Saccadic latency in hepatic encephalopathy: a pilot study

Hepatic encephalopathy is a common complication of cirrhosis. The degree of neuro-psychiatric impairment is highly variable and its clinical staging subjective. We investigated whether eye movement response times—saccadic latencies—could serve as an indicator of encephalopathy. We studied the association between saccadic latency, liver function and paper- and pencil tests in 70 patients with cirrhosis and 31 patients after liver transplantation. The tests included the porto-systemic encephalopathy (PSE-) test, critical flicker frequency, MELD score and ammonia concentration. A normal range for saccades was established in 31 control subjects. Clinical and biochemical parameters of liver, blood, and kidney function were also determined. Median saccadic latencies were significantly longer in patients with liver cirrhosis when compared to patients after liver transplantation (244 ms vs. 278 ms p < 0.001). Both patient groups had prolonged saccadic latency when compared to an age matched control group (175 ms). The reciprocal of median saccadic latency (μ) correlated with PSE tests, MELD score and critical flicker frequency. A significant correlation between the saccadic latency parameter early slope (σE) that represents the prevalence of early saccades and partial pressure of ammonia was also noted. Psychometric test performance, but not saccadic latency, correlated with blood urea and sodium concentrations. Saccadic latency represents an objective and quantitative parameter of hepatic encephalopathy. Unlike psychometric test performance, these ocular responses were unaffected by renal function and can be obtained clinically within a matter of minutes by non-trained personnel

Muscle Cramps: A ‘Complication‘ of Cirrhosis

Muscle cramps are a common complaint in clinical practice. They are associated with various metabolic, endocrine, neurological and electrolyte abnormalities. A variety of hypotheses have been generated to explain the cause of muscle cramping, yet none has been able to support a consistent pathophysiological mechanism. Muscle cramps are painful, involuntary contractions of skeletal muscle. They occur frequently in individuals with cirrhosis, regardless of the etiology, and are thought to be a symptom of cirrhotic-stage liver disease. The pathophysiology of these cramps remains elusive; hence, a specific therapy has not been identified. Many therapeutic approaches have been offered, yet their efficacy, safety and mechanism of action remain poorly defined. This review defines muscle cramps and illuminates its prevalence in the cirrhotic individual. Current theories relating to the pathogenesis of muscle cramps are reviewed, and an overview of the various pharmacological agents that have had therapeutic success for this distressing and frustrating symptom is provided

Transjugular intrahepatic portosystemic shunt in liver transplant recipients

AIM: To evaluate the efficacy of transjugular intrahepatic portosystemic shunts (TIPSs) after liver transplantation (LT). METHODS: Between November 1996 and December 2005, 10 patients with severe recurrent hepatitis C virus infection (n = 4), ductopenic rejection (n = 5) or portal vein thrombosis (n = 1) were included in this analysis. Eleven TIPSs (one patient underwent two TIPS procedures) were placed for management of therapy-refractory ascites (n = 7), hydrothorax (n = 2) or bleeding from colonic varices (n = 1). The median time interval between LT and TIPS placement was 15 (4-158) mo. RESULTS: TIPS placement was successful in all patients. The mean portosystemic pressure gradient was reduced from 12.5 to 8.7 mmHg. Complete and partial remission could be achieved in 43% and 29% of patients with ascites. Both patients with hydrothorax did not respond to TIPS. No recurrent bleeding was seen in the patient with colonic varices. Nine of 10 patients died during the study period. Only one of two patients, who underwent retransplantation after the TIPS procedure, survived. The median survival period after TIPS placement was 3.3 (range 0.4-20) mo. The majority of patients died from sepsis with multiorgan failure. CONCLUSION: Indications for TIPS and technical performance in LT patients correspond to those in non-transplanted patients. At least partial control of therapy-refractory ascites and variceal bleeding could be achieved in most patients. Nevertheless, survival rates were disappointing, most probably because of the advanced stages of liver disease at the time of TIPS placement and the high risk of sepsis as a consequence of immunosuppression

Response to locoregional treatment and alpha-fetoprotein trend in liver transplant candidates for HCC: Dwarfs standing on the shoulders of giants.

We read with great interest the correspondence on the paper published by Otto et al., on the response to repeated trans-arterial chemo-embolization (TACE) as a discriminating tool for selection of liver transplant (LT) candidates with hepatocellular carcinoma (HCC). Paul et al. evidenced the relative small sample size and the lack of information on the role of TACE on waiting-list dropout. Our aim is to support the results obtained by Otto et al. with the strength and the statistical power of a new recently published European study

Alpha-fetoprotein and modified response evaluation criteria in Solid Tumors progression after locoregional therapy as predictors of hepatocellular cancer recurrence and death after transplantation.

Locoregional therapy (LRT) is being increasingly used for the management of hepatocellular cancer (HCC) in patients listed for liver transplantation (LT). Although several selection criteria have been developed, stratifications of survival according to the pathology of explanted livers and pre-LT LRT are lacking. Radiological progression according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) and alpha-fetoprotein (AFP) behavior was reviewed for 306 patients within the Milan criteria (MC-IN) and 116 patients outside the Milan criteria (MC-OUT) who underwent LRT and LT between January 1999 and March 2010. A prospectively collected database originating from 6 collaborating European centers was used for the study. Sixty-one patients (14.5%) developed HCC recurrence. For both MC-IN and MC-OUT patients, an AFP slope > 15 ng/mL/month and mRECIST progression were unique independent risk factors for HCC recurrence and patient death. When the radiological Milan criteria (MC) status was combined with radiological and biological progression, MC-IN and MC-OUT patients without risk factors had similarly excellent 5-year tumor-free and patient survival rates. MC-IN patients with at least 1 risk factor had worse outcomes, and MC-OUT patients with at least 1 risk factor had the poorest survival (P < 0.001). In conclusion, both radiological and biological modifications permit documentation of the response to LRT in patients waiting for LT. According to these 2 parameters, tumor progression significantly increases the risk of recurrence and patient death not only for MC-OUT patients but also for MC-IN patients. The monitoring of both parameters in combination with the initial radiological MC status is an essential element for further refining the selection criteria for potential liver recipients with HCC. Liver Transpl 19:1108-1118, 2013. © 2013 AASLD

GastroHep / Management of patients with chronic hepatitis C failing repeated courses of interferonfree direct acting antiviral combination therapy

Background Only few chronic hepatitis C patients treated with interferon (IFN)free direct acting antiviral (DAA) combinations fail to clear the virus. Most patients can be cured by retreatment with another DAA combination; however, some still fail to eradicate the virus. So far, little is known about how to best retreat these patients. In this study we summarise our real world experience of reretreatments. Methods One hundred and two patients who completed a DAAretreatment after virological failure to an IFNfree DAA therapy and reached at least followup 12 were included in this study.Twentyone (20.6%) of them relapsed again after retreatment (mean age 50.0 10.6, 18 male, three female, GT1a:8, GT1b:4, GT1c:1, GT3a:7; GT4:1; cirrhosis:15; resistance associated substitutions [RAS]: 17/19; relapse after:SOF/SMV:2; 3D RBV:4; SOF/DCV RBV:4; SOF/LDV RBV:6; SOF/VEL:3; SOF/VEL/VOX:1; EBV/GZV:1).Treatment duration and addition of RBV were at the discretion of the treating physician. These 21 patients were studied in detail. Results Seventeen of the 21 patients finished a third DAA therapy: 13 achieved SVR12, three relapsed again (cirrhosis:2; SOF/VEL/RBV:GT3a; SOF/LDV/RBV:GT1a; EBV/GZV/SOF/RBV:GT1b), one was lost to followup. One (GT1a, cirrhosis) achieved SVR12 after the third retherapy with 24 weeks of 3D/SOF/RBV, and one (GT3a, cirrhosis) achieved SVR4 after 24 weeks of glecaprevir/pibrentasvir, but died shortly thereafter. Overall, 95 (93.1%) of 102 patients achieved SVR12 after one or more retreatments. Sex, cirrhosis, genotype, RAS or baseline viral load were not associated with retreatment failure. Conclusion Most patients with failure to a DAA therapy achieved SVR after retreatment with a different regimen; however, 13.7% of patients required multiple retreatments.(VLID)511568