US Liver Research Articles

Mediterranean Diet adherence is decreasing in healthy subjects over the years 1996–2010 also in Mediterranean area.

Mediterranean Diet score (range 0–55) was assessed in 8138 healthy non‐diabetic, overweight/obese subjects, 1996–2010, referred for US liver diagnostic and dietary counseling. Mediterranean food (Pasta and rice;whole‐grain bread, brown rice, legumes; Fruit; Green vegetables; Fish, poultry; Nonfat or low‐fat dairy products; olive oil) had assigned a score of 0: no consumption, a score of 1 for 1 to 4 times/w, 2 for 5 to 8 times/w, 3 for 9 to 11 times/w, 4 for 12 to 14 times/w, and 5 for more than 14 times/w; for westernized food (Red meat; Dairy products‐butter; Potatoes and eggs; Cakes) opposite scores were assigned (i.e., 0 when a participant reported more than 5 weekly consumption to: 5 for no weekly consumption, score 4 for 1 weekly consumption, 3 for 2 weekly consumption, 2 for 4 weekly consumption, 1 for 5 weekly consumption); wine and alcoholics (0–10 g of alcoholics from Red Wine for women score 5; 0–20 g of alcoholics from Red Wine for men score 5; each increment of 10 determines negative scores (20–30= −1. 30–40=−2. 40–50=−3. 50–60=−4, >60= −5 for men; 10 less for women and for all non‐wine alcoholics,: 10–20= −1; 20–30= −2; 30–40= −3; 40–50= −4; >50 = −5).There is a trend toward the loss of the adherence to Mediterranean Diet from 37.06±3.213 to 34.82±5.014 p<0,0001, not associated with BMI or physical activity change.Adherence to Mediterranean Diet is significantly yearly decreasing in Italy in healthy subjects.

An economic analysis of antiviral therapy in patients with advanced hepatitis C virus disease: still not there!

An economic analysis of antiviral therapy in patients with advanced hepatitis C virus disease: still not there!

According to a study conducted in the US, routine endoscopy and percutaneous liver biopsy can safely be performed on the same day

According to a study conducted in the US, routine endoscopy and percutaneous liver biopsy can safely be performed on the same day

Trends in Waiting List Registration for Liver Transplantation for Viral Hepatitis in the United States

In the last decade, significant progress has been made in the treatment of liver disease associated with chronic hepatitis, especially in patients infected with the hepatitis B virus (HBV). To investigate whether the population-wide application of antiviral therapies has impacted liver transplant waiting list registration, we analyzed longitudinal trends in waiting list registration for patients with hepatitis B and C and those with nonviral liver disease. This study represented a retrospective analysis of registry data containing all US liver transplant centers. All adult, primary liver transplantation candidates registered to the Organ Procurement and Transplantation Network between 1985 and 2006 were included in the analysis. Standardized incidence rates were calculated for waiting list registration for liver transplantation by underlying disease (HBV and HCV infection and other) and by indication for transplantation (fulminant liver disease, hepatocellular carcinoma [HCC], and end-stage liver disease [ESLD]). Of 113,927 unique waiting list registrants, 4793 (4.2%) had HBV, and 40,923 (35.9%) had HCV infections; the remaining 68,211 (59.9%) had neither. The incidence of waiting list registration for ESLD and fulminant liver disease decreased, whereas that for HCC increased. The decrease in ESLD registration was most pronounced, and the increase in HCC was least dramatic among registrants with hepatitis B. The decrease in registration for ESLD secondary to HCV infection was also significantly larger than that for ESLD patients with nonviral etiologies. The pattern of liver transplantation waiting list registration among patients with hepatitis B suggests that the widespread application of oral antiviral therapy for HBV contributed to the decreased incidence of decompensated liver disease.

Relationship among fatty liver, adipose tissue distribution and metabolic profile in moderately obese children

We examined the relationship between moderate obesity and glucose metabolism, insulin sensitivity and suspected fatty liver.Methodsz‐score body mass index( zBMI), caliper skinfold tickness, fasting blood glucose, insulin, HOMA score, lipid profile and transaminases (ALT, AST) were measured in 94 participants (mean age 9.7 ±2.2 years). Fatty liver and skinfold tickness were evaluated by ultrasound.ResultsThe zBMI was 2.01 ± 0.39 (mean ± SD), and the duration of obesity was 4.3±3.03 years. Caliper and US skinfold thickness correlated for tricipital (r = 0.33; p= 0.003) and sovrailiac skinfold (r= 0.34; p=0.003). Fatty liver was diagnosed in 64% of children and it was positively related to anthropometric measurements. The three groups ‐ group 0 (normal US liver and normal transaminases); group 1 (US fatty liver and normal transaminases); group 2 (US fatty liver and elevated transaminases) showed difference in zBMI , insulin and HOMA parameters (Tukey test: zBMI group 1 vs group 0 and 2 vs group 0; serum insulin: group 2 vs group 1 and group 2 vs group 0; HOMA IR: group 2 vs group 1 and group 2 vs group 0).DiscussionModerately obese children with steatosis exhibited a clear increase of insulin and insulin resistance, indices of a future metabolic syndrome. Transaminases levels seems to be not adequate for the diagnosis of fatty liver.

Should liver transplantation in patients with model for end-stage liver disease scores ≤ 14 be avoided? A decision analysis approach

Studies have shown that liver transplantation offers no survival benefits to patients with Model for End-Stage Liver Disease (MELD) scores <or= 14 in comparison with remaining on the waitlist. The consensus of a 2003 transplant community national conference was that a minimum MELD score should be required for placement on the liver waitlist, but no minimum listing national policy was enacted at that time. We developed a Markov microsimulation model to compare results under the present US liver allocation policy with outcomes under a "Rule 14" policy of barring patients with a MELD score of <or=14 from the waitlist or transplantation. For probabilities in the microsimulation model, we used data on all adult patients (>or=18 years) listed for or undergoing primary liver transplantation in the United States for chronic liver disease from 1/1/2003 through 12/31/2007 with follow-up until 2/1/2008. The "Rule 14" policy gave a 3% improvement in overall patient survival over the present system at 1, 2, 3, and 4 years and predicted a 13% decrease in overall waitlist time for patients with MELD scores of 15 to 40. Patients with the greatest benefit from a "Rule 14" policy were those with MELD scores of 6 to 10, for whom a 17% survival advantage was predicted from waiting on the list versus undergoing transplantation. Our analysis supports changing the national liver allocation policy to not allow liver transplantation for patients with MELD <or= 14.

Relationship Among Fatty Liver, Adipose Tissue Distribution and Metabolic Profile in Moderately Obese Children: An Ultrasonographic Study

We examined the relationship between moderate obesity and glucose metabolism, insulin sensitivity and suspected fatty liver in children. We measured body mass index (BMI), z-score BMI, caliper skinfold thickness, waist and hip circumference in 94 participants (mean age 9.7 +/-2.2 years). Fasting blood glucose, insulin, HOMA score, lipid profile and transaminases (ALT, AST) were measured. Fatty liver and skinfold thickness were evaluated by means of ultrasound. The z-score BMI was 2.01 +/-0.39 (mean +/- SD), and the duration of obesity was 4.3+/-3.03 years. A positive correlation was found between caliper and US skinfold thickness for tricipital (r= 0.33; p= 0.003) and sovrailiac skinfold (r= 0.34; p=0.003). Fatty liver was diagnosed in 64% of children and it was positively related to anthropometric measurements. The three sub-groups--group 0 (normal US liver and normal transaminases); group 1 (US fatty liver and normal transaminases); group 2 (US fatty liver and elevated transaminases)--showed a difference concerning z-score BMI, insulin and HOMA parameters (Tukey test: z score BMI group 1 vs group 0 and 2 vs group 0; serum insulin: group 2 vs group 1 and group 2 vs group 0; HOMA IR: group 2 vs group 1 and group 2 vs group 0). Moderately obese children with steatosis exhibited a clear increase of insulin and insulin resistance which represents indices of a future metabolic syndrome. In addition, it is important to perform a liver ultrasound since transaminases seems to be not adequate for the diagnosis of fatty liver.

Removing patients from the liver transplant wait list: A survey of US liver transplant programs

Guidelines are in place regarding who is a candidate for liver transplantation. Once a potential candidate is listed, there are no uniform guidelines indicating when he should be removed from the list because of a change in clinical status. A survey with 14 scenarios was sent to the medical and surgical directors of all liver transplant programs in the United States. In each scenario, clinical information was provided about a patient active on the transplant wait list. Data regarding a clinical change were provided, and responders were questioned whether they would remove the patient from the wait list. The scenarios were designed to address the issues of age, etiology of liver disease, renal dysfunction, respiratory failure, infection, failure to thrive, and social support. Two hundred four questionnaires were mailed with 47 responses (23%): 8 return to sender, 24 surgeons, and 15 hepatologists. All 11 United Network for Organ Sharing regions were represented. The responders were well distributed among university programs (n = 28), private practice programs (n = 10), and health maintenance organization programs (n = 1). Nine responses were from small-volume programs (< or =25 transplants), 12 were from medium-volume programs (26-50 transplants), and 18 were from large-volume programs (> or =51 transplants). There was wide variability between responders regarding which patients should be removed from the transplant wait list. Patient age and etiology of liver disease led to the greatest discordance among responders. In conclusion, there is a lack of agreement and standardization among US liver transplant programs regarding who should be removed from the wait list for a change in clinical status.

What is the clinical significance of the high prevalence of occult hepatitis B in US liver transplant patients with chronic hepatitis C?

What is the clinical significance of the high prevalence of occult hepatitis B in US liver transplant patients with chronic hepatitis C?

Improvement in Survival Associated With Adult-to-Adult Living Donor Liver Transplantation

More than 2000 adult-to-adult living donor liver transplantations (LDLT) have been performed in the United States, yet the potential benefit to liver transplant candidates of undergoing LDLT compared with waiting for deceased donor liver transplantation (DDLT) is unknown. The aim of this study was to determine whether there is a survival benefit of adult LDLT. Adults with chronic liver disease who had a potential living donor evaluated from January 1998 to February 2003 at 9 university-based hospitals were analyzed. Starting at the time of a potential donor's evaluation, we compared mortality after LDLT to mortality among those who remained on the waiting list or received DDLT. Median follow-up was 4.4 years. Comparisons were made by hazard ratios (HR) adjusted for LDLT candidate characteristics at the time of donor evaluation. Among 807 potential living donor recipients, 389 underwent LDLT, 249 underwent DDLT, 99 died without transplantation, and 70 were awaiting transplantation at last follow-up. Receipt of LDLT was associated with an adjusted mortality HR of 0.56 (95% confidence interval [CI]: 0.42-0.74; P < .001) relative to candidates who did not undergo LDLT. As centers gained greater experience (>20 LDLT), LDLT benefit was magnified, with a mortality HR of 0.35 (95% CI: 0.23-0.53; P < .001). Adult LDLT was associated with lower mortality than the alternative of waiting for DDLT. This reduction in mortality was magnified as centers gained experience with LDLT. This reduction in transplant candidate mortality must be balanced against the risks undertaken by the living donors themselves.

MELD/PELD: one year later

The liver allocation policy in the United States was changed on February 27, 2002, to a continuous scale with almost no weight given to time waiting on the list. This was based on the dissatisfaction with the old categorical system and an understanding that waiting time as not a good discriminator of medical urgency. To assess the effects of this change, liver allocation results for the first 6 months of this new system (February 27, 2002, to August 30, 2002, era 2) with the corresponding 6 month period 1 year earlier (February 27, 2001, to August 30, 2001, era 1) were compared. Fewer registrations on the waiting list, fewer removals from the waiting list because of death or “too sick,” and an increase in the number of cadaveric transplants under the new system were observed. Patients with hepatocellular cancer received additional priority with the new policy and there was a significant increase in the number of candidates transplanted with this diagnosis in era 2. Early posttransplant patient survival has not changed under the new system. Although there are many areas for improvement, which will be addressed in future refinements, the new US liver allocation plan has provided a more objective, patient-specific system to better rank waiting liver transplant candidates.

Blind and ultrasound-guided percutaneous liver biopsy in children

Percutaneous biopsy of the liver is the most commonly used procedure to obtain tissue for histopathological assessment of liver disease. Although, intuitively, image-guided liver biopsy might be expected to reduce the risk of bleeding, haematoma caused by a penetrating injury of a branch of the hepatic artery or portal vein, and puncture of the gallbladder, no trial has been large enough to show reduced mortality or morbidity with US guidance, and the mechanisms by which the use of US can reduce the risk of bleeding remain speculative. To compare the mortality and morbidity of blind liver biopsy with that of US-guided liver biopsy. A retrospective review of our experience of 140 procedures over a 16-month period. In the blind group, biopsy was unsuccessful in ten children (95% CL 7.3-25.4); no tissue was obtained in eight children and an inadequate sample was obtained in two. Three children (95% CL 9.2-14.7) suffered significant haemorrhage (indicated by a drop in haemoglobin of >20 g/l) with intrahepatic ( n=1) and subcapsular ( n=2) haematomas detectable by US after biopsy. An adequate sample was obtained in all children in the US-guided group. There were no complications requiring treatment in either group. Our results showed a significant difference in the complication rate between liver biopsy undertaken with US guidance and liver biopsy performed blind ( P=0.002).

Hepatitis B infection in patients with acute liver failure in the United States

Occult hepatitis B virus (HBV) infection has been reported in 30% to 50% of patients with acute liver failure (ALF) in small case series. The aim of this study was to determine the prevalence of occult HBV infection in a large series of ALF patients in the United States and the prevalence of precore and core promoter variants in patients with ALF caused by hepatitis B. Sera from patients in the US ALF study and liver, when available, were tested using nested polymerase chain reaction (PCR) with primers in the HBV S and precore regions. PCR-positive samples were sequenced. Sera and/or liver from 139 patients (39 males, 100 females; mean age, 42 years) enrolled between January 1998 and December 1999 were studied. Twelve patients were diagnosed with hepatitis B, 1 with hepatitis B+C+D coinfection, and 22 had indeterminate etiology. HBV DNA was detected in the sera of 9 (6%) patients; all 9 had ALF caused by hepatitis B. HBV genotypes A, B, C, and D were present in 4, 3, 1, and 1 patients, respectively. Seven of these 9 patients had precore and/or core promoter variants. Liver from 19 patients were examined. HBV DNA was detected in the liver of 3 patients with ALF caused by hepatitis B, but in none of the remaining 16 patients with non-B ALF. Contrary to earlier reports, occult HBV infection was not present in this large series of ALF patients in the United States. HBV precore and/or core promoter variants were common among US patients with ALF caused by hepatitis B. (HEPATOLOGY 2001;33:972-976.)

The impact of improvements in procurement and utilization on US liver recipients

The impact of improvements in procurement and utilization on US liver recipients

Tacrolimus. An update of its pharmacology and clinical efficacy in the management of organ transplantation.

Tacrolimus (FK 506) has been evaluated as immunosuppressive therapy in patients with a variety of solid organ and other transplants. Extensive data have now confirmed its efficacy as primary or rescue therapy in renal and hepatic transplantation. In prospective and historically controlled studies of primary therapy, tacrolimus generally demonstrated greater efficacy than the conventional formulation of cyclosporin for preventing episodes of acute rejection and allowed reduction of corticosteroid use. Chronic rejection rates were also significantly lower with tacrolimus in a large randomised liver transplantation trial. However, patient and graft survival rates were similar in both treatment groups (although numerically larger in adults with liver transplants). In children, rejection rates and corticosteroid requirements were usually lower with tacrolimus and patient and graft survival were generally similar with the 2 immunosuppressants. The finding of reduced corticosteroid requirements with tacrolimus may be of particular benefit in prepubertal children, who are still growing. A small amount of evidence has also accumulated regarding the use of tacrolimus as primary therapy in patients who have undergone bone marrow or heart and/or lung transplantation. Data are not conclusive, particularly in children, but tacrolimus appears to be useful for treating patients who have undergone these organ transplantations and may be associated with a lower incidence of obliterative bronchiolitis than cyclosporin in the latter group. Potential efficacy has also been shown in a limited number of patients with pancreas or pancreas-kidney, pancreatic islet and intestinal or multivisceral transplants, and in children who have undergone heart or heart-lung transplantation. Tacrolimus also has a use as rescue therapy in bone marrow, heart, lung and pancreatic transplantation, but data are currently insufficient for conclusions to be made. However, these results support the need for further study in these populations. Adverse effects occurring during tacrolimus therapy are generally of the type common to all immunosuppressive regimens. However, diabetes mellitus, neurotoxicity and nephrotoxicity are more common in tacrolimus than cyclosporin recipients. Hyperlipidaemia, hypertension, hirsutism and gingival hyperplasia are more common with cyclosporin. In 2 large multicentre clinical trials (US liver and European renal), tacrolimus was discontinued more frequently during the first year because of adverse events. However, the tolerability of tacrolimus appears related to dosage, improving as the dose is reduced. Tacrolimus should be considered an effective primary immunosuppressant in renal and hepatic transplantation. The drug is also a useful agent for rescue therapy in patients experiencing rejection or poor tolerability to cyclosporin. Thus, tacrolimus provides the clinician with an effective option for patients requiring immunosuppression and, with a different tolerability and efficacy profile to cyclosporin, it will better allow the tailoring of therapy to meet the needs of individual patients.

Multiple bile duct hamartomas simulating liver metastases on US and CT: case report

The radiological findings in multiple bile duct hamartomas (MBDH) are rare macroscopic manifestations of a more common microscopic entity. We present a patient in which the US and CT appearance simulated liver metastases. Final diagnosis was made by liver biopsy.