R.A. de Man

GLYCYRRHIZIN AS A POTENTIAL TREATMENT FOR CHRONIC HEPATITIS C.

Chronic hepatitis C is a slowly progressive liver disease that may evolve into cirrhosis with its potential complications of liver failure or hepatocellular carcinoma. Current therapy with α‐interferon is directed at viral clearance, but sustained response is only achieved in 20–40% of patients without cirrhosis, and less than 20% in patients with cirrhosis who have the greatest need for therapy. Treatment for those who do not respond to anti‐viral therapy is highly desirable.

ACYCLOVIR ENHANCES THE ANTIVIRAL EFFECT OF INTERFERON IN CHRONIC HEPATITIS B

Patients with chronic hepatitis B with active viral replication had a significantly greater fall in DNA polymerase and hepatitis-Be antigen when treated with interferon and acyclovir together than when treated with either interferon or acyclovir alone. Apart from fatigue and thrombophlebitis, tolerance of the combination therapy was excellent. The combination therapy appears the most promising for conversion of a state of active viral replication into virus latency.

The long-term outcome of patients with polycystic liver disease treated with lanreotide

Aliment Pharmacol Ther 2012; 35: 266–274

Somatostatin analogues reduce liver volume in polycystic liver disease

Polycystic livers occur in the setting of two inherited conditions: (1) autosomal dominant polycystic kidney disease (ADPKD), also characterised by progressive development of renal cysts resulting in loss of renal function, and (2) polycystic liver disease (PCLD), with a polycystic liver as the sole manifestation. Symptoms, such as abdominal distension, result from hepatomegaly. Ascites is a rare complication and might be due to portal hypertension or caused by a ruptured cyst.nnTreatment strategies for polycystic livers are aimed at reducing liver volume. So far, only surgical options are available, but these are associated by considerable morbidity and mortality.1 Alternatively, ascites in the setting of polycystic livers might respond to endovascular stent placement in the narrowed caval vein,2 but medical options are conspicuously lacking so far. We wish to report two cases with severe polycystic liver …

Review article: management of ascites and associated complications in patients with cirrhosis

Backgroundu2002 Ascites is the most common complication of cirrhosis, associated with an expected survival below 50% after 5u2003years. Prognosis is particularly poor for patients with refractory ascites and for those developing complications, including spontaneous bacterial peritonitis (SBP) and hepatorenal syndrome (HRS).

Quantitative hepatitis B virus DNA assessment by the limiting‐dilution polymerase chain reaction in chronic hepatitis B patients: evidence of continuing viral suppression with longer duration and higher dose of lamivudine therapy

Lamivudine, a novel cytosine analogue, exhibits potent antiviral activity against hepatitis B virus (HBV) in vitro and in vivo. The standard HBV DNA hybridization assay used in phase II clinical studies has a low sensitivity, the detection limit of HBV DNA levels being ≈ 107 genome equivalents per ml (geq ml–1). In this work we used a semiquantitative polymerase chain reaction (PCR) assay (detection limit ≈ 103 geq ml–1) to determine HBV DNA levels during a 24‐week study of lamivudine in 51 stable chronic hepatitis B patients who were positive for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg). Patients were randomly allocated to receive oral doses of 25, 100 or 300 mg lamivudine once daily. At week 24 the median serum concentration of HBV DNA had fallen from 108 to 104 geq ml–1, a 4‐log median reduction. A trend towards more profound suppression of viral replication with an increased dose of lamivudine was observed. After 12 weeks of therapy, 12% of patients had an HBV DNA level that was undetectable in the PCR assay; this increased to 26% after 24 weeks, while in an additional 20% of patients, HBV DNA decreased to the level of detection of the PCR assay. We conclude that a 24‐week course of lamivudine decreases serum HBV DNA to the level of PCR detection in 46% of patients. Such additional viral suppressive activity with higher doses and more protracted lamivudine may be of clinical utility prior to liver transplantation. Further studies are needed to define the degree of virus suppression required in clinical practice, and methods are required to increase the efficacy of virus suppression.

Gastrointestinal: Rare cause of hematemesis initially presenting as a bleeding gastric Dieulafoy's lesion

A 60-year-old male, with a medical history of hypertension and idiopathic bilateral dissection of the carotid arteries, presented to the emergency department with transient loss of consciousness. A few days earlier, he had used a nonsteroid anti-inflammatory drug (NSAID) because of headache. Physical examination did not show focal neurological deficits. EMV score was maximal, but he appeared pale and had tachycardia of 105/min. Digital rectal examination did not show melena. Laboratory tests were unremarkable except for normocytic anemia (hemoglobin, 42 g/L [normal, 120–160]; mean corpuscular volume 85 fL [normal, 80–100]). Additional neurological evaluation including cerebral computed tomography (CT) did not reveal abnormalities. The patient was admitted for observation. Twelve hours later, he developedmassive hematemesis with hemodynamic instability. After resuscitation, emergent upper gastrointestinal endoscopy was performed showing fresh blood in the stomach, originating from a small superficial vascular lesion in the gastric fundus, which was classified as a Dieulafoy’s lesion (Fig. 1a). The lesion was treated with band ligation. Two days later, hematemesis recurred, and a second endoscopy was performed. At the site of the previously treated gastric lesion, an adherent clot on elevated edematous mucosa was seen (Fig. 1b), with prominent surrounding gastric folds suggesting varices (Fig. 1c). The lesion was treated with injection of histoacryl glue, and hemoclips were placed on surrounding afferent gastric folds. Given the aspect of congestive variceal-like gastric folds, an estimated high risk of rebleeding, and the previous medical history of idiopathic carotid dissection, CT angiography was performed in order to characterize potential underlying vascular abnormalities (Fig. 2). CT angiography demonstrated a thrombosed splenic arterywith calcifications, without any filling with contrast in the arterial phase (Fig. 2a, arrow). In addition, several gastric collaterals were noted, originating from the left gastric artery and penetrating the wall of the stomach (Fig. 2b, arrowhead). Ultrasound demonstrated a patent splenic vein. We hypothesized that this patient developed gastric bleeding secondary to NSAID-induced erosion of large submucosal arterial collateral vessels. These collateral vessels developed as a consequence of proximal splenic artery occlusion. In contrast to gastric fundal variceal bleeding due to left-sided portal hypertension, bleeding from prominent submucosal arteries providing collateral blood supply to the spleen is exceptional, with only few reported comparable cases. Additional investigation by an internist specialized in vascular medicine, clinical geneticist, and hematologist did not reveal evidence for etiological factors such as hyperlipidemia, Ehler–Danlos type IV, or thromboembolic disease. Given the high risk of rebleeding, the following treatment options were discussed with the patient: (i) selective intravascular catheterization of the left gastric artery and coiling of collaterals, (ii) splenectomy and partial devascularization of the greater curvature of the stomach, and (iii) conservativemanagement with a proton pump inhibitor and discontinuation of NSAIDs. Our patient strongly preferred the last-mentioned option. He was discharged 6 days after admission. During a 1-year follow-up period, he remained free of rebleeding and was completely asymptomatic. In summary, gastric submucosal arterial collaterals due to occlusion of the splenic artery is a rare cause of massive upper gastrointestinal bleeding. Endoscopic findings may mimic Dieulafoy’s lesion or varices due to left-side portal hypertension.CT angiography is essential for the correct diagnosis and subsequent management plan.

Mycophenolate mofetil for patients with autoimmune hepatitis and overlap syndromes: authors’ reply: Letters to the Editors

SIRS, Garcia-Buey and Moreno-Otero nicely summarise the literature on mycophenolate mofetil (MM) in autoimmune hepatitis (AIH) and overlap syndromes. The Dutch Autoimmune Hepatitis Group (DAHG) shows that second-line MM induces remission in 67% of patients with AIH and intolerance to azathioprine (AZA). In AIH and AZA nonresponse, remission was achieved with MMF in only 13%, and all deaths, liver transplantations and decompensations of cirrhosis occurred in this group. Therefore, in AIH and AZA-nonresponse other options, including liver transplantation, seem more appropriate. This is consistent with the findings of Hennes et al. nFor all patients with overlap syndromes, MM appears a valuable treatment option. In the DAHG cohort, MM induced remission in 63% and 57%, and nresponse in 15% and 14% after AZA intolerance and nonresponse respectively. Recently, adding MM and budesonide appeared beneficial in primary biliary cirrhosis (PBC) with insufficient response to ursodeoxycholic acid. Further investigations of MM in PBC and overlap seem warranted. nAs first-line therapy for AIH, one randomised controlled study indicates that budesonide with AZA induces more remission with less side-effects than prednisolone with AZA. However, despite the one prospective cohort with MM as first-line therapy in AIH, and the limitations of earlier studies, most evidence for first-line therapy in AIH still is with AZA and prednisolone. We therefore still consider prednisolone with AZA the first-line treatment in AIH and overlap nsyndromes until further randomised studies prove otherwise. In case of steroid side-effects, in the absence of cirrhosis, budesonide could be considered, although a prospective maintenance study against prednisolone is still lacking. nAs second-line therapy in case of AZA-intolerance in AIH, or for all overlap nsyndrome patients, MM with prednisolone appears useful, but not for AIH with AZA nonresponse. In contrast to AZA, MM is contraindicated in pregnancy.

Mycophenolate mofetil for patients with autoimmune hepatitis and overlap syndromes

SIRS, Garcia-Buey and Moreno-Otero nicely summarise the literature on mycophenolate mofetil (MM) in autoimmune hepatitis (AIH) and overlap syndromes. The Dutch Autoimmune Hepatitis Group (DAHG) shows that second-line MM induces remission in 67% of patients with AIH and intolerance to azathioprine (AZA). In AIH and AZA nonresponse, remission was achieved with MMF in only 13%, and all deaths, liver transplantations and decompensations of cirrhosis occurred in this group. Therefore, in AIH and AZA-nonresponse other options, including liver transplantation, seem more appropriate. This is consistent with the findings of Hennes et al. nFor all patients with overlap syndromes, MM appears a valuable treatment option. In the DAHG cohort, MM induced remission in 63% and 57%, and nresponse in 15% and 14% after AZA intolerance and nonresponse respectively. Recently, adding MM and budesonide appeared beneficial in primary biliary cirrhosis (PBC) with insufficient response to ursodeoxycholic acid. Further investigations of MM in PBC and overlap seem warranted. nAs first-line therapy for AIH, one randomised controlled study indicates that budesonide with AZA induces more remission with less side-effects than prednisolone with AZA. However, despite the one prospective cohort with MM as first-line therapy in AIH, and the limitations of earlier studies, most evidence for first-line therapy in AIH still is with AZA and prednisolone. We therefore still consider prednisolone with AZA the first-line treatment in AIH and overlap nsyndromes until further randomised studies prove otherwise. In case of steroid side-effects, in the absence of cirrhosis, budesonide could be considered, although a prospective maintenance study against prednisolone is still lacking. nAs second-line therapy in case of AZA-intolerance in AIH, or for all overlap nsyndrome patients, MM with prednisolone appears useful, but not for AIH with AZA nonresponse. In contrast to AZA, MM is contraindicated in pregnancy.

235 HEPATOCELLULAR CARCINOMA AND UNDERLYING LIVER CIRRHOSIS; INFLUENCE ON TREATMENT OR A PROGNOSTIC VALUE?

Background: Despite its benign nature, hepatocellular adenomas (HA) have a potential for malignant degeneration or spontaneous rupture and bleeding. Therefore, surgical resection is the treatment of choice in selected patients. However, radio frequency ablation (RFA) could offer a viable alternative, and might prevent these patients from undergoing major hepatic surgery with associated morbidity and costs. Aim: To investigate the safety and efficacy of RFA for the treatment of HA. Methods: From 2000 to 2009, 168 patients diagnosed with HA in a tertiary hepato-biliary centre were included in a database. For patients undergoing RFA, clinicopathologic data with regard to diagnosis, treatment and outcome were collected. RFA was considered successful if no residual HA tissue was visualized on contrast enhanced CT or MRI 4–6 weeks post-RFA. Results: Of 61 patients undergoing treatment for HA, 17 patients (28%) underwent RFA. Mean age was 29 years. All patients were female with a history of hormonal contraceptive use. Nine patients (53%) had multiple HA, with a median number of 2 lesions (range 1–10) per patient. Median size of the largest HA at the time of RFA was 3.9 cm (range 1.5–6.7). 39 lesions were ablated in 25 sessions (open n=5, percutaneous n =20). Complete remission was acquired in eight patients after one (n =4) or two (n =4) RFAsessions. Another five patients (29%) had radiological evidence of residual HA tissue (≤15mm) bordering the thermal lesion, but due to low clinical importance no further treatment was administered. All of these lesions have remained stable or regressed during followup. Four patients are currently awaiting further therapy or followup. Post-operatively, one patient developed a liver abscess requiring re-intervention and one patient suffered from amajor but reversible complication related to concomitant hemi-hepatectomy. Median hospital stay was 7 days in the open group and 2 days in the percutaneous group. Conclusion: HA can be safely treated using both open and percutaneous RFA. However, often multiple sessions are required and signs of residual adenoma persist in some patients despite repetitive treatment. RFA might be especially beneficial for patients not amenable for surgery or those that would require major hepatic resection otherwise.