Halis Simsek

Entecavir therapy for lamivudine‐refractory chronic hepatitis B: Improved virologic, biochemical, and serology outcomes through 96 weeks

In hepatitis B e antigen (HBeAg)‐positive chronic hepatitis B patients who were refractory to current lamivudine therapy, switching to entecavir was superior to continued lamivudine at week 48 for histologic improvement, viral load reduction by polymerase chain reaction and alanine aminotransferase normalization. We assessed the efficacy, safety, and resistance profile of entecavir through 96 weeks of treatment. A total of 286 patients were randomized and treated with entecavir 1 mg (n = 141) or continued lamivudine 100 mg (n = 145). At week 52, 77 entecavir‐treated patients who had a protocol‐defined virologic response (HBV branched DNA [bDNA] < 0.7 MEq/mL but HBeAg‐positive) continued blinded therapy for up to 96 weeks. Patients were assessed for efficacy, safety, and emerging resistance. Cumulative proportions of all treated patients who achieved confirmed efficacy endpoints were also analyzed. Between week 48 and the end of dosing, the proportions of patients with HBV DNA <300 copies/mL by polymerase chain reaction increased from 21% to 40%, and alanine aminotransferase normalization (≤1× upper limit of normal) increased from 65% to 81%. In the second year, HBeAg seroconversion was achieved by 10% of patients. Of the 77 patients in the second year treatment cohort, entecavir resistance emerged in six patients, and seven experienced virologic breakthrough (five with genotypic resistance acquired before year 2). The safety profile of entecavir in the second year of therapy was consistent with that reported during year 1. Conclusion: Through 96 weeks of treatment, 1 mg entecavir resulted in continued clinical benefit in lamivudine‐refractory HBeAg‐positive chronic hepatitis B patients with a safety profile comparable to lamivudine. (HEPATOLOGY 2008.)

Ethanol and the pancreas. Current status.

Abstract Ethanol abuse and alcoholism were estimated to cost the nation 117 billion dollars in 1983, and costs are expected to increase to 130 billion dollars by 1990 (1). Chronic ethanol abuse is the most common cause of acute and chronic pancreatitis in the West. The disease may manifest itself clinically as recurrent acute pancreatitis with bouts of pain and vomiting or continuous pain with exocrine and endocrine insufficiency. The aim of this review is to stress both the acute and chronic aspects of the disease as they relate to ethanol abuse and clinical presentation.

Efficacy and safety of entecavir in patients with chronic hepatitis B and advanced hepatic fibrosis or cirrhosis.

OBJECTIVE: The efficacy and safety of entecavir in patients with chronic hepatitis B and advanced liver fibrosis/cirrhosis was assessed from three large, randomized, multicenter, phase III studies.PATIENTS AND METHODS:These studies enrolled patients (≥16 yr) with chronic hepatitis B, elevated alanine aminotransferase (ALT) levels, and compensated liver disease. Two trials enrolled nucleos(t)ide-naive patients randomized to at least 48 wk of treatment with entecavir 0.5 mg/day or lamivudine 100 mg/day. The third trial randomized lamivudine-refractory patients to 48 wk of entecavir 1 mg/day or lamivudine 100 mg/day. In this post hoc descriptive analysis, the efficacy and safety in patients with advanced liver fibrosis/cirrhosis (Ishak fibrosis stages 4–6) were examined for consistency with those seen in the overall study populations.RESULTS: Of the 1,633 treated patients, 245 had advanced liver fibrosis/cirrhosis (120 entecavir and 125 lamivudine). Among entecavir-treated patients with advanced liver fibrosis, improvement in Ishak fibrosis was observed in 57% of nucleos(t)ide-naive hepatitis B e antigen (HBeAg)-positive patients, 59% of nucleos(t)ide-naive HBeAg-negative patients, and 43% of lamivudine-refractory HBeAg-positive patients versus 49%, 53%, and 33% of lamivudine-treated patients with advanced liver fibrosis. The overall trends in other histologic, virologic, biochemical, and serologic outcomes in entecavir- versus lamivudine-treated patients with advanced liver fibrosis/cirrhosis were consistent with those observed in the overall study populations in each trial. The treatment was well tolerated.CONCLUSION: These data confirm that the performance of entecavir relative to that of lamivudine in patients with advanced liver fibrosis/cirrhosis was consistent with the relationship observed in the overall treated population.

Screening of tissue transglutaminase antibody in healthy blood donors for celiac disease screening in the Turkish population.

Celiac disease (CD) is a disease having the characteristic pathology of the mucosa of the small intestine. The prevalence of CD in the Turkish population has not been investigated previously. The present study was designed to determine the prevalence of CD in healthy blood donors. Serum samples of 2000 healthy blood donors presenting to Hacettepe University Faculty of Medicine Hospital Blood Bank were tested for tissue transglutaminase (tTG) IgA and IgG antibodies with enzyme-linked immunosorbent assay (ELISA; Euroimmune, Germany). The histopathological findings for the cases with positive serology were evaluated. The distribution of sex was 95.7% male, and 4.3% female. The mean age was 33±9. Among 2000 donors, 23 (1.15%) were positive for tTG IgA antibody and 3 (0.15%) were positive for tTG IgG antibody. None of the samples was positive for both antibodies. Serum total IgA was measured in two cases with only tTG IgG positivity and was found to be low in one case. Twelve subjects positive for tTG agreed to endoscopy and biopsy. Histopathological examination revealed changes classified as Marsh III–II in one, Marsh II in two, Marsh I in seven, and Marsh 0 in two donors. This was the first study conducted to determine the prevalence of tTG positivity in the Turkish population. The tTG antibody positivity prevalence in healthy blood donors was as high as 1.3%. This study shows that the prevalence of CD in the Turkish population is relatively high in comparison to that in the Western world.

Increased prevalence of hepatitis C virus antibodies in patients with diabetes mellitus

DEAR SIR, hyperglycaemia and glucose intolerance are frequently observed in patients with chronic liver disease [l. 21. Taliani et al. [3] found the prevalence of diabetes mellitus to be 18.7% amongst patients with chronic hepatitis C virus (HCV) infection. In this study, we investigated hepatitis virus markers in 100 patients with diabetes mellitus. One hundred patients (42 men and 58 women) with diabetes mellitus diagnosed by conventional criteria [4] were studied. Their mean age was 50 (range 20-75) years and mean duration of diabetes was 8.1 (range 6 months-27) years. Twenty-five patients with type 1 diabetes were treated with insulin. Of the 75 patients with type 2 diabetes, 22 received insulin injections and 53 were on oral hypoglycaemic agents or special diet. Hepatitis B surface antigen (HBsAg) and immunoglobulin G antibody to hepatitis B core antigen (anti-HBc) were detected using enzyme-linked immunosorbent assays (ELISA) (Institut Pasteur, Paris, France). HCV antibody (anti-HCV) was detected by second-generation ELISA (Abbott Laboratories) and the positive results were confirmed by recombinant immunoblot assay (RIBA 11) (Ortho Diagnostic). The results were compared using the chi-squared test with Yate’s

Inflammatory bowel disease in 64 black patients: analysis of course, complications, and surgery.

Sixty-four black patients with inflammatory bowel disease (IBD) were seen from 1960 to 1987 at the Medical College of Georgia, representing 22% of all patients with IBD: 38 of them had Crohns disease (CD) and 26 had ulcerative colitis (UC). In those with CD, the small intestine alone was involved in 16% and ileocolitis was found in 58%; joint disease affected 11 patients (29%) and perianal disease 13 patients (34%). Twenty black patients (53%) underwent one disease-related surgical procedure, and 10 (50%) of those required two or more reoperations. Nine UC patients (35%) underwent surgery, and, except for three cases of sclerosing cholangitis (12%), black patients with UC showed no clinical findings different from white UC patients. In our American black patients, the course of IBD was similar to that of white patients, although in Crohns disease the reoperation rate and the rate of joint involvement were higher in our black IBD patients; primary sclerosing cholangitis was also found in a larger percentage of black patients with UC than in our white patient population.

Interferon Therapy for Acute Hepatitis C during Pregnancy

OBJECTIVE: Due to their antiproliferative activity, the probable effects of interferons on a fetus are a concern. We report on a pregnant patient who developed acute hepatitis C during pregnancy and was treated with a short course of interferon alfa therapy with a successful outcome. CASE SUMMARY: A 26-year-old woman was diagnosed with acute hepatitis C at the 16th week of pregnancy. She received a total dose of 72 million units of interferon alfa-2b during a 2 1/2 month period. Although the therapy was discontinued due to adverse effects, a complete biochemical and virologic response was obtained. Premature labor occurred and healthy, but growth-restricted, twin infants were born transvaginally. At 18 months of age, they had normal development, with a negative hepatitis C serology. DISCUSSION: The rate of transmission of hepatitis C virus from mother to infant is within the range of 1–5%. Although acute hepatitis C during pregnancy is a very rare occurrence, the mother is at a great risk for chronic infection. There is scarce literature about the probable effects of interferon use during pregnancy due to a lack of controlled studies in this special population. A total of 8 infants, including ours, exposed to interferon alfa and/or ribavirin during pregnancy showed no congenital anomalies or malformations. CONCLUSIONS: Patients with chronic hepatitis whose therapy can be delayed should not be treated with interferon due to a lack of controlled studies. However, women exposed to interferon inadvertently during pregnancy may be encouraged to continue pregnancy. In patients with acute hepatitis C during pregnancy, the use of interferon therapy should be considered with close monitoring.

Treatment of Behçet disease with indomethacin.

ABSTRACT: Thirty patients with Behçet disease (BD) were treated with oral indomethacin 25 mg four times daily for 3 months as an open label study. The study population consisted of 13 women and 17 men from 15 to 45 years of age (mean 27 years). At the initiation of the therapy, 28 patients had oral aphthous lesions, 23 had joint involvement, 13 had genital ulcerations, 8 had cutaneous lesions, and 4 had eye involvement. Eighty‐eight percent of patients with skin lesions, 80% with joint involvement, 43% with oral aphthous lesions, and 38% with genital ulcerations responded to indomethacin therapy. In three patients indomethacin was changed to the suppository form due to gastrointestinal side effects. Although it is difficult to assess the efficacy of indomethacin in BD because of the intermittent nature of symptoms, the majority of patients showed improvement in their symptoms of arthritis and skin lesions. This study indicates that indomethacin can be used as effective therapy particularly in patients with joint involvement.

Early HBeAg loss during peginterferon α-2b therapy predicts HBsAg loss: results of a long-term follow-up study in chronic hepatitis B patients.

OBJECTIVES:Treatment with pegylated interferon (PEG-IFN) α-2b results in hepatitis B e antigen (HBeAg) loss in 36% of patients at 6 months post treatment. The aim of this study was to determine whether a long-term response to PEG-IFN is dependent on the timing of HBeAg loss.METHODS:A total of 91 patients treated with PEG-IFN α-2b alone (100 μg per week) and 81 patients treated with PEG-IFN α-2b and lamivudine (100 mg/day) for 52 weeks were enrolled in this study. Patients were initially followed up at 4-week intervals and had one additional long-term follow-up (LTFU) visit (mean: 3.03±0.77 years 26 weeks post treatment).RESULTS:Of the 172 patients included, 78 patients (46%) did not have loss of HBeAg, 47 (27%) lost HBeAg within 32 weeks, and 47 patients (27%) had loss of HBeAg after week 32. At LTFU, patients with HBeAg loss≤32 weeks had hepatitis B virus DNA of <400 copies/ml significantly more often than did those who lost HBeAg after week 32 (47 vs. 21%, respectively; P=0.009). Hepatitis B surface antigen (HBsAg) negativity was also observed significantly more often in patients with early HBeAg loss (36 vs. 4%, respectively, P<0.001). Early HBeAg loss tended to occur more often in patients treated with PEG-IFN and lamivudine combination therapy than in those treated with PEG-IFN alone (35 vs. 21%; P=0.10), as did HBsAg loss (15 vs. 8%; P=0.14).CONCLUSIONS:Early PEG-IFN-induced HBeAg loss results in a high likelihood of HBsAg loss and may be associated with more profound viral suppression during the first 32 weeks of therapy in patients treated with lamivudine combinations.

Successful treatment with peginterferon alfa-2b of HBeAg-positive HBV non-responders to standard interferon or lamivudine.

OBJECTIVES:Antiviral therapy leads to HBeAg seroconversion in 10–40% of the patients with HBeAg-positive chronic hepatitis B. Nonresponse may result in progression of liver disease and increased risk of hepatocellular carcinoma. As part of a global randomized controlled trial we investigated the efficacy (i.e., loss of HBeAg at the end of follow-up) of peginterferon alfa-2b (Peg-IFN α2b) in patients who failed to respond to previous courses of standard interferon (IFN) or lamivudine.METHODS:We analyzed a total of 76 previous nonresponders: 37 were nonresponders to standard IFN, 17 were nonresponders to lamivudine, and 22 were nonresponders to both therapies. All patients received a 52-wks course of 100 μg Peg-IFN α2b weekly combined with either 100 mg lamivudine daily or a placebo. After therapy patients were followed for 26 wks.RESULTS:Thirteen (35%) nonresponders to previous IFN, five (29%) nonresponders to previous lamivudine, and four (22%) nonresponders to both IFN and lamivudine responded to treatment with Peg-IFN α2b. No difference in response was found for those treated with Peg-IFN α2b alone or in combination with lamivudine. Nonresponders to prior IFN therapy with baseline ALT (alanine aminotransferase) > 4 × ULN (upper limit of normal) responded better to Peg-IFN α2b than those with ALT levels ≤ 4 × ULN (53% vs 20%, respectively, p = 0.036).CONCLUSIONS:Peg-IFN α2b is effective in approximately one-third of patients who failed to respond to previous treatment with standard IFN or lamivudine. High serum ALT level at baseline of Peg-IFN α2b therapy was the best predictor for response in these patients.