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Background: Hepatocellular carcinoma (HCC) is a prevalent and life-threatening tumor with high morbidity and mortality. Proper prediction and prognosis are incredibly stressed to diagnose HCC and increase patient survival. Objectives: This research aims to evaluate gene expression levels of pre-differentiated transcripts for those suffering from chronic hepatitis B (CHB) and HCC. Methods: To examine the previously analyzed peripheral blood mononuclear cells (PBMCs) transcriptomic array data, we selected seven differentially expressed genes (DEGs) in normal versus CHB and CHB versus HCC (CD44, SP3, USP8, E2F2, UFM1, IFN regulative factor binding protein 2 (IRF2BP2), and T-cell intracellular antigen 1 (TIA1)). The study included individuals with treatment-naïve CHB (n = 30) and primary HCC (n = 25) and healthy controls (n = 15). Subsequently, the expression of genes was assayed using qRT-PCR. A phylogenetic evaluation was performed using direct sequencing of HBsAg. Results: In HCC patients, 60% (n = 15) were HBeAg-positive. HBeAg was negative in all CHB patients, but all were anti-HBe-positive. The hepatitis B virus (HBV) load of HCC patients was more than that of CHB subjects. All patients were of the Iranian race and HBV D genotype. The expression of five transcriptional markers (CD44, SP3, USP8, E2F2, and UFM1) was higher in HCC patients than in CHB and healthy subjects, which was similar to the initial microarray data analysis. Conclusions: Transcriptional signatures may be related to the pathogenesis of HCC and used as diagnostic biological markers for the initial monitoring and prediction of HCC.

BACKGROUND Inflammation has a significant impact on the development and progression of fatty liver diseases.In this study, we aimed to investigate the relation between serum levels of nuclear factor kappa B (NFkB) and Forkhead box protein P3 (FOXP3)with fibrosis severity among patients with non-alcoholic fatty liver disease(NAFLD). METHODS In a prospective study, the patients suspicios of havingfatty liver were enrolled. The exclusion criteria lack of viral hepatitis, autoimmune hepatitis, Wilson’s or other known liver diseases,history of liver or biliary surgery,bariatric surgery, and medications that influence liver metabolism. The participantsunderwent liver fibroscan. According to liver fibrosis, the patients weredivided into two groups; 1)fibrosis less than 7.2 KP,2)advanced NAFLD, fibrosis ≥7.3 KP. A10 cc fasting blood sample was taken from each patient for laboratory assessments.The variables between the two groups were compared using Chi-square or Fisher’s exact test.The independence of cytokines was assessed by a logistic regression test. RESULTS Totally 90 patients were enrolled.The mean age was 42.21 ± 11 years. Of them, 50 and 47 participants were allocated to groups 1 and 2, respectively. In the univariate analysis, we revealed asignificant difference between age, body mass index (BMI), fasting blood glucose, liver enzymes , total cholesterol, andtriglyceride levels. Also, there was a significant difference betweenthe levels of NFKB and FOXP3 in group one compared with group two of the participants,as FOXP3(9.17 ± 10.0 vs. 18.63 ± 12.9; p < 0.001) and NFKB (1.70 ± 1.70; p < 0.01). After excluding the confounding factors, we observed a significant association between fibrosis level and cytokine levels in logistic regression. CONCLUSION Serum levels of NFKB and FOXP3 increased by advancing liver fibrosis in patients with NAFLD.This is an independent association. The identification of intermediary regulatory factors would be necessary.

BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is one of the most common diseases worldwide. Studies have shown that melatonin, as a regulatory hormone, is effective in different cell protective pathways. We aimed to compare serum melatonin levels of patients with NAFLD with different stages of fibrosis with that of healthy individuals. METHODS In this cross-sectional study patients, aged >20 years with elevated serum liver enzymes and trance abdominal sonographic diagnosis of fatty liver who met the exclusion criteria for NAFLD were included. The participants were categorized into three groups as follows: 1) severe fibrosis (fibrosis > 9.1 kPa and steatosis > 285 dbm), 2) mild-moderate fibrosis (fibrosis: 6-9.0 kPa and steatosis 240-285), and 3) normal group with fibrosis < 5.8 kPa and steatosis < 240 dbm based on Fibroscan evaluation. Five ml of fasting venous blood was taken from each patient and the control group for laboratory assessment. A questionnaire including demographic, anthropometric, laboratories (serum ALT, AST, triglyceride, total cholesterol and melatonin level), and clinical data was completed for all participants. RESULTS 97 people with a mean±SD age of 42.21 ± 11 years were enrolled. 59 (60.0%) patients were women. we observed that the melatonin levels were increased by advancing fibrosis. Based on control- attenuated parameter results the melatonin levels significantly differed between the healthy individuals and patients with severe steatosis. There was a direct association between increased melatonin levels and liver enzymes. CONCLUSION As a regulatory hormone, melatonin may directly be associated with liver cell injuries. Therefore, considered regulatory substances such as melatonin either diagnostic or therapeutic can improve the patients’ outcome.

OBJECTIVES Orthotopic liver transplant can be accompanied by an obscure bleeding pattern in patients with severe hepatic malfunction. In the present study, coagulation conditions of patients with cirrhosis of the liver due to primary sclerosing cholangitis and nonbiliary causes of cirrhosis were compared using rotational thromboelastometry assays obtained before orthotopic liver transplant. MATERIALS AND METHODS This case control study analyzed patients who were candidates for orthotopic liver transplant from 2010 to 2016. Eighty patients with cirrhosis of the liver (40 patients with primary sclerosing cholangitis and 40 with nonbiliary causes of cirrhosis) were randomly selected and enrolled into the study. Patients received rotational thromboelastometry assays under anesthesia just before the start of the operation, and results were compared between the 2 patient groups. RESULTS Of 80 patients, 52 were men and 28 were women. In the assays, we found that maximum amplitudes in 10 and in 20 minutes and maximum clot firmness parameters were higher in patients with primary sclerosing cholangitis. The alpha angle and clot formation time were different in the intrinsic and extrinsic assay panels. In the intrinsic assay, we found clotting time to be shorter (P < .05). The average of all parameters in all 3 assays (intrinsic, extrinsic, and fibrinogen contribution) was lower in patients with nonbiliary causes of cirrhosis than in those with primary sclerosing cholangitis. CONCLUSIONS In contrast with previous studies that found that patients with primary sclerosing cholangitis are hypercoagulable, our study observed that they have normal coagulable results. Furthermore, we found that, although mean coagulation indexes in patients with primary sclerosing cholangitis were within normal ranges, in patients with nonbiliary causes of cirrhosis, these indexes were generally lower.

The coronavirus associated disease 2019 (COVID-19) caused by the SARS-CoV-2 virus has rapidly spread all around the world and became pandemic in March 2020. Data on liver transplantation and chronic liver disease during the pandemic has remained scarce, and there is little information on whether immunosuppressed patients are at higher risk of developing severe COVID-19 infection. This review provides information for health care providers who care for patients with liver transplantation and chronic liver diseases.

Background: Several studies have revealed that the hepatitis B virus (HBV) exists in peripheral blood mononuclear cells (PBMCs). It remains poorly understood whether HBV DNA and covalently closed circular DNA (cccDNA) can emerge in PBMCs of patients with different stages of HBV infection. Objectives: This study aimed to compare the detection of HBV DNA and quantification and presence of cccDNA within PBMC from patients with chronic hepatitis B (CHB), cirrhosis, and hepatocellular carcinoma (HCC). Methods: The present study was conducted on 120 participants (30 CHB patients, 30 cirrhosis patients, 30 HCC patients, and 30 healthy controls) from Tehran, Iran. HBV serological markers were tested by enzyme-linked immunosorbent assay (ELISA). PBMCs of all individuals were assayed for HBV DNA detection, quantification, and the presence of cccDNA. Results: Of 90 HBV patients, 58 (64.4%) were positive for HBV DNA in PBMCs. HBV DNA was detected in PBMCs isolated from 13/30 CHB, 20/30 cirrhosis, and 25/30 HCC patients. In addition, 6 (20%) CHB, 13 (43.3%) cirrhosis, and 16 (15.3%) HCC patients were cccDNA positive. The HBV viral loads in serums were statistically higher than the HBV viral loads of PBMCs (P < 0.001). A positive correlation was found between HBV DNA loads in serums and PBMCs of patients. Moreover, HBV DNA quantity of serums and PBMCs showed a significant association in terms of hepatitis B e antigen (HBeAg) status. Conclusions: HBV quantity in PBMCs correlated with serum HBV viral loads. HBV genomes in PBMCs may be a risk factor for HBV disease progression.

BackgroundLiver transplantation is a proven management method for end-stage cirrhosis and is estimated to have increased life expectancy by 15 years. The COVID-19 pandemic posed a challenge to patients who were candid for a solid-organ transplant. It has been suggested that the outcomes of liver transplants could be adversely affected by the infection, as immunosuppression makes liver transplant candidates more susceptible to adverse effects while predisposing them to higher thrombotic events.Material and methodsIn this retrospective study, the cases who received liver transplants from January 2018 to March 2022 were assessed regarding early postoperative mortality rate and hepatic artery thrombosis (HAT) with COVID-19 infection. This study included 614 cases, of which 48 patients were infected.ResultsThis study shows that the early COVID-19-related early postoperative mortality rates substantially increased in the elective setting (OR: 2.697), but the results for the acute liver failure were insignificant. The average model for end-stage liver disease score increased significantly during the pandemic due to new regulations. Although mortality rates increased during the pandemic, the data for the vaccination period show that mortality rates have equalised with the prepandemic era. Meanwhile, COVID-19 infection is assumed to have increased HAT by 1.6 times in the elective setting.ConclusionThis study shows that COVID-19 infection in an acute liver failure poses comparatively little risk; hence transplantation should be considered in such cases. Meanwhile, the hypercoagulative state induced by the infection predisposes this group of patients to higher HAT rates.

The present COVID-19 pandemic is a cause for concern among solid-organ transplant recipients, who are generally at high risk for infection and for whom infection with COVID-19 carries additional risks for complications and mortality that are higher than the COVID-19-associated risks for the general population. We report the case of a liver transplant recipient who presented with COVID-19 and multiple complications. A 39-year-old woman with a liver transplant was diagnosed with COVID-19 within the first week after transplant surgery. Mycophenolate was withheld, and interferon β was administered for management of COVID-19. She developed thrombotic thrombocytopenic purpura, acute antibody-mediated rejection, and posterior reversible leukoencephalopathy syndrome during hospitalization. All of these complications may be related to COVID-19 or its management modalities. We considered 3 possible causes for thrombotic thrombocytopenic purpura in this patient: the COVID-19 infection itself, immunosuppression treatment with cyclosporine, and treatment with interferon β. Immunosuppression reduction and interferon treatment may result in antibody-mediated rejection. COVID-19, thrombotic thrombocytopenic purpura, and cyclosporine may play a combined role in the development of posterior reversible leukoencephalopathy syndrome. In conclusion, thrombotic thrombocytopenic purpura, antibody-mediated rejection, and posterior reversible leukoencephalopathy syndrome may represent a continuum of 3 thrombotic microangiopathy conditions fostered by interplay between the COVID-19 infection and the treatment modalities for COVID-19 management in this patient.

Background: The Post-Liver Transplant Quality of Life (PLTQ) instrument is a specific, disease-based questionnaire to evaluate health-related quality of life (HRQOL) of liver transplantation (LTx) recipients. The aim of this study is translation, cross-cultural adaptation, and evaluation of the psychometric properties of the Persian version of PLTQ (PV-PLTQ) questionnaire.Methods: All of the stages of translation and cross-cultural adaptation of the original PLTQ instrument was carried out according to the published guideline. A total of 175 LTx recipients completed the PLTQ and short form-36 (SF-36) questionnaires. Sixty-eight randomly selected patients were asked to complete the PLTQ, 2 to 3 months later. Face validity, content validity, acceptability internal consistency, test-retest reliability, sensitivity to change, and convergent validity were evaluated.Results: The results of face validity, content validity, and missing data proportion indicate that PV-PLTQ questionnaire is acceptable and easy to understand. Cronbach’s alpha coefficient for the PV-PLTQ questionnaire was 0.97 (0.82 to 0.95) for domains. The results of test-retest reliability show moderate to good intraclass correlation coefficient from 0.6 to 0.86 (P< 0.05). Also, the results of the Kruskal-Wallis test shows that this questionnaire is sensitive to HRQOL changes. The correlations between PV-PLTQ domains and physical and mental components of SF-36 present a good convergent validity (P< 0.05).Conclusio: In general, The PV-PLTQ questionnaire is a valid, reliable and sensitive to change instrument to evaluate HRQOL in LTx recipients and can be applied in further researches and clinical settings in the Persian speaking population.

Acute Liver failure (ALF) is a life-threatening disease and is determined by coagulopathy (with INR ≥ 1.5) and hepatic encephalopathy as a result of severe liver injury in patients without preexisting liver disease. Since there are problems with liver transplantation including lack of donors, use of immunosuppressive drugs, and high costs of this process, new therapeutic approaches alongside current treatments are needed. The placenta is a tissue that is normally discarded after childbirth. On the other hand, human placenta is a rich source of mesenchymal stem cells (MSCs), which is easily available, without moral problems, and its derived cells are less affected by age and environmental factors. Therefore, placenta-derived mesenchymal stem cells (PD-MSCs) can be considered as an allogeneic source for liver disease. Considering the studies on MSCs and their effects on various diseases, it can be stated that MSCs are among the most important agents to be used for novel future therapies of liver diseases. In this paper, we will investigate the effects of mesenchymal stem cells through migration and immigration to the site of injury, cell-to-cell contact, immunomodulatory effects, and secretory factors in ALF.

Background: We studied the clinical characteristics and outcomes of 905 hospitalized coronavirus disease 2019 (COVID-19) patients admitted to Imam Khomeini Hospital Complex (IKHC), Tehran, Iran. Methods: COVID-19 patients were recruited based on clinical symptoms and patterns of computed tomography (CT) imaging between February 20 and March 19. All patients were tested for the presence of COVID-19 RNA. The Poisson regression model estimated the incidence rate ratio (IRR) for different parameters. Results: The average age (± standard deviation) was 56.9 (±15.7) years and 61.77% were male. The most common symptoms were fever (93.59%), dry cough (79.78%), and dyspnea (75.69%). Only 43.76% of patients were positive for the RT-PCR COVID-19 test. Prevalence of lymphopenia was 42.9% and more than 90% had elevated lactate dehydrogenase (LDH) or C-reactive protein (CRP). About 11% were severe cases, and 13.7% died in the hospital. The median length of stay (LOS) was 3 days. We found higher risks of mortality in patients who were older than 70 years (IRR = 11.77, 95% CI 3.63–38.18), underwent mechanical ventilation (IRR = 7.36, 95% CI 5.06–10.7), were admitted to the intensive care unit (ICU) (IRR = 5.47, 95% CI 4.00–8.38), tested positive on the COVID-19 test (IRR = 2.80, 95% CI 1.64–3.55), and reported a history of comorbidity (IRR = 1.76, 95% CI 1.07–2.89) compared to their corresponding reference groups. Hydroxychloroquine therapy was not associated with mortality in our study. Conclusion: Older age, experiencing a severe form of the disease, and having a comorbidity were the most important prognostic factors for COVID-19 infection. Larger studies are needed to perform further subgroup analyses and verify high-risk groups.

Primary graft dysfunction (PGD) and non-function (PNF) happen in 8.7-24.7% and 0.9-7.2% of liver transplant recipients, respectively. These phenomena increase treatment cost and patients’ death. This study assessed the effect of L-carnitine supplementation on the incidences of PNF/PGD in liver transplant recipients. This randomized, placebo-controlled, clinical trial was performed on adult liver transplant recipients. Patients took L-carnitine syrup 500 mg three times daily or placebo from the time of including in transplant waiting list until the day of transplant surgery (median 14 days, 1-192 days). Thirty-three patients in L-carnitine and 39 patients in placebo group completed the study. Although not statistically significant, PNF and PGD happened less frequently among recipients in L-carnitine compared with placebo group (3% vs. 12.8% for PNF; 15.2% vs. 30.8% for PGD). Alanine aminotransferase (ALT) and aspartate aminotransferase were lower in L-carnitine group at day 3 after transplantation. ALT declined more significantly within 48 h after transplantation in L-carnitine arm (median 120.50 vs. 79 IU/L; P = 0.03). One-month patients’ survival was significantly higher in L-carnitine versus placebo group (97% vs. 74.4%; P = 0.008). The rates of PNF and PGD in L-carnitine group were approximately one-fourth and one-half of placebo group respectively. One-month patients’ survival was higher in L-carnitine group.

Introduction: Liver transplantation is known as the only treatment for advanced liver cirrhosis. Considering the importance of identifying the factors affecting the survival of cirrhosis patients after transplantation in order to improve the health of these patients and increase their longevity, this study was conducted to fit the best accelerated failure time model for survival analysis of cirrhosis patients. Methods: This descriptive-analytical study was conducted by collecting the information about 563 patients with liver cirrhosis who underwent liver transplantation in Imam Khomeini Hospital during 2002-2013 and were followed up for at least 5 years. The data were analyzed using Chisquare test, ANOVA, and Kaplan-Meier non-parametric method as well as exponential Accelerated Failure Time, Weibull, Log-Normal, and Log-Logistic survival models. Results: During the study, 92 (16.3%) of the 563 patients under study died and 165 (29.3%) of them suffered liver transplant rejection. The one-year, three-year, and five-year survival of the patients after transplantation was 0.804, 0.653, and 0.420, respectively. Among the fitted Accelerated Failure Time models, the fitted log-logistic model was the most effective (P-value < 0.001). The effective variables in the Multiple regression log-logistic model included bilirubin (P-value < 0.001), INR (P-value < 0.001), creatinine (P-value < 0.001), and white blood cell (P-value = 0.011) logarithms. Conclusion: Regarding the results of the study, bilirubin, INR, creatinine, and white blood cell logarithmic variables were effective in the survival analysis of the patients after liver transplantation. The survival of these patients can be enhanced through necessary care to maximally control these variables.

Background: Procalcitonin (PCT) has been shown as a reliable diagnostic biomarker for identifying sepsis and bacterial infection. Objectives: The present study examined the sensitivity and specificity of PCT evaluation in the diagnosis of infectious diseases after liver transplantation. Methods: The present prospective cohort study was conducted on postoperative liver transplant (LT) patients in the liver transplant ward of Imam Khomeini Hospital Complex affiliated to Tehran University of Medical Sciences between January 2014 and March 2015. Serum PCT levels were evaluated before transplantation and one, two, and six or seven days post-operation by semi-quantitative kits with a 30 seconds response. Results: A total number of 28 LT patients were enrolled in this study. The mean patients’ ages were 48.6 ± 10.9 (range 26 - 66) years old. Serum PCT levels in all patients were < 0.5 ng/mL prior to the operation. At first and second days post-operation, PCT levels were more than 2 ng/mL in all patients and decreased to 0.5 ng/mL after 6 or 7 days in 23 patients. Serum PCT level of higher than 5 ng/mL on the first and second days post-surgery with a sensitivity of 77.8% and specificity of 79% had the most accuracy for the infection diagnosis. The PCT level more than 5 ng/mL in the sixth and seventh days had a 100% positive predictive value in the infection prediction. Conclusions: Serial evaluations of serum PCT after liver transplantation had good sensitivity and specificity to predict postoperative infection. Increased serum PCT level within the first days after transplantation and/or failure to decrease after one week, predicts infectious complications and undesirable outcome.

This letter was written because of the high incidence of acute hepatitis A in our hospital in this period of time. In December 2016 and January 2017, eight patients with acute hepatitis A were admitted to Gastroenterology Ward of Imam Hospital. Some of them had acute liver failure and fulminant hepatitis. DOI : http://dx.doi.org/10.15171/mejdd.2017.83

Aim: The aim of this study was to compare the prevalence and severity of depression in chronic hepatitis B (CHB) patients, chronic hepatitis C (CHC) patients, and healthy participants. Methods: Two hundred and fifty-three persons participated in this cross-sectional study between 2011 and 2012 in Imam Khomeini Hospital. The prevalence and severity of depression were assessed using the Hamilton Scale. Results: There was significantly higher prevalence of depression in CHC patients (35.9%) than in healthy participants (11.3%) and CHB patients (19.8%) (both P 0.05). Inactive HBsAg carriers differed significantly from CHB patients—excluding inactive HBsAg carriers—in depression prevalence (10.0% vs. 29.3%; P 0.05). Conclusion: Depression screening in chronic hepatitis B and chronic hepatitis C patients may be beneficial in disease management.

Background & Aim: Recent studies have suggested the therapeutic effect of antimicrobial agents on primary sclerosing cholangitis (PSC). Therefore, we aimed to evaluate the efficacy of oral vancomycin in patients with PSC. Method: A triple blinded, randomized, placebo-controlled trial was performed on 29 patients (2015-2016) in the Imam Khomeini Hospital, Tehran, Iran (NCT02605213). Patients were divided into two groups by simple randomization method: placebo 11 (37.9%)/vancomycin 18 (62.1%) and were treated with oral vancomycin (125 mg, four times a day) for 12 weeks. All patients in both groups simultaneously underwent treatment with ursodeoxycholic acid (UDCA, 300 mg, three times a day) before and during the study. Patients’ laboratory data and clinical symptoms were recorded at the beginning, first and third month after starting treatment, and the response to treatment was analyzed. Results: 29 patients with a mean age of 36.27±10.60 years were included in the study. Primary endpoints were accomplished in the vancomycin group showing a significant decline in the mean level of PSC Mayo risk score (decrease rate 3rd month – baseline = -322.03%, p=0.026) during follow up time. Moreover, the analysis of the level of alkaline phosphatase (ALP) in the vancomycin group showed a significant decrease in the third month of treatment as compared to its level in the first month (mean difference 3rd month -1st month = -142.92, Decrease rate= -18.24%, p=0.02). Among secondary endpoints, erythrocyte sedimentation rate (p=0.005), gamma-glutamyl transpeptidase (p=0.02) and patients’ symptoms including fatigue, pruritus, diarrhea and anorexia showed a significant decrease in the vancomycin group. Conclusion: This study demonstrated an acceptable efficacy of vancomycin in the treatment of PSC. Abbreviations: BMI: body mass index ; ESR: Erythrocyte sedimentation rate; FIS-P: Fatigue Impact Scale- Persian; IBD: Inflammatory Bowel Disease; LSD: Least significant difference; PSC: Primary Sclerosing Cholangitis; RCT: Randomized, Controlled Trial; UDCA: Ursodeoxycholic acid; VAS: Visual Analogue Scale.

Objectives Oral tacrolimus administration is the common route of drug delivery. Recent studies suggest sublingual administration of tacrolimus as an alternative route may produce comparable drug trough levels with similar or even lower doses than the oral route, especially in lung transplant recipients; however, most of this research does not encompass intraindividual variations compared between the 2 routes. This study sought to compare the bioavailability and blood trough concentrations of orally and sublingually administered tacrolimus in adult liver transplant recipients by considering intraindividual variations in tacrolimus pharmacokinetics properties. Materials and methods Six adult liver transplant recipients received their tacrolimus either orally or sublingually within 2 consecutive days. Blood samples to determine tacrolimus concentrations were gathered at 0, 0.5, 1, 2, 4, 6, and 12 hours after oral and sublingual tacrolimus administration. Mean data values were used to calculate the pharmacokinetics parameters via the feathering or residual method, using the 1-compartment, first-order elimination pharmacokinetics model. Compared pharmacokinetics parameters included drug bioavailability, maximum blood concentration (C(max)), time to reach maximum blood level (T(max)), and trough blood concentrations. Results Trough whole blood levels, area under the concentration-time curve, T(max), and C(max) after oral and sublingual administration of tacrolimus were not significantly different (10.4 ± 7.4 vs 11.2 ± 11.3 ng/mL for trough blood concentration, 181.5 ± 114.1 vs 160.8 ± 115.9 ng.h/mL for AUC, 1.9 ± 1.2 vs 1.4 ± 0.7 h for T(max), and 19.9 ± 10.8 vs 17.2 ± 11.7 ng/mL for C(max)). A double-peak phenomenon was observed in some concentration-time profiles. Conclusions Sublingual tacrolimus administration does provide therapeutic drug concentrations in adult liver transplant recipients. Therefore, sublingual tacrolimus may confidently be considered as an alternative route to oral administration in patients who are unable to swallow their drugs.

Context: Bowel obstruction is one of the most common causes of acute abdomen. Because of heterogeneity of patients’ population and variety of causes, therapeutic strategies are not standardized, so treatment of intestinal obstruction is a surgical challenge in many cases. A traditional medicine approach could help detect some issues that were ignored by modern medicine. One of the major schools of medicine, with a history of several thousand years, is Iranian traditional medicine. In this regard, Avicenna, who lived in the medieval period, has had a great influence on the medical knowledge of the world by writing an encyclopedia of medicine entitled “Qanun of Medicine.” Evidence Acquisition: The aim of this study was to investigate Avicenna’s views on the causes of intestinal obstruction and comparing them to modern medicine views. This is a review study on an Iranian traditional textbook of medicine by Avicenna, entitled “Qanun of Medicine” (in short “Qanun”). We used Qanun in its original language (Arabic) along with its Persian translation. It consists of 5 books. Part 16 of the third book talks about intestinal anatomy and introduces some intestinal diseases such as “qoolinj” and “ilavos.” Intestinal obstruction can be a kind of “qoolinj” or “ilavos” disease. All intestinal obstruction etiologies in Qanun are searched in international and Iranian databases (Scopus, ISI, SID, and Iranmedex) and similar causes in modern medicine will be discussed in this article. Results: According to Qanun, 16 causes are involved in intestinal etiologies of bowel obstruction such as “reeh,” mucoid phlegm, abdominal hot and dry distemperament, decreased bile secretion, job, and so on while modern medicine considers some of them, for instance, volvulus, intestinal herniation, worm, intestinal pseudo-obstruction, and opiate. Conclusions: Attention to the similar causes of intestinal obstruction in modern medicine and traditional medicine is the starting point for investigation of noninvasive diagnostic and therapeutic methods that have been mentioned in Qanun. In addition, etiologies which are missed in modern medicine can open new doors to the researchers and gastroenterologists for the study, diagnosis, and prevention of the disease.

Liver has an important role in metabolism of vitamin D. This study aimed to evaluate the patterns of vitamin D-parathyroid hormone (PTH) disturbance and correlate it in patients with non-cholestatic chronic liver disease (CLD).A total of 40 healthy controls and 90 consecutive patients with evidence of non-cholestatic CLD due to hepatitis C (n = 28), hepatitis B (n = 26), autoimmune hepatitis (n = 19), and cryptogenic causes (n = 17) were enrolled. Cirrhosis was evident in 51 patients. Serum concentrations of 25-hydroxy vitamin D, PTH, calcium, phosphate, and liver enzymes were measured. Child-Pugh classification was determined in cirrhotic patients.Vitamin D deficiency (50 nmol/l) was found in 46 (51.1%) patients and vitamin D insufficiency (50-80 nmol/l) in 15 (16.7%) patients. Secondary hyperparathyroidism (serum PTH 6.8 pmol/l) was present in 6 (6.7%) patients. The prevalence of vitamin D deficiency was significantly higher in cirrhotic versus noncirrhotic patients (76.5 vs. 17.9%; P 0.001), whereas there was no significant difference in serum calcium, phosphate, and PTH levels. Child-Pugh class B and C patients had significantly lower vitamin D level compared with class A patients (P 0.001), whereas there was no significant difference in serum calcium, phosphate, and PTH levels. No significant correlation was seen between vitamin D and PTH, calcium or phosphate levels. Lower serum level of vitamin D was associated with coagulopathy, hyperbilirubinemia, hypoalbuminemia, anemia, and thrombocytopenia.Vitamin D inadequacy and the severity of liver dysfunction move in parallel in patients with non-cholestatic CLD. Vitamin D assessment and replacement should be considered in the management of patients with non-cholestatic CLD.

Pseudoaneurysm happens when the artery wall is injured and the blood is contained by the surrounding tissues with eventual formation of a fibrous sac communicating with the artery. We report a case of a 39-year-old man with inferior epigastric artery (IEA) pseudoaneurysm after paracentesis. The pseudoaneurysm was diagnosed by Doppler ultrasound and treated by surgical intervention regarding the patient’s underlying comorbidity. IEA false aneurysm must be included in the differential diagnosis during investigation of the cause of any swelling after paracentesis. Cirrhotic patients may be more prone to this complication because of thin rectus muscle that could not confine the hematoma.

BACKGROUND: Early post-transplantation alterations in liver tests are caused by a variety of etiologies including rejection, biliary or vascular complications, and preservation/reperfusion injury (PRI). OBJECTIVES: The aim of this study was to show the correlation between histopathologic changes of PRI and the alterations in liver tests in the early post-transplantation period. MATERIALS AND METHODS: Between April 2013 and August 2014, histopathologic findings of protocol, time-zero, Tru-Cut, liver needle biopsies were evaluated in 94 cases of cadaveric liver transplantation. The histopathologic changes included ballooning degeneration, micro- and macro-vesicular steatosis, bilirubinostasis, apoptotic cells, bile plugs and neutrophilic infiltration. These histopathologic changes were compared with the early (15 days) post-transplantation liver laboratory findings. RESULTS: Clinico-pathologic evaluation of all 94 cases was done by assessment of PRI findings in time-zero biopsies and possible causes of allograft injury were appraised. In 21 patients, a specific cause for allograft injury was found including rejection and/or surgical complications. In the remaining 73 cases, there was no specific cause for allograft injury and histopathologic findings of time-zero liver needle biopsies supported PRI. We classified liver laboratory tests alterations as: hepatocellular damage (elevation of transaminases and lactate dehydrogenase), cholestatic damage (elevation of alkaline phosphatase and total bilirubin) and mixed. Hepatocellular and cholestatic alterations in liver function tests were associated with the presence of marked apoptotic bodies and neutrophilic aggregates in time zero biopsies, respectively. On the other hand, macrovesicular steatosis was dominantly associated with mixed (hepatocellular and cholestatic) laboratory alterations of liver tests. CONCLUSIONS: Any discrepancy between histopathologic changes in time-zero biopsies and pattern of early liver laboratory alterations may be considered as a warning for causes other than PRI.

Objectives. The study was aimed at providing a psychosocial profile for Iranian liver transplant candidates referred to an established liver transplantation program.Material and Methods. Patients assessed for liver transplant candidacy in Imam Khomeini Hospital (Tehran, Iran) between March 2013 and September 2014 were included. The following battery of tests were administered: Psychosocial Assessment of Candidates for Transplant (PACT), the Short-Form health survey (SF-36), and Hospital Anxiety and Depression Scale (HADS).Results. Psychosocial assessment in 205 liver transplant candidates revealed significant impairments in several SF-36 domains; social functioning was the least and physical functioning was the most impaired domains. The prevalence of cases with probable anxiety and depressive disorders, according to HADS, was 13.8% and 5.6%, respectively. According to PACT, 24.3% of the assessed individuals were considered good or excellent candidates. In 11.2%, transplantation seemed poor candidate due to at least one major psychosocial or lifestyle risk factor. Poor candidate quality was associated with impaired health-related quality of life and higher scores on anxiety and depression scales (p<0.05).Conclusions. Transplant programs could implement specific intervention programs based on normative databases to address the psychosocial issues in patients in order to improve patient care, quality of life, and transplant outcomes.

Background: Although transcatheter arterial chemoembolization (TACE) has been widely used as a palliative treatment for unresectable hepatocellular carcinoma (HCC), its actual efficacy and prognostic usefulness have not been clarified in past studies. Objectives: The aim of the study is to investigate the efficacy, complications, and prognostic factors of the TACE in unresectable HCC patients. Patients and Methods: Thirty-two patients with unresectable HCC were treated with TACE. The procedure was performed with a combination of Lipiodol, doxorubicin, and cytomycin followed by gelatin-sponge particles embolization. CT-scan imaging and liver function tests (AST, ALT, ALP, BIL, and PT) were performed before and after the TACE. All patients were followed-up for 6-months. Results: Of all patients, 1 and 11 patients respectively, exhibited a complete response (CR) and a partial response (PR) (response rate, CR+PR, 44%). Data have shown that tumor size, number of lesions and number of involved segments are significantly reduced after the TACE performance (P < 0.05). No significant clinical adverse effect was observed in patients after the intervention. Also, liver function tests including AST, ALT, ALP, BIL, and PT did not significantly differ before and after the intervention (P > 0.05). The 6-month cumulative survival rates of the 32 patients were 78.1 %, respectively. Univariate analysis showed that survival correlated significantly with the following factors: tumor size; ≥ 8 cm versus < 8 cm (P < 0.010), serum ALP level; < 300 versus ≥ 300 (P < 0.043), and number of liver involved segments; < 2 versus ≥ 2 (P < 0.020). Conclusions: We showed that in treatment of patients with unresectable hepatocellular carcinoma, TACE significantly improved the disease and the overall survival rate. Also, we introduce the tumor size, serum ALP level, and number of liver involved segments as prognostic factors of the procedure. Finally, TACE can be recommended as the initial treatment for unresectable HCC patients.

Background Liver transplantation is a critical survival point for patients with end stage liver diseases. It can dramatically increase patients' survival if the donor liver is intact. One aspect of liver health is absence of steatosis. Nonalcoholic Steato Hepatitis (NASH) and Nonalcoholic Fatty Liver Disease (NAFLD) are increasing among young adults and patients living with chronic liver diseases. Objectives In this study, we determined the prevalence of NALFD in livers of brain-dead donors in Imam-Khomeini hospital Complex, Tehran, Iran. We assumed that the calculated prevalence would represent NAFLD prevalence in Iranian population in the age range of 20-60 years. Materials and methods All eligible brain dead liver transplant donors were enrolled in the survey from March 21, 2011 to March 21, 2013 in Imam-Khomeini hospital Complex. Eligible participants were donors aged 20 to 60 years without any obvious history of liver disease. Liver needle biopsy was performed at the end of the transplant operation; time zero biopsy. We calculated the prevalence of NAFLD among brain-dead donors. Moreover, the frequency of NASH was calculated based on the NAS (NAFLD Activity Score). Results Among 116 cases, two were diagnosed as probable NASH. There was a significant association between NAFLD and male gender (P = 0.04). Moreover, we found a higher steatosis level in male gender. There was a significant association between NAFLD and BMI (P = 0.05). Those with BMI more than 27 had severe steatosis. Conclusions Our comprehensive literature review showed that our study was the first investigation in Iran and the region, which determined the prevalence of NAFLD based on tissue diagnosis. We believe that the prevalence of NAFLD/NASH in our donors can represent the overall prevalence in this age group in Iran.

Background: Hepatitis B is the most prevalent chronic infectious liver disease worldwide with serious sequelae. Prevention of the infection can be provided by universal vaccination and improvement in knowledge and behavior about disease transmission. Provision of any educational program requires inquiry about target group baseline knowledge. Objectives: The aim of this study was to assess Iranian adolescents’ knowledge about hepatitis B (HBV) and associated factors. Patients and Methods: We conducted a questionnaire-based national survey of 18-year-old adolescents according to stratified cluster random sampling in Iran during 2007. Results: Response rate was 87%. Most adolescents (60%) knew that HBV infects the liver. Percentage of adolescents who gave correct answers to major routes of HBV transmission were as follows: spouse of an infected person 59%, multi-partners 66%, intravenous drug use 73%, body piercing 55% and personal belongings 55%. Higher levels of education, living in rural areas, marriage and (except for body piercing) female gender were associated with better knowledge. The knowledge of HBV infected individuals about major routes of HBV transmission was low (P < 0.001). Conclusions: There are important deficits in adolescents’ knowledge about HBV that requires attention of health educators to tailor educational programs for specific groups.

Background: Various aspects of adherence to HCV treatment such as frequency, risk factors as well as causes of non-adherence, and its real role in clinical and virological outcome of the infected patients have remained largely unknown. Objectives: The current study aimed to evaluate patients’ adherence to anti-HCV medications in Iran. Materials and Methods: From October 2010 to March 2011, socio-demographic characteristics, features of HCV infection, clinical properties, and habitual history of 190 patients were collected. Adherence of each patient to anti-HCV medications was determined at months 1, 3, and 6 of treatment by self-reporting and pill or empty ampoule counting. Adherence to anti-HCV treatment regimen was determined based on the 80/80/80 rule. Results: Adherence rate to interferon, ribavirin, or a combination of them over the first 6 months of therapy in Iranian HCV patients measured by both methods of self-reporting and pill counting were 35.4-65.8%, 46.3-56.8%, and 28.4-51.1%, respectively. Delay in receiving new prescription, financial issues, and adverse drug reactions were the most common causes of non-adherence in the patients. Adherence to ribavirin was identified as an independent predictor of achieving the end of treatment response, or sustained virological response. Conclusions: The rate of adherence to interferon and ribavirin varied significantly according to the method of calculation. Over the treatment course, adherence to interferon alpha and ribavirin, each or their combination, diminished significantly.

Background: Liver transplantation (LT) is the only treatment option for patients with advanced liver disease. Currently, liver donation to these patients, considering priorities, is based on the Model for End-Stage Liver Disease (MELD). MELD score is a tool for predicting the risk of mortality in patients with advanced liver disease. However, few studies have so far been conducted in Iran on the efficacy of MELD score of these patients. Objectives: This study reviews the present status of the MELD score and introduces a new model for optimal prediction of the risk of mortality in Iranian patients with advanced liver disease. Patients and Methods: Data required were collected from 305 patients with advanced liver disease who enrolled in a waiting list (WL) in Imam Khomeini Hospital from May 2008 to May 2009. All of the patients were followed up for at least 3 years until they died or underwent LT. Cox regression analysis was applied to select the factors affecting their mortality. Survival curves were plotted. Wilcoxson test and receiver operating characteristics curves for survival predictive model were used to compare the scores. All calculations were performed with the SPSS (version 13.0) and R softwares. Results: During the study, 71 (23.3%) patients died due to liver cirrhosis and 43 (14.1%) underwent LT. Viral Hepatitis (43.7%) is the most common cause of end-stage liver disease among Iranian patients. A new model (NMELD) was proposed with the use of the natural logarithms of two blood serum variables (total bilirubin and albumin) and the patients' age (year) by applying the Cox model: NMELD = 10 × (0.736 × ln (bilirubin) – 1.312 × ln (albumin) + 0.025 × age + 1.776) Conclusions: The results of the Wilcoxon test showed that there is a significant difference between the usual MELD and our proposed NMELD scores (P < 0.001). Receiver operating characteristics curve for survival predictive model indicated that the NMELD score is more efficient compared with the MELD score in predicting the risk of mortality. Since serum creatinine was not significant in NMELD score, further studies to clarify this issue are suggested.

Background: Insulin-like growth factor is a polypeptide with endocrine, autocrine and paracrine effects which its structure is similar to the insulin molecule. While various tissues secrete IGF-1, 90% of the circulating IGF-1 is secreted by liver. Cirrhosis of liver is a condition accompanied by decreased level of IGF-1, in which the level of IGF-1 may be further decreased thorough the progression of the disease Objectives: The aim of the present study was to demonstrate the relation between the IGF-1 levels and severity of liver disease according to Child- Pugh and Model for end stage liver diseases (MELD) Scores. Patients and Method: This was a descriptive-analytic cross sectional study performed on patients with cirrhosis admitted to gastroenterology clinic of Imam Khomeini Hospital in Tehran, Iran during the years 2007-2008. The diagnosis was based on liver biopsy. Initially for all patients, laboratory investigations including IGF-1, CBC, liver Enzymes, Alkaline phosphates, serum Albumin, Creatinine, direct and total Bilirubin were conducted. Also ultrasound and endoscopy were performed for evaluation of ascites and varices. Results: 100 patients with cirrhosis with a male to Female ratio of 63:37 and a mean age of 44.4 ± 15 years were enrolled in the study. Median IGF-1 was 92.95 ± 91.51 ng/mL. 14 patients (14%) had IGF-1 within normal limits while 86 patients (86%) had abnormal IGF-1 levels. In all patients the correlation coefficient between IGF-1 and MELD was -0.317 (P = 0.001) and 0.478 between IGF-1 and Child- Pugh (P < 0.001). Conclusions: Our findings showed that IGF-1 can be used as an index for evaluating the severity of cirrhosis; also it can be used for determining the severity of the disease, when liver biopsy is not possible.

Background Hepatitis C is prevalent among thalassemia patients in Iran. It is mainly transfusion mediated, in particular among patients treated before 1996 when blood screening was introduced. Objectives The current study aimed to investigate why patients still seroconvert to anti-HCV in Iranian thalassemia centers. Patients and Methods During 2006-2007 sera were sampled from 217 anti-HCV positive thalassemia patients at nine thalassemia centers in Tehran and Amol city, where 34 (16%) patients had been infected after 1996. The HCV subtype could be determined by sequencing and phylogenetic analysis of partial NS5B and/or 5׳NCR-core region in 130 strains. Results 1a (53%) was predominant followed by 3a (30%), 1b (15%), and one strain each of 2k, 3k and 4a. Phylogenetic analysis revealed 19 clades with up to five strains diverging with less than six nucleotides from each other within subtypes 1a and 3a. Strains in seven clades were from nine patients infected between 1999 and 2005 and similar to strains from eight patients infected before 1996, indicating ongoing transmission at the centers. Further epidemiological investigation revealed that 28 patients infected with strains within the same clade had frequently been transfused at the same shift sitting on the same bed. An additional eight patients with related strains had frequently been transfused simultaneously in the same room. Conclusions The results suggest nosocomial transmission at these thalassemia centers both before and after the introduction of blood screening. Further training of staff and strict adherence to preventive measures are thus essential to reduce the incidence of new HCV infections.

AIM: To determine the efficacy and potential complications of oral naltrexone used in the treatment of pruritus in cholestatic patients and to compare them with other studies. METHODS: Thirty-four enrolled cholestatic patients complaining of pruritus were studied. In the initial phase, pruritus scores during day and night were e v a l u a t e d . Subsequently, patients were given a placebo for one week followed by naltrexone for one week. In each therapeutic course (placebo or naltrexone) day and night pruritus scores were distinguished by a visual analogue scale (VAS) system and recorded in patients’ questionnaires. RESULTS: Both naltrexone and placebo decreased VAS scores significantly. Naltrexone was more effective than placebo in decreasing VAS scores. Both day and night scores of pruritus decreased by half of the value prior to therapy in thirteen patients (38%). Daytime pruritus improved completely in two patients (5.9%), but no improvement in the nighttime values was observed in any patient. Sixteen patients (47%) suffered from naltrexone complications, eleven (32%) of them were related to its withdrawal. Complications were often mild. In the case of withdrawal, the complication was transient (within the first 24-28 h of therapy) and self-limited. We had to cease the drug in two cases (5.9%) because of severe withdrawal symptoms. CONCLUSION: Naltrexone can be used in the treatment of pruritus in cholestatic patients and is a safe drug showing few, mild and self-limited complications.