Relative adrenal insufficiency in cirrhotic patients.

Relative adrenal insufficiency (RAI) was demonstrated in patients with cirrhosis and liver failure. A relationship appears to exist between the severity of the liver disease and the presence of RAI. Neither the mechanism nor the exact prevalence of RAI is fully understood. There is though a hypothesis that low high-density lipoprotein (HDL) levels in this group of patients may be responsible for the insufficiency of cortisol. Several questions also arise about the way and the kind of cortisol (total cortisol, free cortisol, or even salivary cortisol) that should be measured. The presence of RAI in patients with cirrhosis is unquestionable, but still several studies should come up in order to properly define it and fully understand it.

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.

Effect of multifactorial treatment on non-alcoholic fatty liver disease in metabolic syndrome: a randomised study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome (MetS). There is no established treatment for NAFLD. AIM: To evaluate a multifactorial intervention in the treatment of NAFLD. METHODS: A prospective, open-label, randomised study in non-diabetic patients (n = 186) with MetS (follow-up: 54 weeks). All patients had both biochemical and ultrasonographic evidence of NAFLD at baseline. Other causes of liver disease were excluded. Patients received lifestyle advice and treatment for hypertension (mainly inhibitors of the renin-angiotensin system), impaired fasting glucose (metformin), obesity (orlistat) and dyslipidaemia [randomly allocated to atorvastatin 20 mg/day (n = 63) or micronised fenofibrate 200 mg/day (n = 62) or both drugs (n = 61)]. Liver ultrasonography was assessed at baseline and at the end of the study. RESULTS: At the end of treatment, 67% of patients on atorvastatin, 42% on fenofibrate and 70% on combination treatment no longer had biochemical plus ultrasonographic evidence of NAFLD (p < 0.05 vs. baseline for all comparisons). The percentage of patients who no longer had evidence of NAFLD was significantly higher (p < 0.009) in the atorvastatin and combination groups compared with the fenofibrate group. This effect was independently related to drug treatment, as well as to reductions in high-sensitivity C-reactive protein, waist circumference, body weight, triglycerides, low-density lipoprotein-cholesterol, total cholesterol, systolic blood pressure and glucose. Four patients discontinued treatment because of adverse effects. CONCLUSIONS: Multifactorial intervention in MetS patients with both biochemical and ultrasonographic evidence of NAFLD offsets surrogate markers of NAFLD (i.e. elevated aminotransferase plus echogenic liver).

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.

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.

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.