Christopher Doerig

Management of viral hepatitis in patients with haematological malignancy and in patients undergoing haemopoietic stem cell transplantation: recommendations of the 5th European Conference on Infections in Leukaemia (ECIL-5)

Viral hepatitis affects millions of people worldwide, and host immunity is the key determinant of patient outcome. Viral hepatitis can be life threatening in patients with haematological malignancy, including haemopoietic stem cell transplant recipients, because of the virus itself, or through a need to decrease the dose of chemotherapy. A past or currently infected haemopoietic stem cell donor could also transmit viral hepatitis. The burden of viral hepatitis in patients with haematological malignancies and the weak evidence on which previous guidelines are based has prompted the European Conference on Infection in Leukaemia (ECIL-5) to convene a group of experts in the fields of viral hepatitis and of haematological malignancy to specifically address previously unconsidered issues and grade the available quality of evidence according to the Infectious Diseases Society of America grading system. The group recommends that all patients should be screened for hepatotropic viruses before haematological treatment and that patients or haemopoietic stem cell donors with markers of past or current viral hepatitis should be assessed by an expert. Screening, vaccination, and treatment rules are reported in this Review.

Alcohol intake increases the risk of HCC in hepatitis C virus-related compensated cirrhosis: A prospective study.

BACKGROUND & AIMS Whether alcohol intake increases the risk of complications in patients with HCV-related cirrhosis remains unclear. The aim of this study was to determine the impact of alcohol intake and viral eradication on the risk of hepatocellular carcinoma (HCC), decompensation of cirrhosis and death. METHODS Data on alcohol intake and viral eradication were prospectively collected in 192 patients with compensated HCV-related cirrhosis. RESULTS 74 patients consumed alcohol (median alcohol intake: 15g/day); 68 reached viral eradication. During a median follow-up of 58months, 33 patients developed HCC, 53 experienced at least one decompensation event, and 39 died. The 5-year cumulative incidence rate of HCC was 10.6% (95% CI: 4.6-16.6) in abstainers vs. 23.8% (95% CI: 13.5-34.1) in consumers (p=0.087), and 2.0% (95% CI: 0-5.8) vs. 21.7% (95% CI: 14.2-29.2) in patients with and without viral eradication (p=0.002), respectively. The lowest risk of HCC was observed for patients without alcohol intake and with viral eradication (0%) followed by patients with alcohol intake and viral eradication (6.2% [95% CI: 0-18.4]), patients without alcohol intake and no viral eradication (15.9% [95% CI: 7.1-24.7]), and patients with alcohol intake and no viral eradication (29.2% [95% CI: 16.5-41.9]) (p=0.009). In multivariate analysis, lack of viral eradication and alcohol consumption were associated with the risk of HCC (hazard ratio for alcohol consumption: 3.43, 95% CI: 1.49-7.92, p=0.004). Alcohol intake did not influence the risk of decompensation or death. CONCLUSIONS Light-to-moderate alcohol intake increases the risk of HCC in patients with HCV-related cirrhosis. Patient care should include measures to ensure abstinence. LAY SUMMARY Whether alcohol intake increases the risk of complications in patients with HCV-related cirrhosis remains unclear. In this prospective study, light-to-moderate alcohol intake was associated with the risk of hepatocellular carcinoma in multivariate analysis. No patients who did not use alcohol and who reached viral eradication developed hepatocellular carcinoma during follow-up. The risk of hepatocellular carcinoma increased with alcohol intake or in patients without viral eradication and was highest when alcohol intake was present in the absence of viral eradication. Patients with HCV-related cirrhosis should be strongly advised against any alcohol intake. Patient care should include measures to ensure abstinence.

Liver stiffness and platelet count for identifying patients with compensated liver disease at low risk of variceal bleeding

The 2015 Baveno VI guidelines recommend against performing upper gastrointestinal endoscopy in patients with compensated cirrhosis who have a liver stiffness <20 kPa and a platelet count >150 000/mm³ because of a low prevalence of varices at risk of bleeding in this population. The aim was to synthesize the available evidence on the usefulness of the combined use of liver stiffness and platelet count to identify patients without oesophageal varices.

Systematic review with meta-analysis: self-expanding metal stents in patients with cirrhosis and severe or refractory oesophageal variceal bleeding.

The prognosis of patients with cirrhosis and acute variceal bleeding is very poor when the standard‐of‐care fails to control bleeding. New treatment modalities are needed in these patients.

Hepatitis E virus infection as a direct cause of neuralgic amyotrophy

Introduction: We describe a patient who developed neuralgic amyotrophy (NA) related to hepatitis E virus (HEV) infection. Methods: The patient underwent neurological and electrodiagnostic examinations, high‐resolution analysis of serological changes, and HEV load profile, and was treated with intravenous immunoglobulin. Results: There was evidence of bilateral, asymmetric acute inflammatory cervical polyradiculopathy and possible brachial plexopathy. Positive serum anti‐HEV IgM was followed by seroconversion to anti‐HEV IgG positivity. A calculated anti‐HEV antibody index was compatible with intrathecal synthesis, and HEV genotype 3 RNA was found in serum and cerebrospinal fluid (CSF). Liver function tests returned to normal within 6 weeks. Conclusions: Bilateral involvement of cervical nerve roots and/or plexus, elevated liver function tests, and abnormal CSF are typical features of HEV‐associated NA. The pathogenesis involves possible immune‐mediated mechanisms. However, our findings support the hypothesis that HEV‐related NA is associated with direct infection. Muscle Nerve 54: 325–327, 2016

Hepatitis E Virus as a Cause of Acute Hepatitis Acquired in Switzerland

Autochthonous hepatitis E is increasingly recognized as zoonotic infection in western countries. Serological assays have varying sensitivity and specificity.

Effect of abstinence on the prognosis of patients with alcoholic liver disease: A word of caution

To the Editor: We read the article by Lackner and collaborators [1] with great interest. The main goal of this study was to assess factors associated with long-term prognosis in patients with biopsy-proven alcoholic liver disease (ALD). Although this study is of major clinical relevance, we believe it deserves several comments. The authors concluded that alcohol abstinence determines the long-term prognosis of patients with ALD. However, this statement is not supported by the study results because abstinence was not associated with improved survival in multivariate analysis. As this study included a limited number of patients, the lack of significance may be related to false negative results. In addition, the authors choose to perform separate analyses in patients with early/compensated and decompensated ALD, which further increased the risk of type II error, especially in the group of patients with compensated ALD which comprised of only 60 patients. Furthermore, the authors also chose to include all variables that reached a p value <0.20 in univariate analyses, in the multivariate model. As a result, a significant number of variables were taken into account in these analyses. Considering that only 13% of the patients with compensated ALD had died from liverrelated complications at 5 years, only a couple variables should have been included in the Cox regression analysis. Unfortunately, a power calculation was not available. Finally, non-significant results of the univariate analyses as well as the results of all multivariate analyses were not provided. Hence, the reader does not have access to many relevant data allowing for an accurate interpretation of the study results. In studies like this one, a large number of patients, followed for a long period of time are required to ensure that enough events occur. Thus, the statistical analyses performed in both compensated and decompensated patients should have been of interest to assess the impact of abstinence on patient prognosis in the whole study population. Another matter of debate concerns the statistical approach used in this study. While we acknowledge that liver-related causes accounted for most of the deaths in patients with cirrhosis related to ALD, not taking into account other causes of deaths would have require the use of appropriate models of disease progression. It is unclear why authors used a Cox regression analysis rather than competing risk analysis, as recommended [2]. Hence, even if the study of Lackner and collaborators brought some useful data, many drawbacks limit the interpretation of their

Characteristics of patients with hepatitis B virus and hepatitis C virus dual infection in a Western European country: Comparison with monoinfected patients

The epidemiology of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections is continuously evolving. Updated data on dual HBV and HCV infection are still needed. AIMS To assess the main characteristics of patients with HBV and HCV dual infection, to compare these with those of patients infected with either HBV or HCV and, among patients with dual infection, to assess fibrosis according to HCV replication. METHODS Data of 23 patients with dual infection were compared to data from 92 age and sex-matched HBV or HCV monoinfected patients. RESULTS Patients with dual infection were more often immigrants from Africa or Asia than HCV or HBV patients (52% vs. 20% and 22%, respectively, P=0.01). Intravenous drug use was the route of transmission in 22% of patients with dual infection, which was less frequent than in HCV patients (41%) but more frequent than in HBV patients (0%). Extensive fibrosis or cirrhosis was as frequent among dual-infected patients as among those with HCV or chronic hepatitis B infection (19% vs. 29% vs. 14%, respectively, P=0.4), even when fibrosis stage was reported considering the duration of infection. In dual-infected patients, the prevalence of extensive fibrosis or cirrhosis was similar in patients with and without detectable HCV RNA (18% vs. 20%). CONCLUSIONS Patients with HBV and HCV dual infection were more often immigrants from Africa or Asia and had similar fibrosis stages than HCV or HBV monoinfected patients. In patients with dual infection, extensive fibrosis or cirrhosis was not associated with HCV replication.

SEMS should be considered in patients with cirrhosis and uncontrolled variceal bleeding

We read the article by Escorsell et al. with great interest. This is the first randomized, controlled trial comparing self-expanding metal stent (SEMS) and balloon tamponade in acute refractory variceal bleeding in patients with cirrhosis. Although this study showed that SEMSs have greater efficacy in the control of bleeding and present less serious adverse events than does balloon tamponade, it failed to demonstrate a survival benefit. Even if randomized, controlled trials are considered the best way to assess the impact of an intervention, this is probably not the case when SEMSs are used to control acute refractory variceal bleeding for the following reasons. First, blinding the therapeutic intervention was not possible. Second, the investigators used patients treated with balloon tamponade as controls despite high rates of serious adverse events and rebleeding after balloon deflation. Thus, patients treated with balloon tamponade were not perfect controls. Third, patients enrolled in this study likely differed from the average patient seen in daily practice. This statement is supported by the 11 exclusion criteria mentioned in the study design and by the low number of patients included during a 3-year period, despite the many centers participating in the study. This is a clear limitation of this study that reduces the robustness of the conclusions. In the specific setting of acute refractory variceal bleeding, the results from observational studies may seem more relevant to clinical practice. In line with this comment, a recent meta-analysis (which already included Escorsell’s results) assessed the usefulness of SEMS in patients with cirrhosis and severe or refractory variceal bleeding. This metaanalysis showed that failure to control bleeding occurred in 18% of cases. Fewer than 40% of patients treated with SEMS died after 30 days and only 12% died from recurrent bleeding. Even if these results are not a proof that SEMS reduce mortality, this percentage compares favorably to the mortality rates reported in previous studies. Furthermore, a significant percentage of patients had access to transjugular intrahepatic portosystemic shunt (26%) or to liver transplantation (10%), which underlines that SEMS can also serve as a bridge to a more definitive treatment. Overall, we believe that SEMS should be considered in patients with cirrhosis and uncontrolled variceal bleeding. How early SEMS should be placed during the course of acute variceal bleeding to achieve better control of bleeding and prevention of rebleeding before the development of more-severe liver dysfunction remains to be assessed.