Double probe pH-monitoring findings in patients with benign lesions of the true vocal folds: comparison with typical GERD and the effect of smoking.

We conducted a pH-monitoring study to determine the prevalence of pathologic gastroesophageal reflux (GER+) and laryngopharyngeal reflux (LPR+) in patients with resected benign true vocal fold lesions (TVFLs) and positive reflux finding score (RFS). We compared our findings with those of patients with typical GER disease (GERD) symptoms and normal laryngoscopy. In the group of patients with TVFLs, we compared the pH-monitoring findings of smokers with those of non-smokers. Seventy-two [females 32, mean (SD) age 49.3 (13.1) years] patients with resected TVFLs (polyps: 32, nodules: 20, Reinke's edema: 12, granulomas: 4, leukoplakia: 4) and 24 [females 14, mean (SD) age 42.2 (13.4) years] patients with typical GERD symptoms, who served as controls for the hypopharyngeal measurements, underwent 24-h double probe, hypopharyngeal and distal esophageal, ambulatory pH monitoring. Thirty-eight (52.8%) patients with TVFLs had GER+ and 52 (72.2%) had LPR+. More laryngopharyngeal reflux episodes (LPREs) were detected in patients with TVFLs compared to those with GERD (P < 0.001). With respect to the specific TVFLs, 12 (37.5%) patients with polyps had GER+ and 24 (75%) had LPR+, 6 (30%) patients with nodules had GER+ and 12 (60%) had LPR+, 6 (50%) patients with Reinke's edema had GER+ and 8 (66.7%) had LPR+ and all the patients with granuloma or leucoplakia had both GER+ and LPR+. Twenty (55.6%) of the 36 smokers and 32 (88.9%) of the 36 non-smokers with TVFLs had LPR+ (P = 0.003), while GER+ was recorded in 16 (44.4%) smokers and 22 (61.1%) non-smokers (P = 0.238). Smokers had significantly less LPREs (P < 0.001). In conclusion, 24-h double probe pH monitoring may detect GER+ and/or LPR+ in a substantial proportion of patients with resected TVFLs and positive RFS. Our study suggests that LPR+ is more prevalent in patients with TVFLs compared with typical GERD patients and that non-smokers with TVFLs are more likely to have LPR+ than smokers with TVFLs.

Adefovir plus lamivudine are more effective than adefovir alone in lamivudine-resistant HBeAg- chronic hepatitis B patients: a 4-year study.

BACKGROUND AND AIM: Adefovir dipivoxil (ADV) is effective in lamivudine (LAM)-resistant hepatitis B e antigen-negative (HBeAg(-)) chronic hepatitis B (CHB). However, it is unclear whether LAM treatment should be continued in these patients. We aimed to compare the long-term efficacy of adding ADV to ongoing LAM treatment versus switching to ADV monotherapy in LAM-resistant HBeAg(-) CHB. METHODS: Sixty LAM-resistant patients with HBeAg(-) CHB were randomly assigned (3:1) to combination therapy (10 mg ADV once daily plus ongoing LAM at 100 mg once daily [n = 45]) or 10 mg ADV monotherapy once daily (n = 15). Virological and biochemical responses were defined as hepatitis B virus (HBV)-DNA <400 copies/mL and as normalization of alanine aminotransferase levels, respectively. RESULTS: The median follow-up time was 53 months (range 20-60 months). A virological response was observed in 38/45 (84.4%) and 11/15 (73.3%) patients in the ADV/LAM and ADV monotherapy groups, respectively (P = 0.56). Biochemical response rates were higher in the ADV/LAM group than in the ADV monotherapy group (90.9% vs 57.1%, respectively; P = 0.01). In the ADV/LAM group, serum HBV-DNA remained undetectable in all patients who achieved a virological response (n = 38). In the ADV monotherapy group, virological breakthrough occurred in four of the 11 patients who achieved a virological response (36.4%; P < 0.001 vs the ADV/LAM group, log-rank test). In addition, two patients in each group who did not achieve a virological response eventually developed ADV resistance. CONCLUSIONS: Adding ADV to LAM is more effective than switching to ADV monotherapy in LAM-resistant patients with HBeAg(-) CHB.

Ductal plate malformation and congenital hepatic fibrosis Clinical and histological findings in four patients.

Congenital hepatic fibrosis belongs to the fibrocystic diseases of the liver and represents ductal plate malformation of interlobular bile ducts, along with a destructive cholangiopathy associated with fibrosis. Four patients with congenital hepatic fibrosis are described. Their median age at presentation was 25 years; none of them had a family history of liver or renal disease. Variceal bleeding was the initial manifestation in three patients. All of them required frequent endoscopic variceal ligation sessions and distal splenorenal shunting was also performed in two, almost obviating the need for further variceal ligation. Variceal bleeding did not recur during follow-up. One of these three patients rarely exhibited acute cholangitis; administration of ursodeoxycholic acid resulted in complete remission. In contrast, the fourth patient showed frequent severe episodes of acute cholangitis but normal cholangiographic findings. He underwent liver transplantation but died 2 months later. Laboratory findings disclosed pancytopenia in all patients whereas hepatic synthetic capacity was well preserved. Renal function was unaffected despite the presence of polycystic kidneys in two patients. In summary, congenital hepatic fibrosis can also be diagnosed in older ages, might have strikingly different manifestations and is associated with prominent portal hypertension necessitating aggressive management in order to prevent variceal bleeding.

Pegylated IFN-alpha 2b added to ongoing lamivudine therapy in patients with lamivudine-resistant chronic hepatitis B.

AIM: To investigate the role of pegylated-interferon (IFN) alpha-2b in the management of patients with lamivudine-resistant chronic hepatitis B. METHODS: Twenty consecutive anti-HBe positive patients were treated with pegylated IFN alpha-2b (100 mug sc once weekly) for 12 mo. There was no interruption in lamivudine therapy. Hematology, liver biochemistry, serum HBV DNA levels were detected by PCR, and vital signs were also assessed. Liver histology was assessed in some patients at entry and at wk 52 for comparison. RESULTS: Nine patients (45%) had a partial virological end-treatment response; seven patients (35%) showed complete virological end-treatment response. Eight patients (40%) showed biochemical end-treatment response. There was a trend for higher virological response rates in patients who had previously responded to IFN and relapsed compared to IFN non-responders (four out of seven patients vs none out of six patients, respectively; P=0.1). Patients without virological end-treatment response showed significant worsening of fibrosis [median score 2 (range, 1 to 3) vs median score 3 (range, 1 to 4)], in the first and second biopsy respectively (P=0.014), whereas necroinflammatory activity was not significantly affected. Patients with complete or partial virological end-treatment response did not show any significant changes in histological findings, possibly due to the small number of patients with paired biopsies (n=5). Nevertheless, after 12 mo of follow-up, only one patient (5%) showed sustained virological response and only 2 patients (10%) showed sustained biochemical response. Two patients (10%) discontinued pegylated IFN both after 6 mo of treatment due to flu-like symptoms. CONCLUSION: Pegylated IFNalpha-2b, when added to ongoing lamivudine therapy in patients with lamivudine-resistant chronic hepatitis B, induces sustained responses only in a small minority of cases.

A case of successful management with splenectomy of intractable ascites due to congenital dyserythropoietic anemia type II-induced cirrhosis.

The congenital dyserythropoietic anemias comprise a group of rare hereditary disorders of erythropoiesis, characterized by ineffective erythropoiesis as the predominant mechanism of anemia and by characteristic morphological aberrations of the majority of erythroblasts in the bone marrow. Congenital dyserythropoietic anemia type II is the most frequent type. All types of congenital dyserythropoietic anemias distinctly share a high incidence of iron loading. Iron accumulation occurs even in untransfused patients and can result in heart failure and liver cirrhosis. We have reported about a patient who presented with liver cirrhosis and intractable ascites caused by congenital dyserythropoietic anemia type II. Her clinical course was further complicated by the development of autoimmune hemolytic anemia. Splenectomy was eventually performed which achieved complete resolution of ascites, increase of hemoglobin concentration and abrogation of transfusion requirements.

Pathogenesis of osteoporosis in liver cirrhosis.

BACKGROUND/AIMS: Osteoporosis has been recognized in patients with liver cirrhosis, although the prevalence and the exact mechanisms vary considerably in the literature. We have studied the prevalence of bone disease in cirrhotic patients, the pathogenesis and the relation to the etiology and the severity of liver failure. METHODOLOGY: The study included 83 hospitalized patients with various types of cirrhosis, where 25 healthy individuals served as controls. Patients were classified according to Child-Pugh's stages as follows: Child A: 49, Child B: 20, Child C: 14. Serum levels of iPTH, 250HD, LH, FSH, SHBG, testosterone, estradiol, IGF-I, osteocalcin and urine levels of cross-linked N-telopeptides of collagen type 1 (NTX) were measured in all patients. Bone mineral density (BMD) was measured by DEXA at the spine of both patients and controls. RESULTS: The prevalence of osteoporosis was higher in patients (26/83) 31.3% than in controls (4/25) 16%. Osteopenia was positively related with the elevated levels of crosslinked N-telopeptides (p=0.048). There were no differences in BMD between the types of cirrhosis. BMD was found to be significantly lower in Child B and C male patients than in Child A (p=0.043). Patients' groups B, and C had lower testosterone levels with a trend to contribute to the low BMD (p=0.15). 250HD and IGF-1 were significantly lower in decompensated cirrhosis (p<0.002), but did not correlate with BMD. CONCLUSIONS: Cirrhosis is a major cause of osteoporosis and the degree of osteopenia is related to the severity and not the etiology of the liver disease. The biochemical markers of bone remodeling suggest a high-turnover osteoporosis in cirrhosis.

Colchicine treatment of liver fibrosis.

BACKGROUND/AIMS: Because of its antifibrotic and anti-inflammatory effects, colchicine has been proposed as a treatment for liver disease. The results from clinical trials have however been inconsistent. The aim of the present study was to evaluate the effect of colchicine in the treatment of patients with hepatic fibrosis of various etiologies. METHODOLOGY: Thirty-eight patients were randomized to receive either colchicine 1 mg per day (n=21, group A) or no antifibrotic agent (n=17, group B). Treatment lasted for at least 12 months. Liver biopsy was performed prior to entry and after 12 months. Liver function tests, serum aminoterminal peptide of procollagen III (PIIINP) levels and CD4:CD8 ratio of peripheral blood T lymphocytes (PBTLs) were performed at baseline and bimonthly or every 4 months post-treatment. RESULTS: Mean albumin serum levels increased 12 months post-treatment period only in group A (p<0.05). Mean serum PIIINP levels did not change significantly after 12 months of treatment in group A; in 7 patients a reduction in mean serum PIIINP levels was noticed during 24-month post-treatment follow-up period (p<0.05). At baseline, a correlation between focal or bridging necrosis and CD4:CD8 ratio of PBTLs was noticed in group A (p < 0.05). The mean serum CD4:CD8 ratio was increased after 12 months of colchicine treatment (p<0.05) associated with abrogation of this correlation; comparison between the two groups revealed increased CD4:CD8 ratio in group A at 12 months (p<0.05). The histological findings according to Knodell criteria in both groups remained unchanged after 12 months follow-up. The treatment was well tolerated in all patients. CONCLUSIONS: Long-term colchicine treatment in patients with hepatic fibrosis appears to exert an anti-inflammatory, anti-fibrotic and immunomodulatory effect.

Protein-losing enteropathy as the principal manifestation of constrictive pericarditis.

Constrictive pericarditis represents a rare cause of protein-losing enteropathy due to intestinal lymphangiectasia. We report the case of a patient with an atypical clinical presentation of constrictive pericarditis and protein-losing enteropathy as its principal manifestation; he was successfully treated with pericardiectomy. We conclude that, constrictive pericarditis should be considered in the presence of protein losing enteropathy and also, protein-losing enteropathy should be considered in the differential diagnosis of hypoalbuminemia.

Thyroid dysfunction and long-term outcome during and after interferon-alpha therapy in patients with chronic hepatitis C.

INTRODUCTION: Thyroid dysfunction (TD) is a well-established adverse effect in chronic hepatitis C virus (HCV)-infected patients, treated with interferon-alpha (IFN-α), with or without ribavirin. However, the long-term outcome is not well-studied. The purpose of this study was to estimate the prevalence and long-term outcome of TD after HCV-therapy. MATERIALS AND METHODS: Retrospective analysis of 109 HCV-treated patients (for 6 to 12 months, according to HCV genotype), for the period 1996 to 2008. Thyroid function tests were performed every 3 months during therapy and after discontinuation (3 months to 12 years). Routine laboratory tests and virological assessment were performed according to generally accepted practice. RESULTS: TD was observed in 26 patients (23.85%). The positive and negative predictive value for thyroid autoantibodies (ATA) was 80% and 72.7%, respectively. Relative risk for those with positive ATA was 2.9 (95% CI: 1.6 to 5.3, P = 0.014). The median duration of TD was 12.0 months (min: 3; max: 132). The median follow-up period for the patients with TD was 25.5 months (min: 12; max: 144). Finally, 15 patients developed permanent TD (57.69%), compared to 11 with temporary TD (42.31%). Sex is a risk factor for TD, as there were more females than males affected (P = 0.011). Genotype, viral load, time of HCV-exposure prior to therapy, and virological response did not differ between patients with and without TD. CONCLUSION: TD among HCV-treated patients was more frequent than usually reported, with >50% developing permanent TD. ATA status may play a role in estimating the risk of subsequent TD. Women appear to be more vulnerable to TD than men.

Sarcoidosis-induced pericarditis in a patient with portopulmonary hypertension: a case report.

Portopulmonary hypertension is a rare and severe complication of patients with cirrhosis. Sarcoidosis, a disease of unknown etiology, is also a cause of pulonary hypertension and right heart dysfunction. We report the case of a 51-year-old male patient, suffering from cirrhosis due to Wilson's disease, portal hypertension and pulmonary hypertension (PH), who developed severe pericarditis. Wilson's disease was diagnosed 8 years before his last admission to our hospital and was being successfully treated with D-penicillamine. PH was recognized 2 years before admission and being treated with bosentan. The patient complained for dyspnea at rest and the 2D echocardiogram revealed a significant amount of pericardial fluid. All other causes of acute pericarditis were excluded and his laboratory, imaging and histopathological investigation showed evidence of sarcoidosis. He underwent a therapy with corticosteroids (methylprednisolone) and his follow-up examination showed remarkable decrease of the levels of mean pulmonary artery pressure and pericardial fluid.

Idiopathic portal hypertension in an "inactive" HBV carrier: a case report.

Idiopathic portal hypertension belongs to the group of non-cirrhotic portal hypertension, its etiology is still unknown but its prognosis is excellent. We report a case of 45 year old female with inactive hepatitis B virus (HBV) carrier status and persistently elevated alpha-fetoprotein (AFP), presented with features of portal hypertension and without evidence of cirrhosis or fibrosis on liver biopsy.

Lamivudine/pegylated interferon alfa-2b sequential combination therapy compared with lamivudine monotherapy in HBeAg-negative chronic hepatitis B.

BACKGROUND AND AIM: Monotherapy has been proven insufficient in achieving sustained control of chronic hepatitis B. We aimed to assess the efficacy of combined sequential administration of lamivudine and pegylated interferon alfa-2b in patients with hepatitis Be antigen (HBeAg)-negative chronic hepatitis B. METHODS: Eighteen patients were given sequential combination treatment starting with 3 months of lamivudine monotherapy followed by 9 months of pegylated interferon alfa-2b (after a 3-month period of concomitant administration of the two drugs) and 24 patients received lamivudine monotherapy. RESULTS: At the end of treatment, 88.9% of the patients who received sequential combination treatment and 70.8% of those who received lamivudine monotherapy had hepatitis B virus (HBV) DNA levels below 400 copies/mL (P = not significant). At the end of treatment, 72.2% of the patients who received sequential combination treatment and 70.8% of those who received lamivudine monotherapy achieved alanine aminotransferase normalization (P = not significant). After 12 months of follow up, 33.3% of the patients who received sequential combination treatment and 16.7% of those who received lamivudine monotherapy had HBV-DNA levels below 400 copies/mL (P = 0.4). After 12 months of follow up, 72.2% of the patients who received sequential combination treatment and 25.0% of those who received lamivudine monotherapy had normal alanine aminotransferase levels (P < 0.01). Twenty-five percent of the patients in the lamivudine monotherapy group had virological breakthrough compared to none in the sequential combination treatment group (P = 0.06). CONCLUSIONS: Sequential combination treatment is able to improve sustained biochemical response rates and prevent the emergence of lamivudine-resistant mutants in patients with HBeAg-negative chronic hepatitis B.

Thyroid dysfunction and long-term outcome during and after interferon-alpha therapy in patients with chronic hepatitis C

<p><b>INTRODUCTION</b>Thyroid dysfunction (TD) is a well-established adverse effect in chronic hepatitis C virus (HCV)-infected patients, treated with interferon-alpha (IFN-α), with or without ribavirin. However, the long-term outcome is not well-studied. The purpose of this study was to estimate the prevalence and long-term outcome of TD after HCV-therapy.</p><p><b>MATERIALS AND METHODS</b>Retrospective analysis of 109 HCV-treated patients (for 6 to 12 months, according to HCV genotype), for the period 1996 to 2008. Thyroid function tests were performed every 3 months during therapy and after discontinuation (3 months to 12 years). Routine laboratory tests and virological assessment were performed according to generally accepted practice.</p><p><b>RESULTS</b>TD was observed in 26 patients (23.85%). The positive and negative predictive value for thyroid autoantibodies (ATA) was 80% and 72.7%, respectively. Relative risk for those with positive ATA was 2.9 (95% CI: 1.6 to 5.3, P = 0.014). The median duration of TD was 12.0 months (min: 3; max: 132). The median follow-up period for the patients with TD was 25.5 months (min: 12; max: 144). Finally, 15 patients developed permanent TD (57.69%), compared to 11 with temporary TD (42.31%). Sex is a risk factor for TD, as there were more females than males affected (P = 0.011). Genotype, viral load, time of HCV-exposure prior to therapy, and virological response did not differ between patients with and without TD.</p><p><b>CONCLUSION</b>TD among HCV-treated patients was more frequent than usually reported, with >50% developing permanent TD. ATA status may play a role in estimating the risk of subsequent TD. Women appear to be more vulnerable to TD than men.</p>

Effect of lamivudine treatment in patients with decompensated cirrhosis due to anti-HBe positive/HBeAg-negative chronic hepatitis B.

Lamivudine has been shown to improve liver function and reduce the need for liver transplantation (LT) in patients with decompensated HBeAg-positive cirrhosis. Nevertheless, there is only limited experience with lamivudine in patients with anti-HBe-positive/HBeAg-negative cirrhosis. The primary aim of this study was to determine whether lamivudine treatment improves liver function and subsequently pre-LT survival or delays or obviates the need for LT in patients with anti-HBe-positive/HBeAg-negative cirrhosis. Between July 1998 and June 2003, 20 consecutive patients awaiting LT were enrolled in the study. All patients showed active viral replication and were treated with lamivudine 100 mg daily. Significant clinical improvement, defined as a decrease in the Child-Pugh-Turcotte score by >or=2 points, was observed in 11 (55%) patients. The median change in the Child-Pugh-Turcotte score was -2 (range -5 to +2). The median time required to achieve a 2-point or greater reduction in Child-Pugh-Turcotte score was 6 months (range 3-12 months). In nine patients (45%), the Child-Pugh-Turcotte score decreased to

Small-duct primary sclerosing cholangitis. A single-center seven-year experience.

Patients with cholestatic liver function tests and histological features of primary sclerosing cholangitis (PSC) but without the typical cholangiographic changes are considered to have small-duct PSC. The incidence of small-duct PSC and the natural history still is not known. We performed a retrospective search for patients diagnosed with small-duct PSC between January 1997 and December 2003. The diagnosis of small-duct PSC was based on biochemical features of chronic cholestasis, liver biopsy findings consistent with PSC, and a normal cholangiogram on endoscopic retrograde cholangiography. Six patients fulfilled the diagnostic criteria for small-duct PSC. All patients received medical therapy. After a mean follow-up time of 26.0 +/- 29.8 months (range, 7-84 months), all patients are alive. Repeated liver biopsy was performed in one patient, 58 months after the initial one, and disclosed amelioration of histological findings (reduction in the Ludwig fibrosis score from 4 to 2). During follow-up symptoms disappeared in all patients who were symptomatic at diagnosis; none of those who were asymptomatic at diagnosis developed symptoms. At the time of last follow-up all patients showed significant improvement of their biochemical variables compared to baseline. Administration of aminosalicylates seemed to be of benefit irrespective of the presence of inflammatory bowel disease. No patients underwent liver transplantation or developed cholangiocarcinoma. Even though our study included a low number of patients and the follow-up time was relatively short, we can suggest that small-duct PSC rarely progresses to large-duct PSC and does not seem to be associated with development of cholangiocarcinoma. It thus seems to represent a separate entity with a favorable prognosis.

Interferon/long-term lamivudine combination therapy in anti-HBe positive chronic hepatitis B patients.

BACKGROUND: Monotherapy with a single antiviral agent is insufficient in controlling hepatitis B virus infection in the majority of patients with anti-HBe positive chronic hepatitis B. Interferon/long-term lamivudine combination therapy was evaluated to determine if this strategy would improve treatment efficacy and reduce the emergence of lamivudine resistance. METHODS: In total, 36 consecutive anti-HBe positive patients were treated with interferon (3 MU subcutaneously three times weekly) and lamivudine (100 mg orally once a day) for 12 months. After completion of the combined treatment, all patients continued to receive lamivudine monotherapy indefinitely. RESULTS: Overall, 35 patients (97%) showed virological response at 12 months. Four patients (11%) cleared HBsAg and developed anti-HBs. During the follow-up time, after the discontinuation of interferon, of 30 +/- 12 months (range: 7-57 months), 13 patients (36%) exhibited breakthrough infection. The cumulative rates of breakthrough infection at the end of 1, 2, 3 and 4 years of treatment were 0%, 14%, 32%, and 59%, respectively. CONCLUSIONS: Combination therapy appears to be effective and may also delay the selection of lamivudine-resistant variants. However, controlled trials are definitely warranted to clarify the potential benefits of combination antiviral treatment over monotherapy.

Long-term follow-up of patients with acute hypertriglyceridemia-induced pancreatitis.

BACKGROUND: An acute and potentially life-threatening complication of hypertriglyceridemia (HTG) is acute pancreatitis (AP). Hypertriglyceridemia, usually severe, may be primary in origin or secondary to alcohol abuse, diabetes mellitus, pregnancy, and use of drugs. STUDY: The efficacy of treatment to prevent relapses in 17 patients with AP attributed to HTG was investigated in the current prospective study. The mean follow-up period of patients was 42 months. Hypertriglyceridemia-induced AP comprised 6.9% of all patients with AP (n = 246) hospitalized in our clinic during the study (6 years). RESULTS: Causative conditions of HTG-induced AP were familial HTG in eight patients, HTG caused by uncontrolled diabetes mellitus in five, HTG aggravated by drugs in two (one by tamoxifen and one by fluvastatin), familial hyperchylomicronemia (HCM) in one, and lipemia of pregnancy in one. During the acute phase of pancreatitis, patients underwent standard treatment. Thereafter, HTG was efficiently controlled with high dosages of fibrates or a fibrate plus acipimox, except for the patient with HCM, who was on a specific diet (the only source of fat was a special oil consisting of medium chain triglyceride) and taking a high dosage of acipimox. One of the patients died during the acute phase of pancreatitis with acute respiratory distress syndrome. During follow-up, maintenance treatment was successful and only one patient relapsed, because he discontinued diet and drug treatment. CONCLUSION: Appropriate diet and drug treatment, including dose titration, of severe HTG is very effective in preventing relapses of HTG-induced AP.