By C. Rasarus. Stratford University.

Femini- Investigations sation in males and amenorrhea in females are common Chronic hepatitis is diagnosed by a combination of per- in alcoholic liver disease and haemochromatosis due to sistently abnormal liver function tests and the findings alterations in the hypothalamic–pituitary–gonadal axis discount phenytoin 100mg line. Other investigations are aimed at diag- Reduced immune competence and increased suscepti- nosing the underlying cause and providing a prediction bility to infection also occur discount phenytoin 100 mg line. Patients may present with complications such as bleed- ingfromoesophagealvaricesorencephalopathy. Patients Management withactivechronichepatitismaypresentwithfeaturesof r Symptomatic management includes adequate nutri- chronic liver disease before cirrhosis is established. Cirrhosis 2 Hands: Leuconychia (if hypoalbuminaemic), club- Definition bing,palmarerythema,Dupuytren’scontracture,hep- Cirrhosis is an irreversible change of the liver architec- atic flap (asterixis, sign of hepatic encephalopathy), ture,characterisedbynodulesofregeneratedlivercells tremor may occur in alcoholism and Wilson’s disease. The liver is usually enlarged, firm and irregular, but is shrunken Aetiology in late disease. The spleen may be enlarged due to Cirrhosis results from continued hepatocellular necro- portal hypertension. Fibrous scarring causes disruption of the normal architecture, although regen- eration of hepatocytes occurs between the fibrous tracts, Macroscopy their function, which depends on intact architecture, is The liver is often enlarged and nodular, with a bosselated impaired. The cut surface shows nodules of liver tissue, r Alcohol accounts for more than 80% of cirrhosis in separatedbyfineorcoarsefibrousstrands. Other rare but impor- Grading system 1 2 3 tant drug-induced causes are halothane, isoniazid and rifampicin. Hepatic time (seconds encephalopathy is thought to be due to failure of the over control) liver to metabolise toxins. Serum amino acid levels rise Child–Pugh grade A = score of 5–6; Child–Pugh grade B = score affectingthebalanceofcerebralneurotransmitters. Hep- of 7–9; Child–Pugh grade C = score of 10–15 atic dysfunction also results in renal failure (hepatorenal syndrome). Investigations Aimed at diagnosis of underlying cause and assessment of severity/degree of reversible liver injury. The severity Clinical features of liver disease may be graded A–C by means of a mod- Patients may have altered behaviour, euphoria or se- ified Child–Pugh grading system (see Table 5. On examination patients are jaundiced, there may be Management fetor hepaticus (sickly sweet odour on breath), flapping Treatment is largely supportive. Withdrawal from alco- tremor, slurred speech, difficulty in writing and copy- hol is essential in all patients. Malnutrition is common ing simple diagrams (constructional apraxia) and gen- and may require nutritional support. Prognosis Complications Cirrhosis is an irreversible, progressive condition which r Central nervous system: Cerebral oedema in 80% oftencontinuestoend-stageliverfailuredespitethewith- causing raised intracranial pressure. The higher the Child– r Cardiovascular system: Hypotension, arrhythmias Pugh grade, the worse the prognosis, particularly for due to hypokalaemia including cardiac arrest. Over50%ofcasesintheUnitedKingdom Chapter 5: Disorders of the liver 197 Investigations encephalopathy. Specific tests depend on the sus- Complications of chronic pected underlying cause, e. Othertestsincludefullbloodcount,ureaandelec- trolytes, glucose, calcium, phosphate and magnesium Portal hypertension levels. Definition Management Raised portal venous pressure is usually caused by in- Treatment is supportive as the liver failure may resolve: creased resistance to portal venous blood flow and is a r Specialisthepatologyinputisessential,ideallypatients common sequel of cirrhosis. Position- pressure is consistently above 25 cm H2O, serious com- ing at a 20˚ head up tilt can help ameliorate the ef- plications may develop. Aetiology Whilst adequate nutrition is essential the protein in- By far the most common cause in the United Kingdom take should be restricted to 0. Causes may be divided into those tulose and phosphate enemas may be used to empty due to obstruction of blood flow, and rare cases due to the bowel and minimise the absorption of nitroge- increased blood flow (see Fig. Venous blood from the gastrointestinal tract, spleen and r Complications should be anticipated and avoided pancreas (and a small amount from the skin via the pa- wherever possible. Regular monitoring of blood glu- raumbilical veins) enters the liver via the portal vein. As cose and 10% dextrose infusions are used to avoid the portal vein becomes congested, the pressure within hypoglycaemia. Other electrolyte imbalances should it rises and the veins that drain into the portal vein be- be corrected. If the portal pressure continues to rise travenous vitamin K (although this may not be effec- the flow in these vessels reverses and blood bypasses the tive due to poor synthetic liver function), fresh frozen liver through the porto-systemic anastamoses (paraum- plasma should be avoided unless active bleeding is bilical,oesophageal,rectal). Thisportosystemicshunting present or prior to invasive procedures as it can pre- eventually results in encephalopathy.

Use of erythromycin and ampicillin was further evaluated in three different trials conducted by Eschenbach et al discount phenytoin 100mg without a prescription. Furthermore purchase phenytoin 100 mg without a prescription, there were no significant differences between erythromycin and placebo-treated women in infant birth weight, frequency of premature rupture of membranes, or neonatal outcome. No differences were noted between placebo (n= 43) and study patients (n= 43) in gestational age at delivery, term deliveries, or neonatal outcome. The third trial enrolled 277 women with singleton pregnancies and preterm labor with intact membranes (24 to 34 weeks), and randomly allocated them to receive either antibiotics or placebo (n= 133 for antibiotics group vs n= 144 for placebo group). No significant difference 46 between the treatment group and the placebo group was found in maternal outcomes, including duration of randomization-to-delivery interval, frequency of preterm delivery (< 37 weeks), frequency of preterm premature rupture of membranes, clinical chorioamnionitis, endometritis, and number of subsequent admissions for preterm labor. Intravenous treatment with another beta-lactam drug, mezlocillin in association with and erythromycin was compared to tocolytic treatment in women in preterm labor [187]. Women in the antibiotic group had a significantly lower incidence of postpartum infections compared with women in the placebo group. In a prospective, randomized, double-blinded, placebo-controlled trial, Gordon et al. The groups consisted of women receiving either 2 g of ceftizoxime (n= 58) or a placebo (n= 59) every 8 hours. Thirty-nine women with preterm labor received antimicrobial therapy and 39 received placebos. The effect of amoxicillin was further investigated in another trial conducted by Oyarzún et al. The authors randomly allocated 196 women with singleton pregnancies and preterm labor with intact membranes (22-36 weeks) to receive antibiotics or placebo, plus adjunctive parenteral tocolysis. In those receiving ampicillin and metronidazole the pregnancy was significantly 48 prolonged (median 15 days versus 2. Compared to the placebo group, patients in the metronidazole group had significantly fewer hospital admissions for preterm labor (27% versus 78%), preterm births (18% versus 39%) and premature rupture of membranes (5% versus 33%). The potential benefit of metronidazole showed by these studies leaded to the conduction of several trials that evaluated the efficacy of this drug during gestation. Twenty-six percent of women assigned to metronidazole and erythromycin delivered prematurely, as compared with 36% assigned to placebo (p= 0. When compared to placebo, treatment was associated with a significant prolongation of pregnancy (admission to delivery 47. Intention-to-treat analysis showed no difference between metronidazole and placebo groups in overall preterm birth (7. In the subgroup of women with a previous preterm birth, the use of metronidazole was associated with a significant reduction in spontaneous preterm birth (9. Nevertheless, these results suggested that benefit could be obtained with treatment of women with a previous preterm birth. The same team also showed in another trial, that pregnant women diagnosed with asymptomatic trichomoniasis had an 80% increase in the risk of preterm birth after use of metronidazole treatment, when compared to placebo [198]. The authors randomly assigned 617 women with asymptomatic trichomoniasis who were 16 to 23 weeks pregnant to receive two doses of metronidazole (320 women) or placebo (297 women) 48 hours apart. The infection resolved in 92% women in the metronidazole 50 group and in 35% of women in the placebo group. Faillure of metronidazole to prevent preterm birth was also demonstrated by Odendaal et al. In this former trial, 900 pregnant women with at least one previous risk factor for preterm delivery (including mid-trimester loss or previous preterm delivery, uterine abnormality, cervical surgery or cerclage) were screened for fetal fibronectin at 24 and 27 weeks of gestation. Most recent evidence from two larger trials did not corroborate the findings of previous studies. Current consensus is that topical intra-vaginal treatment with this agent is not recommended during pregnancy. Given these results, the authors conclude that the benefits in some short-term outcomes should be balanced against a lack of evidence of benefit for others, including perinatal mortality, and longer-term outcomes. The same drug was further evaluated in another cohort study designed by Vinther-Skriver et al. The authors used population-based registries in North Jutland County, Denmark of 63 659 women with a live birth, or stillbirth after the 28th week of gestation. Another retrospective cohort study of maternal use of amoxicillin was conducted by Jepsen et al. Lack of evidence for amoxycillin/clavulanic acid was also detected in a cohort study conducted in Israel by Berkovitcz et al. In this study, the exposed group (n= 191) was composed of women treated with amoxycillin/clavulanic acid during the first trimester of pregnancy, and recruited from two teratogen information centres in Israel. Women were matched for age, smoking habits and alcohol consumption with 191 controls exposed to amoxycillin only for similar medical indications. Results showed that treated women had the same mean gestational age at delivery when compared to women exposed to amoxicillin alone (39. Studies assessing the risk of preterm birth after exposure to anti-infective drugs A population-based follow-up study conducted by Dencker et al.