Non-invasive assessment of bone density in primary biliary cirrhosis.

BACKGROUND/AIMS: Low bone mass is an important complication of primary biliary cirrhosis (PBC), resulting in an increased risk of fractures and reduced mobility. In the present study, we sought to determine the frequency of low bone mass in PBC, and its relationship to disease severity and non-invasive markers of bone turnover. METHODS: In 36 women with PBC, bone mineral density of the lumbar spine and hip was assessed by dual emission X-ray absorptiometry. Serum and urinary markers of bone turnover were compared with those from age- and sex-matched controls. RESULTS: Spinal osteopenia (T score, -1.5 to -2.5) was present in 15 of the 36 patients (42%), while six others (16%) had established osteoporosis (T < -2.5). Osteopenia of the femoral neck was found in 17 patients (47%), and osteoporosis in five (14%). The severity of liver disease, as determined by Mayo Clinic R score and histological stage, correlated negatively with both regional bone mineral density and total bone mineral content expressed as a ratio to lean body mass. There was a strong positive correlation between serum levels of the procollagen degradation peptides, PICP and PIIINP (r = 0.65, P < 0.001), and both peptides correlated significantly (P < 0.001) with histological stage and Mayo Clinic R score. Fasting urinary pyridinoline and deoxypyridinoline to creatinine ratios were also significantly raised. CONCLUSIONS: Low bone mass in PBC correlates positively with disease severity, and is associated with a net increase in bone resorption, as assessed by urinary collagen cross-link excretion. These markers of bone turnover may be of value in controlled clinical trials aimed at improving bone mass in PBC.

Pancreatic abnormalities and AIDS related sclerosing cholangitis.

OBJECTIVES: Biliary tract abnormalities are well recognised in AIDS, most frequently related to opportunistic infection with Cryptosporidium, Microsporidium, and cytomegalovirus. We noted a high frequency of pancreatic abnormalities associated with biliary tract disease. To define these further we reviewed the clinical and radiological features in these patients. METHODS: Notes and radiographs were available from two centres for 83 HIV positive patients who had undergone endoscopic retrograde cholangiopancreatography for the investigation of cholestatic liver function tests or abdominal pain. RESULTS: 56 patients had AIDS related sclerosing cholangitis (ARSC); 86% of these patients had epigastric or right upper quadrant pain and 52% had hepatomegaly. Of the patients with ARSC, 10 had papillary stenosis alone, 11 had intra- and extrahepatic sclerosing cholangitis alone, and 35 had a combination of the two. Ampullary biopsies performed in 24 patients confirmed an opportunistic infection in 16. In 15 patients, intraluminal polyps were noted on the cholangiogram. Pancreatograms were available in 34 of the 45 patients with papillary stenosis, in which 29 (81%) had associated pancreatic duct dilatation, often with associated features of chronic pancreatitis. In the remaining 27 patients, final diagnoses included drug induced liver disease, acalculous cholecystitis, gall bladder empyema, chronic B virus hepatitis, and alcoholic liver disease. CONCLUSION: Pancreatic abnormalities are commonly seen with ARSC and may be responsible for some of the pain not relieved by biliary sphincterotomy. The most frequent radiographic biliary abnormality is papillary stenosis combined with ductal sclerosis.

Prevalence and pattern of familial disease in primary biliary cirrhosis.

Susceptibility to primary biliary cirrhosis (PBC) may be partly inherited although instances of PBC within families are only infrequently described. The records of 736 patients with PBC seen over a 25 year period were examined to identify those with a positive family history. Ten patients originating from eight families were identified, giving a frequency of 1.33%. They comprised mother and daughter pairs; in two families both mother and daughter had been seen at our clinic. The daughters presented at an earlier age, median 36 years (range 24-54), than the mothers, 52 years (50-81). During follow up one daughter (45 years) and six mothers have died (range 53-81 years) and two mothers and one daughter have had a transplant aged 57, 57, and 30 years respectively. It is concluded that familial PBC is not rare, that it is related to maternally inherited factors, and that disease tends to present earlier in the second generation.

Resolution of danazol-induced cholestasis with S-adenosylmethionine.

In a case of danazol-induced cholestasis, the anti-cholestatic agent S-adenosylmethionine was given intravenously for 3 weeks and then orally for 6 weeks. This was well tolerated and led to prompt resolution of both jaundice and associated renal impairment.

Pericoronitis and accidental paracetamol overdose: a cautionary tale.

A case of accidental paracetamol overdose in a patient suffering from pericoronitis is described. Self-medication with paracetamol was exacerbated by the prescription of a compound analgesic containing paracetamol by the patient's dental practitioner. The consequent overdose of paracetamol resulted in liver toxicity and acute liver failure. The hazards of accidental paracetamol overdose are discussed and analgesic preparations containing paracetamol described.

Long-term anticonvulsant therapy worsens outcome in paracetamol-induced fulminant hepatic failure.

1. Paracetamol hepatotoxicity has been found to be potentiated by anticonvulsant drugs in animal experiments; isolated case reports in humans suggest that long-term anticonvulsant therapy may also adversely influence outcome following overdose. 2. We compared the clinical course, after paracetamol overdose, of 18 patients on long-term anticonvulsant therapy with corresponding features in two published series of paracetamol-induced fulminant hepatic failure from this unit: 297 patients seen between 1973 and 1985 and a further 99 between October 1986 and April 1988. 3. Mortality in those patients who were taking anticonvulsants, but who did not receive N-acetylcysteine, was higher than in either of these series (93.3% vs 64.6% and vs 57.9%, P less than 0.025). Although not statistically significant, there were also trends towards more severe coma (grade 3 or 4: 93.3% vs 75.4%, 1986-88), acidosis (pH less than 7.30: 40% vs 22.6%, 1973-85) and coagulopathy (prothrombin time greater than 100 s: 53.3% vs 33.7%, 1973-85). In the small number of patients given N-acetylcysteine, mortality was similar to that in the 1986-88 series (1/3 vs 15/42). 4. We conclude that chronic use of anticonvulsants enhances clinical features of paracetamol toxicity and discuss possible mechanisms by which this could be mediated.

Immunointervention in primary biliary cirrhosis: an overview.

Since autoimmune processes are probably involved in the early stages of primary biliary cirrhosis (PBC), immunomodulatory drugs have been investigated with the aim of prolonging survival, delaying transplantation, slowing histological progression and relieving symptoms. Corticosteroids, azathioprine, chlorambucil and, more recently, cyclosporin A and methotrexate have all be subjected to clinical investigation. In the latest of these, a European multicentre trial, cyclosporin A has been shown to delay death or transplantation with a reduction in liver related deaths and slowing of the rise of serum bilirubin. The incidence of nephrotoxicity and hypertension are low at the doses used.

S-adenosylmethionine protects against acetaminophen hepatotoxicity in two mouse models.

Because S-adenosylmethionine promotes synthesis of hepatic glutathione in chronic liver disease and is well tolerated in man, we investigated its use as an antidote to acetaminophen hepatotoxicity in two mouse models. In C57Bl6 mice, deaths were abolished by S-adenosylmethionine given within 1 hr of 3.3 mmol/kg body wt acetaminophen (0 of 32 vs. 13 of 49, p less than 0.005) and reduced if given 2 to 5 hours after acetaminophen administration (4 of 42 vs. 13 of 49, p less than 0.01). Mixed disulfate/tosylate salt of S-adenosylmethionine abolished mortality in C3H mice given 2 mmol/kg body wt acetaminophen (0 of 24 vs. 4 of 18; p less than 0.05). In both mouse models, S-adenosylmethionine reduced depletion of plasma (median = 20.8 mumol/L vs. 14.6 mumol/L) and liver glutathione (198% vs. 100%; p less than 0.05), liver damage and release of AST after acetaminophen administration. Pretreatment with buthionine sulfoximine, which inhibits glutathione synthesis, abolished the beneficial effect of S-adenosylmethionine on survival and plasma glutathione level. S-adenosylmethionine reduces acetaminophen hepatotoxicity by metabolism of the active moiety to glutathione. This benefit may last as long as 5 hr after acetaminophen ingestion.

The effect of chronic alcohol intake on prognosis and outcome in paracetamol overdose.

1. In a retrospective study, we stratified 79 patients with paracetamol hepatotoxicity into two groups according to weekly alcohol consumption below (n = 49) or above (n = 30) Royal College of Physicians' guidelines of 21 units week-1 for males and 14 for females. 2. Survival was lower (33%) and serum creatinine on admission higher (median 207 mumol) in patients whose alcohol consumption was above recommended guidelines than in those whose drank less than this (65.9% and 138 mumol, P less than 0.01 and P = 0.027, respectively). An arterial blood pH less than 7.30 on admission was also more common in those patients with a higher alcohol consumption (30% v 12.2%, P = 0.05). 3. In all patients whose alcohol consumption exceeded the guidelines, paracetamol overdose was fatal if associated with a serum creatinine greater than 300 mumol in conjunction with a prothrombin time over 100 s and grade 3 or 4 encephalopathy or a peak prothrombin time over 180 s. 4. Chronic alcohol intake above suggested limits is an adverse prognostic feature in cases of severe paracetamol overdose. This effect is partly related to increased nephrotoxicity.

Improved outcome of paracetamol-induced fulminant hepatic failure by late administration of acetylcysteine.

The influence of acetylcysteine, administered at presentation to hospital, on the subsequent clinical course of 100 patients who developed paracetamol-induced fulminant hepatic failure was analysed retrospectively. Mortality was 37% in patients who received acetylcysteine 10-36 h after the overdose, compared with 58% in patients not given the antidote. In patients given acetylcysteine, progression to grade III/IV coma was significantly less common than in those who did not receive the antidote (51% vs 75%), although the median peak prothrombin time was similar for both groups. Whether the beneficial effect is related to replenishment of glutathione stores or a consequence of another hepatic protective mechanism of acetylcysteine requires further study.

Hepatitis C virus antibodies in chronic active hepatitis: pathogenetic factor or false-positive result?

An enzyme immunoassay (Ortho-HCV ELISA) for antibodies against the hepatitis C virus (HCV) was used to test 143 serum samples from 53 patients with autoimmune chronic active hepatitis (AI-CAH). Optical density (OD) values in the assay correlated closely with serum globulin (r = 0.8846, p much less than 0.0005) and IgG (r = 0.6281, p less than 0.0005) concentrations but not with immunosuppressant therapy. OD values were positive in 20 (65%) of 31 with active disease and in only 1 (5%) of 22 in remission (p less than 0.0005). The association between positive results and active disease and high serum globulin levels was confirmed by serial studies in 6 of the patients. In contrast, none of 31 patients with primary biliary cirrhosis and only 2 of 24 with non-hepatic disorders associated with high IgG concentrations were positive, and these controls showed no correlation between OD values and serum globulins or IgG. The findings suggest that serum from AI-CAH patients may contain a component that gives false-positive results in the assay.

Sexual functioning in stroke survivors.

Investigation of sexual interest, function and attitudes of 35 patients (24 men and 11 women) before and after stroke showed no significant changes in sexual interest or desire for either men or women. However, men experienced significant decrease in ability to achieve erection and to ejaculate, and all of the 5 women who were premenopausal at the time of stroke reported major alterations in menses. Only 1 woman reported orgasm following stroke. Nineteen (79%) of the men and eight (73%) of th women reported sexual function to be of importance to themselves while all of the men and eight (73%) of the women believed it to be of importance to others of their age. The findings from this small sample indicate that although the majority of stroke survivors maintain consistent levels of sexual desire and believe that sexual function is important, most will experience sexual dysfunction following stroke. The sexual problems experienced by post-stroke patients appear to be of sufficient magnitude and frequency to warrant further investigation.