Background & Aims Transient elastography is a non-invasive method, for the assessment of hepatic fibrosis, developed as an alternative to liver biopsy. We studied the performance of elastography for ...diagnosis of fibrosis using meta-analysis. Methods MEDLINE, EMBASE, SCI, Cochrane Library, conference abstracts books, and article references were searched. We included studies using biopsy as a reference standard, with the data necessary to calculate the true and false positive, true and false negative diagnostic results of elastography for a fibrosis stage, and with a 3-month maximum interval between tests. The quality of the studies was rated with the QUADAS tool. Results We identified 40 eligible studies. Summary sensitivity and specificity was 0.79 (95% CI 0.74–0.82) and 0.78 (95% CI 0.72–0.83) for F2 stage and 0.83 (95% CI 0.79–0.86) and 0.89 (95% CI 0.87–0.91) for cirrhosis. After an elastography result at/over the threshold value for F2 or cirrhosis (“positive” result), the corresponding post-test probability for their presence (if pre-test probability was 50%) was 78%, and 88% respectively, while, if values were below these thresholds (“negative” result), the post-test probability was 21% and 16%, respectively. No optimal stiffness cut-offs for individual fibrosis stages were validated in independent cohorts and cut-offs had a wide range and overlap within and between stages. Conclusions Elastography theoretically has good sensitivity and specificity for cirrhosis (and less for lesser degrees of fibrosis); however, it should be cautiously applied to everyday clinical practice because there is no validation of the stiffness cut-offs for the various stages. Such validation is required before elastography is considered sufficiently accurate for non-invasive staging of fibrosis.
The prognosis for patients with hepatocellular cancer (HCC) undergoing transarterial therapy (TACE/TAE) is variable.
We carried out Cox regression analysis of prognostic factors using a training ...dataset of 114 patients treated with TACE/TAE. A simple prognostic score (PS) was developed, validated using an independent dataset of 167 patients and compared with Child–Pugh, CLIP, Okuda, Barcelona Clinic Liver Cancer (BCLC) and MELD.
Low albumin, high bilirubin or α-fetoprotein (AFP) and large tumour size were associated with a two- to threefold increase in the risk of death. Patients were assigned one point if albumin <36 g/dl, bilirubin >17 μmol/l, AFP >400 ng/ml or size of dominant tumour >7 cm. The Hepatoma arterial-embolisation prognostic (HAP) score was calculated by summing these points. Patients were divided into four risk groups based on their HAP scores; HAP A, B, C and D (scores 0, 1, 2 and >2, respectively). The median survival for the groups A, B, C and D was 27.6, 18.5, 9.0 and 3.6 months, respectively. The HAP score validated well with the independent dataset and performed better than other scoring systems in differentiating high- and low-risk groups.
The HAP score predicts outcomes in patients with HCC undergoing TACE/TAE and may help guide treatment selection, allow stratification in clinical trials and facilitate meaningful comparisons across reported series.
Patients with cirrhosis can have abnormalities in laboratory tests reflecting changes in primary haemostasis, including bleeding time, platelet function tests, markers of platelet activation, and ...platelet count. Such changes have been considered particularly relevant in the bleeding complications that occur in cirrhosis. However, several studies have shown that routine diagnostic tests, such as platelet count, bleeding time, PFA-100, thromboelastography are not clinically useful to stratify bleeding risk in patients with cirrhosis. Moreover, treatments used to increase platelet count or to modulate platelet function could potentially do harm. Consequently the optimal management of bleeding complications is still a matter of discussion. Moreover, in the last two decades there has been an increased recognition that not only bleeding but also thrombosis complicates the clinical course of cirrhosis. Thus, we performed a literature search looking at publications studying both qualitative and quantitative aspects of platelet function to verify which primary haemostasis defects occur in cirrhosis. In addition, we evaluated the contribution of qualitative and quantitative aspects of platelet function to the clinical outcome in cirrhosis and their therapeutic management according to the data available in the literature. From the detailed analysis of the literature, it appears clear that primary haemostasis may not be defective in cirrhosis, and a low platelet count should not necessarily be considered as an automatic index of an increased risk of bleeding. Conversely, caution should be observed in patients with severe thrombocytopenia where its correction is advised if bleeding occurs and before invasive diagnostic and therapeutic procedures.
Recently we validated the donor risk index (DRI) as conducted by Feng et al. for the Eurotransplant region. Although this scoring system is a valid tool for scoring donor liver quality, for ...allocation purposes a scoring system tailored for the Eurotransplant region may be more appropriate. Objective of our study was to investigate various donor and transplant risk factors and design a risk model for the Eurotransplant region. This study is a database analysis of all 5939 liver transplantations from deceased donors into adult recipients from the 1st of January 2003 until the 31st of December 2007 in Eurotransplant. Data were analyzed with Kaplan–Meier and Cox regression models. From 5723 patients follow‐up data were available with a mean of 2.5 years. After multivariate analysis the DRI (p < 0.0001), latest lab GGT (p = 0.005) and rescue allocation (p = 0.007) remained significant. These factors were used to create the Eurotransplant Donor Risk Index (ET‐DRI). Concordance‐index calculation shows this ET‐DRI to have high predictive value for outcome after liver transplantation. Therefore, we advise the use of this ET‐DRI for risk indication and possibly for allocation purposes within the Eurotrans‐plant region.
This article describes the Eurotransplant Donor Risk Index, a model based on donor and transplant parameters with high predictive value for outcome after orthotopic liver transplantation in the Eurotransplant region.
Aliment Pharmacol Ther 2011; 34: 901–910
Summary
Background There is no satisfactory medical treatment for patients with primary sclerosing cholangitis. There are conflicting data regarding the ...clinical benefit of high doses of ursodeoxycholic acid (UDCA) in primary sclerosing cholangitis.
Aim To evaluate using meta‐analysis, if UDCA (standard or high‐dose) is useful in primary sclerosing cholangitis.
Methods We searched MEDLINE using the textwords ‘PSC’, ‘treatment’, ‘UDCA’ and retrieved all s from the major Gastroenterology and Liver meetings. We included randomised clinical trials comparing standard or high‐dose of UDCA (>15 mg/kg body weight per day) vs. placebo or no intervention. End‐points: mortality or liver transplantation, pruritus, fatigue, cholangiocarcinoma and histological progression.
Results We identified eight randomised clinical trials comprising 567 patients. Five used standard doses and three high doses of UDCA. There was no significant difference in mortality OR, 0.6 (95% CI, 0.4–1.4), in pruritus OR, 1.5 (95% CI, 0.3–7.2), in fatigue OR, 0.0 (95% CI, 0.1–7.7), in cholangiocarcinoma OR, 1.7 (95% CI, 0.6–5.1) and in histology stage progression OR, 0.9 (95% CI, 0.34–2.44). No differences were found in the subgroup analyses.
Conclusion Neither standard nor high‐dose UDCA influence favourably the progression of primary sclerosing cholangitis.
We hypothesized that current trough concentrations of tacrolimus after liver transplantation are set too high, considering that clinical consequences of rejection are not severe while side effects ...are increased. We systematically reviewed 64 studies (32 randomized controlled trials and 32 observational studies) to determine how lower tacrolimus trough concentrations than currently recommended affect acute rejection rates and renal impairment. Among randomized trials the mean of tacrolimus trough concentration during the first month was positively correlated with renal impairment within 1 year (r = 0.73; p = 0.003), but not with acute rejection, either defined using protocol biopsies (r =−0.37; p = 0.32) or not (r = 0.11; p = 0.49). A meta‐analysis of randomized trials directly comparing tacrolimus trough concentrations (five trials for acute rejection n = 957 and two trials for renal impairment n = 712) showed that “reduced tacrolimus” trough concentrations (<10 ng/mL) within the first month after liver transplantation were associated with less renal impairment at 1 year (RR = 0.51 0.38–0.69), with no significant influence on acute rejection (RR = 0.92 0.65–1.31) compared to “conventional tacrolimus” trough levels (>10 ng/mL). Lower trough concentrations of tacrolimus (6–10 ng/mL during the first month) would be more appropriate after liver transplantation. Regulatory authorities and the pharmaceutical industry should allow changes of regulatory drug information.
Evaluation of trough concentrations of tacrolimus after liver transplantation indicate that lower concentrations than currently recommended are safe in terms of acute cellular rejection, while reducing rates of renal impairment.
After allotransplantation, cytomegalovirus (CMV) may be transmitted from the donor organ, giving rise to primary infection in a CMV negative recipient or reinfection in one who is CMV positive. In ...addition, latent CMV may reactivate in a CMV positive recipient. In this study, serial blood samples from 689 kidney or liver transplant recipients were tested for CMV DNA by quantitative PCR. CMV was managed using preemptive antiviral therapy and no patient received antiviral prophylaxis. Dynamic and quantitative measures of viremia and treatment were assessed. Median peak viral load, duration of viremia and duration of treatment were highest during primary infection, followed by reinfection then reactivation. In patients who experienced a second episode of viremia, the viral replication rate was significantly slower than in the first episode. Our data provide a clear demonstration of the immune control of CMV in immunosuppressed patients and emphasize the effectiveness of the preemptive approach for prevention of CMV syndrome and end organ disease. Overall, our findings provide quantitative biomarkers which can be used in pharmacodynamic assessments of the ability of novel CMV vaccines or antiviral drugs to reduce or even interrupt such transmission.
The authors show that preemptive antiviral therapy is an effective approach for control and prevention of cytomegalovirus replication after renal and liver transplantation, even in high‐risk patients.
Summary
Background Prognostic scores in an intensive care unit (ICU) evaluate outcomes, but derive from cohorts containing few cirrhotic patients.
Aims To evaluate 6‐week mortality in cirrhotic ...patients admitted to an ICU, and to compare general and liver‐specific prognostic scores.
Methods A total of 312 consecutive cirrhotic patients (65% alcoholic; mean age 49.6 years). Multivariable logistic regression to evaluate admission factors associated with survival. Child–Pugh, Model for End‐stage Liver Disease (MELD), Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores were compared by receiver operating characteristic curves.
Results Major indication for admission was respiratory failure (35.6%). Median (range) Child–Pugh, APACHE II, MELD and SOFA scores were 11 (5–15), 18 (0–44), 24 (6–40) and 11 (0–21), respectively; 65% (n = 203) died. Survival improved over time (P = 0.005). Multivariate model factors: more organs failing (FOS) (<3 = 49.5%, ≥3 = 90%), higher FiO2, lactate, urea and bilirubin; resulting in good discrimination area under receiver operating characteristic curve (AUC) = 0.83, similar to SOFA and MELD (AUC = 0.83 and 0.81, respectively) and superior to APACHE II and Child–Pugh (AUC = 0.78 and 0.72, respectively).
Conclusions Cirrhotics admitted to ICU with ≥3 failing organ systems have 90% mortality. The Royal Free model discriminated well and contained key variables of organ function. SOFA and MELD were better predictors than APACHE II or Child–Pugh scores.
Aliment Pharmacol Ther 31, 366‐374
Summary
Background As current imaging techniques in cirrhosis allow detection of asymptomatic portal vein thrombosis during routine ultrasonography, more patients ...with cirrhosis are diagnosed with portal vein thrombosis. Although a consensus on noncirrhotic extra‐hepatic portal vein thrombosis has been published, no such consensus exists for portal vein thrombosis with cirrhosis.
Aim To perform a systematic review of nonmalignant portal vein thrombosis in cirrhosis in terms of prevalence, pathogenesis, diagnosis, clinical course and management.
Methods Studies were identified by a search strategy using MEDLINE and EMBASE.
Results Portal vein thrombosis is encountered in 10–25% of cirrhotics. In terms of pathophysiology, cirrhosis is no longer considered a hypocoagulable state; rather than a bleeding risk in cirrhosis, various clinical studies support a thrombotic potential. Clinical findings of portal vein thrombosis in cirrhosis vary from asymptomatic disease to a life‐threatening condition at first presentation. Optimal management of portal vein thrombosis in cirrhosis is currently not addressed in any consensus publication. Treatment strategies most often include the use of anticoagulation, while thrombectomy and transjugular intrahepatic portosystemic shunts are considered second‐line options.
Conclusions Portal vein thrombosis in cirrhosis has many unresolved issues, which are often the critical problems clinicians encounter in their everyday practice. We propose a possible research agenda to address these unresolved issues.
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