In persons who are homozygous for the C282Y mutation, iron-overload-related disease developed in a substantial proportion of men but in a small proportion of women.

In heavily pretreated patients with a high rate of genotypic resistance, TDF retains significant activity against HBV although this appears diminished in comparison with studies of naïve patients.

The risk of hemochromatosis-related morbidity is unknown among HFE compound heterozygotes (C282Y/H63D). We used a prospective population-based cohort study to estimate the prevalence of elevated iron indices and hemochromatosis-related morbidity for compound heterozygotes. In all, 31,192 subjects of northern European descent were genotyped for HFE C282Y and H63D. An HFE-genotype stratified random sample of 1,438 subjects, followed for an average of 12 years to a mean age of 65 years, completed questionnaires and gave blood. Clinical examinations were blinded to HFE genotype. A total of 180 (84 males) clinically examined C282Y/H63D participants were compared with 330 (149 males) controls with neither HFE mutation; 132 (65 males) and 270 (122 males), respectively, had serum iron measures at both timepoints. Mean serum ferritin (SF) and transferrin saturation (TS) were significantly greater for male and female compound heterozygotes than for wild-types at baseline and follow-up (all P < 0.02) except for females who were pre-menopausal at baseline, where SF was similar in both genotype groups. For subjects with serum measures from both baseline and follow-up, mean SF and TS levels did not change significantly for men or for postmenopausal women, but for premenopausal women SF levels increased from 43 to 109 μg/L for compound heterozygotes and from 35 to 64 μg/L for wild-types (both P < 0.001). Male and female compound heterozygotes had a similar prevalence of hemochromatosis-related morbidity to wild-types. One of 82 males and zero of 95 females had documented iron overload-related disease. Conclusion For male compound heterozygotes, mean iron indices do not change during middle age but for female compound heterozygotes menopause results in increased mean SF. Although compound heterozygotes might maintain elevated iron indices during middle age, documented iron overload-related disease is rare.

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. In the absence of effective pharmacotherapies, clinical guidelines focus primarily on weight loss to treat this condition. Established consensus, evidence-based, and clinical dietary recommendations for NAFLD are currently lacking. The aim of this paper is to provide evidence-based practical dietary recommendations for the prevention and management of NAFLD in adults. A literature review focusing on established principles for the development of clinical practice recommendations was employed using the following criteria: based on substantial evidence, ensures risk minimization, is flexible for an individual patient approach, and is open to further modification as evidence emerges. The Practice-based Evidence in Nutrition classification system was used to grade these principles. Five key dietary recommendations were developed: 1) follow traditional dietary patterns, such as the Mediterranean diet; 2) limit excess fructose consumption and avoid processed foods and beverages with added fructose; 3) PUFAs, especially long-chain omega-3 rich foods and MUFAs, should replace SFAs in the diet; 4) replace processed food, fast food, commercial bakery goods, and sweets with unprocessed foods high in fiber, including whole grains, vegetables, fruits, legumes, nuts, and seeds; and 5) avoid excess alcohol consumption. Improving diet quality may reduce the incidence and progression of NAFLD and associated risk factors. Many of the benefits are likely to result from the collective effect of dietary patterns. High-quality research-in particular, randomized clinical trials assessing dietary interventions that focus on liver-specific endpoints-are needed as a priority.

The choice of analgesic agent in cirrhotic patients is problematic and must be individualized taking into account several factors including severity of liver disease, history of opioid dependence, and potential drug interactions. With a cautious approach including slow dose up-titration and careful monitoring, effective analgesia can be achieved in most cirrhotic patients without significant side effects or decompensation of their liver disease. Paracetamol is safe in patients with chronic liver disease but reduced doses of 2-3 grams daily is recommended for long-term use. Non-steroidal anti-inflammatory drugs are best avoided because of risk of renal impairment, hepatorenal syndrome, and gastrointestinal hemorrhage. Opioids have an increased risk of toxicity particularly in patients with hypoalbuminaemia, and immediate-release as opposed to controlled-release formulations are advised. Co-prescription of laxatives is mandatory to avoid constipation and encephalopathy. Adjuvant analgesics such as tricyclic antidepressants and anti-convulsants may be used cautiously for cirrhotic patients with neuropathic pain. Gabapentin or pregabalin may be better tolerated in cirrhosis because of non-hepatic metabolism and a lack of anticholinergic side effects.