here, only older age and family history of renal disease were correlated with development of renal dysfunction after liver transplant.

Hyperlipidemia in Iranian liver transplant recipients: prevalence and risk factors.

BACKGROUND: Hyperlipidemia is a metabolic complication after liver transplantation (LT). The aim of this study was to investigate the prevalence and risk factors for developing hyperlipidemia in patients who underwent LT in the Shiraz Organ Transplantation Center. METHODS: Our patients were 170 liver recipients who underwent LT from 1994 to 2006 in the Organ Transplantation Center of the Shiraz University of Medical Sciences. To perform this study we administered questionnaires, including information about age, sex, body mass index (BMI), underlying liver disease, graft type, immunosuppressive medications, and serum levels of triglycerides and cholesterol, before and 6 months after LT. Serum triglyceride and cholesterol levels were considered elevated if they were >150 mg/dl and >250 mg/dl, respectively. Data were analyzed with SPSS software. RESULTS: There were 108 male and 62 female patients, with a mean age of 31.4 +/- 13.3 years, and the mean duration of follow-up was 25.9 +/- 23.5 months. The average pretransplant serum triglyceride and cholesterol (mean of individual means) levels were 104.6 +/- 73.2 and 109.5 +/- 51.5 mg/dl, respectively, and the average posttransplant levels were 230.1 +/- 131 and 185 +/- 77 mg/dl, respectively. Six months after LT, 119 (70%) and 26 (15.3%) patients developed hypertriglyceridemia and hypercholesterolemia, respectively. Age, sex, BMI, and underlying liver disease were not predictors of hypertriglyceridemia or hypercholesterolemia (P > 0.05). Posttransplant hypertriglyceridemia was significantly more common in patients receiving tacrolimus than in those receiving cyclosporine (P = 0.040), but posttransplant hypercholesterolemia had no significant correlation with type of immune suppression (P > 0.05). CONCLUSIONS: Hyperlipidemia was common after LT, and hypertriglyceridemia was more common than hypercholesterolemia. Among all risk factors, tacrolimus therapy was correlated with development of hypertriglyceridemia after LT.

Analysis of patients listed for liver transplantation in Shiraz, Iran.

AIM: To analyze records of patients listed for liver transplantation (LT) at our hospital, the first and the largest LT center in Iran. METHODS: We analyzed medical records of patients aged 14 years or older, who were listed for LT for chronic liver disease between 1994 and 2004. Outcome was determined from records or follow-up data. RESULTS: Among the 480 patients (mean age 39 [SD 13] years; 327 [68.1%] men) listed for LT, common causes of cirrhosis were cryptogenic (143; 29.9%) and hepatitis B (127; 26.5%). Child-Turcott-Pugh (CTP) class distribution of these patients was: A - 37 (7.7%), B - 258 (53.7%) and C - 185 (38.6%). Mean (SD) follow-up duration was 11.4 (11.8) months (range 1-108). One hundred and four (21.7%) patients received LT and 173 (36%) died while awaiting LT. CTP class influenced 1-year (90%, 73% and 55% in class A, B and C, respectively) and 2-year (84%, 48% and 25%, respectively) survival rates. MELD score also influenced survival. Survival was better in patients who underwent LT than in those who continued on the waiting list (p< 0.01). CONCLUSION: Only about one-fifth of patients listed for LT in Iran received LT and a large proportion died without LT.