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Current Issue

July - September, 2010

Vol. 9 Issue 3

On the cover: Official Journal of the Mexican Association of Hepatology and the Latin-American Association for the Study of the Liver

HEPATOLOGY HIGHLIGHTS

CONCISE REVIEW

  • Kava hepatotoxicity - a clinical review Rolf Teschke Page 251-265

    This review critically analyzes the clinical data of patients with suspected kava hepatotoxicity and suggests recommendations for minimizing risk. Kava is a plant (Piper methysticum) of the pepper family Piperaceae, and its rhizome is used for traditional aqueous extracts in the South Pacific Islands and for commercial ethanolic and acetonic medicinal products as anxiolytic herbs in Western countries. A regulatory ban for ethanolic and acetonic kava extracts was issued in 2002 for Germany on the basis of reports connecting liver disease with the use of kava, but the regulatory causality assessment was a matter of international discussions. Based on one positive reexposure test with the kava drug, it was indeed confirmed that kava is potentially hepatotoxic. In subsequent studies using a structured, quantitative and hepatotoxicity specific causality assessment method in 14 patients with liver disease described worldwide, causality for kava ± comedicated drugs and dietary supplements including herbal ones was highly probable (n = 1), probable (n = 4) or possible (n = 9) regarding aqueous extracts (n = 3), ethanolic extracts (n = 5), acetonic extracts (n = 4), and mixtures containing kava (n = 2). Risk factors included overdose, prolonged treatment, and comedication with synthetic drugs and dietary supplements comprizing herbal ones in most of the 14 patients. Hepatotoxicity occurred independently of the used solvent, suggesting poor kava raw material quality as additional causative factor. In conclusion, in a few individuals kava may be hepatotoxic due to overdose, prolonged treatment, comedication, and probably triggered by an unacceptable quality of the kava raw material; standardization is now required, minimizing thereby hepatotoxic risks.

ORIGINAL ARTICLES

Clinical Studies

  • Comparison of acoustic radiation force impulse imaging (ARFI) to liver biopsy histologic scores in the evaluation of chronic liver disease: A pilot study Mazhar Haque, Charlotte Robinson, David Owen, Eric M. Yoshida, Alison Harris Page 289-293

    Background and aims. Acoustic Radiation Force Impulse Imaging (ARFI) is a novel non invasive technique studying the localized mechanical properties of tissue by utilising short, high intensity acoustic pulses (shear wave pulses) to assess the mechanical response (tissue displacement), providing a measure of tissue elasticity. The aim of this study is to investigate the feasibility of ARFI imaging as a non-invasive method for the assessment of liver fibrosis compared to liver biopsy scores. Materials and methods. A prospective blind comparison study of ARFI elastography (Virtual Touch Imaging™, ACUSON S2000 Ultrasound Unit, Siemens, Mountain View CA) in a consecutive series of patients who underwent liver biopsy for assessment of fibrosis in chronic liver disease. ARFI shear-wave propagation velocity was measured in meters per second. Mean ARFI velocities were compared with both Batts-Ludwig (F0 to F4) and Modified Ishak scores (F0 to F4) for fibrosis in liver biopsy findings. Twenty-one patients with chronic liver disease (Hepatitis C (HCV) =16, Hepatitis B (HBV) = 1, both HCV and HBV = 1 Alcoholic liver disease (ALD) = 1, others = 2) underwent ARFI and liver biopsy on the same day. Results. The Spearman correlation coefficients between the median values of the ARFI measurements and the histological fibrosis stage of the Modified Ishak score and Batts-Lud- ³ wig score were both highly significant (p < 0.01) with rho = 0.69 and rho = 0.72 respectively. The median ARFI (total 180 replications; minimum 5, maximum 10 measurements per patients) velocities for our study population range from 0.92 to 4.17 m/sec. Areas under the receiver operating characteristic curve for the accuracy of ARFI imaging was 1.00 and 0.35, for the diagnosis of moderate fibrosis (histologic fibrosis stage, F ³ 2) and 0.85 and 0.85 respectively for Ishak and Batts-Ludwig score, for the diagnosis of cirrhosis. Conclusion. ARFI imaging has a strong correlation with the fibrosis stage of both Batts-Ludwig and shak score in chronic liver disease. It’s accuracy in prediction of severe fibrosis and cirrhosis is maximal in comparison with earlier stages.

  • Visceral adipose tissue visfatin in nonalcoholic fatty liver disease Radhika Gaddipati, Sasikala Mitnala, Nagarajarao Padaki, Rathindra Mohan Mukherjee, Anuradha Sekaran, Magnus Jayaraj-Mansard, Pradeep Rabella, Venkat Rao-Guduru, Nageshwar Reddy-Duvvuru Page 266-270

    Background. Visfatin is a novel adipocytokine predominantly expressed and secreted by visceral adipose tissue. It is realized for its multiple functions of central importance in NAD biosynthesis, innate immunity and inflammation. Its phosphoribosyl transferase activity regulates cellular energetics and NAD dependent enzymes such as SIRTUINS. Although its expression in various tissues and circulating levels are documented, visceral visfatin levels in Nonalcoholic fatty liver disease (NAFLD) patients have not been reported. Objective. The aim of the present study was to assess visceral adipose tissue visfatin levels in NAFLD. Materials and methods. A total of 115 patients undergoing diagnostic laparoscopy were recruited in the study and categorized into two groups based on standard criteria for NAFLD. Visceral adipose tissue TNF-a, IL-6 and visfatin levels were measured by ELISA. Blood glucose, lipids, liver enzymes and non esterified fatty acids (NEFA) were estimated using standard procedures. Formalin fixed, Hematoxylene Eosin stained liver biopsy specimens were examined for the presence of steatosis and the degree of steatosis was ascertained as per Brunt’s classification. Results. The visceral visfatin level declined significantly (P < 0.001) in all groups of NAFLD as compared to non NAFLD group, while plasma NEFA level increased with progressive steatosis (P < 0.02). Significant increase in TNF a was observed in all groups of NAFLD, while IL-6 increased in NASH only. Conclusion. A significant decline in visceral adipose tissue visfatin level was found to be associated with degree of steatosis in NAFLD patients.

  • Short and long term outcome of kidney transplanted patients with chronic viral hepatitis B and C Ezequiel Ridruejo, Carlos Díaz, Mario Dávalos Michel, Gervasio Soler Pujol, Alfredo Martínez, Sebastián Marciano, Oscar G. Mandó, Antonio Vilches Page 271-277

    Introduction. Liver disease related to chronic viral hepatitis is a major cause of morbidity and mortality in renal transplant patients. There is no agreement upon the influence of chronic hepatitis B (HBV) and hepatitis C (HCV) infection in patient and graft survival. Aims. The aim of the study was to evaluate the influence of HBV and HCV on patient and graft short and long term survival, in the patients transplanted at our institution. Materials and methods. We evaluated the influence of antiHCV and HBsAg status (positive vs. negative); sex; age (> 49 years vs. < 49 years at transplantation); time on dialysis (> 3 vs. < 3 years); acute rejection; kind of graft (deceased vs. living donor, and kidney versus kidney and pancreas); number of transplantations; use of induction immunosuppression; and maintenance immunosuppression treatment (comparing the traditional triple therapy containing azathioprine, cyclosporine and prednisone vs. newer regimens which include tacrolimus, mycophenolate mofetil, sirolimus, etc) on the survival, long term and within the first month of transplantation, of the graft and the patients transplanted in our Institution between January 1991 and August 2009. Results. We included 542 patients, 60% males’ median age of 42.03 years (SD 13.06 years). 180 patients (33%) were antiHCV positive and 23 (4%) were HBsAg positive. AntiHCV positive, traditional triple therapy and acute rejection were associated with diminished graft survival. Older age, antiHCV positive, HBsAg positive, deceased donor, kidney-pancreas transplantation and traditional triple therapy were associated with diminished patient survival. Traditional triple therapy was associated with diminished one month graft survival; and older age and antiHCV positive were associated with diminished one month patient survival. Conclusion. In our experience, antiHCV positive status was associated with diminished long term patient and graft survival, and diminished six month graft survival; and HBsAg positive was associated with diminished patient survival.

  • Clinical outcomes of liver transplantation for polycystic liver disease: A single center experience Natasha Chandok, Julia Uhanova, Paul Marotta Page 278-281

    Polycystic liver disease (PLD) is a celiopathy characterized by progressive growth of multiple hepatic cysts. In a minority of patients, severe symptomatic hepatomegaly necessitates liver transplantation (LT). The purpose of this study is to describe the postoperative and long-term outcomes of all patients transplanted for PLD at our center. All patients who underwent LT for PLD were identified through our database. Using patient charts, data were extracted on patient demographics and medical history, postoperative surgical and medical complications, length of hospitalization, prevalence of chronic kidney failure, and patient and graft survival. Subjects were contacted in April 2010 to verify their survival and confirm their need, if any, for hemodialysis and/or kidney transplantation. Descriptive statistics for patient and graft survival were performed. From 1993 to 2010, 14 subjects underwent LT and 1 subject underwent combined kidney and LT; all subjects were female and the mean age was 49.0 years. 10 (66.7%) subjects had polycystic kidney disease. Patients experienced a high rate of vascular complications, including hepatic artery thrombosis (HAT) or stenosis in 3 (20%) and 2 (13.3%) subjects, respectively. One subject had early graft loss due to HAT and underwent re-transplantation. The mean length of hospitalization was 18.8 days. After a mean of 66.8 months of follow-up (3-200), 13 (86.7%) subjects are alive with satisfactory graft function, and no patients had renal failure. In conclusion, patients who underwent LT for PLD had a high rate of postoperative vascular complications. However, long-term patient and graft survival, and kidney function, is excellent.

  • Prevalence of type 2 diabetes mellitus and chronic liver disease: A retrospective study of the association of two increasingly common diseases in Mexico Ramón Arturo Kobashi-Margáin, Ylse Gutiérrez-Grobe, Guadalupe Ponciano-Rodríguez, Misael Uribe, Nahum Méndez-Sánchez Page 282-288

    Background. Recent studies have demonstrated a relationship between insulin resistance (IR) and type 2 diabetes mellitus (T2DM). The aim of this study was to determine the prevalence of T2DM among patients with liver disease. Methods. A retrospective study was performed by examining the charts of patients who presented with a diagnosis of liver disease at a university hospital between January 2006 and April 2010. Results. Liver disease was found in 129 patients. The most prevalent liver disease was cirrhosis, with 61 patients (47.2%), 44 patients had hepatitis C virus (34.1%) and 28 patients had hepatocellular carcinoma (21.7%). T2DM was diagnosed in 30 patients, 18 of whom were male (18/60; 30%) and 12 of whom were female (12/69; 17.4%). Only liver cirrhosis was significantly related to T2DM (21 of 61 patients; 34.4%, p < 0.004). Conclusions. The prevalence of T2DM among patients with liver disease (23.2%) is well established and similar to that reported in Western and some Eastern countries.

IMAGES IN HEPATOLOGY

CASE REPORTS

  • The CT Quadrate lobe hot spot sign Vivek Virmani, Anupam Lal, Chirag K Ahuja, Niranjan Khandelwal Page 296-298

    Intense enhancement of the quadrate lobe in the arterial phase may be seen on computed tomography in patients of superior vena cava syndrome. We present this imaging finding in a case of lymphoma causing superior vena cava syndrome and discuss the physiological cause and importance of this sign.

  • NISCH syndrome with hypothyroxinemia Ira Shah, Susmita Bhatnagar Page 299-301

    Neonatal Ichthyosis Sclerosing Cholangitis (NISCH) syndrome is a rare autosomal recessive condition characterized by ichthyosis, sclerosing cholangitis and alopecia. Only 5 patients have been described till now. We report a patient presenting with clinical characteristics of NISCH syndrome and hypothyroxinemia.

LETTER TO EDITOR

LIVER NEWS ELSEWHERE

  • Early warning of liver disease in diabetics Juan Pablo Arab, Carolina Ramírez, Marco Arrese Page 307-309

    Background. The negative impact of diabetes mellitus is well recognized, yet little is known about the effect of this disease on the liver, an organ susceptible to nonalcoholic fatty liver disease related to insulin resistance. We evaluated whether adults with newly diagnosed diabetes were at increased risk of serious liver disease. Methods. We used administrative health databases for the province of Ontario (1994-2006) to perform a population based matched retrospective cohort study. The exposed group comprised 438 069 adults with newly diagnosed diabetes. The unexposed comparison group- those without known diabetes-consisted of 2 059 708 individuals, matched 5:1 to exposed persons, by birth year, sex and local health region. We excluded individuals with preexisting liver or alcohol-related disease. The primary study outcome was the subsequent development of serious liver disease, namely, liver cirrhosis, liver failure and its sequelae, or receipt of a liver transplant. Results. The incidence rate of serious liver disease was 8.19 per 10 000 person- years among those with newly diagnosed diabetes and 4.17 per 10 000 person-years among those without diabetes. The unadjusted hazard ratio was 1.92 (95% confidence interval [CI] 1.83-2.01). After adjustment for age, income, urban residence, health care utilization and pre-existing hypertension, dyslipidemia, obesity and cardiovascular disease, the hazard ratio was 1.77 (95% CI 1.68-1.86). Interpretation. Adults with newly diagnosed diabetes appeared to be at higher risk of advanced liver disease, also known as diabetic hepatopathy. Whether this reflects nonalcoholic fatty liver disease or direct glycemic injury of the liver remains to be determined.

ANNUAL MEETING OF THE MEXICAN ASSOCIATION OF HEPATOLOGY

The Official Journal of the Mexican Association of Hepatology, the Latin-American Association for the Study of the Liver and the Canadian Association for the Study of the Liver

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