Summary
Background
Emerging data suggest that oral antibiotics may have therapeutic effects in primary sclerosing cholangitis (PSC), but published studies are limited.
Aims
To investigate the safety ...and efficacy of oral vancomycin and metronidazole in patients with PSC.
Methods
Thirty‐five patients with PSC were randomised in a double‐blind manner into four groups: vancomycin 125 mg or 250 mg four times/day, or metronidazole 250 mg or 500 mg three times/day for 12 weeks. The primary endpoint was decrease in alkaline phosphatase (ALK) at 12 weeks. Secondary end points included serum bilirubin and Mayo PSC risk score; pruritus; and adverse effects (AEs). Nonparametric tests were used for analysis.
Results
The primary endpoint was reached in the low‐dose (−43% change in ALK, P = 0.03) and high‐dose (−40%, P = 0.02) vancomycin groups, with two patients in the former experiencing ALK normalisation. Bilirubin decreased significantly in the low‐dose metronidazole group (−20%, P = 0.03) and trended towards significance in the low‐dose vancomycin group (−33%, P = 0.06). Mayo PSC risk score decreased significantly in the low‐dose vancomycin (−0.55, P = 0.02) and low‐dose metronidazole group (−0.16, P = 0.03). Pruritus decreased significantly in the high‐dose metronidazole group (−3.4, P = 0.03). AEs led to medication discontinuation in six patients, four of whom were receiving metronidazole.
Conclusions
Both vancomycin and metronidazole demonstrated efficacy; however, only patients in the vancomycin groups reached the primary endpoint, and with less adverse effects. Larger, longer‐term studies are needed to further examine the safety and efficacy of antibiotics as a potential treatment for patients with primary sclerosing cholangitis (clinicaltrials.gov NCT01085760).
Recurrent primary biliary cirrhosis (PBC) is an important clinical outcome after liver transplantation (LT) in selected patients. Prevalence rates for recurrent PBC (rPBC) reported by individual LT ...programs range between 9% and 35%. The diagnostic hallmark of rPBC is histologic identification of granulomatous changes. Clinical and biochemical features are frequently absent with rPBC and cannot be used alone for diagnostic purposes. Some of the risk factors of rPBC may include recipient factors such as age, gender, HLA status and immunosuppression, as well as donor factors such as age, gender and ischemic time, although controversy exists. Most patients have early stage disease at the time of diagnosis, and there may be a role for therapy with ursodeoxycholic acid. While short‐ and medium‐term outcomes remain favorable, especially if compared to patients transplanted for other indications, continued follow‐up may identify reduced long‐term graft and patient survival.
Recurrent primary biliary cirrhosis is a frequent clinical outcome after liver transplantation in selected patients, though only a few individuals to date have developed end‐stage liver disease leading to death or requiring hepatic re‐transplantation.
Summary
Drug‐induced liver injury (DILI) is often caused by innate and adaptive host immune responses. Characterization of inflammatory infiltrates in the liver may improve understanding of the ...underlying pathogenesis of DILI. This study aimed to enumerate and characterize leucocytes infiltrating liver tissue from subjects with acute DILI (n = 32) versus non‐DILI causes of acute liver injury (n = 25). Immunostains for CD11b/CD4 (Kupffer and T helper cells), CD3/CD20 (T and B cells) and CD8/CD56 T cytotoxic and natural killer (NK) cells were evaluated in biopsies from subjects with acute DILI, either immunoallergic (IAD) or autoimmune (AID) and idiopathic autoimmune (AIH) and viral hepatitis (VH) and correlated with clinical and pathological features. All biopsies showed numerous CD8+ T cells and macrophages. DILI cases had significantly fewer B lymphocytes than AIH and VH and significantly fewer NK cells than VH. Prominent plasma cells were unusual in IAD (three of 10 cases), but were associated strongly with AIH (eight of nine) and also observed in most with AID (six of nine). They were also found in five of 10 cases with VH. Liver biopsies from subjects with DILI were characterized by low counts of mature B cells and NK cells in portal triads in contrast to VH. NK cells were found only in cases of VH, whereas AIH and VH both showed higher counts of B cells than DILI. Plasma cells were associated most strongly with AIH and less so with AID, but were uncommon in IAD.
Aliment Pharmacol Ther 2011; 34: 83–91
Summary
Background Liver stiffness assessed using transient elastography is described as a potential risk factor for hepatocellular carcinoma (HCC) in ...cirrhosis. However, the strict assessment of hepatic parenchymal areas uninvolved with HCC has not been investigated.
Aim To determine if liver stiffness of nonmalignant hepatic parenchyma using magnetic resonance elastography (MRE) is higher in patients with HCC compared with controls.
Methods Cases were defined by compensated cirrhosis with a Child–Turcotte–Pugh score <7 and HCC by radiological criteria or histology. Control subjects with compensated cirrhosis were frequency matched with cases by gender and disease aetiology. Overt manifestations of portal hypertension and previous therapy for liver disease or HCC were exclusion criteria. Region of interest analyses were performed on hepatic parenchyma regions distant to HCC location among cases.
Results Thirty patients with HCC and 60 matched controls comprised the study cohort. The mean age for cases was 64 ± 10 years (range, 45–85) with 70% being men. Major disease aetiologies were chronic viral hepatitis (57%), non‐alcoholic fatty liver disease (33%) and alcohol (10%). Twenty‐eight (93%) patients had solitary HCC lesions with a mean size of 5.2 cm (range, 2–14 cm). However, patients with HCC had similar liver stiffness among uninvolved areas distant to HCC lesions, when compared with controls without HCC (mean, 6.1 ± 2.0 vs. 6.3 ± 2.5 kPa, P = 0.7).
Conclusion In contrast to previous studies with transient elastography, we did not observe a systematic association between liver stiffness assessed using MRE and the presence of HCC in patients with compensated cirrhosis.
Summary
Background
Patients with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC) are at an increased risk of colorectal neoplasia, but it is unknown if liver transplantation (LT) ...alters neoplasia progression.
Aim
To examine the natural history of indefinite dysplasia (IND) and low‐grade dysplasia (LGD) that develop in patients with PSC‐UC with and without LT.
Methods
We performed a retrospective review of patients with PSC and UC evaluated at our institution between 1993 and 2011 who were diagnosed with IND or LGD before or after LT for PSC. The primary end point was neoplasia progression or persistent LGD.
Results
Ninety‐six patients (non‐LT n = 63, LT n = 33) were examined. For the IND group, multifocal lesions were significantly associated with time to neoplasia progression hazard ratio (HR), 3.5; 95% confidence interval (CI), 1.3–9.7, while 5‐aminosalicylate (5‐ASA) use was protective (HR, 0.2; 95% CI, 0.1–0.6). For patients with LGD, multifocal lesions were significantly associated with the primary end point (HR, 7.1; 95% CI, 1.7–28.3), while LT was protective (HR, 0.3; 95% CI, 0.1–0.9).
Conclusions
In PSC‐UC patients with IND, 5‐ASA use was associated with a decreased the risk of neoplasia progression, regardless of transplant status. In contrast, multifocal IND and LGD were associated with neoplasia progression or persistent LGD. Patients who developed LGD following LT for PSC were less likely to have progressive neoplasia or persistent LGD, compared with those who had not been transplanted.
Summary
What is known and objective
The presence of cirrhosis has a multifaceted impact on hepatic drug metabolism. An area of concern and uncertainty in the care of patients with cirrhosis is the ...safe use of both prescription and over‐the‐counter medications.
Comment
Retrospective studies indicate a high incidence of adverse drug reactions (ADRs) among patients with cirrhosis related to use of certain medication classes including angiotensin‐converting enzyme inhibitors, angiotensin receptor blockers and non‐steroidal anti‐inflammatory drugs. Conversely, use of appropriate medications, such as statins, may be decreased in this population due to fear of precipitating hepatotoxicity.
What is new and conclusion
Pharmacotherapy in cirrhosis is an area of uncertainty and heterogeneity in clinical practice. Prescribing and dosing guidelines are needed to decrease the risk of serious ADRs in this high‐risk patient population.
Pharmacotherapy in cirrhosis is an area of uncertainty and heterogeneity in clinical practice. Retrospective studies demonstrate a high incidence of ADRs related to unsafe medication prescribing habits or incorrect dosing. Safe prescribing in cirrhosis could be augmented through the creation of specific dosing guidelines and perhaps increased involvement of pharmacists.
The objective was to review the current state of knowledge and recommend future research directions related to long‐term outcomes for pediatric liver transplant recipients. A 1‐day Clinical Research ...Workshop on Improving Long‐Term Outcomes for Pediatric Liver Transplant Recipients was held on February 12, 2007, in Washington, DC. The speaker topics were germane to research priorities delineated in the chapters on Pediatric Liver Diseases and on Liver Transplantation in the Trans‐NIH Action Plan for Liver Disease Research. Issues that compromise long‐term well‐being and survival but are amenable to existing and new research efforts were presented and discussed. Areas of research that further enhanced the research priorities in the Action Plan for Liver Disease Research included collection of longitudinal data to define emerging trends of clinical challenges; identification of risk factors associated with long‐term immunosuppression complications; development of tolerance‐inducing regimens; definition of biomarkers that reflect the level of clinical immunosuppression; development of instruments for the measurement of health wellness; identification of risk factors that impede growth and intellectual development before and after liver transplantation and identification of barriers and facilitators that impact nonadherence and transition of care for adolescents.
The current knowledge and gaps in knowledge were discussed at a one‐day conference sponsored by NIDDK concerning long‐term outcome after liver transplantation in children.
BACKGROUND:Obesity as a cause of lower extremity deformity in children has been well established. This deformity is most often seen as tibia vara, however, at our institution we have observed more ...obese children and adolescents over age 7 years with excessive or progressive idiopathic genu valgum. Our hypothesis is that children with idiopathic genu valgum have high rates of obesity which impact the severity of their disease.
METHODS:Retrospective review of existing data was performed on 66 consecutive children/112 limbs over age 7 years with idiopathic genu valgum, seen from 2010 to 2013. Children with known metabolic or skeletal disease were excluded. Genu valgum was defined as mechanical axis in zone II or III and mechanical tibiofemoral angle ≥4 degrees on standing anteroposterior radiograph of the lower extremities. Body mass index (BMI) was calculated and classified by Center for Disease Control percentiles. Skeletal maturation was rated by closure of pelvic and peri-genu physes. Severity of genu valgum was also assessed by femoral and tibial mechanical axes and the mechanical axis deviation.
RESULTS:Mean patient age was 12.2±2.2 years. 47% of patients had BMI≥30 and 71% were categorized as obese (>95th percentile). No sex differences were identified. Skeletal maturation explained 25% of the variance in the mechanical axis deviation and 22% of the mechanical tibiofemoral angle. BMI predicted 9.8% of the tibial valgus. Because of its skewed distribution, BMI percentile was a less useful parameter for assessment.
CONCLUSIONS:The 71% obesity rate found in our children with idiopathic genu valgum is significantly higher than the normal population. Higher BMI is associated with more tibial valgum but skeletal maturation was the main predictor of overall valgus severity. This suggests that obesity may play a role in the etiology of idiopathic genu valgum which progresses with skeletal maturation, thereby increasing the risk of osteoarthritis in adulthood.
LEVEL OF EVIDENCE:Level III.
Obesity as a cause of lower extremity deformity in children has been well established. This deformity is most often seen as tibia vara, however, at our institution we have observed more obese ...children and adolescents over age 7 years with excessive or progressive idiopathic genu valgum. Our hypothesis is that children with idiopathic genu valgum have high rates of obesity which impact the severity of their disease.
Retrospective review of existing data was performed on 66 consecutive children/112 limbs over age 7 years with idiopathic genu valgum, seen from 2010 to 2013. Children with known metabolic or skeletal disease were excluded. Genu valgum was defined as mechanical axis in zone II or III and mechanical tibiofemoral angle ≥4 degrees on standing anteroposterior radiograph of the lower extremities. Body mass index (BMI) was calculated and classified by Center for Disease Control percentiles. Skeletal maturation was rated by closure of pelvic and peri-genu physes. Severity of genu valgum was also assessed by femoral and tibial mechanical axes and the mechanical axis deviation.
Mean patient age was 12.2±2.2 years. 47% of patients had BMI≥30 and 71% were categorized as obese (>95th percentile). No sex differences were identified. Skeletal maturation explained 25% of the variance in the mechanical axis deviation and 22% of the mechanical tibiofemoral angle. BMI predicted 9.8% of the tibial valgus. Because of its skewed distribution, BMI percentile was a less useful parameter for assessment.
The 71% obesity rate found in our children with idiopathic genu valgum is significantly higher than the normal population. Higher BMI is associated with more tibial valgum but skeletal maturation was the main predictor of overall valgus severity. This suggests that obesity may play a role in the etiology of idiopathic genu valgum which progresses with skeletal maturation, thereby increasing the risk of osteoarthritis in adulthood.
Level III.
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