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Chloroquine was used unsuccessfully in attempts to treat opisthorchiasis in 1951-1968. Control of opisthorchiasis relies predominantly on antihelminthic treatment with praziquantel. The single dose of praziquantel of 40 mg/kg is effective against opisthorchiasis (and also against schistosomiasis). Despite the efficacy of this compound, the lack of an acquired immunity to infection predisposes humans to reinfections in endemic regions. In addition, under experimental conditions, the short-term treatment of "Opisthorchis viverrini"-infected hamsters with praziquantel (400 mg per kg of live weight) induced a dispersion of parasite antigens, resulting in adverse immunopathological changes as a result of oxidative and nitrative stresses following re-infection with "Opisthorchis viverrini", a process which has been proposed to initiate and/or promote the development of cholangiocarcinoma in humans. Albendazole can be used as an alternative.
A randomised-controlled trial published in 2011 showed that the broad-spectrum anti-helminthic, tribendimidine, appears to be at least as efficacious as praziquantel. Artemisinin was also found to have anthelmintic activity against "Opisthorchis viverrini".
Effective prevention could be readily achieved by persuading people to consume cooked fish (via education programs), but the ancient cultural custom to consume raw, undercooked or freshly pickled fish persists in endemic areas. One community health program, known as the "Lawa" model, has achieved success in the Lawa Lakes region south of Khon Kaen. Currently, there is no effective chemotherapy to combat cholangiocarcinoma, such that intervention strategies need to rely on the prevention or treatment of liver fluke infection/disease.
Cooking or deep-freezing (-20 °C for 7 days) of food made of fish is sure method of prevention. Methods for prevention of "Opisthorchis viverrini" in aquaculture fish ponds were proposed by Khamboonruang et al. (1997).
Several drugs are effective for fascioliasis, both in humans and in domestic animals. The drug of choice in the treatment of fasciolosis is triclabendazole, a member of the benzimidazole family of anthelmintics. The drug works by preventing the polymerization of the molecule tubulin into the cytoskeletal structures, microtubules. Resistance of "F. hepatica" to triclabendazole has been recorded in Australia in 1995 and Ireland in 1998.
Praziquantel treatment is ineffective.
There are case reports of nitazoxanide being successfully used in human fasciolosis treatment in Mexico. There are also reports of bithionol being used successfully.
More recently, Mirazid, an Egyptian drug made from myrrh, has been investigated as an oral treatment of trematode-caused ailments including fascioliasis.
Nitazoxanide has been found effective in trials, but is currently not recommended. The life cycle includes freshwater snails as an intermediate host of the parasite.
Praziquantel is the drug of choice for treatment. Treatment is effective in early or light infections. Heavy infections are more difficult to treat. Studies of the effectiveness of various drugs for treatment of children with "F. buski" have shown tetrachloroethylene as capable of reducing faecal egg counts by up to 99%. Other anthelmintics that can be used include thiabendazole, mebendazole, levamisole and pyrantel pamoate. Oxyclozanide, hexachlorophene and nitroxynil are also highly effective.
The drug of choice to treat paragonimiasis is praziquantel, although bithionol may also be used.
Praziquantel is recommended in both adult and pediatric cases with dosages of 75 mg/kg/d in 3 doses for 1 day. Praziquantel is a Praziniozoquinoline derivative that alters the calcium flux through the parasite tectum and causes muscular paralysis and detachment of the fluke. Prizaquantel should be taken with liquids during a meal and as provided commercially as Biltricide. Praziquantel is not approved by the U.S. Food and Drug Administration (FDA) for treatment of metagonimiasis, but is approved for use on other parasitic infections.
Praziquantel has some side effects but they are generally relatively mild and transient and a review of evidence shows it overall a well-tolerated drug. Possible side effects include abdominal pain, allergy, diarrhea, headache, liver problems, nausea or vomiting, exacerbation of porphyries, pruritis, rash, somnolence, vertigo, or dizziness. In fact, in 2002, the World Health Organization recommended the use of Praziquantel in pregnant and lactating women, though controlled trials are still needed to verify this.
Another possible drug option is Tetrachloroethylene, a chlorinated hydrocarbon, but its use has been superseded by new antihelminthic drugs (like Praziquantel). A 1978 study also looked at the efficacy of several drugs on metagonimiasis infection, including bithionol, niclosamide, nicoflan, and Praziquantel. All drugs showed lower prevalence of eggs in feces, however only Praziquantel showed complete radical cure. Therefore, the authors concluded Praziquantel was the most highly effective, was very well tolerated, and was the most promising drug against metagonimiasis.
Amphistomiasis is considered a neglected tropical disease, with no prescription drug for treatment and control. Therefore, management of infestation is based mainly on control of the snail population, which transmit the infective larvae of the flukes. However, there are now drugs shown to be effective including resorantel, oxyclozanide, clorsulon, ivermectin, niclosamide, bithional and levamisole. An in vitro demonstration shows that plumbagin exhibits high efficacy on adult flukes. Since the juvenile flukes are the causative individuals of the disease, effective treatment means control of the immature fluke population. Prophylaxis is therefore based on disruption of the environment (such as proper drainage) where the carrier snails inhabit, or more drastic action of using molluscicides to eradicate the entire population. For treatment of the infection, drugs effective against the immature flukes are recommended for drenching. For this reason oxyclozanide is advocated as the drug of choice. It effectively kills the flukes within a few hours and it effective against the flukes resistant to other drugs. The commercially prescribed dosage is 5 mg/kg body weight or 18.7 mg/kg body weight in two divided dose within 72 hours. Niclosamide is also extensively used in mass drenching of sheep. Successfully treated sheep regain appetite within a week, diarrhoea stops in about three days, and physiological indicators (such as plasma protein and albumin levels) return to normal in a month.
Infection can be prevented by immersing vegetables in boiling water for a few seconds to kill the infective metacercariae, avoiding the use of untreated feces ("nightsoil") as a fertilizer, and maintenance of proper sanitation and good hygiene. Additionally, snail control should be attempted.
Several public health prevention strategies could help lower the rates of metagonimiasis. One is to control the intermediate host (snails). This can be done through use of molluscidals. Another is to use education to ensure all people, especially in areas were the disease regularly occurs, fully cook all fish. This could potentially be problematic and not as effective as hoped as many of the people affected by metagonimiasis eat raw or pickled fish as part of a traditional, long-seated dietary practice. Additionally, implementing more sanitary water conditions would reduce the continual reintroduction of eggs to water sources, thus restarting the lifecycle. Complete control of metagonimiasis presents several potential problems because it does have several reservoir hosts, thus eradication is unlikely.
In order to control for the disease, the "Lymnaea" spp snails, which are the intermediate host for the liver flukes, need to be controlled. There are three ways that have proven most effective when controlling the snail populations:
- The first is by treating pastures and water channels with copper sulfate. This method is not always practical, because it is too expensive to treat in large areas. Lack of cooperation between neighbors is also a problem, snails are easily transported, and treated pastures become re-infested by neighboring fields and streams.
- Drenching the sheep with carbon tetra-chloride in paraffin oil has proven to be an alternative. However, drenching in more than recommended doses can be fatal, by causing liver damage, which could initiate the disease in sheep carrying "B. oedematiens" spores.
- Drainage is an effective option to eliminate the snails. However, draining the places where the grass grows eliminates a source of food for the sheep and creates other unwanted problems.
Liver fluke is a collective name of a polyphyletic group of parasitic trematodes under the phylum Platyhelminthes.
They are principally parasites of the liver of various mammals, including humans. Capable of moving along the blood circulation, they can occur also in bile ducts, gallbladder, and liver parenchyma. In these organs, they produce pathological lesions leading to parasitic diseases. They have complex life cycles requiring two or three different hosts, with free-living larval stages in water.
The body of liver flukes is leaf-like, and flattened. The body is covered with a tegument. They are hermaphrodites having complete sets of both male and female reproductive systems. They have simple digestive systems, and primarily feed on blood. The anterior end is the oral sucker opening into the mouth. Inside, mouth lead to a small pharynx which is followed by an extended intestine that runs through the entire length of the body. The intestine is heavily branched and anus is absent. Instead the intestine runs along an excretory canal that opens at the posterior end. Adult flukes produce eggs which are passed out through the excretory pore. The eggs infect different species of snails (as intermediate hosts) in which they grow into larvae. The larvae are released into the environment from where the definitive hosts (humans and other mammals) get the infection. In some species, another intermediate host is required, generally a cyprinid fish. In this case, the definitive hosts are infected from eating infected fish. Hence, they are food-borne parasites.
This is another derivative of the parent drug and its results are better than niridazole. This amoebicide acts directly on the trophozoites of "E. Histolytica". Studies showed that because of very high concentration in the liver extremely small amounts of the drug were effective in amoebic liver abscess, but with such low doses, eradication of amoebae in the bowel was uncertain. The drug is quickly absorbed, partly metabolized, and rapidly excreted without any cumulative effect. It is more active in the tissues than in the gut lumen. It follows that a higher dosage is needed in the cure of luminal than systemic infection.
The side effects of metronidazole are infrequent. Gastro-intestinal symptoms and headache occur occasionally. Heavy coating of tongue, brownish urine, metallic taste, dry mouth, and nausea occur more often. Vertigo, incoordinate ataxia, and paraesthesias have been reported on rare occasions. Tsai et al. observed psychosis which usually disappeared within a day or two after metronidazole was withdrawn, but tremors and muscle spasm lasted for several days. It has an antabuse-like action and alcohol should be avoided during its use. A transitory leucopenia may occur. Cardiovascular symptoms are rare. Treatment should be discontinued promptly if ataxia or any other symptoms of C.N.S. involvement occur.
Only a few years ago when metronidazole was introduced it was considered to be the last word in the therapy of amoebiasis. However, the recent evidence that this drug is carcinogenic and possibly mutagenic in animals is disturbing. Due to such reports the use of the drug remains controversial, especially as metornidazole is a very widely and commonly used antibiotic. The potential risk in human beings must be weighed against the severity of the disease.
The oral dose of 400 mg. thrice daily for 5 days suffices for the treatment of amoebic liver abscess. Adams29 in his analysis of 2,074 cases of liver abscess preferred metronidazole to other amoebicidal agents. A single oral dose of 2.5 G. metronidazole combined with closed aspiration has also produced dramatic response and cure in patients with amoebic liver abscess. Recently the use of intravenous preparation of metronidazole has been reported. Studies by Lazarachick et a revealed presence of anaerobic bacteroides in as many as 26% cases of amoebic liver abscess with so called 'sterile' pus. Intravenous metronidazole is a drug of choice for anaerobic infections Therefore it may be of extra advantage, if used in amoebic liver abscess.
Metronidazole should not be used as a single agent for the eradication of bowel infection.33 When used alone, a few cases are known to have developed amoebic liver abscess, months after apparently successful cure of dysentery. Cases refractory to metronidazole have been occasionally described.
This nitroimidazole compound, like metronidazole, has shown a marked therapeutic response in amoebic liver abscess. Occasional side effects include nausea and dizziness. Tinidazole is not widely available though it is more effective than metronidazole. Zuberi and Ibrahim found tinidazole to be effective in 86.7% cases of intestinal amoebiasis and in 100% cases of amoebic liver abscess.
Luminal amoebicides like halogenated oxyquinolines, e.g. diiodohydroxyquinoline in a dose of 0.6 G. thrice daily for 3 weeks, diloxanide furoate 0.5 G. three times a day for 10 days and sometimes tetracyclines 1–2 G./day for 5 days should be used concurrently with any of the above drugs as adjuncts to eliminate intestinal infection.
Clonorchiasis is an infectious disease caused by the Chinese liver fluke, "Clonorchis sinensis", and two related species.
Clonorchiasis is a known risk factor for the development of cholangiocarcinoma, a neoplasm of the biliary system.
Symptoms of opisthorchiasis caused by "Opisthorchis viverrini" and by "Opisthorchis felineus" are indistinguishable from clonorchiasis caused by "Clonorchis sinensis", so the disease by these three parasites should be referred as clonorchiasis.
No pharmacologic treatment has been approved by the U.S. Food and Drug Administration for PSC. Some experts recommend a trial of ursodeoxycholic acid (UDCA), a bile acid occurring naturally in small quantities in humans, as it has been shown to lower elevated liver enzyme numbers in patients with PSC and has proven effective in other cholestatic liver diseases. However, UDCA has yet to be shown to clearly lead to improved liver histology and survival. Guidelines from the American Association for the Study of Liver Diseases and the American College of Gastroenterology do not support the use of UDCA but guidelines from the European Association for the Study of the Liver do endorse the use of moderate doses (13-15 milligrams per kilogram) of UDCA for PSC.
Supportive treatment for PSC symptoms is the cornerstone of management. These therapies are aimed at relieving symptoms such as itching with antipruritics (e.g. bile acid sequestrants such as (cholestyramine)); antibiotics to treat episodes of acute cholangitis; and vitamin supplements, as people with PSC are often deficient in fat-soluble vitamins (vitamin A, vitamin D, vitamin E, and vitamin K).
ERCP and specialized techniques may also be needed to help distinguish between a benign PSC stricture and a bile duct cancer (cholangiocarcinoma).
Liver transplantation is the only proven long-term treatment of PSC, although only a fraction of individuals with PSC will need it. Indications for transplantation include recurrent bacterial cholangitis, decompensated cirrhosis, hepatocellular carcinoma, hilar cholangiocarcinoma, and complications of portal hypertension. Not all patients are candidates for liver transplantation, and some will experience disease recurrence afterward.
The treatment of chronic liver disease depends on the cause. Specific conditions may be treated with medications including corticosteroids, interferon, antivirals, bile acids or other drugs. Supportive therapy for complications of cirrhosis include diuretics, albumin, vitamin K, blood products, antibiotics and nutritional therapy. Other patients may require surgery or a transplant. Transplant is required when the liver fails and there is no other alternative.
Many herbal and antioxidant remedies have been advocated for chronic liver disease but the evidence is not conclusive. Some support may be found in the orthodox medical use of two of these: N-acetyl cysteine (NAC), is the treatment of choice for acetaminophen overdose; both NAC and milk-thistle (Silybum marianum) or its derivative silibinin are used in liver poisoning from certain mushrooms, notably amanita phalloides, although the use of milk-thistle is controversial. Some common herbs are known or suspected to be harmful to the liver, including black cohosh, ma huang, chaparral, comfrey, germander, greater celandine, kava, mistletoe, pennyroyal, skull cap and valerian.
If complications cannot be controlled or when the liver ceases functioning, liver transplantation is necessary. Survival from liver transplantation has been improving over the 1990s, and the five-year survival rate is now around 80%. The survival rate depends largely on the severity of disease and other medical risk factors in the recipient. In the United States, the MELD score is used to prioritize patients for transplantation. Transplantation necessitates the use of immune suppressants (ciclosporin or tacrolimus).
The treatment depends on clinical features and the location of the biliary abnormality. When the disease is localized to one hepatic lobe, hepatectomy relieves symptoms and appears to remove the risk of malignancy. Good evidence suggests that malignancy complicates Caroli disease in roughly 7% of cases.
Antibiotics are used to treat the inflammation of the bile duct, and ursodeoxycholic acid is used for hepatolithiasis. Ursodiol is given to treat cholelithiasis. In diffuse cases of Caroli disease, treatment options include conservative or endoscopic therapy, internal biliary bypass procedures, and liver transplantation in carefully selected cases. Surgical resection has been used successfully in patients with monolobar disease. An orthotopic liver transplant is another option, used only when antibiotics have no effect, in combination with recurring cholangitis. With a liver transplant, cholangiocarcinoma is usually avoided in the long run.
Family studies are necessary to determine if Caroli disease is due to inheritable causes. Regular follow-ups, including ultrasounds and liver biopsies, are performed.
Generally, liver damage from cirrhosis cannot be reversed, but treatment can stop or delay further progression and reduce complications. A healthy diet is encouraged, as cirrhosis may be an energy-consuming process. Close follow-up is often necessary. Antibiotics are prescribed for infections, and various medications can help with itching. Laxatives, such as lactulose, decrease the risk of constipation; their role in preventing encephalopathy is limited.
Alcoholic cirrhosis caused by alcohol abuse is treated by abstaining from alcohol. Treatment for hepatitis-related cirrhosis involves medications used to treat the different types of hepatitis, such as interferon for viral hepatitis and corticosteroids for autoimmune hepatitis. Cirrhosis caused by Wilson's disease, in which copper builds up in organs, is treated with chelation therapy (for example, penicillamine) to remove the copper.
Anti-viral medications are available to treat infections such as hepatitis B. Other conditions may be managed by slowing down disease progression, for example:
- By using steroid-based drugs in autoimmune hepatitis.
- Regularly removing a quantity of blood from a vein (venesection) in the iron overload condition, hemochromatosis.
- Wilson’s disease, a condition where copper builds up in the body, can be managed with drugs which bind copper allowing it to be passed from your body in urine.
- In cholestatic liver disease, (where the flow of bile is affected due to cystic fibrosis) a medication called ursodeoxycholic acid (URSO, also referred to as UDCA) may be given.
Fasciolosis (also known as fascioliasis, fasciolasis, distomatosis and liver rot) is a parasitic worm infection caused by the common liver fluke "Fasciola hepatica" as well as by "Fasciola gigantica". The disease is a plant-borne trematode zoonosis, and is classified as a neglected tropical disease (NTD). It affects humans, but its main host is ruminants such as cattle and sheep. The disease progresses through four distinct phases; an initial incubation phase of between a few days up to three months with little or no symptoms; an invasive or acute phase which may manifest with: fever, malaise, abdominal pain, gastrointestinal symptoms, urticaria, anemia, jaundice, and respiratory symptoms. The disease later progresses to a latent phase with less symptoms and ultimately into a chronic or obstructive phase months to years later. In the chronic state the disease causes inflammation of the bile ducts, gall bladder and may cause gall stones as well as fibrosis. While chronic inflammation is connected to increased cancer rates, it is unclear whether fasciolosis is associated with increased cancer risk.
Up to half of those infected display no symptoms, and diagnosis is difficult because the worm eggs are often missed in fecal examination. The methods of detection are through fecal examination, parasite-specific antibody detection, or radiological diagnosis, as well as laparotomy. In case of a suspected outbreak it may be useful to keep track of dietary history, which is also useful for exclusion of differential diagnoses. Fecal examination is generally not helpful because the worm eggs can seldom be detected in the chronic phase of the infection. Eggs appear in the feces first between 9–11 weeks post-infection. The cause of this is unknown, and it is also difficult to distinguish between the different species of fasciola as well distinguishing them from echinostomes and "Fasciolopsis". Most immunodiagnostic tests detect infection with very high sensitivity, and as concentration drops after treatment, it is a very good diagnostic method. Clinically it is not possible to differentiate from other liver and bile diseases. Radiological methods can detect lesions in both acute and chronic infection, while laparotomy will detect lesions and also occasionally eggs and live worms.
Because of the size of the parasite, as adult "F. hepatica": or adult "F. gigantica:" 25–75×12 mm, fasciolosis is a big concern. The amount of symptoms depend on how many worms and what stage the infection is in. The death rate is significant in both sheep and cattle, but generally low among humans. Treatment with triclabendazole has been highly effective against the adult worms as well as various developing stages. Praziquantel is not effective, and older drugs such as bithionol are moderately effective but also cause more side effects. Secondary bacterial infection causing cholangitis has also been a concern and can be treated with antibiotics, and toxaemia may be treated with prednisolone.
Humans are infected by eating watergrown plants, primarily wild-grown watercress in Europe or morning glory in Asia. Infection may also occur by drinking contaminated water with floating young fasciola or when using utensils washed with contaminated water. Cultivated plants do not spread the disease in the same capacity. Human infection is rare, even if the infection rate is high among animals. Especially high rates of human infection have been found in Bolivia, Peru and Egypt, and this may be due to consumption of certain foods. No vaccine is available to protect people against "Fasciola" infection. Preventative measures are primarily treating and immunization of the livestock, which are required to host the live cycle of the worms. Veterinary vaccines are in development, and their use is being considered by a number of countries on account of the risk to human health and economic losses resulting from livestock infection. Other methods include using molluscicides to decrease the number of snails that act as vectors, but it is not practical. Educational methods to decrease consumption of wild watercress and other waterplants has been shown to work in areas with a high disease burden.
In some areas special control programs are in place or have been planned. The types of control measures depend on the setting (such as epidemiologic, ecologic, and cultural factors). Strict control of the growth and sale of watercress and other edible water plants is important. Individual people can protect themselves by not eating raw watercress and other water plants, especially from endemic grazing areas. Travelers to areas with poor sanitation should avoid food and water that might be contaminated (tainted). Vegetables grown in fields, that might have been irrigated with polluted water, should be thoroughly cooked, as should viscera from potentially infected animals.
Fascioliasis occurs in Europe, Africa, the Americas as well as Oceania. Recently, worldwide losses in animal productivity due to fasciolosis were conservatively estimated at over US$3.2 billion per annum. Fasciolosis is now recognized as an emerging human disease: the World Health Organization (WHO) has estimated that 2.4 million people are infected with "Fasciola", and a further 180 million are at risk of infection.
Untreated, the disease has a mortality rate upwards of 90%. Cats treated in the early stages can have a recovery rate of 80–90%. Left untreated, the cats usually die from severe malnutrition or complications from liver failure. Treatment usually involves aggressive feeding through one of several methods.
Cats can have a feeding tube inserted by a veterinarian so that the owner can feed the cat a liquid diet several times a day. They can also be force-fed through the mouth with a syringe. If the cat stops vomiting and regains its appetite, it can be fed in a food dish normally. The key is aggressive feeding so the body stops converting fat in the liver. The cat liver has a high regeneration rate and the disease will eventually reverse assuming that irreparable damage has not been done to the liver.
The best method to combat feline hepatic lipidosis is prevention and early detection. Obesity increases the chances of onset. In addition, if a cat stops eating for 1–2 days, it should be taken to a vet immediately. The longer the disease goes untreated, the higher the mortality rate.
There is no specific treatment for neonatal hepatitis. Vitamin supplements are usually prescribed and many infants are given phenobarbital, a drug used to control seizures, but which also stimulates the liver to excrete additional bile. Formulas containing more easily digested fats are also given to the infant.
Neonatal hepatitis caused by the hepatitis A virus also usually resolves itself within six months, but cases that are the result of infection with the hepatitis B or hepatitis C viruses most likely will result in chronic liver disease. Infants who develop cirrhosis ultimately will need a liver transplant.