Proton pump inhibitors in cirrhosis:Tradition or evidence based practice?

Proton Pump Inhibitors (PPI) are very effective in inhibiting acid secretion and are extensively used in many acid related diseases. They are also often used in patients with cirrhosis sometimes in the absence of a specific acid related disease, with the aim of preventing peptic complications in patients with variceal or hypertensive gastropathic bleeding receiving multidrug treatment. Contradicting reports support their use in cirrhosis and evidence of their efficacy in this condition is poor. Moreover there are convincing papers suggesting that acid secretion is reduced in patients with liver cirrhosis. With regard to Helicobacter pylori (H pylori) infection, its prevalence in patients with cirrhosis is largely variable among different studies, and it seems that H pylori eradication does not prevent gastro-duodenal ulcer formation and bleeding. With regard to the prevention and treatment of oesophageal complications after banding or sclerotherapy of oesophageal varices, there is little evidence for a protective role of PPI. Moreover, due to liver metabolism of PPI, the dose of most available PPIs should be reduced in cirrhotics. In conclusion, the use of this class of drugs seems more habit related than evidence- based eventually leading to an increase in health costs.

ESWL for difficult bile duct stones:A 15-year single centre experience

AIM:To evaluate the efficacy of extracorporeal shock wave lithotripsy(ESWL)for the management of refractory bile duct cholelithiasis in a third level referral centre.METHODS:The clinical records of all patients treated with a second generation electromagnetic lithotripter (Lithostar Plus,SIEMENS)from October 1990 to April 2005 were evaluated.All patients were monitored during the procedure and antibiotics were administered in case of cholangitis.Theχ 2 test and logistic regression analysis were performed as appropriate.RESULTS:Two hundred and fourteen patients(102 males,112 females;mean age 74.8±0.84 years-single stone 97,multiple stones 117)underwent ESWL.The mean number of sessions and shock waves were 3.5 ±0.13 and 3477.06±66.17,respectively.The maximum stone size was 5 cm.Complete stone clearance was achieved in 192(89.7%)patients.Of the remain-ing patients 15 required surgery,2 a palliative stent and in 5 patients stone fragmentation led to effective bile drainage with clinical resolution despite incomplete clearance.Age,sex and stone characteristics were not related to treatment outcome.Major complications occurred in two patients(haemobilia and rectal bleeding) and minor complications in 25(3 vomiting,22 arrhythmias).No procedure-related deaths occurred.CONCLUSION:ESWL is a safe and effective technique for clearance of refractory bile duct stones.

Severe immune thrombocytopenia after peg-interferonalpha2a, ribavirin and telaprevir treatment completion: a case report and systematic review of literature

Mild to moderate autoimmune thrombocytopenia(AITP) is a common finding in patients receiving interferonbased antiviral treatment, due to bone marrow suppression. Here we report the case of a patient with chronic genotype 1b hepatitis C virus(HCV) infection treated with pegylated-interferon alpha-2a, ribavirin and telaprevir for 24 wk; the patient developed severe AITP three weeks after treatment withdrawal. We performed a systematic literature search in order to review all published cases of AITP related to HCV antiviral treatment. To our knowledge, this is the second case of AITP observed after antiviral treatment withdrawal. In most published cases AITP occurred during treatment; in fact, among 24 cases of AITP related to interferonbased antiviral treatment, only one occurred after discontinuation. Early diagnosis of AITP is a key factor in order to achieve an early interferon discontinuation; in the era of new direct antiviral agents those patients have to be considered for interferon-free treatment regimens. Prompt prescription of immuno-suppressant treatment(i.e., corticosteroids, immunoglobulin infusion and even rituximab for unresponsive cases) leads to favourable prognosis in most of cases. Physicians using interferonbased treatments should be aware that AITP can occur both during and after treatment, specially in the new era of interferon-free antiviral treatment. Finally, in the case of suspected AITP, presence of anti-platelet antibodies should be checked not only during treatment but alsoafter discontinuation.

G-CSF in Peg-IFN induced neutropenia in liver transplanted patients with HCV recurrence

AIM:To evaluate the efficacy of granulocyte colony stimulating factors(G-CSF)in liver transplanted patients with hepatitis C(HCV)recurrence and Pegylated-IFN α-2b induced neutropenia,and to evaluate the impact of G-CSF administration on virological response. METHODS:Sixty-eight patients undergoing antiviral treatment for post-liver transplantation(OLT)HCV recurrence were enrolled.All patients developing neutropenia received G-CSF. RESULTS:Twenty three(34%)received G-CSF.Mean neutrophil count at the onset of neutropenia was 700/mmc(range 400-750/mmc);after 1 mo of G-CSF it increased to 1210/mmc(range 300-5590/mmc) (P<0.0001).Three patients did not respond to G-CSF. Treatment duration was similar in neutropenic and non-neutropenic patients.No differences in the rate of discontinuation,infections or virological response were observed between the two groups.G-CSF was protective for the onset of de novo autoimmune hepatitis(P<0.003). CONCLUSION:G-CSF administration is effective in the case of Peg-IFN induced neutropenia increasingneutrophil count,prolonging treatment and leading to sustained virological response(SVR)rates comparable to non-neutropenic patients.It prevents the occurrence of de novo autoimmune hepatitis.

Long-term leukocyte natural α-interferon and ribavirin treatment in hepatitis C virus recurrence after liver transplantation

AIM:To evaluate the effect of long-term treatment with leukocyte natural-interferon(ln-α-IFN)plus ribavirin(RBV).METHODS:Forty-six patients with hepatitis C virus(HCV)recurrence received 3 MU three times a week of ln-α-IFN plus RBV for 1 mo;then,patients with good tolerability(n=30)were switched to daily IFN administration,while the remaining were treated with the same schedule.Patients have been treated for 12 mo after viral clearance while non-responders(NR)entered in the longterm treatment group.Liver biopsies were planned at baseline,1 year after sustained virological response(SVR)and at 36 mo after start of therapy in NR.MedCalc software package was used for statistical analysis.RESULTS:About 16.7%of genotype 1-4 and 70%of genotype 2-3 patients achieved SVR.Nine patients withdrew therapy because of non-tolerance or noncompliance.A significant improvement in serum biochemistry and histological activity was observed in all SVR patients and long-term treated;100%of patients with SVR achieved a histological response(fibrosis stabilization or improvement)with a significant reduction in mean staging value(from 2.1 to 1.0;P=0.0031);histological response was observed in 84%of long-term treated patients compared to 57%of drop-out.Six patients died during the entire study period(follow-up 40.6±7.7 mo);of them,5 presented with severe HCV recurrence on enrollment.Diabetes(OR=0.38,95%CI:0.08-0.59,P=0.01),leukopenia(OR=0.54,95%CI:0.03-0.57,P=0.03)and severe HCV recurrence(OR=0.51,95%CI:0.25-0.69,P=0.0003)were variables associated to survival.Long-term treatment was well tolerated;no patients developed rejection or autoimmune disease.CONCLUSION:Long-term treatment improves histology in SVR patients and slows disease progression also in NR,leading to a reduction in liver decompensation,graft failure and liver-related death.