ACUTE HEPATITIS A
There is no specific treatment for hepatitis A other than supportive care.Equilibrated diet and relative rest can be advised during symptomatic phase.

HEPATITIS B
No therapy for acute hepatitis.Currently the only two approved therapies for chronic hepatitis B in most countries are interferon alpha and lamivudine.
Less than 50% of patients are candidate for interferon therapy. Initially 40% of HbeAg positive patients respond to treatment; however, some relapse when interferon is stopped. Overall about 30% of the eligible patients benefit. In HbeAb negative patients the response is less evident with a sustained response non superior to 20-25% of treated patients.
Lamivudine is an orally administered nucleoside analog which is highly effective in inhibiting HBV replication.Many studies have shown that a 1-year course of lamivudine monotherapy induces HbeAg seroconversion in about 18% of patients. Follow-up has found that the antiviral response is durable in about 85% of patients. This drug has also been demonstrated to be effective in HbeAg negative hepatitis.Lamivudine is very well tolerated and it has been reported to be safe and effective in improving liver function in patients with decompensated cirrhosis or recurrent hepatitis B post liver transplantation.
A major problem of lamivudine treatment is the development of drug-resistent mutants of the HBV.
The association of lamivudine and interferon and other new antiviral drugs are being evaluated in clinical trials.

GUIDE LINES ON HEPATITIS B THERAPY 
(10th INTERNATIONAL SYMPOSIUM ON VIRAL HEPATITIS AND LIVER DISEASE: ATLANTA, APRIL 2000)

HEPATITIS C
The objective of therapy is to inhibit viral replication or better to eliminate the virus, to decrease inflammation, to reduce fibrosis.
These goals are believed to be associated with a reduced risk of occurrence of cirrhosis and hepatocellular carcinoma.
In chronic hepatitis C the antiviral effect of alpha-interferon is well demonstrated.
Sustained responses with persistently normal ALT and undetectable HCVRNA 6 months after stopping the treatment, are obtained in about 20-25% of subjects treated with interferon.
The dosage of this drug varied from 3 to 6 MU/3 three times weekly for 6 or 12 months.
Today the therapy is the association of interferon + ribavirin for 6 or 12 months. The response rate of this association is superior to interferon alone. Two large controlled international trials showed that combination therapy for 24 or 48 weeks gives overall sustained virological and biochemical response rate of 33% and 41% respectively, versus 6% and 16% with interferon alone.
These results led to the consideration of combination therapy as reference treatment for chronic hepatitis C, as stated by the European Association Study of The Liver (International Consensus Conference on Hepatitis C, Paris, 26th-28th February 1999).
Pegylated interferon, which is under study, is an alpha interferon attached to Polyethylene glycol (PEG), resulting in longer-acting ativity of the drug. If the activity of interferon, is prolonged by the attachment to PEG, the frequency that interferon would need to be administered each week would be decreased.
In fact, a once- a week dose of PEG-interferon showed efficacy against HCV similar or superior to that of interferon administered three times a week.. This, in turn, would result in improved patient compliance, as one injection per week is easier to handle than three.. Further evaluation is needed before definitive conclusions can be drawn.
Other studies now are evaluating the efficacy of the association of Pegylate interferon and ribavirin. Initial results are encouraging. If response rates prove to be as expected, this therapy may become the standard of care for people with chronic hepatitis C.

CRITERIA FOR TREATMENT OF CHRONIC HEPATITIS C

• Increased serum ALT for more than 6 months

• Detectable serum HCVRNA

• Compensated liver disease

• Abstinence (drugs and alcohol)

• Age less than 65 years

• A compliant patient

• No contraindication to therapy

CONTRAINDICATIONS TO ANTIVIRAL THERAPY FOR CHRONIC HEPATITIS C

OPTIMAL TREATMENT IN NAIVE PATIENTS
(EASL INTERNATIONAL CONSENSUS CONFERENCE
ON HEPATITIS C : Paris 26th-28th February 1999)

OPTIMAL TREATMENT IN RELAPSER PATIENTS
(EASL INTERNATIONAL CONSENSUS CONFERENCE
ON HEPATITIS C : Paris 26th-28th February 1999)

• IFN 3 MU x 3 weekly+ Ribavirine (1000-1200mg daily) for 24 weeks

• IFN > 3 MU x 3 weekly for 48 months

OPTIMAL TREATMENT IN NON-RESPONDER PATIENTS                        
(EASL INTERNATIONAL CONSENSUS CONFERENCE
ON HEPATITIS C : Paris 26th-28th February 1999)
There are no clear data to indicate that retreatment will be beneficial

SIDE EFFECTS OF THERAPY

HEPATITIS D
The only partially useful drug is interferon, which should be used at high dosage and for long time.
Prevention of HDV infection is based on HBV vaccination in susceptible individuals.

ACUTE HEPATITIS E
There is no specific treatment. Equilibrated diet and relative rest are advisable during symptomatic phase.

AUTOIMMUNE HEPATITIS
Patients with Autoimmune Hepatitis are efficiently treated by immunisoppressive therapy.
Currently the treatment consists in prednisone, often associated to azathioprine.
These drugs are tapered in months depending on the patient response.
In non-responsive patients (about 10%) other immunosoppressive drugs can be used (cyclosporine, tacrolimus, micophenolate mofetil etc.)

ALCOHOL-RELATED LIVER DISEASE
The most important therapeutic approach is the immediate and total alcohol withdrawal. This often requires period of admission to hospital in order to treat abstinence syndrome (delirium tremens and seizures).
Moreover the patient should follow a programme of psychological rehabilitation partecipating in support groups such as Alcoholics Anonymus.
The cessation of alcohol has often a favourable prognosis and even cirrhotic patients can ameliorate and progressive liver deterioration can be avoided.
In case of very advanced liver disease, if there is no improvement in liver function tests within 6 months and if the abstinence has continued, liver transplantation can be the only chance for the patient. 

DRUG-INDUCED LIVER DISEASE
There is no specific therapy for drug-induced liver disease, the main approach being to immediately stop the administration of the involved drug.
In fulminant hepatitis only liver transplantation can save the patient. 

LIVER CIRRHOSIS
Liver cirrhosis is irreversible but treatment of the underlying disease may slow or stop the progression.The therapy is related to the cause of the cirrhosis.
In alcoholic forms total abstinence from alcohol is mandatory
In cirrhosis related to Hepatitis B virus, lamivudine is effective even in advanced cases.
In cirrhosis due to Hepatitis C Virus, interferon, interferon+ ribavirin can reduce inflammation, fibrosis and probably the risk of hepatocellular carcinoma occurrence. The new pegylated interferon, under study , administered once a week for long time, might be the drug of choice for this aim in the future. These drugs cannot be administrated to advanced liver cirrhosis because of the side effects.
In these cases treatment must be directed at the complications.
Ascites and edema are treated with low sodium diet, water restriction and administration of diuretics. In non-responding patients paracenthesis has to be performed (evacuation by a needle of fluids from abdomen)
Bleeding esophageal varices are treated with endoscopic sclerotherapy or rubber band ligation. The rupture can be prevented by the administration of some drugs (e.g.betablockers)
Encephalopathy responds to low protein diet and lactulose.
Liver transplantation is highly effective for the treatment of end-stage cirrhosis.

HEPATOCELLULAR CARCINOMA
A complete cure for an early HCC is only possible with liver transplantion .This ideal treatment is rarely achieved because of the extension of the majority of HCC when diagnosed and because of the limited availability of liver donors. It is possible that this problem could be overcome in the future with living donors or the xenotransplant
Surgical resection is another therapeutic approach limited to patient with good liver function tests and to small superficial tumors. These patients must be accurately studied before  surgery to exclude the presence of other nodules.
Among non surgical options local ablation therapy has been demonstrated to be useful.
Percoutaneous ethanol and more recently acetic acid injected directly into the tumour, can be considered the treatment of choice for patients with small (3cm) unresectable HCC.
Studies showed the achievement of complete necrosis of such small tumours, without adverse effect.Patients treated with this methodology had high long-term survival rates similar to that of patients submitted to surgical resection. Another more recent approach utilizes the heat produced by laser or radiofrequency.
Transarterial chemoembolization  which is performed by intraarterial injection and infusion of antineoplatic agent mixed with iodized oil, lipiodol,and closing peripherally the artery with spongostan is advised in cases of larger HCC. Massive tumor necrosis has been demonstrated in many treated patients: however complete necrosis is rarely achieved particularly in large tumours (superior to 5-6 cm.): consequently residual tumour can be found in a certain number of the treated lesions.
The liver tumours can also be treated with a combination of therapy suchs as chemoebolization and alcohol injection.