Impact of controlled attenuation parameter on detecting fibrosis using liver stiffness measurement.

BACKGROUND: Liver fibrosis is often accompanied by steatosis, particularly in patients with non-alcoholic fatty liver disease (NAFLD), and its non-invasive characterisation is of utmost importance. Vibration-controlled transient elastography is the non-invasive method of choice; however, recent research suggests that steatosis may influence its diagnostic performance. Controlled Attenuation Parameter (CAP) added to transient elastography enables simultaneous assessment of steatosis and fibrosis. AIM: To determine how to use CAP in interpreting liver stiffness measurements. METHODS: This is a secondary analysis of data from an individual patient data meta-analysis on CAP. The main exclusion criteria for the current analysis were unknown aetiology, unreliable elastography measurement and data already used for the same research question. Aetiology-specific liver stiffness measurement cut-offs were determined and used to estimate positive and negative predictive values (PPV/NPV) with logistic regression as functions of CAP. RESULTS: Two thousand and fifty eight patients fulfilled the inclusion criteria (37% women, 18% NAFLD/NASH, 42% HBV, 40% HCV, 51% significant fibrosis ≥ F2). Youden optimised cut-offs were only sufficient for ruling out cirrhosis (NPV of 98%). With sensitivity and specificity-optimised cut-offs, NPV for ruling out significant fibrosis was moderate (70%) and could be improved slightly through consideration of CAP. PPV for significant fibrosis and cirrhosis were 68% and 55% respectively, despite specificity-optimised cut-offs for cirrhosis. CONCLUSIONS: Liver stiffness measurement values below aetiology-specific cut-offs are very useful for ruling out cirrhosis, and to a lesser extent for ruling out significant fibrosis. In the case of the latter, Controlled Attenuation Parameter can improve interpretation slightly. Even if cut-offs are very high, liver stiffness measurements are not very reliable for ruling in fibrosis or cirrhosis.

Value of liver elastography and abdominal ultrasound for detection of complications of allogeneic hemopoietic SCT.

Hepatic complications contribute to morbidity and mortality after allogeneic hemopoietic SCT. Liver Doppler ultrasound and elastography represent promising methods for pretransplant risk assessment and early detection of complications. Ultrasound (liver and spleen size, liver perfusion) and elastography (transient elastography (TE); right liver lobe acoustic radiation force impulse imaging (r-ARFI); left liver lobe ARFI (l-ARFI)) were prospectively evaluated in patients with indications for allo-SCT. Measurements were performed before and repeatedly after SCT. Results were compared with the incidence of life-threatening complications and death during the first 150 days after SCT. Of 59 included patients, 16 suffered from major complications and 9 of them died within the follow-up period. At baseline, liver and spleen size, liver perfusion, TE and r-ARFI did not differ significantly between patients with and without severe complications. In contrast, l-ARFI was significantly elevated in patients who later developed severe complications (1.58±0.30 m/s vs 1.37±0.27 m/s, P=0.030). After SCT, l-ARFI values remained elevated and TE showed increasing liver stiffness in patients with complications. The value of conventional liver ultrasound for prediction of severe SCT complications is limited. Increased values for TE and l-ARFI are associated with severe SCT complications and demand further evaluation.

Assessment of spleen stiffness using acoustic radiation force impulse imaging (ARFI): definition of examination standards and impact of breathing maneuvers.

PURPOSE: Spleen elastography is a promising method for the characterization of portal hypertension in cirrhotic individuals. However, standardized examination procedures for spleen stiffness measurement have not been defined yet. We analyzed the distribution characteristics of spleen shear-wave velocity (ARFI) and assessed the influence of the respiratory position on spleen stiffness measured by ARFI. MATERIALS AND METHODS: 25 healthy probands and 25 patients with Child A liver cirrhosis were prospectively characterized with conventional ultrasound, transient elastography, liver ARFI, and underwent spleen ARFI in two respiratory positions: breath hold after expiration (exp) and deep inspiration (insp). For each position 20 single measurements were performed. The distribution of spleen ARFI values was analyzed for normality and the appropriate number of measurements for spleen stiffness estimation was investigated. RESULTS: Spleen ARFI results were normally distributed in > 95 % of cases. Performing 20 instead of 10 single measurements resulted in < 5 % deviation from the mean value after 20 measurements in the majority of cases. Cirrhotic patients had a higher spleen stiffness compared to healthy probands (exp: 3.25 ±â€Š0.58 vs. 2.46 ±â€Š0.35 m/s; p < 0.001). Deep inspiration caused an overall increase in spleen stiffness in both groups: probands 2.46 ± 0.35 m/s (exp) vs. 2.66 ±â€Š0.36 m/s (insp), p = 0.01; cirrhotics 3.25 ±â€Š0.58 m/s (exp) vs. 3.46 ±â€Š0.38 m/s (insp), p = 0.03. However, cases with high spleen stiffness values (exp) show decreasing ARFI values in deep inspiration. CONCLUSION: ARFI values of the spleen are normally distributed and the mean of 10 valid measurements can be used as a representative value. Deep inspiration significantly modulates spleen stiffness. Therefore, the respiratory position needs careful standardization.

Acoustic radiation force impulse (ARFI) elastography in acute liver failure: necrosis mimics cirrhosis.

Acoustic radiation force Impulse (ARFI) technology correlates shear-wave velocity with fibrosis. It can differentiate between advanced fibrosis and normal tissue in chronic liver disease. However, specificity is impaired by cholestasis, inflammation or oedema in acute hepatitis. In patients with acute liver failure (ALF) necessitating liver transplantation ARFI has not been evaluated yet. We investigated 3 patients with ALF and compared their ARFI results to those of healthy controls (n = 33) and cases with liver cirrhosis (n = 21). In the 3 ALF patients shear-wave velocities were 3.0, 2.5, and 2.7 m/s, respectively. These results were significantly increased compared to those of healthy controls (median: 1.13 m/s; p < 0.001) and similar to those of cirrhotic individuals (median: 2.93 m/s). Two individuals underwent liver transplantation. Explants showed massive necrosis, but no signs of chronic liver disease. Patient 3 recovered spontaneously and showed decreasing ARFI results during follow-up. In conclusion, hepatic necrosis can mimic liver cirrhosis at ARFI evaluation in ALF patients and this impairs the specificity of ARFI.

Prevention of lamivudine-resistant hepatitis B recurrence after liver transplantation with entecavir plus tenofovir combination therapy and perioperative hepatitis B immunoglobulin only.

Combination therapy with antivirals plus hepatitis B immunoglobulin (HBIg) has become the standard treatment for prevention of post-liver transplant hepatitis B virus (HBV) recurrence. However, HBIg therapy is inconvenient and expensive. Alternative therapeutic approaches with modern nucleos(t)ide analogues are limited so far. The present case report describes prevention of HBV recurrence with entecavir and tenofovir. A 48-year-old male patient with hepatitis B-induced decompensated liver cirrhosis initially improved on lamivudine (LAM) until LAM resistance (rtL180M and rtM204V) emerged followed by renewed decompensation. Therefore, tenofovir was added to LAM leading to undetectable HBV DNA (<200 copies/mL). Six months later, low-level viremia (479 copies/mL) was detected. Treatment was escalated to tenofovir plus entecavir. HBV DNA became negative again, and the patient underwent orthotopic liver transplantation. HBIg was administered during transplantation (10,000 IU) and on the second and third postoperative days (total dose 26,000 IU). Subsequently, the anti-hepatitis B surface (HBs) titer rose to 1477 IU/L at day 4 post transplantation. Although HBIg should have been continued, the patient remained on combination therapy with tenofovir plus entecavir only. The anti-HBs titer decreased and became negative 4 months later. However, under continued combination therapy with oral antivirals, HBV DNA and hepatitis B surface antigen remained negative during the entire follow-up of 21 months after liver transplantation. Combination therapy with entecavir plus tenofovir may prevent post-liver transplant hepatitis B recurrence even without HBIg maintenance therapy. This case illustrates that combination oral antiviral therapy might substitute for HBIg as indefinite prophylactic regimen due to profound antiviral efficacy and low risk of viral resistance. Efficacy and safety must be further investigated in randomized controlled trials.

Resistance management in chronic hepatitis B complicated by renal failure.

Therapy of chronic hepatitis B has improved by the invention of the potent nucleos(t)ide analogues entecavir, telbivudine and tenofovir disoproxil. Due to increasing prevalence of lamivudine resistance the appropriate first line therapy may prevent emergence of any new resistance and avoid combination therapy. The present case describes a complex history of chronic hepatitis B in the setting of renal failure after two renal transplants illustrating why lamivudine should not be used as first line treatment option any more. Instead, entecavir offers high antiviral potency, low risk for resistance and possible individual dose titration by an oral solution.