Prisons and HCV: a review and a report on an experience in New South Wales Australia.

Prison populations in Western countries are characterised by a high hepatitis C prevalence. This reflects a high rate of imprisonment for drug related offences. Prison entrants who are HCV-negative face a significant risk of acquiring hepatitis C. Effective prevention strategies and successful treatment of a significant percentage of hepatitis C-positive inmates could reduce the risk of transmission in the prison context significantly. Several reports of treating hepatitis C in prisoners in major facilities have been published. We report our experience of establishing a liver clinic service in two regional prisons in New South Wales, Australia. Liver biopsy requirements to access treatment in Australia meant that only 46 of 196 reviewed patients were able to commence treatment in our 5-year experience. Treatment completion rate was 61% and end of treatment viral response was 57%. The removal of liver biopsy requirements in Australia in April 2006 has freed up access to treatment and our results encourage further effort to optimise the process of assessment and treatment in this high-risk population.

Traditional Chinese medicine prevents inflammation in CCl4-related liver injury in mice.

Alternative medicines are being increasingly used and investigated in the management of a variety of disorders. Hepatitis is a common indication for the use of alternative therapies but evidence for the efficacy of many compounds is lacking. We have utilized a well-defined model of liver injury to study the efficacy of three herbal products designed to assist in the management of liver disease. Mice were exposed to carbon tetrachloride (CCL4) given intragastrically after they had been pretreated for five days with either saline or one of four doses of silymarin extract or CH100 (a Chinese herbal medicine comprising of 19 herbs) or one of two doses of CH101 (a Chinese herbal preparation designed to reduce fibrosis). Animals were sacrificed 24 hours after receiving CCL4. Liver enzymes and hepatic histology formed the basis for evaluating efficacy of the treatments. Each of the alternative medicines reduced the alanine amino transferase (ALT) elevation demonstrated after CCL4 injection. The high dose CH100 regimen was most effective in protecting against injury and this was confirmed with hepatic histology. Other doses of CH100, CH101 and silymarin were not shown to provide protection against the histological damage. In conclusion, Silymarin, CH100 and CH101 are able to reduce ALT elevation in animals exposed to CCL4. High dose CH100 provides protection from hepatocyte necrosis in this model. The data add to our understanding of the capacity some herbal medicines have to modify the reaction of the liver to a variety of insults and suggest the value of studying these agents further in human liver diseases.

Alcoholic hepatitis as a T-cell mediated disorder: an hypothesis.

BACKGROUND: The mechanism by which alcohol induces alcoholic hepatitis, the precursor lesion for cirrhosis, has never been elucidated. In particular, direct toxicity has not been proven. This article reviews the hypothesis that a primary target of chronic alcohol ingestion is the T lymphocyte. The lesion in the T lymphocyte is characterized by reduced baseline secretion of cytokines, including tumor necrosis factor-alpha; although characterized by an exaggerated release of cytokines when stimulated by polyclonal activators such as endotoxin. High concentrations of cytokines, especially tumor necrosis factor-alpha, within the liver induce necrosis/apoptosis of hepatocytes. METHODS: Data supporting this hypothesis in rodent models are reviewed. CONCLUSION: A strategic approach for testing this concept in man is defined.

Enhancing compliance not a prerequisite for effective eradication of Helicobacter pylori: the HelP Study.

OBJECTIVE: The aim of this study was to compare cure rates of Helicobacter pylori (H. pylori) infection, compliance, and side effects in patients given 10 days of omeprazole 20 mg b.d., amoxycillin 500 mg t.d.s., and metronidazole 400 mg t.d.s. (OAM) or 10 days OAM plus compliance enhancing measures. METHODS: A total of 119 H. pylori-positive patients were prospectively randomized to receive either 10 days OAM or 10 days OAM plus compliance enhancing measures (medication in a dose dispensing unit, medication chart, an information sheet about H. pylori treatment, and phone call 2 days after starting therapy). H. pylori eradication was assessed by 13C-UBT at least 4 wk after cessation of therapy, compliance by phone interview on the last day of therapy and returned pill count, and side effects by phone interview and returned side effects form. RESULTS: In 113 patients attending 13C-UBT H. pylori was eradicated in 51 of 57 patients (89.5%) after 10 days OAM and in 48 of 56 (85.7%) after 10 days OAM plus compliance enhancing measures (p = 0.54). In both groups 97% of medications were taken. Side effects were common (82% of patients). Both side effects (p = 0.001) and ulcer versus nonulcer at endoscopy (p = 0.016) were independent predictors of treatment failure; side effects also predicted noncompliance (p = 0.02). CONCLUSIONS: Ten days of OAM was effective for H. pylori eradication in our clinical population. Patient compliance was excellent and attempts to increase compliance had no impact on outcome or compliance. Side effects were very common and were significantly associated with treatment failure and decreased compliance.

Preliminary report of a randomized, double-blind placebo-controlled trial of a Chinese herbal medicine preparation CH-100 in the treatment of chronic hepatitis C.

The treatment of chronic hepatitis C is relatively unsatisfactory and many patients have turned to unproven alternative medicines to modify the course of their illness. We report a study of a Chinese herbal medicine preparation CH-100 in the management of chronic hepatitis C. Patients with documented chronic hepatitis C were randomly allocated to receive active herbal or placebo tablets (five tablets thrice daily). Patients were followed monthly and evaluated by a Western and a traditional Chinese medical practitioner. Therapy was monitored by measurement of liver function tests, creatinine and full blood count on a monthly basis. Twenty patients in each group were well matched for age, sex, duration of illness, previous interferon therapy and alcohol intake. Active Chinese herbal medication was associated with a significant reduction in alanine aminotransferase (ALT) levels over the 6 month study period (P < 0.03). No patient cleared the virus but four normalized their ALT on treatment. Appropriately prescribed Chinese herbal medicine may have a role in the management of chronic hepatitis C and further controlled studies are indicated.

The carbohydrate-deficient transferrin test in hospital practice.

We report an experience in two hospital populations of the use of a commercially available kit for the detection of carbohydrate-deficient transferrin (CDT). Patients from a drug and alcohol unit and a gastroenterology clinic at two hospitals were selected for the study. Sera were used from blood samples collected for routine biochemical assays. All patients had a specific alcohol history taken by one clinician and CDT results were correlated with reported alcohol intake by the patient and where relevant by their relatives. Sensitivity and specificity of the CDT assay were calculated using an alcohol intake of 60 g/day as the cut-off point for detection of heavy drinking. The CDT assay had a specificity of 95%; a sensitivity of 80% and a 90% positive and 89% negative predictive value. The severity and type of liver disease had little influence on the CDT result and a high alcohol intake was the only predictor of a raised CDT concentration. The assay provided information not available from routine investigations in some patients and also proved useful in monitoring patients over periods of up to 4 years. The test has a role in the evaluation of patients in a hospital practice where routine histories of alcohol intake may lack sensitivity and where other diseases may cause routine liver tests to be unreliable.

Denying treatment to drug and alcohol-dependent patients.

There has been a concerted move in the West to reduce health care expenditure and multiple moves have been made to achieve these cost reductions. Many approaches have been taken including the restriction of services to subsets within the population. Drug and alcohol dependent patients have often been targeted as individuals and as groups who should not be seen as having equal access to certain forms of therapy. In this article it is argued that many of these decisions are inappropriate and in many instances they are not based on evidence which suggests that patients who are dependent may do just as well as non-dependent patients with some forms of treatment. It is argued that clinicians should regard each individual patient separately and make decisions that are appropriate to the clinical setting rather than taking a policy decision to restrict treatment to dependent individuals.

Hepatitis B.

Hepatitis B remains a major public health problem around the world. The discovery of the hepatitis C virus has diverted interest from hepatitis B to this new virus and the epidemic associated with it, but hepatitis B remains a significant pathogen for millions of people worldwide. The World Health Organization has suggested that universal vaccination of children against hepatitis B should be implemented in an attempt to reduce the enormous morbidity and mortality associated with infection of this virus group. The review seeks to identify all the newer discoveries relating to hepatitis B that have been made in the past decade. Reference is made to the appearance of hepatitis B mutants which are able to infect patients previously infected with the wild strain of the virus. The implications of mutants on vaccination programmes is raised, as are issues relating to treatment of hepatitis B infection.

The case for liver transplantation in end-stage alcoholic liver disease.

Liver transplantation is now a routine procedure and is seen as a valid treatment option for end-stage liver disease. Alcoholism has been regarded as a relative or absolute contraindication to liver transplantation in many transplant units. Recent data document a success rate for transplantation in alcoholic patients that equals that in other patient groups. Issues relating to the ethical and scientific arguments surrounding this complex area of treatment are discussed. It is concluded that individual patients should be assessed in their own right for this treatment option. It is argued that patient groups should not be denied access to specific life-saving treatments.

Alcohol-related liver disease: treatment controversies.

The therapy of alcohol-related liver disease remains relatively unsatisfactory despite years of research designed to understand the pathogenesis of alcoholic liver injury and the processes involved in recovery from alcohol-related liver injury. Drugs such as the corticosteroids and colchicine appear to have a place in the management of some patients with alcohol-related liver disease but their use is not widespread in clinical practice. Liver transplantation has become an increasingly used therapy in patients with advanced liver disease but the enthusiasm of the early 1990s is now being replaced by a more cautious approach, particularly to those who have not abstained from alcohol for a significant period prior to transplant assessment. The brightest area in any discussion of treatment approaches to alcoholic liver disease is that of predicting the future. A number of agents designed to modify the inflammatory response and the endotoxaemia associated with significant alcoholic liver injury may be more beneficial than current drugs used for severe alcoholic hepatitis or cirrhosis. As in all discussions of alcohol-related liver disease and its management, it is important to highlight the need to exclude other forms of liver injury in patients who drink heavily as those diseases respond more to specific therapies than does alcoholic liver disease. The underlying therapy for all patients with alcoholic liver disease is abstinence from alcohol and the importance of encouraging patients to cease their damaging intake of alcohol can not be overemphasised.

Effects of alcohol, carbon tetrachloride, and choline deficiency on iron metabolism in the rat.

The effects of alcohol on hepatic iron uptake and intestinal iron transport were studied in rats fed a nutritionally replete liquid diet containing varying quantities of ethanol. Results were compared with those from animals exposed to carbon tetrachloride (CCl4) to produce hepatocellular necrosis or a choline-deficient diet to produce steatosis and cirrhosis. A high ethanol intake for 4 or 10 weeks produced hepatic steatosis. CCl4 produced hepatocellular necrosis. Choline deficiency was associated with steatosis +/- cirrhosis. Intestinal iron transport was unaffected by ethanol, CCl4, or choline deficiency. Hepatic iron uptake was significantly depressed in rats consuming 11.7 g/kg/day ethanol (p < 0.01) for 4 weeks. Choline-deficient animals studied at 14 weeks also had significantly decreased hepatic iron uptake (p < 0.01); results were similar in the cirrhotic and noncirrhotic animals. Conversely, CCl4 exposure produced a significant 5-fold increase in hepatic iron uptake (p < 0.001). Results suggest that ethanol consumption, fatty liver, and cirrhosis are not responsible for any increase in iron absorption or of hepatic iron uptake in the rat model. Acute hepatocellular injury is followed by increased hepatic iron uptake.