SURVEILLANCE

• HBV carriers at high risk for HCC such as men over 45 years, persons with cirrhosis, and persons with a family history of HCC, should be screened periodically with both AFP and US.
• While there are insufficient data to recommend routine screening in low-risk patients with chronic HBV infection, periodic screening for HCC with AFP in carriers from endemic areas should be considered.

PROGNOSIS
• The rate of progression from acute to chronic hepatitis B is primarily determined by the age at infection. The rate is approximately 90 percent for perinatally acquired infection [57], 20 to 50 percent for infections between the age of one and five years [58,59], and less than 5 percent for adult-acquired infection
• Approximately 30 to 50 percent of patients with chronic HBV infection have a past history of acute hepatitis
• In a 16-year follow-up study of 317 HBsAg positive blood donors from Montreal, for example, only three died from HBV-related cirrhosis and none developed HCC [60]. Another report included 296 potential blood donors who were excluded from donation after they were found to be HBsAg positive and were followed for 30 years [61]. The incidence of clinically significant liver disease, HCC, or other liver-related morbidity or mortality was not significantly greater than a control population of HBV negative blood donors.
• The prognosis is not so good in HBV-infected patients from endemic areas and in patients with chronic hepatitis B [62-65]. The estimated five-year rates of progression are: Chronic hepatitis to cirrhosis — 12 to 20 percent, Compensated cirrhosis to hepatic decompensation — 20 to 23 percent, Compensated cirrhosis to HCC — 6 to 15 percent.


COUNCELLING
• Patients with chronic HBV infection should be counseled regarding lifestyle modifications and prevention of transmission.
• There are no specific dietary measures that have been shown to have any effect on the progression of chronic hepatitis B. However, heavy use of alcohol (>40 g/day) has been associated with higher ALT levels and development of cirrhosis. In addition, the development of cirrhosis and HCC occurs at a younger age in heavy drinkers with chronic hepatitis B. So advise abstinence or only limited use of alcohol is recommended in hepatitis B carriers
• Persons who are HBsAg-positive should
1. Have sexual contacts vaccinated
2. Use barrier protection during sexual intercourse if partner not vaccinated or naturally immune
3. Not share toothbrushes or razors
4. Cover open cuts and scratches
5. Clean blood spills with detergent or bleach
6. Not donate blood, organs or sperms
• Children and adults who are HBsAg-positive:
1. Can participate in all activities including contact sports
2. Should not be excluded from daycare or school participation and should not be isolated from other children
3. Can share food, utensils or kiss others

HEPATITIS D
• Hepatitis D which is an incomplete ribonucleic acid (RNA) virus that requires the hepatitis B virus outer coat so cannot occur without it and is cleared when the latter is cleared [66].
EPIDEMIOLOGY [67]
• Available data suggest that approximately 5 percent of the HBV carriers worldwide may be infected with HDV [31].
• Since the number of HBV carriers has been estimated to be around 300 million, the number of individuals infected with HDV worldwide is estimated to be 15 million.
• The geographical distribution of HDV infection, however, does not parallel that of HBV, as areas endemic for HBV may be almost HDV-free. The level of HDV endemicity is partly related to the route of transmission.
RISK FACTORS
• Intravenous drug users (IVDUs)
• Their sexual partners but also is seen in
• Female sex workers, and
• Sporadically occurs in other groups

CLINICAL FEATURES
• Due to its dependence upon HBV, HDV infection always occurs in association with HBV infection. The clinical and laboratory findings vary with the type of infection
• Coinfection — Coinfection of HBV and HDV in an individual susceptible to HBV infection (ie, anti-HBs-negative) results in acute hepatitis B + D. This entity is clinically indistinguishable from classical acute hepatitis B and is usually transient and self-limited. However, a high incidence of liver failure has been reported among drug addicts [68].
• Superinfection — HDV superinfection of a chronic HBsAg carrier may present as an unusually severe acute hepatitis in a previously unrecognized HBV carrier, or as an exacerbation of preexisting chronic hepatitis B. Progression to chronic HDV infection occurs in almost all patients [69]. However, HBV replication is usually suppressed by HDV.
• Helper-independent latent infection — A third form of infection is a helper-independent latent infection which can be rescued by the helper virus at a later time. This form of infection was initially observed in the liver transplantation setting.[70]




SYMPTOMS
• If patient of Hepatitis B develops acute hepatitis, if chronic hepatitis B carriers get a further attack of acute hepatitis, or if the liver disease in chronic hepatitis B virus is rapidly progressive suspect Hepatitis D [71]
• If patient has Hepatitis D there is a high rate of fulminant hepatitis and progression of chronic hepatitis to cirrhosis
• If patient has Hepatitis long-standing chronic hepatitis D and B often have inactive cirrhosis [71].
• If patient has Hepatitis D, they have a threefold increased risk of hepatocellular carcinoma.

INVESTIGATIONS
• In acute HDV infection, serum HDAg appears early but is very short-lived and may escape detection if repeated testing is not performed [72].
• In chronic HDV infection, anti-HDV is present in high titers.
• Diagnosis is confirmed by a positive - anti-HDV antibody or hepatitis delta virus - ribonucleic acid (HDV-RNA) test

TREATMENT
• If patient has Hepatitis D response to anti-viral therapy is poor
• There is no specific treatment for acute hepatitis D. In one report, all three patients treated with foscarnet for fulminant hepatitis due to HDV recovered, as did two additional patients with fulminant hepatitis due to HBV alone. Although these results are encouraging, they need to be confirmed [73].
• The only drug approved at present for treatment of chronic hepatitis D is interferon alfa (IFNa). There is no experience with either IFN beta or gamma in this disorder [74].
• If patient has Hepatitis D, the recommended dose regimen is standard IFNa 9 MU TIW for at least 12 months, although longer treatment has been advocated [74].
• If patient has Hepatitis D, in light of new data, pegylated IFN may replace standard IFNa as the treatment of choice for chronic hepatitis D [74].
• If patient has Hepatitis D, early attempts to treat hepatitis D with immunomodulatory drugs, such as corticosteroids or levamisole, were unsuccessful [74].
• If patient has Hepatitis D, several drugs have been evaluated as alternatives to interferon. They include ribavarin, foscarnet, acyclovir, Suramin, THF gamma 2, lamivudine, and famciclovir and Antisense therapy. Overall, the results are discouraging.

FOLLOW UP
• If patient is asymptomatic HDV carriers with normal ALT levels, they do not require therapy but should be monitored for signs of active disease [74].
PRIMARY PREVENTION
• If patient is to be prevented from Hepatitis D, the mainstay of prevention of HDV infection is vaccination against its helper virus, the HBV [75].
PREVENTION AFTER LIVER TRANSPLANTATION
• If patient has Hepatitis D, passive prophylaxis with hepatitis B immunoglobulin has not completely prevented reinfection of transplanted livers by HDV [76].
• In some patients, HDV virions were able to infect and replicate within the liver allograft. Nonetheless, HDV infection is abortive and does not result in recurrent liver disease unless the allograft is simultaneously reinfected with HBV [76].



PROGNOSIS
• If patient has Hepatitis D, in view of the poor overall response, it is difficult to identify factors that may predict response. The only feature which may be associated with an increased likelihood of response is a short duration of disease [74]


HEPATITIS C

• Hepatitis C virus (HCV) is a major public health problem and a leading cause of chronic liver disease
• Hepatitis C virus, a member of the Flaviviridae family, was discovered as a new viral agent of non-A, non-B hepatitis virus by Choo and co-workers in 1989 [77].


DEFINITION
Hepatitis C is an inflammation of liver caused by hepatitis C virus, a virus of Flaviviridae family causing usually chronic hepatitis [78]

DIAGNOSTIC CONSIDERATIONS [79]
• Infection with the hepatitis C virus (HCV) can result in both acute and chronic hepatitis.
• Acute HCV:
Clinical Description -
An acute illness with
• Discrete onset of symptoms consistent with acute viral hepatitis, and
• Jaundice or elevated serum aminotransferase levels (ALT)
Laboratory criteria -
• Serum aminotransferase levels >7 times the upper limit of normal, and
• IgM anti-HAV negative, and
• IgM anti-HBc negative (if done) or HBsAg negative and
• Hepatitis C Virus Antibody (Anti-HCV) positive (repeat reactive)by an enzyme immunoassay
(EIA) with a signal to cut-off (s/c) ratio of > 3.8
Or
Anti-HCV positive (repeat reactive) by EIA, verified by an additional more specific assay (e.g.
recombinant immunoblot strip assay [RIBA]* for anti-HCV or RT-PCR for HCV RNA [Test to
detect HCV RNA by amplification of viral genetic sequences]
Or
• Anti-HCV positive by RIBA alone
Or
• HCV RNA positive
Chronic HCV:
Clinical Description -
The course of chronic liver disease is usually insidious, progressing at a slow rate without
symptoms or physical signs in the majority of individuals during the first two or more decades
after infection.
Laboratory criteria -
• Hepatitis C Virus Antibody (Anti-HCV) positive (repeat reactive)by an enzyme immunoassay
(EIA) with a signal to cut-off ratio of > 3.8
Or
• Anti-HCV positive (repeat reactive) by EIA, verified by an additional more specific assay (e.g.
RIBA for anti-HCV or RT-PCR for HCV RNA)
Or
• Anti-HCV positive by RIBA alone
Or
• HCV RNA positive