H.L.A. Janssen

Lamivudine treatment during pregnancy to prevent perinatal transmission of hepatitis B virus infection

Summary.  Vertical transmission of hepatitis B virus (HBV) can occur occasionally despite vaccination of the child. This vaccination breakthrough has been associated with high maternal viraemia. We treated eight highly viraemic (HBV‐DNA ≥ 1.2 × 109 geq/mL) mothers with 150 mg of lamivudine daily during the last month of pregnancy. HBV‐DNA, hepatitis B surface antigen (HBsAg), anti‐HBs and anti‐HBc of their offspring were measured at birth and at 3, 6 and 12 months, respectively. Twenty‐four children, born to untreated HBsAg‐positive mothers with HBV‐DNA levels ≥1.2 × 109 geq/mL served as historical controls. All children received passive‐active immunization at birth and were followed‐up for 12 months. In the lamivudine group one of the eight children (12.5%) was still HBsAg and HBV‐DNA positive at the age of 12 months. All other children seroconverted to anti‐HBs and maintained seroprotection. In three children, HBV‐DNA was temporarily detected by polymerase chain reaction. In the untreated historical control group, perinatal transmission occurred in seven of 25 children (28%). In highly viraemic HBsAg‐positive mothers, reduction of viraemia by lamivudine therapy in the last month of pregnancy may be an effective and safe measure to reduce the risk of child vaccination breakthrough. This approach should be evaluated in a large controlled trial.

The state of hepatitis B and C in Europe: report from the hepatitis B and C summit conference*.

Summary.  Worldwide, the hepatitis B virus (HBV) and the hepatitis C virus (HCV) cause, respectively, 600 000 and 350 000 deaths each year. Viral hepatitis is the leading cause of cirrhosis and liver cancer, which in turn ranks as the third cause of cancer death worldwide. Within the WHO European region, approximately 14 million people are chronically infected with HBV, and nine million people are chronically infected with HCV. Lack of reliable epidemiological data on HBV and HCV is one of the biggest hurdles to advancing policy. Risk groups such as migrants and injecting drug users (IDU) tend to be under‐represented in existing prevalence studies; thus, targeted surveillance is urgently needed to correctly estimate the burden of HBV and HCV. The most effective means of prevention against HBV is vaccination, and most European Union (EU) countries have universal vaccination programmes. For both HBV and HCV, screening of individuals who present a high risk of contracting the virus is critical given the asymptomatic, and thereby silent, nature of disease. Screening of migrants and IDUs has been shown to be effective and potentially cost‐effective. There have been significant advances in the treatment of HCV and HBV in recent years, but health care professionals remain poorly aware of treatment options. Greater professional training is needed on the management of hepatitis including the treatment of liver cancer to encourage adherence to guidelines and offer patients the best possible outcomes. Viral hepatitis knows no borders. EU Member States, guided by the EU, need to work in a concerted manner to implement lasting, effective policies and programmes and make tackling viral hepatitis a public health priority.

Exacerbation of chronic hepatitis B infection after delivery

Summary.  During pregnancy several alterations in the immune status allow mothers to tolerate the genetically different foetal tissues. We investigated the evolution of liver disease during and after pregnancy in chronic hepatitis B patients. Between 1998 and 2006 there were 38 pregnancies in 31 chronic hepatitis B ‘s’ antigen‐positive women at our liver unit. Twenty‐four subjects (63%) were hepatitis B ‘e’ antigen (HBeAg)‐positive, 14 (37%) HBeAg‐negative. In 13 pregnancies (34%), lamivudine therapy was started during the last trimester of pregnancy to lower hepatitis B virus (HBV) DNA levels to reduce the risk of vertical transmission. A significant increase in liver disease activity after pregnancy, defined as a three times increase in alanine aminotransferase (ALT) within 6 months after delivery, occurred in 17 of 38 patients (45%). In those treated with lamivudine during the last trimester of pregnancy, this occurred in even 8/13 patients (62%). Prediction during pregnancy of these exacerbations was not possible using HBV DNA, ALT level, HBeAg status or any other characteristic. The median maximal ALT of these exacerbations was 4.0 × ULN and none led to decompensated liver disease. In conclusion, a significant increase in liver inflammation occurs often after pregnancy. This may be due to a reactivation of the immune system after delivery. Based on our data we recommend monitoring closely and if necessary treating women with chronic HBV shortly after delivery.

Sensitive detection of hepatocellular injury in chronic hepatitis C patients with circulating hepatocyte-derived microRNA-122

As chronic hepatitis C patients with progressive disease can present themselves with normal ALT levels, more sensitive biomarkers are needed. MicroRNAs are newly discovered small noncoding RNAs that are stable and detectable in the circulation. We aimed to investigate the association between hepatocyte‐derived microRNAs in serum and liver injury in patients with chronic hepatitis C. The hepatocyte‐derived miR‐122 and miR‐192 were analysed in sera of 102 chronic HCV‐infected patients and 24 healthy controls. Serum levels of miR‐122 and miR‐192 correlated strongly with ALT (R = 0.67 and R = 0.65, respectively, P < 0.001 for both). Median levels of miR‐122 and miR‐192 in HCV‐infected patients were 23 times and 8 times higher as in healthy controls (P < 0.001 for both). Even within the HCV‐infected patients with a normal ALT (n = 38), the levels of miR‐122 and miR‐192 were 12 times and 4 times higher compared with healthy controls (P < 0.001 for both). Multivariate logistic regression analyses showed that only miR‐122 was a significant predictor of the presence of chronic HCV infection (P = 0.026). Importantly, miR‐122 was also superior in discriminating chronic HCV‐infected patients with a normal ALT from healthy controls compared with the ALT level (AUC = 0.97 vs AUC = 0.78, P = 0.007). In conclusion, our study confirmed that liver injury is associated with high levels of hepatocyte‐derived microRNAs in circulation and demonstrated that in particular miR‐122 is a sensitive marker to distinguish chronic hepatitis C patients from healthy controls. More sensitive blood markers would benefit especially those patients with minor levels of hepatocellular injury, who are not identified by current screening with ALT testing.

The safety of pegylated interferon alpha-2b in the treatment of chronic hepatitis B: predictive factors for dose reduction and treatment discontinuation.

Background : Treatment with interferon‐alpha has been shown to be effective in one‐third of hepatitis B e antigen‐positive chronic hepatitis B patients, but is clinically associated with relevant adverse events.

Reduced risk of relapse after long-term nucleos(t)ide analogue consolidation therapy for chronic hepatitis B

Before stopping nucleos(t)ide analogue (NA) treatment in chronic hepatitis B (CHB), 6–12 months of consolidation therapy is recommended.

Viral dynamics during tenofovir therapy in patients infected with lamivudine-resistant hepatitis B virus mutants

Summary.  Tenofovir, an antihuman immunodeficiency virus (HIV) drug, has activity against lamivudine‐resistant hepatitis B virus (HBV) mutants. To describe the efficacy of tenofovir in patients with lamivudine‐resistant hepatitis B we applied two investigative approaches based on mathematical models of viral dynamics: the individual nonlinear fitting and the mixed‐effect group fitting approaches.

Miravirsen dosing in chronic hepatitis C patients results in decreased microRNA-122 levels without affecting other microRNAs in plasma

MicroRNA‐122 (miR‐122) is an important host factor for hepatitis C virus replication. Administration of miravirsen, an anti‐miR‐122 oligonucleotide, resulted in a dose dependent and prolonged decrease in HCV RNA levels in chronic hepatitis C patients.

Review article: the management of non-cirrhotic non-malignant portal vein thrombosis and concurrent portal hypertension in adults

Background  Extrahepatic portal vein thrombosis is an important cause of non‐cirrhotic portal hypertension.

Randomised clinical trial: escitalopram for the prevention of psychiatric adverse events during treatment with peginterferon-alfa-2a and ribavirin for chronic hepatitis C

Aliment Pharmacol Ther 2011; 34: 1306–1317