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1.
Cancers (Basel) ; 11(10)2019 Sep 20.
Article in English | MEDLINE | ID: mdl-31547152

ABSTRACT

Hepatitis C virus (HCV) infection compromises the natural defense mechanisms of the liver leading to a progressive end stage disease such as cirrhosis and hepatocellular carcinoma (HCC). The hepatic stress response generated due to viral replication in the endoplasmic reticulum (ER) undergoes a stepwise transition from adaptive to pro-survival signaling to improve host cell survival and liver disease progression. The minute details of hepatic pro-survival unfolded protein response (UPR) signaling that contribute to HCC development in cirrhosis are unknown. This study shows that the UPR sensor, the protein kinase RNA-like ER kinase (PERK), mediates the pro-survival signaling through nuclear factor erythroid 2-related factor 2 (NRF2)-mediated signal transducer and activator of transcription 3 (STAT3) activation in a persistent HCV infection model of Huh-7.5 liver cells. The NRF2-mediated STAT3 activation in persistently infected HCV cell culture model resulted in the decreased expression of hepatocyte nuclear factor 4 alpha (HNF4A), a major liver-specific transcription factor. The stress-induced inhibition of HNF4A expression resulted in a significant reduction of liver-specific microRNA-122 (miR-122) transcription. It was found that the reversal of hepatic adaptive pro-survival signaling and restoration of miR-122 level was more efficient by interferon (IFN)-based antiviral treatment than direct-acting antivirals (DAAs). To test whether miR-122 levels could be utilized as a biomarker of hepatic adaptive stress response in HCV infection, serum miR-122 level was measured among healthy controls, and chronic HCV patients with or without cirrhosis. Our data show that serum miR-122 expression level remained undetectable in most of the patients with cirrhosis (stage IV fibrosis), suggesting that the pro-survival UPR signaling increases the risk of HCC through STAT3-mediated suppression of miR-122. In conclusion, our data indicate that hepatic pro-survival UPR signaling suppresses the liver-specific HNF4A and its downstream target miR-122 in cirrhosis. These results provide an explanation as to why cirrhosis is a risk factor for the development of HCC in chronic HCV infection.

2.
Clinics ; 70(12): 790-796, Dec. 2015. tab, graf
Article in English | LILACS | ID: lil-769706

ABSTRACT

OBJECTIVE: To determine peroxisome proliferator activated receptor α and γ mRNA expression in liver tissue of hepatitis C virus-infected patients with and without human immunodeficiency virus and its possible contribution to an acceleration of liver disease progression. METHODS: We measured peroxisome proliferator-activated receptor α and γ mRNA expression by real-time polymerase chain reaction in liver tissues from 40 subjects infected only with hepatitis C virus, 36 subjects co-infected with hepatitis C virus and human immunodeficiency virus and 11 normal adults. RESULTS: Hepatic mRNA expression of both peroxisome proliferator-activated receptors was significantly lower in hepatitis C virus-infected subjects with and without human immunodeficiency virus co-infection compared to the controls. Non-black race was also identified as a predictor of lower peroxisome receptor α and γ mRNA expression. Compared to subjects infected only with hepatitis C virus, liver peroxisome receptor γ mRNA expression was significantly lower in hepatitis C virus/human immunodeficiency virus-co-infected subjects (0.0092 in hepatitis C virus/human immunodeficiency virus-co-infection vs. 0.0120 in hepatitis C virus-only; p=0.004). Hepatic peroxisome receptor α mRNA expression in the hepatitis C virus-infected patients was lower in the presence of human immunodeficiency virus co-infection in non-black subjects (0.0769 vs. 0.1061; p=0.02), whereas the levels did not vary based on human immunodeficiency virus status among black subjects. CONCLUSION: mRNA expression of both peroxisome proliferator-activated receptors is impaired in hepatitis C virus-infected liver and further reduced by human immunodeficiency virus co-infection, although the suppressive effects of the viruses are substantially mitigated in black patients.


Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Coinfection/pathology , HIV Infections/pathology , Hepatitis C, Chronic/pathology , PPAR alpha/analysis , PPAR gamma/analysis , RNA, Messenger/analysis , Analysis of Variance , Biopsy , Cross-Sectional Studies , Coinfection/complications , Coinfection/ethnology , HIV Infections/complications , HIV Infections/ethnology , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/ethnology , Linear Models , Liver Cirrhosis/etiology , Liver Cirrhosis/pathology , Liver/pathology , PPAR alpha/genetics , PPAR gamma/genetics , Real-Time Polymerase Chain Reaction , Reference Values , Severity of Illness Index
3.
Clinics (Sao Paulo) ; 70(12): 790-6, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26735218

ABSTRACT

OBJECTIVE: To determine peroxisome proliferator activated receptor α and γ mRNA expression in liver tissue of hepatitis C virus-infected patients with and without human immunodeficiency virus and its possible contribution to an acceleration of liver disease progression. METHODS: We measured peroxisome proliferator-activated receptor α and γ mRNA expression by real-time polymerase chain reaction in liver tissues from 40 subjects infected only with hepatitis C virus, 36 subjects co-infected with hepatitis C virus and human immunodeficiency virus and 11 normal adults. RESULTS: Hepatic mRNA expression of both peroxisome proliferator-activated receptors was significantly lower in hepatitis C virus-infected subjects with and without human immunodeficiency virus co-infection compared to the controls. Non-black race was also identified as a predictor of lower peroxisome receptor α and γ mRNA expression. Compared to subjects infected only with hepatitis C virus, liver peroxisome receptor γ mRNA expression was significantly lower in hepatitis C virus/human immunodeficiency virus-co-infected subjects (0.0092 in hepatitis C virus/human immunodeficiency virus-co-infection vs. 0.0120 in hepatitis C virus-only; p=0.004). Hepatic peroxisome receptor α mRNA expression in the hepatitis C virus-infected patients was lower in the presence of human immunodeficiency virus co-infection in non-black subjects (0.0769 vs. 0.1061; p=0.02), whereas the levels did not vary based on human immunodeficiency virus status among black subjects. CONCLUSION: mRNA expression of both peroxisome proliferator-activated receptors is impaired in hepatitis C virus-infected liver and further reduced by human immunodeficiency virus co-infection, although the suppressive effects of the viruses are substantially mitigated in black patients.


Subject(s)
Coinfection/pathology , HIV Infections/pathology , Hepatitis C, Chronic/pathology , PPAR alpha/analysis , PPAR gamma/analysis , RNA, Messenger/analysis , Adult , Aged , Analysis of Variance , Biopsy , Coinfection/complications , Coinfection/ethnology , Cross-Sectional Studies , Female , HIV Infections/complications , HIV Infections/ethnology , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/ethnology , Humans , Linear Models , Liver/pathology , Liver Cirrhosis/etiology , Liver Cirrhosis/pathology , Male , Middle Aged , PPAR alpha/genetics , PPAR gamma/genetics , Real-Time Polymerase Chain Reaction , Reference Values , Severity of Illness Index
4.
Case Rep Transplant ; 2014: 838949, 2014.
Article in English | MEDLINE | ID: mdl-25120936

ABSTRACT

Cutaneous metastasis from hepatobiliary tumors is a rare event, especially following liver transplantation. We report our experience with two cases of cutaneous metastases from both hepatocellular carcinoma and mixed hepatocellular/cholangiocarcinoma following liver transplantation, along with a review of the literature.

5.
Ann Otol Rhinol Laryngol ; 122(11): 679-82, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24358627

ABSTRACT

OBJECTIVES: Thyroid storm is a presentation of severe thyrotoxicosis that has a mortality rate of up to 20% to 30%. Fulminant hepatic failure (FHF) entails encephalopathy with severe coagulopathy in the setting of liver disease. It carries a high mortality rate, with an approximately 60% rate of overall survival for patients who undergo orthotopic liver transplantation (OLT). Fulminant hepatic failure is a rare but serious complication of thyroid storm. There have been only 6 previously reported cases of FHF with thyroid storm. METHODS: We present a patient from our institution with thyroid storm and FHF. A literature review was performed to analyze the outcomes of the 6 additional cases of concomitant thyroid storm and FHF. RESULTS: Our patient underwent thyroidectomy followed by OLT. Her serum levels of thyroid-stimulating hormone, triiodothyronine, thyroxine, and transaminase normalized, and she was ready for discharge within 10 days of surgery. She has survived without complication. There is a 40% mortality rate for the reported patients treated medically with these conditions. Of the 7 total cases of reported FHF and thyroid storm, 2 patients died. Only 2 of the 7 patients underwent thyroidectomy and OLT--both at our institution. Both patients survived without complications. CONCLUSIONS: Thyroid storm and FHF each independently carry high mortality rates, and managing patients with both conditions simultaneously is an extraordinary challenge. These cases should compel clinicians to investigate liver function in hyperthyroid patients and to be wary of its rapid decline in patients who present in thyroid storm with symptoms of liver dysfunction. Patients with rapidly progressing thyroid storm and FHF should be considered for total thyroidectomy and OLT.


Subject(s)
Liver Failure, Acute/etiology , Liver Transplantation/methods , Thyroid Crisis/complications , Thyroidectomy/methods , Female , Follow-Up Studies , Humans , Liver Failure, Acute/surgery , Thyroid Crisis/surgery , Young Adult
6.
Hepatology ; 58(4): 1263-9, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23696235

ABSTRACT

UNLABELLED: African American (AA) liver transplant (LT) recipients with hepatitis C virus (HCV) have higher rates of graft loss than other racial/ethnic groups. The Donor Risk Index (DRI) predicts graft loss but is neither race- nor disease-specific and may not be optimal for assessing donor risk for AA HCV-positive LT recipients. We developed a DRI for AA with HCV with the goal of enhancing graft loss predictions. All U.S. HCV-positive adult AA first deceased donor LTs surviving ≥30 days from March 2002 to December 2009 were included. A total of 1,766 AA LT recipients were followed for median 2.8 (interquartile range [IQR] 1.3-4.9) years. Independent predictors of graft loss were donor age (40-49 years: hazard ratio [HR] 1.54; 50-59 years: HR 1.80; 60+ years: HR 2.34, P < 0.001), non-AA donor (HR 1.66, P < 0.001), and cold ischemia time (CIT) (HR 1.03 per hour >8 hours, P = 0.03). Importantly, the negative effect of increasing donor age on graft and patient survival among AAs was attenuated by receipt of an AA donor. A new donor risk model for AA (AADRI-C) consisting of donor age, race, and CIT yielded 1-year, 3-year, and 5-year predicted graft survival rates of 91%, 77%, and 68% for AADRI <1.60; 86%, 67%, and 55% for AADRI 1.60-2.44; and 78%, 53%, and 39% for AADRI >2.44. In the validation dataset, AADRI-C correctly reclassified 27% of patients (net reclassification improvement P = 0.04) compared to the original DRI. CONCLUSION: AADRI-C identifies grafts at higher risk of failure and this information is useful for risk-benefit discussions with recipients. Use of AA donors allows consideration of older donors.


Subject(s)
Black or African American/ethnology , Graft Rejection/epidemiology , Hepacivirus , Hepatitis C/ethnology , Hepatitis C/surgery , Liver Transplantation , Tissue Donors , Transplantation , Adolescent , Adult , Age Factors , Aged , Child , Female , Follow-Up Studies , Hepatitis C/mortality , Humans , Male , Middle Aged , Prevalence , Proportional Hazards Models , Retrospective Studies , Risk Assessment , Survival Rate , Treatment Outcome , Young Adult
7.
World J Hepatol ; 5(3): 133-6, 2013 Mar 27.
Article in English | MEDLINE | ID: mdl-23556046

ABSTRACT

A 26-year-old male presented with three weeks of jaundice after the self-initiation of the injectable anabolic steroid, Mastabol [Dromastanolone Di-Propionate (17 beta-Hydroxy-2alpha-methyl-5alpha-androstan-3-one propionate)]. He reported dark urine, light stools, and pruritus. He denied abdominal pain, intravenous drug use, intranasal cocaine, blood transfusions, newly placed tattoos, or sexually transmitted diseases. He used alcohol sparingly. Physical exam revealed jaundice with deep scleral icterus. The liver was palpable 2 cm below the right costal margin with no ascites. The peak bilirubin was 23.6 mg/dL, alkaline phosphatase was 441 units/L, and aspartate aminotransferase/alanine aminotransferase were 70 units/L and 117 units/L respectively. A working diagnosis of acute intrahepatic cholestasis was made. Liver biopsy revealed a centrilobular insult with neutrophilic infiltrates and Ito cell hyperplasia consistent with acute drug induced cholestasis. The patient's clinical symptoms resolved and his liver enzymes, bilirubin, and alkaline phosphatase normalized. Anabolic steroids with 17 alpha carbon substitutions have been associated with a bland variety of cholestatic injury with little hepatocellular injury. Cholestasis, under these circumstances, may be secondary to the binding of drugs to canalicular membrane transporters, accumulation of toxic bile acids from canalicular pump failure, or genetic defects in canalicular transport proteins. Mastabol is an injectable, 17 beta hydroxyl compound with no alpha alkyl groups at the 17 carbon position. As such, it has been reported to have little potential toxic effects on the liver. This is the first known reported case of Mastabol-induced cholestatic liver injury. It highlights the need for physicians to consider such widely available substances when faced with hepatic injury of unclear etiology.

8.
PLoS One ; 8(2): e56193, 2013.
Article in English | MEDLINE | ID: mdl-23460794

ABSTRACT

Acetyl coenzyme A carboxylase B gene (ACACB) single nucleotide polymorphism (SNP) rs2268388 is reproducibly associated with type 2 diabetes (T2DM)-associated nephropathy (DN). ACACB knock-out mice are also protected from obesity. This study assessed relationships between rs2268388, body mass index (BMI) and gene expression in multiple populations, with and without T2DM. Among subjects without T2DM, rs2268388 DN risk allele (T) associated with higher BMI in Pima Indian children (n = 2021; p-additive = 0.029) and African Americans (AAs) (n = 177; p-additive = 0.05), with a trend in European Americans (EAs) (n = 512; p-additive = 0.09), but not Germans (n = 858; p-additive = 0.765). Association with BMI was seen in a meta-analysis including all non-T2DM subjects (n = 3568; p-additive = 0.02). Among subjects with T2DM, rs2268388 was not associated with BMI in Japanese (n = 2912) or EAs (n = 1149); however, the T allele associated with higher BMI in the subset with BMI≥30 kg/m(2) (n = 568 EAs; p-additive = 0.049, n = 196 Japanese; p-additive = 0.049). Association with BMI was strengthened in a T2DM meta-analysis that included an additional 756 AAs (p-additive = 0.080) and 48 Hong Kong Chinese (p-additive = 0.81) with BMI≥30 kg/m(2) (n = 1575; p-additive = 0.0033). The effect of rs2268388 on gene expression revealed that the T risk allele associated with higher ACACB messenger levels in adipose tissue (41 EAs and 20 AAs with BMI>30 kg/m(2); p-additive = 0.018) and ACACB protein levels in the liver tissue (mixed model p-additive = 0.03, in 25 EA bariatric surgery patients with BMI>30 kg/m(2) for 75 exams). The T allele also associated with higher hepatic triglyceride levels. These data support a role for ACACB in obesity and potential roles for altered lipid metabolism in susceptibility to DN.


Subject(s)
Acetyl-CoA Carboxylase/genetics , Body Mass Index , Diabetic Nephropathies/enzymology , Gene Expression Regulation, Enzymologic , Genetic Predisposition to Disease , Obesity/genetics , Polymorphism, Single Nucleotide/genetics , Acetyl-CoA Carboxylase/metabolism , Adipose Tissue/enzymology , Adolescent , Adult , Black or African American/genetics , Aged , Animals , Demography , Diabetic Nephropathies/complications , Diabetic Nephropathies/genetics , Female , Genetic Association Studies , Humans , Indians, North American/genetics , Liver/enzymology , Longitudinal Studies , Male , Mice , Mice, Knockout , Middle Aged , Obesity/complications , Obesity/enzymology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Triglycerides/metabolism
11.
Surgery ; 152(4): 661-6; discussion 666-7, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22935095

ABSTRACT

BACKGROUND: The role of socioeconomic factors that affect survival, particularly for hepatocellular cancer (HCC), has yet to be fully analyzed. This study attempts to elucidate those racial and socioeconomic factors that affect differences in survival for patients with HCC. METHODS: In a retrospective cohort study of 206 patients with HCC diagnosed in an inner-city urban center from 2003 to 2011, outcomes by race (African Americans versus white) were analyzed. Additional attention was paid to socioeconomic factors. Continuous variables were compared with the Student t-test, and categorical variables were compared with the χ(2) or Fisher exact test. Multivariate analysis was conducted using a logistic regression model. Patient death and survival data were analyzed with Kaplan-Meier and Cox proportional hazards. RESULTS: Comparison of 138 white and 68 African-American patients revealed that African-American patients were more likely to present with larger tumor size at the time of diagnosis (4.7 vs 3.7 cm; P < .05). African-American patients were also more likely to be intravenous drug users (25.4% vs 11.6%; P < .05) and have cirrhosis from hepatitis C (81% vs 60%; P < .01). African-American patients were less likely to have private insurance compared with white patients (68% vs 92%; P < .01). Despite these findings in our inner-city practice, there was no difference in liver transplantation rates or survival rates between the 2 groups. CONCLUSION: Despite presentation with less-favorable tumor characteristics, African-American patients are able to achieve survival that is comparable with their white counterparts when treated in a program that is attuned to the challenges faced by their specific population.


Subject(s)
Black or African American , Carcinoma, Hepatocellular/surgery , Healthcare Disparities , Liver Neoplasms/surgery , White People , Aged , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Cohort Studies , Female , Humans , Kaplan-Meier Estimate , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Middle Aged , Multivariate Analysis , New Orleans/epidemiology , Retrospective Studies , Socioeconomic Factors , Treatment Outcome , Urban Population
12.
Dig Dis Sci ; 56(7): 2145-51, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21318585

ABSTRACT

BACKGROUND: Hepatic macrosteatosis (HMS) is prevalent among high BMI patients, but a lack of validation of non-invasive measures of liver fat hampers non-alcoholic liver disease (NAFLD) investigation in general. Recent work suggests BMI adjusted, non-contrasted computed tomography (nc-CT) attenuation data (Hounsfield units) reflects liver fat accumulation in a normal weight population. However, this and other CT-based HMS studies have only approximated macrosteatosis (%) histologically, but have not validated findings with chemical liver triglyceride (TG) concentrations (mg/gram protein). Also, all previous CT based steatosis studies excluded high BMI subjects, whose habitus may affect properties of the scan. We hypothesized that in high BMI patients nc-CT attenuation measurements expressed in Hounsfield units (HU) accurately estimate liver triglyceride concentrations as well as histological macrosteatosis. METHODS: With informed consent, 15 patients underwent nc-CT scan of the abdomen prior to weight loss surgery with intraoperative wedge and core needle liver biopsy. Mean left lobe nc-CT Hounsfield units (CT(L)), liver TG (mg/g Pr), HMS (%), BMI (kg/m(2)), liver-spleen index (CT(L/S) = hepatic HU/splenic HU), and liver-spleen difference (CT(L-S) = hepatic HU - splenic HU) were a priori outcomes. RESULTS: In 15 patients (11 female) with a BMI of 44.4 ± 1.1 (mean ± SEM), CT(L/S), CT(L-S), and CT(L) measures were significantly associated with liver TG concentrations (r = -0.80, P < 0.001; r = -0.80, P < 0.001; and r = -0.71, P < 0.01, respectively; Table 1). Macrosteatosis (%) and liver triglyceride concentration were positively associated (r = 0.83; P < 0.0001). BMI did not correlate strongly to liver triglyceride (r = 0.44, P = NS). CONCLUSION: Estimates of liver fat obtained by nc- CT scans (esp. CT(L/S), CT(L-S)) correlate to chemical measurement of liver triglyceride concentrations, suggesting non-contrasted CT may be a suitable non-invasive "gold standard" for hepatic steatosis quantification in these patients.


Subject(s)
Fatty Liver/diagnostic imaging , Fatty Liver/etiology , Obesity/complications , Tomography, X-Ray Computed/methods , Adult , Cross-Sectional Studies , Fatty Liver/epidemiology , Female , Humans , Liver/diagnostic imaging , Male , Middle Aged , Obesity/epidemiology , Prospective Studies
13.
Article in English | MEDLINE | ID: mdl-20071593

ABSTRACT

Alanine aminotransferase (ALT) is a routine parameter in the assessment and monitoring of chronic hepatitis C viral (HCV) infection. Hepatitis C virus-infected African Americans (AAs) have been reported to have lower ALT levels. In this retrospective, cross-sectional, multicenter study, host and virological factors possibly associated with ALT levels were analyzed by multivariate regression analyses among HIV/HCV-coinfected patients. Of the 289 patients included, 142 were African Americans and 144 Caucasians. In multivariate analysis, only HCV genotype 3 (B 0.2 [95% CI 13.39-52.33]; P = .001) and HCV RNA >500 000 IU/mL (B 3.1 [95% CI 7.67-34.75]; P = .002) were independent predictors of higher ALT levels. Per the American Association for the Study of Liver Disease (AASLD) definition, 18.2% had ALT levels within normal limits. Male sex and HCV RNA <500 000 IU/mL predicted ALT within normal limits. Hepatitis C viral factors rather than race were associated with ALT levels in this HIV/HCV-coinfected population. ALT were within normal limits in 18% of patients, who more often were male and had lower Hepatitis C viral load.


Subject(s)
Alanine Transaminase/analysis , HIV Infections/enzymology , Hepatitis C/enzymology , Adult , Black or African American , Comorbidity , Cross-Sectional Studies , Female , Genotype , HIV , HIV Infections/virology , Hepacivirus/genetics , Hepatitis C/virology , Humans , Italy , Male , Multivariate Analysis , North Carolina , Retrospective Studies , Viral Load , White People
14.
J Hepatol ; 49(3): 323-8, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18486266

ABSTRACT

BACKGROUND/AIMS: There are conflicting data regarding the incidence and factors implicated in the spontaneous clearance of hepatitis C virus (HCV) after acute infection. The aim of this study was to determine the epidemiological factors that predict the resolution of acute HCV infection without therapy in patients with human immunodeficiency virus (HIV) infection. METHODS: We conducted a retrospective, multivariate analysis of epidemiological data from HIV-infected patients presenting from 2000 to 2007 with evidence of past or present HCV infection. Data were collected from one American and two European HIV treatment clinics. A final cohort of 769 HIV-infected patients referred for treatment with available test results for antibody to HCV, HCV RNA, and hepatitis B surface antigen were included for the analysis. We calculated spontaneous clearance rates based on race, geographical location, gender, transmission risk factors, and hepatitis B virus coinfection. RESULTS: Patients who admitted to a history of injection drug use spontaneously cleared the HCV infection significantly less often (11.6%) than those in whom sexual transmission was the presumed route of HCV infection (21.9%) (p=0.004). This difference was more pronounced when heterosexual contact as the source of infection was analyzed separately. Multivariate analysis identified heterosexual HCV transmission (OR 2.81, 95% CI 1.55-5.09) and hepatitis B surface antigen carrier status (OR 10.3, 95% CI 4.29-24.73) as independent factors predicting spontaneous HCV clearance. No differences according to gender, race or geographical origin were observed. CONCLUSIONS: In summary, sexual transmission, particularly heterosexual, and hepatitis B virus coinfection were the only factors associated with spontaneous HCV clearance in this HIV-infected population.


Subject(s)
HIV Infections/epidemiology , Hepacivirus/pathogenicity , Hepatitis C/epidemiology , Hepatitis C/transmission , Sexually Transmitted Diseases, Viral/epidemiology , Sexually Transmitted Diseases, Viral/transmission , Adult , Cross-Sectional Studies , Europe/epidemiology , Female , HIV Infections/complications , HIV-1/genetics , Hepacivirus/genetics , Hepatitis C/complications , Humans , Male , Middle Aged , Multivariate Analysis , RNA, Viral/blood , Recurrence , Retrospective Studies , Risk Factors , Risk-Taking , Sexually Transmitted Diseases, Viral/complications , Substance Abuse, Intravenous , Time Factors , United States/epidemiology
15.
Dig Dis Sci ; 53(9): 2330-3, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18270833

ABSTRACT

Hepatic encephalopathy (HE) is a significant cause of morbidity and mortality in patients with advanced chronic liver disease. Current therapies are associated with inconvenient side-effects, high cost, and incomplete efficacy. The quanternary ammonium compound L-acyl-carnitine has been suggested as a potent, low-cost, and safe alternative therapy for patients with cirrhosis and HE. A systematic review of the literature assessing the use of carnitine in the treatment of HE identified three high-quality human trials for review. Analysis of the selected carnitine trials compared to currently accepted therapies suggests that L-acyl-carnitine is promising as a safe and effective treatment for HE, and further trials of this drug are warranted.


Subject(s)
Carnitine/analogs & derivatives , Hepatic Encephalopathy/drug therapy , Administration, Oral , Carnitine/administration & dosage , Carnitine/adverse effects , Carnitine/therapeutic use , Humans , Randomized Controlled Trials as Topic , Treatment Outcome
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