Transplant international : official journal of the European Society for Organ Transplantation, Jan 11, 2015
There are reports of pre-transplant sofosbuvir (SOF) plus ribavirin being effective in preventing... more There are reports of pre-transplant sofosbuvir (SOF) plus ribavirin being effective in preventing recurrent HCV infection after liver transplantation (LT). The aim of this study was to assess the cost-effectiveness of this strategy in the area served by the North Italy Transplant program. We retrospectively assessed the impact of HCV infection on post-LT survival in 2376 consecutive adult patients (MELD ≤ 25, unknown genotype, period 2004-2009) and the prevalence-costs of conventional standard of care (SOC) antiviral therapy (pegylated interferon plus ribavirin) after LT. A Markov model was developed to compare two strategies: 12 to 24 weeks of SOF + ribavirin for pre-LT anti-HCV treatment, versus on-demand post-LT SOC antiviral therapy. Among the 1794 patients undergoing LT, 860 (48%) were HCV+ and 50% of them were given SOC therapy after LT (mean cost of drugs and adverse effect management =14,421€ per patient). HCV etiology had a strong impact on post-LT survival (hazard ratio=1....
We report two cases of Kaposi's sarcoma in recipients of solid organ transplants, presenting ... more We report two cases of Kaposi's sarcoma in recipients of solid organ transplants, presenting (Case 1) 12 months after liver transplantation and (Case 2) 7 months after kidney transplantation. Both patients share the following features: natives from the Mediterranean area (Southern Italy), multiple immunosuppressive regimen, infection with hepatitis B and cytomegalovirus. During the 3 yr of follow-up after the diagnosis, their immunosuppressive regimen was reduced and they were treated with alpha interferon with remission of the clinical findings. The management of Kaposi's sarcoma in organ transplant recipients remains a controversial issue because of the risks of organ rejection associated with the reduction of immunosuppression and with the use of interferon.
Transplant international : official journal of the European Society for Organ Transplantation, 2014
Calcineurin inhibitors (CNIs) have been associated in a dose-dependent fashion with an increased ... more Calcineurin inhibitors (CNIs) have been associated in a dose-dependent fashion with an increased risk of post-transplant hepatocellular carcinoma (HCC) recurrence. The mammalian target of rapamycin inhibitors (mTORi) (sirolimus/everolimus) might represent an alternative immunosuppressive regimen with antineoplastic effect. In the present systematic review, the association between mTORi and HCC recurrence after liver transplantation (LT) was evaluated and compared against that of CNIs-treated patients. In total, 3666 HCC liver transplant recipients from 42 studies met the inclusion criteria. Patients under CNIs developed HCC recurrence significantly more frequently, compared with patients under mTORi (448/3227 or 13.8% vs. 35/439 or 8%, P < 0.001), although patients treated with CNIs had a higher proportion of HCC within Milan criteria (74% vs. 69%) and lower rates of microvascular invasion, compared with mTORi-treated patients (22% vs. 44%) (P < 0.05). Patients on everolimus h...
World journal of gastroenterology : WJG, Jan 7, 2011
About 50% of patients with hepatitis C virus (HCV) infection complain of neuropsychiatric symptom... more About 50% of patients with hepatitis C virus (HCV) infection complain of neuropsychiatric symptoms, "brain fog", weakness, fatigue, and exhibit some degree of quality of life impairment, irrespective of the severity of liver disease. Since the first observation of HCV-related cognitive deficits, 10 studies have been published that have evaluated neuropsychiatric performance in patients with HCV infection and different degrees of hepatic impairment. Unfortunately, these have often included patients with cirrhosis, patients who had acquired the infection through previous intravenous drug misuse, who had a history of relatively recent treatment with interferon, or were on psychoactive medication. In addition, different neuropsychological batteries and tests that explored different cognitive domains were used, which makes the results of the studies difficult to compare. Finally, limited information is available on the pathogenesis of HCV-related cognitive impairment. Cerebral ...
The use of hepatitis B immunoglobulin (HBIg) combined with nucleos(t)ide analogues (NUCs) has imp... more The use of hepatitis B immunoglobulin (HBIg) combined with nucleos(t)ide analogues (NUCs) has improved outcomes in post-hepatitis B (PHB) liver transplant (LT), reducing the 1-year recurrence rate below 10%. The aim of this study was to evaluate efficacy and pharmacokinetics of prophylaxis with NUC(s) and intravenous (iv-) or intramuscular (im-) HBIg in 33 PHBLTs, transplanted for more than 1 year. During the first six months of the study, 18 subjects received 5000 IU of iv-HBIg every four weeks and 15 patients 2160 IU/12 mL of im-HBIg every two weeks. In the following six months, 31 subjects were switched to two different concentrations of im-HBIg, 2160/12 mL (16 patients) or 2000 IU/6 mL every two weeks (15 patients). All patients remained HBsAg-negative and 30/31 maintained anti-HBs >100 IU/L. Overall mean anti-HBs titer during treatment was 363 IU/mL. Mean HBIg half-life was 21.4, 27.3 and 26 days with intravenous, diluted or concentrated im-preparations, respectively. These ...
Micronuclei (MNi) and broken eggs (BE) are both considered sensitive markers of genotoxic damage ... more Micronuclei (MNi) and broken eggs (BE) are both considered sensitive markers of genotoxic damage and chromosomal instability. In humans, a high frequency of MNi is reported in both cirrhosis and hepatocellular carcinoma, but no information is available on MNi/BE expression in dysplastic nodules. MNi/BE formation may result in activation of the p53-mediated cell cycle checkpoint. MNi, BE (Feulgen staining) and immunohistochemical expression of p53 and Mib1 were assessed in 95 liver lesions representing the whole spectrum of liver carcinogenesis. Seven normal liver tissue samples served as controls. MNi and BE were assessed by video-assisted microscopy and expressed as a crude number per 1,000 hepatocytes. MNi and BE were significantly more frequent in all the pathological samples than in the controls (p<0.001). A progressively increasing number of MNi/BEs was documented from cirrhotic nodules (CN) to large regenerative nodules (LRN), to dysplastic nodules (DN) and hepatocellular c...
World journal of gastroenterology : WJG, Jan 28, 2006
The liver is an essential player in the pathway of coagulation in both primary and secondary haem... more The liver is an essential player in the pathway of coagulation in both primary and secondary haemostasis. Only von Willebrand factor is not synthetised by the liver, thus liver failure is associated with impairment of coagulation. However, recently it has been shown that the delicate balance between pro and antithrombotic factors synthetised by the liver might be reset to a lower level in patients with chronic liver disease. Therefore, these patients might not be really anticoagulated in stable condition and bleeding may be caused only when additional factors, such as infections, supervene. Portal hypertension plays an important role in coagulopathy in liver disease, reducing the number of circulating platelets, but platelet function and secretion of thrombopoietin have been also shown to be impaired in patients with liver disease. Vitamin K deficiency may coexist, so that abnormal clotting factors are produced due to lack of gamma carboxylation. Moreover during liver failure, there...
The shortage of organ donations is a major limiting factor in transplant programs. Since a favora... more The shortage of organ donations is a major limiting factor in transplant programs. Since a favorable attitude of health professionals to organ donation can positively influence the decision of families of potential donors, educating physicians early in their careers may become crucial in this setting. The aim of this study was to compare medical student opinions on organ donation and transplantation at different stages in their undergraduate career. Medical students were prospectively surveyed in their first and fourth years by an anonymous 10-item questionnaire. The 100 of 195 (51.3%) students completed both questionnaires including 29 men, of an overall cohort mean age 23.7 (range, 22-32 years). 91% of the students had attended classical or scientific high school and 83% were Catholic. Their attitude to transplantation remained strongly positive (96% vs 92%, fourth vs first year). 96% of the fourth year students would accept an human donor organ or an artificial organ (vs 95% of f...
Since lipid peroxidation is a well-know mechanism of alcohol-related liver damage, the aim of the... more Since lipid peroxidation is a well-know mechanism of alcohol-related liver damage, the aim of the present study was to assess the role of serum malondialdehyde (MDA), a secondary product of lipoperoxidation, in the detection of alcoholism and different stages of alcoholic liver disease and to correlate serum levels of malondialdehyde with other markers. Sixty-five patients with a mean alcohol intake of 151 gr/day, were divided into three groups: alcoholics with normal liver function (ANLF, 7 pts), non-cirrhotic alcoholic liver disease (NCALD, 26 pts) and alcoholic cirrhosis (ALC, 32 pts). The control group consisted of 15 healthy subjects. Serum MDA was measured by the thiobarbituric acid reaction test, and mitochondrial aspartate aminotransferase (mAST) with immunochemical assay. MDA had a higher sensitivity (70% vs 37.5%) and specificity (100% vs 93%) than mAST in detecting alcohol abuse, irrespective of the presence of liver disease. Serum MDA levels were significantly higher in ...
In 20% to 30% of infected individuals, hepatitis C virus (HCV) can cause cirrhosis and hepatocell... more In 20% to 30% of infected individuals, hepatitis C virus (HCV) can cause cirrhosis and hepatocellular carcinoma, for which liver transplantation is the best treatment available. HCV re-infection is universal, and hepatitis disease recurrence occurs in most cases with a 30% probability of progression to graft cirrhosis at 5 years post-transplant. The immunological response to HCV involves natural killer (NK) cells and killer cell immunoglobulin-like receptors (KIRs), which specifically recognize human leukocyte antigen (HLA) class I antigens present on target cells. The effector functions of NK cells are influenced by inhibitory KIR interaction with self-HLA class I ligands, with HLA-C being the most predominant. This study examines the roles of KIR genotypes and their HLA ligands in both HCV disease recurrence and its progression. A total of 151 patients were included in the cohort, and their clinical details were recorded. Liver biopsies were used to define the absence/presence of recurrent hepatitis, the degree of fibrosis, and the progression to cirrhosis over a 10-year period. Mismatching of KIR-HLA-C ligands between donor-recipient pairs was associated with the recurrence of hepatitis (P ϭ 0.008). The presence of KIR2DL3 in the recipient correlated with progression to liver fibrosis (P ϭ 0.04). The mismatching of HLA-KIR ligands favored the progression of the recurrent hepatitis to fibrosis only in the presence of KIR2DL3 (P ϭ 0.04). These preliminary results indicate that the KIR genotype and KIR-HLA-C ligand compatibility play roles in the recurrence and progression of hepatitis C disease in liver transplant recipients. Liver Transpl 15: [390][391][392][393][394][395][396][397][398][399] 2009.
The first liver transplant in Italy was performed in 1982. With the improvement in results, the n... more The first liver transplant in Italy was performed in 1982. With the improvement in results, the number of patients followed, in recent years, has substantially increased in all centres. In parallel, the indications for liver transplantation have expanded and have raised the need for more organized structures where patients can be referred for evaluation and transplantation. Indications and contraindications to
We read with great interest the letter by Parsikia and co-workers concerning the review recently ... more We read with great interest the letter by Parsikia and co-workers concerning the review recently published on the management of HCV in patients with end stage renal disease and kidney transplantation(1), and thank the authors for bringing up such a stimulating discussion, which reflects the contrasting European and American practices regarding compensated cirrhosis in the setting of kidney transplantation. Coinciding with the comment by Parsikia and collaborators, both the KDIGO(2) and the AASLD(3) guidelines do not provide precise recommendations on the management of HCV-related cirrhosis patients with end stage renal disease. This article is protected by copyright. All rights reserved.
Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohep... more Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohepatitis, fibrosis, and cirrhosis to hepatocellular carcinoma. Forty-four per cent of all deaths from cirrhosis are attributed to alcohol. Alcoholic liver disease is the second most common diagnosis among patients undergoing liver transplantation (LT). The vast majority of transplant programmes (85%) require 6 mo of abstinence prior to transplantation; commonly referred to as the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;6-mo rule&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;. Both in the case of progressive end-stage liver disease (ESLD) and in the case of severe acute alcoholic hepatitis (AAH), not responding to medical therapy, there is a lack of evidence to support a 6-mo sobriety period. It is necessary to identify other risk factors that could be associated with the resumption of alcohol drinking. The &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;Group of Italian Regions&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; suggests that: in a case of ESLD with model for end-stage liver disease &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 19 a 6-mo abstinence period is required; in a case of ESLD, a 3-mo sober period before LT may be more ideal than a 6-mo period, in selected patients; and in a case of severe AAH, not responding to medical therapies (up to 70% of patients die within 6 mo), LT is mandatory, even without achieving abstinence. The multidisciplinary transplant team must include an addiction specialist/hepato-alcohologist. Patients have to participate in self-help groups.
ABSTRACT We thank Drs. Mancuso and Perricone for their comments on our systematic review in Trans... more ABSTRACT We thank Drs. Mancuso and Perricone for their comments on our systematic review in Transplant International[1], which is the first systematic analysis comparing mammalian target of rapamycin inhibitors (mTORi) (including both sirolimus and everolimus) and calcineurin inhibitors (CNIs) with evaluation of particular characteristics associated with HCC recurrence after liver transplantation (LT). The authors in their letter emphasized that m-TORi have no proven anti-cancer attitude for HCC treatment based on a recently published randomized controlled trial (EVOLVE-1)[2]. However, we have to mention that the latter study was performed in patients with advanced HCC after failure of sorafenib, i.e. a completely different setting, compared to our systematic review, in which we evaluated the impact of mTORi on prevention of HCC recurrence after LT and not the treatment of recurrent HCC[1].This article is protected by copyright. All rights reserved.
Transplant international : official journal of the European Society for Organ Transplantation, Jan 11, 2015
There are reports of pre-transplant sofosbuvir (SOF) plus ribavirin being effective in preventing... more There are reports of pre-transplant sofosbuvir (SOF) plus ribavirin being effective in preventing recurrent HCV infection after liver transplantation (LT). The aim of this study was to assess the cost-effectiveness of this strategy in the area served by the North Italy Transplant program. We retrospectively assessed the impact of HCV infection on post-LT survival in 2376 consecutive adult patients (MELD ≤ 25, unknown genotype, period 2004-2009) and the prevalence-costs of conventional standard of care (SOC) antiviral therapy (pegylated interferon plus ribavirin) after LT. A Markov model was developed to compare two strategies: 12 to 24 weeks of SOF + ribavirin for pre-LT anti-HCV treatment, versus on-demand post-LT SOC antiviral therapy. Among the 1794 patients undergoing LT, 860 (48%) were HCV+ and 50% of them were given SOC therapy after LT (mean cost of drugs and adverse effect management =14,421€ per patient). HCV etiology had a strong impact on post-LT survival (hazard ratio=1....
We report two cases of Kaposi's sarcoma in recipients of solid organ transplants, presenting ... more We report two cases of Kaposi's sarcoma in recipients of solid organ transplants, presenting (Case 1) 12 months after liver transplantation and (Case 2) 7 months after kidney transplantation. Both patients share the following features: natives from the Mediterranean area (Southern Italy), multiple immunosuppressive regimen, infection with hepatitis B and cytomegalovirus. During the 3 yr of follow-up after the diagnosis, their immunosuppressive regimen was reduced and they were treated with alpha interferon with remission of the clinical findings. The management of Kaposi's sarcoma in organ transplant recipients remains a controversial issue because of the risks of organ rejection associated with the reduction of immunosuppression and with the use of interferon.
Transplant international : official journal of the European Society for Organ Transplantation, 2014
Calcineurin inhibitors (CNIs) have been associated in a dose-dependent fashion with an increased ... more Calcineurin inhibitors (CNIs) have been associated in a dose-dependent fashion with an increased risk of post-transplant hepatocellular carcinoma (HCC) recurrence. The mammalian target of rapamycin inhibitors (mTORi) (sirolimus/everolimus) might represent an alternative immunosuppressive regimen with antineoplastic effect. In the present systematic review, the association between mTORi and HCC recurrence after liver transplantation (LT) was evaluated and compared against that of CNIs-treated patients. In total, 3666 HCC liver transplant recipients from 42 studies met the inclusion criteria. Patients under CNIs developed HCC recurrence significantly more frequently, compared with patients under mTORi (448/3227 or 13.8% vs. 35/439 or 8%, P < 0.001), although patients treated with CNIs had a higher proportion of HCC within Milan criteria (74% vs. 69%) and lower rates of microvascular invasion, compared with mTORi-treated patients (22% vs. 44%) (P < 0.05). Patients on everolimus h...
World journal of gastroenterology : WJG, Jan 7, 2011
About 50% of patients with hepatitis C virus (HCV) infection complain of neuropsychiatric symptom... more About 50% of patients with hepatitis C virus (HCV) infection complain of neuropsychiatric symptoms, "brain fog", weakness, fatigue, and exhibit some degree of quality of life impairment, irrespective of the severity of liver disease. Since the first observation of HCV-related cognitive deficits, 10 studies have been published that have evaluated neuropsychiatric performance in patients with HCV infection and different degrees of hepatic impairment. Unfortunately, these have often included patients with cirrhosis, patients who had acquired the infection through previous intravenous drug misuse, who had a history of relatively recent treatment with interferon, or were on psychoactive medication. In addition, different neuropsychological batteries and tests that explored different cognitive domains were used, which makes the results of the studies difficult to compare. Finally, limited information is available on the pathogenesis of HCV-related cognitive impairment. Cerebral ...
The use of hepatitis B immunoglobulin (HBIg) combined with nucleos(t)ide analogues (NUCs) has imp... more The use of hepatitis B immunoglobulin (HBIg) combined with nucleos(t)ide analogues (NUCs) has improved outcomes in post-hepatitis B (PHB) liver transplant (LT), reducing the 1-year recurrence rate below 10%. The aim of this study was to evaluate efficacy and pharmacokinetics of prophylaxis with NUC(s) and intravenous (iv-) or intramuscular (im-) HBIg in 33 PHBLTs, transplanted for more than 1 year. During the first six months of the study, 18 subjects received 5000 IU of iv-HBIg every four weeks and 15 patients 2160 IU/12 mL of im-HBIg every two weeks. In the following six months, 31 subjects were switched to two different concentrations of im-HBIg, 2160/12 mL (16 patients) or 2000 IU/6 mL every two weeks (15 patients). All patients remained HBsAg-negative and 30/31 maintained anti-HBs >100 IU/L. Overall mean anti-HBs titer during treatment was 363 IU/mL. Mean HBIg half-life was 21.4, 27.3 and 26 days with intravenous, diluted or concentrated im-preparations, respectively. These ...
Micronuclei (MNi) and broken eggs (BE) are both considered sensitive markers of genotoxic damage ... more Micronuclei (MNi) and broken eggs (BE) are both considered sensitive markers of genotoxic damage and chromosomal instability. In humans, a high frequency of MNi is reported in both cirrhosis and hepatocellular carcinoma, but no information is available on MNi/BE expression in dysplastic nodules. MNi/BE formation may result in activation of the p53-mediated cell cycle checkpoint. MNi, BE (Feulgen staining) and immunohistochemical expression of p53 and Mib1 were assessed in 95 liver lesions representing the whole spectrum of liver carcinogenesis. Seven normal liver tissue samples served as controls. MNi and BE were assessed by video-assisted microscopy and expressed as a crude number per 1,000 hepatocytes. MNi and BE were significantly more frequent in all the pathological samples than in the controls (p<0.001). A progressively increasing number of MNi/BEs was documented from cirrhotic nodules (CN) to large regenerative nodules (LRN), to dysplastic nodules (DN) and hepatocellular c...
World journal of gastroenterology : WJG, Jan 28, 2006
The liver is an essential player in the pathway of coagulation in both primary and secondary haem... more The liver is an essential player in the pathway of coagulation in both primary and secondary haemostasis. Only von Willebrand factor is not synthetised by the liver, thus liver failure is associated with impairment of coagulation. However, recently it has been shown that the delicate balance between pro and antithrombotic factors synthetised by the liver might be reset to a lower level in patients with chronic liver disease. Therefore, these patients might not be really anticoagulated in stable condition and bleeding may be caused only when additional factors, such as infections, supervene. Portal hypertension plays an important role in coagulopathy in liver disease, reducing the number of circulating platelets, but platelet function and secretion of thrombopoietin have been also shown to be impaired in patients with liver disease. Vitamin K deficiency may coexist, so that abnormal clotting factors are produced due to lack of gamma carboxylation. Moreover during liver failure, there...
The shortage of organ donations is a major limiting factor in transplant programs. Since a favora... more The shortage of organ donations is a major limiting factor in transplant programs. Since a favorable attitude of health professionals to organ donation can positively influence the decision of families of potential donors, educating physicians early in their careers may become crucial in this setting. The aim of this study was to compare medical student opinions on organ donation and transplantation at different stages in their undergraduate career. Medical students were prospectively surveyed in their first and fourth years by an anonymous 10-item questionnaire. The 100 of 195 (51.3%) students completed both questionnaires including 29 men, of an overall cohort mean age 23.7 (range, 22-32 years). 91% of the students had attended classical or scientific high school and 83% were Catholic. Their attitude to transplantation remained strongly positive (96% vs 92%, fourth vs first year). 96% of the fourth year students would accept an human donor organ or an artificial organ (vs 95% of f...
Since lipid peroxidation is a well-know mechanism of alcohol-related liver damage, the aim of the... more Since lipid peroxidation is a well-know mechanism of alcohol-related liver damage, the aim of the present study was to assess the role of serum malondialdehyde (MDA), a secondary product of lipoperoxidation, in the detection of alcoholism and different stages of alcoholic liver disease and to correlate serum levels of malondialdehyde with other markers. Sixty-five patients with a mean alcohol intake of 151 gr/day, were divided into three groups: alcoholics with normal liver function (ANLF, 7 pts), non-cirrhotic alcoholic liver disease (NCALD, 26 pts) and alcoholic cirrhosis (ALC, 32 pts). The control group consisted of 15 healthy subjects. Serum MDA was measured by the thiobarbituric acid reaction test, and mitochondrial aspartate aminotransferase (mAST) with immunochemical assay. MDA had a higher sensitivity (70% vs 37.5%) and specificity (100% vs 93%) than mAST in detecting alcohol abuse, irrespective of the presence of liver disease. Serum MDA levels were significantly higher in ...
In 20% to 30% of infected individuals, hepatitis C virus (HCV) can cause cirrhosis and hepatocell... more In 20% to 30% of infected individuals, hepatitis C virus (HCV) can cause cirrhosis and hepatocellular carcinoma, for which liver transplantation is the best treatment available. HCV re-infection is universal, and hepatitis disease recurrence occurs in most cases with a 30% probability of progression to graft cirrhosis at 5 years post-transplant. The immunological response to HCV involves natural killer (NK) cells and killer cell immunoglobulin-like receptors (KIRs), which specifically recognize human leukocyte antigen (HLA) class I antigens present on target cells. The effector functions of NK cells are influenced by inhibitory KIR interaction with self-HLA class I ligands, with HLA-C being the most predominant. This study examines the roles of KIR genotypes and their HLA ligands in both HCV disease recurrence and its progression. A total of 151 patients were included in the cohort, and their clinical details were recorded. Liver biopsies were used to define the absence/presence of recurrent hepatitis, the degree of fibrosis, and the progression to cirrhosis over a 10-year period. Mismatching of KIR-HLA-C ligands between donor-recipient pairs was associated with the recurrence of hepatitis (P ϭ 0.008). The presence of KIR2DL3 in the recipient correlated with progression to liver fibrosis (P ϭ 0.04). The mismatching of HLA-KIR ligands favored the progression of the recurrent hepatitis to fibrosis only in the presence of KIR2DL3 (P ϭ 0.04). These preliminary results indicate that the KIR genotype and KIR-HLA-C ligand compatibility play roles in the recurrence and progression of hepatitis C disease in liver transplant recipients. Liver Transpl 15: [390][391][392][393][394][395][396][397][398][399] 2009.
The first liver transplant in Italy was performed in 1982. With the improvement in results, the n... more The first liver transplant in Italy was performed in 1982. With the improvement in results, the number of patients followed, in recent years, has substantially increased in all centres. In parallel, the indications for liver transplantation have expanded and have raised the need for more organized structures where patients can be referred for evaluation and transplantation. Indications and contraindications to
We read with great interest the letter by Parsikia and co-workers concerning the review recently ... more We read with great interest the letter by Parsikia and co-workers concerning the review recently published on the management of HCV in patients with end stage renal disease and kidney transplantation(1), and thank the authors for bringing up such a stimulating discussion, which reflects the contrasting European and American practices regarding compensated cirrhosis in the setting of kidney transplantation. Coinciding with the comment by Parsikia and collaborators, both the KDIGO(2) and the AASLD(3) guidelines do not provide precise recommendations on the management of HCV-related cirrhosis patients with end stage renal disease. This article is protected by copyright. All rights reserved.
Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohep... more Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohepatitis, fibrosis, and cirrhosis to hepatocellular carcinoma. Forty-four per cent of all deaths from cirrhosis are attributed to alcohol. Alcoholic liver disease is the second most common diagnosis among patients undergoing liver transplantation (LT). The vast majority of transplant programmes (85%) require 6 mo of abstinence prior to transplantation; commonly referred to as the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;6-mo rule&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;. Both in the case of progressive end-stage liver disease (ESLD) and in the case of severe acute alcoholic hepatitis (AAH), not responding to medical therapy, there is a lack of evidence to support a 6-mo sobriety period. It is necessary to identify other risk factors that could be associated with the resumption of alcohol drinking. The &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;Group of Italian Regions&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; suggests that: in a case of ESLD with model for end-stage liver disease &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 19 a 6-mo abstinence period is required; in a case of ESLD, a 3-mo sober period before LT may be more ideal than a 6-mo period, in selected patients; and in a case of severe AAH, not responding to medical therapies (up to 70% of patients die within 6 mo), LT is mandatory, even without achieving abstinence. The multidisciplinary transplant team must include an addiction specialist/hepato-alcohologist. Patients have to participate in self-help groups.
ABSTRACT We thank Drs. Mancuso and Perricone for their comments on our systematic review in Trans... more ABSTRACT We thank Drs. Mancuso and Perricone for their comments on our systematic review in Transplant International[1], which is the first systematic analysis comparing mammalian target of rapamycin inhibitors (mTORi) (including both sirolimus and everolimus) and calcineurin inhibitors (CNIs) with evaluation of particular characteristics associated with HCC recurrence after liver transplantation (LT). The authors in their letter emphasized that m-TORi have no proven anti-cancer attitude for HCC treatment based on a recently published randomized controlled trial (EVOLVE-1)[2]. However, we have to mention that the latter study was performed in patients with advanced HCC after failure of sorafenib, i.e. a completely different setting, compared to our systematic review, in which we evaluated the impact of mTORi on prevention of HCC recurrence after LT and not the treatment of recurrent HCC[1].This article is protected by copyright. All rights reserved.
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