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 combination of hepatitis B immunoglobulin (HBIG) and nucleos(t)ide analogues NA(s) is considered as the standard of care for prophylaxis against HBV recurrence after liver transplantation (LT), ...but the optimal protocol is controversial. We evaluated the efficacy of the newer NAs with high genetic barrier (hgbNA) i.e. entecavir (ETV) or tenofovir (TDF) with or without HBIG as prophylaxis against HBV recurrence after LT. In total, 519 HBV liver transplant recipients from 17 studies met the inclusion criteria and they were compared to those under lamivudine (LAM) and HBIG who had been selected in our previous review. Patients under HBIG and LAM developed HBV recurrence (115/1889 or 6.1%): (a) significantly more frequently compared to patients under HBIG and a hgbNA 1.0% (3/303), p < 0.001, and (b) numerically but not significantly more frequently compared to the patients who received a newer NA after discontinuation of HBIG 3.9% (4/102), p = 0.52. The use of a hgbNA without any HBIG offered similar antiviral prophylaxis compared to HBIG and LAM combination, if the definition of HBV recurrence was based on HBV DNA detectability 0.9% vs. 3.8%, p = 0.11. Our findings favor the use of HBIG and a hgbNA instead of HBIG and LAM combined prophylaxis against HBV recurrence after LT.
The authors find that the use of hepatitis B immunoglobulin and a newer nucleos(t)ide analogue with high genetic barrier provides the best prophylaxis against HBV recurrence after liver transplantation. See related article by Di Costanzo et al (page 348).
Summary
Background
The treatment of chronic hepatitis B (CHB) in patients with chronic kidney disease (CKD) is based on nucleoside (lamivudine, telbivudine, entecavir) or nucleotide (adefovir, ...tenofovir) analogues (NAs), but it may be complex and the information is scarce. Entecavir and tenofovir represent the currently recommended first‐line NAs for NA‐naive CHB patients, while tenofovir is the NA of choice for CHB patients with resistance to nucleosides.
Aim
To review the efficacy and safety of NAs in adult CHB patients with CKD and to provide reasonable recommendations for their optimal management.
Methods
Literature search in PubMed/Medline and manual search of relevant articles, reviews and book chapters.
Results
NAs are cleared by kidneys and their dosage should be adjusted in patients with creatinine clearance <50 mL/min. There are concerns about nephrotoxic potential of the nucleotides, particularly adefovir, while improvements of creatinine clearance have been reported under telbivudine. Most existing data in CHB patients with CKD are for lamivudine and, less frequently, for other NAs, mostly entecavir. Besides CHB, NA should be used in case of immunosuppressive therapy in any HBsAg‐positive patient with CKD including renal transplant (RT) recipients and in anti‐HBs‐positive recipients of kidney grafts from HBsAg‐positive donors.
Conclusions
Chronic hepatitis B patients with chronic kidney disease receiving nucleoside analogues should be followed carefully for treatment efficacy and renal safety. Despite the absence of strong data, entecavir and telbivudine seem to be the preferred options for nucleoside analogue‐naive CHB patients with chronic kidney disease, depending on viraemia and severity of renal dysfunction. More studies are certainly needed in this setting.
Summary
Background: Prognosis in cirrhotic patients has had a resurgence of interest because of liver transplantation and new therapies for complications of end‐stage cirrhosis. The model for ...end‐stage liver disease score is now used for allocation in liver transplantation waiting lists, replacing Child‐Turcotte‐Pugh score. However, there is debate as whether it is better in other settings of cirrhosis.
Aim: To review studies comparing the accuracy of model for end‐stage liver disease score vs. Child‐Turcotte‐Pugh score in non‐transplant settings.
Results: Transjugular intrahepatic portosystemic shunt studies (with 1360 cirrhotics) only one of five, showed model for end‐stage liver disease to be superior to Child‐Turcotte‐Pugh to predict 3‐month mortality, but not for 12‐month mortality. Prognosis of cirrhosis studies (with 2569 patients) none of four showed significant differences between the two scores for either short‐ or long‐term prognosis whereas no differences for variceal bleeding studies (with 411 cirrhotics). Modified Child‐Turcotte‐Pugh score, by adding creatinine, performed similarly to model for end‐stage liver disease score. Hepatic encephalopathy and hyponatraemia (as an index of ascites), both components of Child‐Turcotte‐Pugh score, add to the prognostic performance of model for end‐stage liver disease score.
Conclusions: Based on current literature, model for end‐stage liver disease score does not perform better than Child‐Turcotte‐Pugh score in non‐transplant settings. Modified Child‐Turcotte‐Pugh and model for end‐stage liver disease scores need further evaluation.
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.
Summary
Hepatitis C virus (HCV) infection is a major public health problem in the European Union (EU). An estimated 5.6 million Europeans are chronically infected with a wide range of variation in ...prevalence across European Union countries. Although HCV continues to spread as a largely “silent pandemic,” its elimination is made possible through the availability of the new antiviral drugs and the implementation of prevention practices. On 17 February 2016, the Hepatitis B & C Public Policy Association held the first EU HCV Policy Summit in Brussels. This summit was an historic event as it was the first high‐level conference focusing on the elimination of HCV at the European Union level. The meeting brought together the main stakeholders in the field of HCV: clinicians, patient advocacy groups, representatives of key institutions and regional bodies from across European Union; it served as a platform for one of the most significant disease elimination campaigns in Europe and culminated in the presentation of the HCV Elimination Manifesto, calling for the elimination of HCV in Europe by 2030. The launch of the Elimination Manifesto provides a starting point for action in order to make HCV and its elimination in Europe an explicit public health priority, to ensure that patients, civil society groups and other relevant stakeholders will be directly involved in developing and implementing HCV elimination strategies, to pay particular attention to the links between hepatitis C and social marginalization and to introduce a European Hepatitis Awareness Week.
Summary
Background Renal function in patients with cirrhosis is important prognostically, both before and following liver transplantation. Its prognostic impact is reflected by the inclusion of ...serum creatinine in the model for end‐stage liver disease score, which is now used for recipient prioritization on liver transplantation waiting lists in the USA.
Aim To review the accuracy of the surrogate markers for the assessment of renal function, i.e. glomerular filtration rate, particularly in patients with cirrhosis.
Method We reviewed the available literature in PubMed regarding the markers for GFR evaluation and the factors which affect their accuracy in cirrhosis.
Results Although creatinine is widely available, it is an unreliable marker of glomerular filtration rate, particularly in patients with cirrhosis. Clearance of exogenous markers is considered the ‘gold standard’, but this methodology has many drawbacks, particularly poor applicability. Several mathematical formulae for estimated glomerular filtration rate are used to overcome some of these limitations: Cockcroft‐Gault and Modification of Diet in Renal Disease formulae are the most frequently applied, but they are based on serum creatinine.
Conclusions Due to the inaccuracy of serum creatinine and its derived formulae in estimating glomerular filtration rate, alternative serum markers, such as cystatin C, and new formulae are desirable. These need formal evaluation in patients with cirrhosis so as to have a reliable surrogate of glomerular filtration rate, and to obviate many problems that are associated with using creatinine and estimated glomerular filtration rate.
Newer nucleos(t)ide analogues (NUCs) have better resistance profiles making hepatitis B immunoglobulin (HBIG)‐sparing protocol an attractive prophylactic approach against hepatitis B virus (HBV) ...recurrence after liver transplantation (LT). We evaluated the risk of HBV recurrence after withdrawal of HBIG in patients who had been under HBIG plus NUCs after LT. Stable patients without HBV recurrence after LT while receiving combination of HBIG plus NUCs for at least 12 months were eligible for HBIG discontinuation. The patients were at low risk for HBV recurrence (only 4.5% had detectable HBV DNA at the time of LT, and 32% had HBV/hepatitis D virus co‐infection). All patients were followed up with HBV serum markers, HBV‐DNA, and evaluation of renal function, including glomerular filtration rate. Forty‐seven recipients discontinued HBIG and were maintained on newer NUCs. Median follow‐up post‐HBIG withdrawal was 24 months (range: 6–40 months). Twenty‐eight (60%) patients continued on lamivudine in combination with adefovir dipivoxil (n = 23, 82%) or tenofovir (n = 5, 18%); 10 (21%) and 9 (19%) of the 47 patients continued on tenofovir and entecavir monoprophylaxis, respectively. Although 3 (6.3%) patients developed detectable hepatitis B surface antigen, all of them had undetectable HBV DNA and no clinical manifestations of HBV recurrence. Renal function was similar between the different groups of patients. In conclusion, maintenance therapy with newer NUCs after discontinuation of HBIG prophylaxis was effective, but further studies in larger cohorts with longer follow‐up are needed.
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